Nutrafol for Acne, Top Skin Care Ingredients, Hand Eczema Advances & More

[Music] Welcome to Derms on Drugs. A video podcast brought to you by scholars and medicine, the best educational platform in dermatology, and provided at no cost to medical providers. Derms on Drugs is where cutting edge derm meets Cedar Miss Comedy. A meds ire is in each week I'm joined by my residency buddies Dr. Laura Ferris and Dr. Tim Patton to use our 60 years of combined derm experience to discuss, debate, and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of derm and you'll actually have fun listening. New episodes drop every Friday on scholars and medicine, Apple podcasts, Spotify, and other major podcast platforms. Just a note for everybody, the video component has the key figures and tables from the articles we talk about and the episode description has a link that'll get you to the links to the articles and other resources that we discuss on the episode. So this week we've got one of our patented six pack episodes where we are going to go through our six favorite articles from the recent literature and we are going to jump right in with Dr. Ferris. Dr. Ferris, what do you got? Okay, Matt, so my first article was in the Journal of Cosmetic Dermatology, Zoe Drelos, at all. And this is a 12 week randomized double-bind placebo-controlled trial for the efficacy and safety of a novel, Nutri-Sutical for mild-demoderate acne. What is that Nutri-Sutical? It is Nutri-Full Acne. Okay, what is a Nutri-Sutical? These are basically things that are botanicals but it doesn't like beat the criteria to be a drug. So it goes through a different approval process. But this is basically a combination of a bunch of things that address the root cause of acne. I think we all get tired of hearing the words root cause from patients. But that is what they do. So root cause stress, you address that with holy basil? Diet? What's that? Nothing. I love that name. Holy basil. And on our, you know, an honor of our new Pope, we've got holy basil. Not sinful basil. Holy basil. Holy basil. Okay. All right. Burberry. For diet, metabolism, hormones, macchia, HP, and selenium, the microbiome, the couple pro and postbiotics, oxidative stress, some Sicilian orange, lycopene, and the whole of extract, ginger, extract, and then the immune response curcumin. So it gets at the root cause of acne. Okay. So this is a 12 week randomized double-blind placebo controlled study, which you don't always see with neutrosuiticles. This was only done in women who had mild to moderate acne. They were washed out of all their other acne products, like top of all retinoids. And they were put on a standardized skin regimen, and they had a planzer, cedar fallotian, and some, neutrogenous sunscreen. And they were given that. And then they had the option of using a rescue medicine, which was a dappelin 0.1%, but nobody did it. Okay. So what were the inclusion criteria? They had to be women 18 to 50, mild to moderate acne, like five inflammatory lesions, ten non-inflammatory lesions. And IGA of 2 to 3, so this is a score of 0 to 0 to clear, to 4 severe, so 2 is mild, 3 is moderate. So at baseline, the groups were pretty matched. They had an average IGA of 2.2 and 2.3. And then if you look at, you know, then the patients were given their medication at week 12. And the mean IGA for the active group was went from 2.2 to 1.47. And in placebo, it went from 2.33 to 1.98. This was a statistically significant difference. The percentage of subjects that were clear or almost clear, meaning they had an IGA of 0 or 1, was greater in the active group by week 8 and continued to increase to week 12. So it was 44% in the active versus 13% in the placebo group, or clear are almost clear. The percentage of subjects improving over the course of the study was also significantly greater. What did not differ, which was kind of interesting, was a lesion count at week 12 between the two groups. Now, if you look at the graph, you'd be like, that looks like a statistically significant number. But what they found was that the p-value was showing that the lesion count was statistically significantly different at week 12. Then it was at baseline, but the two groups did not differ between each other. So wait, wait, wait, wait, the two little asterisks that they have are just saying it is statistically significant from baseline, but not to compare to each other. Not compared to each other. A lot of acne studies do that. They have the two asterisks, and you're like, okay, yes, statistical significance, but they're comparing it to the baseline, not to each other. Right. Pastards. Pastards. Yeah. Which is weird, right? How do you get great, like the, how do you get a much better score to getting to clear or whatever almost clear when there's no difference in lesion count? That didn't make any sense to me. Yeah, I have a hard time, and I don't do acne studies, so I'm not super well calibrated on, you know, how that would be. But it would seem, I mean, maybe there's like, so one of the things