Podcasts about Translational research

Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe, wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

Cory grew up in Maine and after spending time as a sea kayak guide and a ski instructor, found his way to biology and laboratory research. Currently a Postdoctoral Researcher in the Haller Lab at MDI Biological Laboratory, Cory is interested in the cell biology of kidney vascularization and uses renal organoids and zebrafish to investigate how we may, one day, be able to rebuild the kidney and develop non-donor solutions to kidney transplantation.Cory was one of the 5 Minute Genius™ speakers at this past year's Maine Science Festival; you can see his talk on our YouTube channel.This conversation was recorded in May 2025. ~~~~~The Maine Science Podcast is a production of the Maine Discovery Museum. It is recorded at Discovery Studios, at the Maine Discovery Museum, in Bangor, ME. The Maine Science Podcast is hosted and executive produced by Kate Dickerson; edited and produced by Scott Loiselle. The Discover Maine theme was composed and performed by Nick Parker. To support our work: https://www.mainediscoverymuseum.org/donate. Find us online:Maine Discovery MuseumMaine Discovery Museum on social media: Facebook Instagram LinkedIn Bluesky Maine Science Festival on social media: Facebook Instagram LinkedInMaine Science Podcast on social media: Facebook Instagram © 2025 Maine Discovery Museum

On today's show we're excited to welcome Rick Peng, the Innovation Hub Manager and Digital Licensing Professional at Memorial Sloan Kettering Cancer Center. We talk about how your organization can build an outside-in, external innovation program to deliver outsized results. Rick breaks down the secret sauce of the MSK Innovation Hub, an accelerator program designed to encourage collaborations between Memorial Sloan Kettering Cancer Center and digital health companies, focused on the diagnosis, treatment, and care of cancer patients. We discuss their new Innovation Hub Challenge focused on AI Drug Discovery – and why the access to data sets, is a key unlock for ai driven solutions.

Spontaneous intracranial hypotension reflects a disruption of the normal continuous production, circulation, and reabsorption of CSF. Diagnosis requires the recognition of common and uncommon presentations, careful selection and scrutiny of brain and spine imaging, and, frequently, referral to specialist centers.  In this episode, Gordon Smith, MD, FAAN speaks with Jill C. Rau, MD, PhD, author of the article “Clinical Features and Diagnosis of Spontaneous Intracranial Hypotension” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Rau is an assistant professor of clinical neurology at the University of Arizona, School of Medicine-Phoenix in Phoenix, Arizona. Additional Resources Read the article: continuumjournal.com Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full episode transcript available here Interview with Jill Rau, MD Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Jill Rau about her article on clinical features and diagnosis of spontaneous intracranial hypotension, which she wrote with Dr Jeremy Cutsworth-Gregory from the Mayo Clinic. This article appears in the 2025 Continuum issue on disorders of CSF dynamics. I'm really excited to welcome you to the Continuum podcast. Maybe you can start by just telling our listeners a little bit about yourself? Dr Rau: Hi, thanks for having me. I'm really honored to be here, and I really enjoyed writing the paper with Dr Cutsforth-Gregory. I hope you guys enjoy it. I am the director of headache medicine at the Baba Bay Neuroscience Institute at Honor Health in Scottsdale, Arizona. I'm also currently the chair of the special interest group in CSF Dynamics at the American Headache Society, and I've had a special interest in this field since I first watched Dr Linda Gray speak at a conference where she talked about spinal CSF leaks and their different presentations. And they were so different than what I had been taught in residency. They're not just the post-LP headache. They have such a wide variety of presentations and how devastating they can be, and how much impact there is on someone's life when you find it and fix it. And I've been super interested in the field and involved in research since that time. And, yeah. Love it. Dr Smith: Well, thanks for sharing your story. And as I reflected on our conversation ahead of time and have been thinking about this issue… this is a cool topic, and every time I read one of these manuscripts and have the opportunity to speak with one of the authors, I learn a ton, because this was something that wasn't even on the radar when I trained back in the 1800's. So, really looking forward to the conversation. I wonder if you could really briefly just summarize or remind for everyone the normal physiology about CSF dynamics, you know, production, absorption, and so forth? Dr Rau: So, the CSF is the fluid that surrounds the brain and the spinal cord, and it's contained by the dura, which is like a canvas or a sac that covers that whole brain and spinal cord. And within the ventricles of the brain, the choroid plexus produce CSF. It's constantly producing and then being reabsorbed by the arachnoid granulations and pushed into the venous space, the cerebral sinuses, venous