that they did do is they had readers basically look at photos, and then they looked to say, you know, what percentage of subject achieved a zero or one in different parameters? So, you know, post-inflammatory, air-thema hyperpigmentation, scarring, tone, smoothness, softness, overall, you know. So they did, like, it does seem like, you know, there's probably a difference in things like hyperpigmentation, air-thema, scarring may have looked better. So I guess you could say that there was an improvement. So, you know, so I thought that was kind of, that is maybe like if you're doing a global assessment, you're not basing it on the number of lesions, you're basing it on all these other factors as well. I mean, it's a great drug, right? I can't wait to tell the patients that are like, I don't want to do antibiotics. Yeah, I don't want to be antibiotics. I don't want to take anything that's going to mess up my hormones. Isitretinoans is going to give me depression. Please help me. I'll be like, I have your answer. Yeah, I went and I looked up it, like, I was like, let me look at studies of like, cab trio and win levy to see what they looked like. And so, you know, if they look at like treatment success, they'll find like 50 for cab trio, it's about 50% in the cab trio group versus about 25%, 20% to 25% in the plus vehicle group. Inflammatory lesion reduction, they did see like a significant difference. It was like 75 to 80% reduction with cab trio versus about a 60% reduction in inflammatory lesion count with vehicle. And so, you know, they did. And then win levy was IGA success, so clear, almost clear, sort of the same endpoint. It was 18% in the win levy group versus about 9% in the vehicle group. And were they enrolling mild moderate in those trials? Or they're enrolling moderate severe? So it is a, it is a, harder to harder endpoint right because the two point improvement is, yeah. Yeah, as a child. Yeah, IGA success, cab trio, about 50% win levy, 18 to 20%, but you know, there is a difference here. So, you know, I agree, like I like the idea that like this is not an antibiotic. There are a lot of patients who don't want an antibiotic, they want something natural, they want to get it the root cause of their acne, gosh darn it. And I can like now say that this will do that. It is out of pocket about 80 bucks a month. Yeah, they don't need our prescription, they don't need refill. I like, I can't wait to start telling patients about it. Only if they like refuse isotretinone. Yeah. Don't get me wrong. I'm still giving my. Yeah, and this is not our citretinone level of patients. So, yeah. Yeah. Oh, I think mild acne totally deserves isotretinone. Yeah, that's when my, when my daughter got like four pimples at once. Isotretinone. Yep. Yeah. Yeah, it's crazy to me how many, it's a, I really believe there's a huge nocebo effect with isotretinone. It's the reason that that anybody gets depressed on it is because they read they could get depressed on it. Yeah, absolutely. And then if they just naturally normally get depressed, they base blame it on the isotretinone. Yeah, I agree. Yeah, I get to. So, so you guys are both going to, so 80 bucks, see 80 bucks seems, it's a thousand dollars a year, but I guess if you've got acne and you're one of those 44% who get to clear almost clear. So, I guess the thing to tell people is, hey, you, you know, go on this. There's a 50, 50 chance. It's going to be amazing for you. And after three months, if you're not doing amazing, probably not worth it, but, you know, you spent 250 bucks. bucks to find out, it'd be, I feel like it'd be smarter the company to give like three month starter packs, you know, or something like that, let people find out if it was going to work or not, because that $80 is a pretty big sticker price. Yeah. Sometimes co-pays are that much. And you know, also like, this may work in combination with some, you know, topical retinoid, right? I mean, so this is monotherapy, who knows what it's going to do in addition to, you know, benzoyl peroxide, treadmill in and clindamysin, right? So I think it'll be interesting. I like having it as an option. Yep. What I've been doing a little more of lately is, especially for postmen, apostle women or for guys, is just very low dose, acutane almost indefinitely. So like 10 milligrams, three times a week, because you don't really get any dry anything. And it's actually really, really effective. So she can't do it for women of child-bearing potential, because it's too hard to, it's too much, it is a real risk that people are going to accidentally get pregnant if you have on it for years. But the low dose long term for isotretino, and it has been really good. Yep. All right, let's move on to our next article. So again, that was for just before I forget, because we're not sponsored by anybody, so I don't want anybody to use a plug, but that was for the neutrophil acne. And people get it on Amazon, or do they have to buy it in a Durham office? Like you have to sell it online. Yeah, I looked it up. You can buy it online. I don't know if Amazon specifically, but. Okay. Let's say from neutrophil. Yeah. Yeah, I'm going to get the counterfeit stuff from Amazon that's got lead in it. But it'll be $65 a month for an ineffective toxin. So it'll be fine. Good. All right, Pat, and what do you got? All right, from the JAD, and available in April 2025 titled, Skincare Ingredients Recommended by Cosmetic Dermatologist, a Delphi Consensus Study by Gabriela V. Alvarez at all. I've been excited ever since you picked this article. I hate abs. I love this paper. Like I love it. I will reference this probably more than any other thing that I've read in the last five years. So what did they do? Literature review from 1990 to 2020 generated a list of 318 ingredients. And that got whittled down to 89 ingredients by one group of experts. And then those 89 ingredients were evaluated by a second group of experts. And it went through two rounds of the Delphi panel made up of cosmetic dermatology experts. If 70% of the experts gave an ingredient a ranking of 7 to 9, 1 being the worst, 9 being the best, and no more than 15% of the experts gave it a ranking of 1 to 3, ingredient was said to have reached consensus for the condition being studied. So the final answer is in Table 2, a list of ingredients that we can now tell all our patients experts recommend for fine lines and wrinkles, acne, redness, dark spots, large pores, dry skin, oily skin. Table 3 goes through the consensus ingredients and lists the evidence supporting their use. So there's some signs here. So I didn't let me see. Yeah. So these are the ingredients. So for fine lines and wrinkles, it's mineral sunscreens, retinoids, vitamin C, chemical sunscreens, for redness, mineral sunscreens, sulfacetamide, nice cinamide, green tinted products, metro, brumondidine, iburemectin. Right. And when patients are like, well, what about for large pores? Experts say retinoids. That's it. They looked at other stuff, but they're not recommending it. It's a really, really table two. I am going to carry this around with me every day and I will bring it out all the time. And they did look at things like they looked at things like growth hormones and peptides and how uronic acid and they didn't make the cut. So we can tell those patients, yeah, don't worry about that stuff. All these experts said that is advertisements and a bunch of crap. Class go to Rome talking about win levy, didn't make the cut. But I think that that's things like this highlights what's often discouraging about being a dermatologist, right? If somebody comes in and says they tried their sisters win levy and they absolutely loved it and it worked so much better than anything else they ever got, like I'm not going to say, hey, yeah, experts said it was crap. I'm not prescribing it. I tell them it's great. I send in a script and I don't think that happens with like real doctors. Like no one goes to their oncologist saying I tried some of my sisters at the carbosing and it worked way better than your boy. You know, and one of the things from personal experience, like I use mineral oil for my dry skin, I just put it on right after I shower. And you know, the expert said, yeah, mineral oil, that didn't make the cut. But so like, are they just making stuff up like systemine hydrochloride? That has good data for treating the lasma. Did it not make the cut? Because experts didn't like it. I don't know. I don't know what to make of this. Like I don't know how real this opinion, expert opinion is, but it's just going to be very helpful because I can voucher patients and say, here's what experts say. So see, I think systemine has had good evidence for, and what I liked about this article was it's not evidence because so many of these ingredients, we don't have like great because no one's going to spend, you know, $20 million to do a study for, you know, a topical that cost nine bucks. But so what we're getting here is really the, when you look at the list of authors, it's like a lot of the heavy hitters in the aesthetic space. And so I think it's a blend of like what have they seen in their patients, you know, what they did. They went through like what re-fernal consensus, they went through what evidence was available. And most of it had like one B to B evidence. It's not like there's none studies have been done, one B like the really good studies to be smaller, but like still a study. And then the two things that that had actually no evidence was the green tinted like cream to reduce erythema and benzal peroxide to treat oily skin. So experts still recommended it with very little evidence. Most of the other stuff actually had good evidence, but right, some of the stuff they said was not good also has good evidence. So I'm curious like what about that makes them say we didn't recommend it. I don't know. Like it's their experience. So I hadn't thought of using this list that way. I'm going to use it now because this is all stuff you can give to a patient and say go find a good product on Amazon. Find