sinuses. And also some absorption and push into the lymphatics that we've just learned about in the past year. This is kind of new data coming out, so always learning more and more about CSF, but we know that it bathes the brain and the spinal cord, helps keep some buoyancy of the brain as well as pushing nutrients in and pulling out metabolic waste. And it sort of keeps the brain in the state of homeostasis that's happy. And so, when there's a disruption of that flow and the amount of fluid there, that disrupts that, that can cause lots of different symptoms and problems for people. Dr Smith: One of the many new things I learned is that even the name of this---spontaneous intracranial hypotension---is misleading. And I think this is clinically relevant, as we'll probably get to in a moment, but can you talk a little bit about this? Is this really like a pressure disorder or a volume disorder? Dr Rau: Yeah. It's almost certainly a volume disorder. We do see in some people that they have low pressure, and it's still part of the diagnostic criteria. But it's there because if you have a low pressure, if you measure an opening pressure and it's below six, if you're measuring it in the spine in the right place, then you have indication that there's low volume. But there's over 50% of people's opening pressure who have a spinal CSF leak, have all the symptoms and can be fixed. So, they have normal pressure in 50% of the people. So, it is an inaccurate term, hypotension, but it was originally discovered because of the thought that it was a low-pressure situation. Some of the findings would suggest low pressure, but ultimately, we are pretty sure it's a low-volume condition. Dr Smith: Another new thing that I learned that really blew me away is how bad this can be. I did a podcast with Mark Burish about cluster, and I was reminded many cluster patients are pushed to the point of suicidal ideation or committing suicide by the severity of pain. And this sounds like for many patients it's equally severe. Can you maybe paint a picture for our listeners why this is so clinically important? Dr Rau: A large number of people, even people who are known to have leaks because they've had them before or they've releaked, they have a lot of brain fog and cognitive impairment. They often have severe headaches when they're upright. So, orthostatic headache is probably the number one most common symptom, and those headaches are one of the worst headaches out there. When people stand up, their fluid is not supporting the brain and there's an intense amount of pain. And so, they spend a large portion of their lives horizontal. And there's associated symptoms with that, it's not just headache pain and brain fog. There's neck pain. There's often subsequent disorders that accompany this, like partial orthostatic tachycardia syndrome. We don't know if that's because of deconditioning or an actual sequela of the disease, but it's a frequent comorbidity. We have patients that have extreme dizziness with their symptoms, but many patients are limited to hours, if that, upright per day, combined, total. And so they live their lives, often, just in the dark, lots of photophobia, sensitive to the light, really unable to function. It's also very hard to find and so underrecognized that a lot of patients, especially if they don't have that really clinical symptom of orthostatic headache. So, it's often missed. So, they're just debilitated. You know, treatments don't work because it's not a migraine and it's not a typical headache. It's a mechanical issue as well as a metabolic issue and not found, not a lot helps it. Dr Smith: So, you know, I have always thought about this as really primarily an orthostatic symptom. I wonder if you can talk about the complexity of this; in particular, kind of how this evolves over time, because it's not quite that simple. And maybe in doing so, you can give our listeners some pearls on when they should be thinking about this disorder? Dr Rau: A large portion of people do have headache with spinal CSF leak, in particular, spontaneous intracranial hypertension- hypotension, excuse me. And that's something to be thought about, is that there are spontaneous conditions where people have either rupture of the dural sac, or an erosion of the dural sac, or a development of a connection between the dura and the venous system. And that is taking away or allowing CSF to escape. In these instances that patients have spontaneous, there may be a different presentation than if they have, like, a postdural puncture or a chronic traumatic or iatrogenic leak. And we're not sure of that yet, but we're looking into that. Still, the largest presentation is headache, and orthostatic headache is very dominant in the headache realm. But over time, patients' brains can compensate for that lack of CSF and start overproducing---or at least we think that's probably what's happening. And you may see a reduction in the orthostatic symptoms over time, and you may see an improvement in the radiographic findings. So, there are some interesting papers that have been published that look at these changes over time, and we do see that sometimes within that first three to four months; this is the most common time to see that change. Other patients may worsen. You may actually see someone going from looking sort