something or online. Look for stuff with good reviews and whatever. Make sure you're getting the real stuff. But yeah, this does make a ton of sense. I hadn't thought about how useful it could be. And you know, the newer stuff, the growth hormones, the peptides, how are you on a acid? I think it'll be great to be like, yeah, as of now experts like looked at that. They said no. I don't know. I mean, from Dr. Ted Lane, I'm now a big believer in exosomes. And he was not included and that is kind of disappointing. That is. That is. They were probably intimidated. Didn't want to bring on the real experiment. He's the germs on drugs like cosmetic guy. Yeah, he should have been included. I don't know if I trust anything anyone else would say. Yeah, I would agree. Ferris, you got anything to add about this? No, I agree. It's just nice to be able to say like the pain in my existence is like, like, what do I do about large pores? I've adopted the phrase, I'm a doctor who treats disease. I'm not somebody who does skincare, but now I can say if he want data, here's what it is, but I'm not going to do a prior off. Go get a retinoid. Go get some OTC adapolline. Exactly. No, no pearl for everybody that I actually really like. If you ever get a patient who's asked about like wrinkles and whatever on their arms and their body and the whatever, retinoids work. They have some effect even at very low concentrations. I will have people get a 30 gram tube of OTC adapolline, squeeze it into a jar of usually serivie, but it could be C to fill or V whatever. Probably would if you did it forever, but it's cheap and easy. That's what I like. Cheap and easy. That's right. Let's go on to my studies. I've got two that we're going to do back to back and this is going to be a topic that I think we're all starting to see more and more about because Leo has a drug coming, Delgocytinib, and so there's turned into a lot of disease state awareness messaging for hand eczema. We had a couple of really useful things that just came out. The first one that I want to talk about is the head to head trial of Copicodelgocytinib, which we're expecting to be approved here in the next couple of months in the US already approved in Europe. So Topicodelgocytinib, Creme versus oral, allotrettonone capsules and adults with severe chronic hand eczema, Delta Force, so named it after a cheesy movie from the 90s, I believe, a 24 week randomized head to head phase three trial. So essentially people had to have severe hand eczema, which when you look at the way that the IGA was developed like there, people that we would say had severe hand eczema could be any It wasn't like, oh, you had to get patch tested and got contact dermatologist. If you had a hand excement, it was severe. You could be in the study. People got randomized one-to-one to either delgocetinum cream or alitretinone capsules. And the alitretinone is a systemic retinoid side effect profile. Not that different from, say, serriotane. It depends on the dosing. I likely already get dry skin and that kind of stuff. But alitretinone, 30 milligrams, ones daily, which could be reduced to 10 milligrams a day. And really, what it showed, the delgo was substantially better than the approved oral drug. So alitretinone is approved in the EU and Canada. It's the only drug out there that's been approved over the years for chronic hand excement. Now they've got delgo as well. But it was clearly better, like, meaningfully better. Asian, hexiae. At baseline, the average hexiae score and hexiae is hand-to-exemist severity index. You could think of it. Same general concept as a passie or an easy score. So it's a zero to 360 scale. But severe usually is considered to start at about 70. And so the mean hexiae baseline was 92. Of the delgocet inhibited patients, a significant number, so about 40%, 39% to be exact, got to hexiae 90 at three months, as opposed to 26% of the alitretinone patients. So about 50% more people got to, in fact, exactly 50% more people got to hexiae 90 at three months, which is a big deal. But it was interesting in the study, patients could, it was a really kind of cool design. Once people got better, the investigator could stop the drug. And then whenever if the disease came back, they would restart it. About 28% of delgo patients got so good that they stopped the drug, 20% of alitretinone patients, same thing. Both groups, about 60% of the patients restarted at some point. But that explains why in the figure showing hexiae 90 proportion, you saw the delgo have like a drop from week 16 to 20. And that was because at week 16 is when they could stop some people. And then they stopped them. And so they lost hexiae 20 or hexiae 90 and then they restarted and regained it. But so, you know, useful data, 40% of people did spectacularly well. They didn't really give data that on say in the main article on say hexiae 50, which is sort of the like in my mind, the okay, the drug is like, we're helpful. So, but good numbers. And then we got a second article. So for our listeners, you know that here in Derms on Drugs, we love oral reflumalast. Basically a free drug. So about six bucks a month through Mark Cuban's Cosmos Pharmacy and think of it as a premalast that is more potent, but exact same adverse event profile, GI side effects, but not maybe depression, but no immunosuppression. So in this study, it was an open label, 14 patients with chronic hand-examemine baseline hexiae of 86. So these people had, you know, hand-examemine that was comparably bad to the double-sit to nib, allotretto-noan trial. Of those 14 patients, 13 got to three months. So only one of the 14 dropped out in those first series of months and that was due to the adverse events. And the vast majority of the patients had GI adverse events at some point. So I think four didn't have any GI side effects, but so, you know, 75% of them had some GI side effects, which I think is a useful number to keep in mind. And so of them though, at three months, so pretty comparable to the study we were just talking about, about 29% got to hexiae 90. So four out of 14, so we're right, this is, we're doing an intent to treat analysis. So the person who dropped out, we're still counting them. So four out of 14 got to hexiae 90. Nine patients made it to nine months. Eight of those patients got to hexiae 50, so over half of patients, so eight out of the original 14, it at least got them what I would call very meaningfully better. And the nice part about this drug, you know, once Delgo comes out for hand-examine or, you know, to a significant extent, you could call a lot of hand-examine atopic derm and you could use Fatama or Absulara or Zorevi if you wanted to. But so Delgo is going to be the only one that has an FDA approval for chronic hand-examine of all types. You can use Ruflumales together with Delgo. And I think it's going to be, they're mechanistically, they're so little overlap. I actually think we're going to have super effective treatment for the vast majority of patients with hand-examine. If we, assuming we're able to get the Delgo covered. So really nice article gives an idea that this is probably in the same ballpark as efficacy as Delgo. But so now we've got a good oral that will be available in the U.S. that's very safe and easy to use. Not terribly effective, but safe and easy to use and cheap and, however, a highly effective topic, although we compare with it. Any thoughts or comments from you guys? Yeah, I thought they were, I mean, I thought it was interesting and it's going to be good to have options for these patients. I oftentimes use like Acetret and, I mean, as long as it's not totally exemotous, like if it's like hyper-charitotic. But yeah, I think it's interesting and, you know, more options is always good. Yeah, it's Pat and what do you, any thoughts? No, I mean, why does Delgo go up against steroids? That's what I would want to see. Because I think if this is anything like topical, rectilidib, it's just going to be hard to get and am I just going to be like, just steroids might be just as good. Well, it'll certainly be, you know, for hand excellent particular. I think everybody will give a trial of glubators all first and then if it doesn't work, we'll go to Delgo. The challenge with hand exema is that every case of hand exema has a component of irritant germ. While glubators all helps with the inflammatory component, it makes the underlying irritant germ worse by impairing barrier formation. So it'll be interesting, right? Once we get to play with it because nobody in the US is used any Delgo. The trials were completely done in the EU. So I have no sense of like, how does this compare to say, "Obsolera" or "vitamor" or "Zareeave"? Just don't know. That would be interesting to see. All right. Let's move on to our next article. We're back speaking of Zoreeave. We're back over to Dr. Ferris. What do you got? Back on Ruflumalast. This time talking about the foam or Ruflumalast foam 0.3 percent for psoriasis of the scalp embody the erector phase 3 randomized clinical trial. Melinda Gooderham at all just published in JAMA dermatology. So phase 3 double blind vehicle controlled randomized clinical trial. So patients were 12 and older. Plac psoriasis affecting up to 25 percent of the scalp embody, but they had to have at least 10 percent of the scalp involved. They also had to have non-scalp involvement as well. So they had to have. Wait, it wasn't an either or it was they had to have both scalp and body. No, sorry. I said that wrong. So they had. No, yes, sorry. They did have to have scalp and body. So they had up to 25 percent total. They had to have at least 10 percent of the scalp involved and up to 20 percent of non-scalp involved. Sorry. Okay. They also had to have a scalp IGA of at least 3, which is moderate. So they had to have, you know, significant scalp diseases. It wasn't just like a little bit of flaking. And then a minimum body IGA of 2, which is mild. No primary importance were scalp IGA and body IGA success, which is clear, almost clear with the two point improvements of 