of normal radiographically to developing more of a SIH-type of picture on the brain. And so it's not predictable which patients have gone from orthostatic to improvement or the other way around, both radiographically and clinically. So, it can be quite difficult to tell. So, for me, if I have a patient that comes to me and they're struggling with headache… if it's orthostatic, very clearly orthostatic: I lay down, I get considerably better or my headache completely goes away. And then when I stand up, it comes on relatively quickly, within an hour. And sometimes it's a worsening-throughout-the-day type of thing, it's lowest in the morning and it worsens throughout the day. These are the times that it's most obvious to think about CSF leak. Especially if that headache onset relatively suddenly, if it onset after a small trauma. Like I've had patients that say, you know, I was doing yoga and I did some twists and I felt kind of a pop. And then I've had this headache that is horrible when I'm upright but is better when I lay down ever since, you know, since that time. That's kind of a very classic presentation of spinal CSF leak or spontaneous intracranial hypotension. Maybe a less common presentation would be someone who comes to you, they've had a persistent headache for a couple years, they kind of remember it started in March of a couple years ago, but they don't know. Maybe it's, you know, it's a little better when they lay down. It may be a little worse when they're up moving around, but so is migraine, and it's a migrainous headache. But they've tried every migraine drug you can think of. Nothing is responding, nothing helps. I'm always looking at patients who are new daily, persistent headaches and patients who aren't responding to meds even if it's not new daily, but they have just barely any response. I will always go back and examine their brain imaging and get full spine to make sure I'm not missing. And you can never be 100% sure, but it's always good to consider those patients to the best of your ability, if that- have that in the back of your mind. Dr Smith: So obviously, goes without saying, this is something people need to have on their radar and think about. And then we'll talk more about diagnostic tools here in a second. But how common is this? If you're a headache doc, you see a lot of patients who have intractable headaches. And how often do you see this in your headache practice? Now you're- this is your thing, so probably a little more than others, but, you know, how common will someone who sees a lot of headache encounter these patients? Dr Rau: If you see a lot of headache, I mean, currently the thought is it's about 5 in 100,000. That was from a study before we were finding CSF venous fistulas. I think a lot of us think it's more common than that, but it's not super common. We don't have good estimates, but I would guess between 5 and 10 for 100,000 persons, not “persons who come to a tertiary headache clinic with intractable headaches”. So, it's hard to gauge how frequent it is, but I would say it's considerably more frequent than we currently think it is. There's still a group of people with orthostatic headaches that we can't find leaks on; that, once you treat other things that can cause or look for other things that can cause orthostatic headaches. So, there may be even still a pathophysiology out there that is still a leak type. Before 2014, we didn't even know about CSF venous fistulas. And now here we are; like, 50% of them are CSF venous fistulas. So, you know, we're still in a huge learning curve right now. Dr Smith: So, I definitely want to talk about the fistulas in a second. But before moving on, one of the things that I found really interesting is the wide spectrum of clinical phenotype. And we obviously don't have a lot of time to get into all of these different ones, but the one that I was hoping you might talk about---and there's a really great case, and you're on bunch of great case, a great case of this---is brain sagging dementia, not a term I've used before. Can you really briefly just tell our listeners about that, because that's a really interesting story and a great case in your article? Dr Rau: Yeah. So, brain sag dementia is a… almost like an extreme version of a spontaneous intracranial hypotension. Where there is clear brain sag in the imaging---so that's helpful---but the patients present kind of like a frontotemporal dementia. And when this was first started to being determined, you could turn the patient into Trendelenburg, and sometimes they would improve. There are some practitioners that have introduced fluid into the thecal sac and had temporary improvement. Patching has improvement, then they leak again, sometimes  not. But the clinical changes with this have been pretty tremendous to be able to identify that that's a real thing. And in some cases, out of Cedars Sinai, you know, who does a lot of the best research in this, they've had lots of cases where they can't find the leak, but there's clear brain sag that fits with our clinical picture of CSF leaks. So, we're on a learning curve. But yeah, this- they really present. They have disinhibition and cognitive impairment that is very similar to frontotemporal dementia. Dr Smith: Well, so let's talk about what causes this. You mentioned CSF venous fistulas. I