0 or 1. And this wasn't 8. This is at week 8, okay. And so a 432 patients at week 8, basically 2/3, 66.4 of the flume last group achieved a scalp IGA success versus 27 percent in the vehicle. And in terms of body IGA, it was 45.5 percent of flume last versus 20 percent of the vehicle. So I thought this was really interesting. You know, one foam is something that sometimes patients really like to. The efficacy in the scalp was really good. Like tooth and it was better than what we saw on the body. So, you know, other things that were. How is that possible? Fairs. Because normally the scalp is. Like you think of scalp as a reason to do systemic therapy. because topicals don't work on the scalp. So how can I say that? - I think scalp psoriasis is a different entity and that it overlaps with sort of sebaria versus body psoriasis. I just think psoriasis on the scalp is different. I think it behaves a little bit differently. I think it is probably driven by other factors. Like, you know, the scalp oil is very different than the sort of microbiome of the body. I think that it responds differently. I don't know, Pat and what do you think? - I know, did the patients have to have hair? But that matter. Like if you're a bald, is your response just like the skin? Like is there something the hair mixed with the zuri is doing? - So most people had hair is my assumption. And if you look at their photos, most people, I mean, I was only two pictures. - I like two pictures. Yeah. My guess is this was not a study full of bald men. (laughing) - Pat, did you get invited? - Even you. - I thought pretty good coverage. - Yes. - So wait, I talked to the company about this and I have a theory for why it's better on the scalp. And my theory is this, the vehicle that they used is codifoss and the reflumless itself. They're negatively charged and your hair is negatively charged. And so, right, whenever, if you think about like, here's a hair. If you put a drop of this foam on there, it should spread. It's trying to get off the hair. And so it's being repelled by the hair. So it spreads in both directions. Well, if you're putting it on near the scalp, so we'll say here, as it spreads in both directions, it's actually pushing it down into the follicle. And so I think, and this is totally made up. - So my hair, the hair versus bald is, that's a good. I think you're right on. I think that it uses the hair as a delivery mechanism. - Okay. - That is my, that is my use for reflumalist foam. 'Cause for sebderm, I think I did the trials, 93% of people had scalp disease. So it was hard to like separate out in the trials. But my experience is, I think it's a really good for sebderm on the face in other places. Miracle for sebderm on the scalp. And that got me, was what got me thinking about this originally, it's like, how can it work so well on the scalp? That is my made up answer, is that it's using the hair shaft as a delivery mechanism. - All right. Is that a different like, Olax foam? Does not have that super repound? - No, they are like very proud of their vehicle. It has like, yeah, this like-- - I've seen that. - Yes. I can't explain the science of it super well. - Oh, I can. - So Matt, are he gonna make up some science? - I always, when-- - They are made up, be real. When drug companies talk about how great the vehicle is, I'm like, okay, your drugs are not that good. - Yeah, I agree. I agree, but here's what's special about there. So this, it's that the surfactant is not a surfactant, is what is very unique about it. So they had to do special trials to be allowed to use this ingredient. It wasn't previously FDA approved for use in vehicles. And basically with it, you can think of it as, it's a solid up to 140 degrees. When it gets to 140 degrees, it melts. And then it's a surfactant. And so they make the product at 140 degrees to disperse at all. And then when they cool it all back down, it now sort of, you can picture it as like recilifying into tiny little specks, but those little specks are no longer a surfactant. So there's, it's the first cream in history that you can legitimately say, there's no surfactant in the cream. Because surfactant, you have to have it in there to allow the oil and water to mix. Well, they mix them in high temperature. Then whenever it came down to high temperature, now there's no surfactant in there. And so I also like this a lot for things that have it, like I'll use it especially in the face. If somebody's got dry, irritable skin, I think this is a, as a moisturizer would be them, probably be the most effective cream moisturizer I've ever had because of this unique idea of heating it up, making it a surfactant and then cool it back down. Now it's not a surfactant that's going to interrupt your skin lipids. Yeah, now and it should, it looks like they have these nice drawings of their little micellular things and now they go into the lipid bilayer. So yeah, so essentially, so just a couple of like quick, interesting things. I was like, all right, is the foam really better? So I pulled the New England Journal phase two data and IGA with the cream, right? So same drug, but in a cream, not, you know, not a foam. So their IGA success was 31% versus 14% in vehicle. So that's like a Delta, you know, the spread between them of 17% on the body. If you look at the foam on this study, the Delta is about 25%. So there actually was a bigger separation. But if you look at the scalp, it's like 38.6%. So it does look better. And then I was like, all right, how about like a premise? They did scalp studies. Their phase three B, if you look at, you know, the patient, what percentage of patients were clear or almost clear with a premise? It was 43% at week 16 versus 13% on placebo. So that is kind of like a Delta of, you know, again, 30%, which is actually not quite as high as it was for Zory foam. That is my post-talk analysis comparing two trials, which you should never ever do comparing three. Really? Yeah. So the bio statisticians are going to shut down UNC dermatology for people to stop. Exactly. But now I thought it was interesting. So I have a very good luck with Zory foam. So I am, it was good to see the data. And that's where I do that study. So I also have to give you the kudos that you did convince me of like that Zory cream. It has a role that the long term, we know the mechanism of actually we know it's safe. That there is a real, it's got a meaningful place in a topic dermatitis therapy because of that, the long safety record that we've got with PDE4 inhibitors for little kids with a topic term. So thank you. Good. Hey, anything. I'm here to serve. The servant leadership. That's right. That's how you got that chair job. Exactly. All right, Patton, what's your last article here? May 2025 issue of American Journal of Dermatopathology has tied to clinical pathologic features of Prame positive common melanocytic Nevi case control study by Ronin Niddle at all. We talked about Prame when Dr. Whitney High was our guest. So Prame stands for Preferrentially Expressed Antigen and Melanoma, which is actually Peme, not Prame, but let's move along. It's felt to be relatively sensitive and specific for Melanoma. Dr. High said like in the last 10 years, what has been the biggest thing? And he mentioned Prame when we were talking to him about that. So in the introduction, the authors, they all work in Australia. They mention that it's not infrequent to see otherwise benign legions be stained for Prame. And then referred for second opinion because of Prame positivity. So during a one month period, their religions coded as benign Nevi with Prame staining before performed. And after some exclusions, they basically came away with 41 Prame positive legions and they compared these to 43 Prame negative legions. They didn't really say how they selected the negative ones. I mean, I got interested in that. So I dug into it. I used AI and fed the article in. They basically took 43 consecutive-- just the first 43 that came in, 43 consecutive Prame negative ones. Because that was my-- how did they match? They didn't match them. Right, right. I read that, but like consecutive from the beginning, from the middle, around the tip, just 43, they were negative. But I mean, so the number of Prame positive legions, so it was like 800-some benign Nevi. The pain for Prame. Yeah, that got stained for Prame. Only 62. So it was like 7.7%. And then they excluded partial ones. And then there was a melanoma in site too. They're like, that's not part of our study, because that's not benign. And there was one that was a typo, whatever. So that's how they got-- they whittled it down to like that 41. I just-- you get whittled twice. Podcast. Yeah. Of course, I was still a little-- [LAUGHTER] So the legions were examined by three Derm Pass. We didn't know the original diagnosis or the original Prame staining. And they were scored as no atypia, mild atypia, severe atypia, and then scored on a five point scale for Prame staining. The Prame staining was-- don't much to say there. It was pretty reproducible. Like what was called Prame by the original Dermotot-- like, Prame positive. It was also called Prame positive. Like there weren't any discrepancy of that. So that's good. Prame staining seems to be pretty reproducible and consistent. Compared to Prame negative Nevi. Prame. Prame negative Nevi. Prame positive Nevi more often demonstrated solar elastosis and lentiginous growth. That reached statistical significance. Prame positive Nevi more often had hypermelanosus. But this wasn't statistically significant more than Prame negative Nevi. Figure one, I think, really was kind of impressive. it suggests. preinstaining seems to influence the pathologist assessment of atypia. So if you look at the original diagnosis where the pathologist knew what the preinstaining was, way more lesions were classified as having severe atypia. So when the pathologist had no idea what the preinstaining was, so the three dermatopathologists that kind of were reviewing these cases did not know what preinstaining was. Only three of the preinstaining positive knee-vi were classified as severe. The original dermatologist like 22 of those preinstaining positive knee-vi were stained of severe. So like preinstaining is influencing seems to be it's influencing the diagnosis of severe atypia. This does have clinical significance. Reicision was performed on 44% of the preinstaining positive knee-vi read by the original dermatologist compared only 19% of the preinstaining negative knee-vi. So yeah, it's that has to be I would think because preinstaining positive knee-vi are diagnosed as having severe atypia. It's that is very analogous to so when I was a residency director, I got really into the research of like interviewing people and it is the same thing you're not. If you look at someone's CV in grades before you interview them, it dramatically influences your if we if you then say, okay, now tell us how the interview was don't think about their grades or their CV. Just tell us how the interview was. If they had a great CV, you were like if they were like a weirdo, you're like, well, they're a little bit odd in the but they, you know, very smart. Just blah, blah, whereas if they're like at bad grades and whatever and they were a little bit odd, then you're more like, oh, they're just weird. They wouldn't be good in the blah, blah, blah, blah. So yeah, that pre-existing knowledge influences what is supposed to be an independent assessment. So it's kind of the exact same thing here, pre-existing knowledge of frame makes people more likely to call atypia. Interesting. It was like these are tiny lesions, right? I mean, I think it's like three to four millimeter lesions. Do you guys Bob see three to four millimeter melanocytic? I mean, like just as a general rule, I'm like, this is too small. I mean, if it looks really atypia, I mean, I've had, we've all three or four millimeter diameter melanomas, but I don't know if I have because I've not been biopsy. There you go. You would miss in them. They came to me and I biopsy them. They got a second opinion. No, I agree. I'm much more thoughtful about, you know, size as a factor for considering that. But yeah, I think, you know, it's like, you really need clinical pathologic correlation. It frame is not the magic bullet. So it's like, you need your kind of pre-test probability, right? So if this is a three millimeter, Nevis, that the pathologist thinks looks benign, and then you go stain it with frame, you're like, don't even go straight, stirring it, stain it with frame, right? It's like when we talked about GEP, if it's a point two millimeter, point three millimeter melanoma, don't get GEP. The pre-test probability is so low that that is going to be a metastatic melanoma that, you know, you don't have the predictive value of the test becomes very poor, right? Pre-test probabilities key. It's similar. They were willy nilly like staining everything with frame. They had like 800 lesions in one month that they stained with frame. Yeah, so the other take would be like call your, call your atypia before you know what the frame is. Like that seems to be the lesson here. And maybe for severe atypia that is frame positive, maybe that those are the real, you know, incipient, what's the report we get? May represent an early evolving melanoma in site two. Like maybe the frame positive severe atypia, where you classify severity before you even know what frame is, maybe those are the real melanoma precursor lesions. I don't know. I'd like Dermpass to be to be more honest in the reports and say may represent a lesion I could get sued over. So you should re-excise it. I'm always so grateful that I'm not the one who has to make that final call. I respect our Dermpass. That would be so hard to have to make that call. I thought about doing Dermpath and the reason I didn't was because I literally didn't do a Dermpath Fellowship because I didn't want to have to do that. Yeah. That was before frame now with frame. Maybe you should reconsider that. There's a ton of pharma money in Dermpath. You've been sitting right in. Big frame, big frames out to get you. All right. Those were some good articles, a good clinically useful six pack and any final comments for the week here, Dr. Pat and Dr. Ferris. I'm good. No. Saving lives. Saving lives, right? Skins doing it. It's right. Exactly. Who was talking to somebody recently who didn't know that there was a TV show called Pimple Popper MD. Whenever I brought up, oh, Pimple Popper was there. They were like, "Sinephob was there." They've been moving on here. Rock everybody. Have a clinic day where nobody mentions Pimple Popper. That's very surprising to me. It was bizarre. It was hard to believe. I want to thank everybody for joining us today. If you got questions, comments, ideas for topics which cover on the show, shoot us an email at termsandrugs.com. I hope you learned a few things with the last one-ster twice and mostly we're hoping you're planning to join us next week. Until then, I'm Matt Cyrus. I'm Tim Patten. I'm Laura Ferris and we are gyrmsandrugs.