mean, that was reported now just over a decade ago, it's pretty amazing. That accounts for about half of cases, if I understand correctly. What are the other causes? And then we'll talk more about therapy in a minute, but what causes this? Dr Rau: So, within the realm of spontaneous, you know, we say it's spontaneous. But the spontaneous cases we account for, they can be tears in the dura, which are usually sort of lateral tears in the dura. They can be little places that rubbed a hole, often on an osteophyte from the spine. They can come from these spinal diverticuli. So, I always describe it to my patients like those balls that have mesh and squishy, and you squeeze them in the- through the mesh, there's the extra little bubbling out. If you think of like the dura bubbling, out in some cases, through the framing of the spine, right where the spinal nerve roots come out, they should poke out like wires from the dura. But in many cases they poke out with this extra dura surrounding them, and we call that spinal diverticuli. And if you imagine like the weakening of where you squeeze that, you know, balloon through your fingers, in those locations, that's a very common place to find a CSF leak, and you can imagine that the integrity of the dura there may be less than it would be if it were not being expanded in that direction. And that's often the most common place we see these CSF venous fistulas. So, you can get minor traumas; like I said, it can be spontaneous, like someone just develops a leak one day. It can be rubbed off, and it can be a development of a connection between the dura and the venous system. There are also iatrogenic causes, but we don't consider them spontaneous. But when you're considering your patients for spontaneous cases, you should consider if they've ever had chronic---even long, long time ago---had any spinal implementation, procedures near the spine, spinal injections, LPs in the past, and especially women who've had epidurals in pregnancy. Dr Smith: All right, so we see a patient, positional severe headache, who meets the clinical criteria. Next step, MRI scan? Dr Rau: Yeah. So, the first thing is always to get the brain MRI with and without contrast. Most places will have a SIH or a spinal CSF leak protocol, but you should get contrast because one of the most pathognomonic findings on brain MRI is that smooth diffuse dural enhancement. And that's a really fantastic thing when you find it, because it's kind of a slam dunk. If you find it, then you will see other findings. It almost never exists alone. But if you see that, it's pretty much a spinal CSF leak. But you're also looking for subdural collections, any indication of brain sag. We do have these new algorithms that have come out in the past couple of years that are helpful. They're not exclusionary---you can have negative findings on the brain and still have spinal CSF leak---but the brain MRI is extremely helpful. If it's positive for the findings, it really does help you nudge you in the direction of further investigations and treatments. Dr Smith: And what about those further investigations and treatments, right? So, you see that there's findings consistent with low pressure, and I guess I should say low intracranial CSF volume. Be that as it may, what's the next step after that? Dr Rau: Depends on where you are and what you can do. I almost always will get a full spine MRI: so, C spine, T spine, and L spine separately. Not, you know, we don't want it all in one picture, because we want to get the full view. And you want to get that with at least T2 highly- heavily T2 weighted with fat saturation in at least the sagittal and axial planes. It's really helpful if you can get it in the coronal planes, but we have to have- often have good talks with your radiologist to get the coronal plane. I spoke about the spinal diverticuli earlier, and I want to clarify a little bit of something. The coronal image will show those really nicely. It's interesting, but 44% of people have those. So just having the spinal diverticuli does not indicate that you have a leak. But if you have a lot of those, there may be more likelihood of having leak than if you don't have any of those. So, I will get all of those and I will look at them myself, but I've been looking at them myself for a long time. But a lot of radiologists in community hospitals, especially not- nonneuroradiologists, but even neuroradiologists, this isn't something that's that everybody's been educated about, and we've been learning so much about it so rapidly in the past ten years. It's not easy to do and it's often missed. And if it's not protocoled properly, the fat saturation's not there, it's very hard to see… you can have a leak and not see it. Even the best people, like- it's not always something that's visible. And these CSF venous fistulas that we talked about are never visible on normal MRI imaging. Nonetheless, I will run those because if I can find a leak---and 90% of the ones that are found on MRI imaging are in the thoracic spine. So that's where I spend the most of my time looking. But if you find it, that's another thing to take to your team to say, hey, look, here it is, let's try and do this, or, let's try and do that, or, I've got more evidence. And there are other findings on the spine; not just the leak, but other findings, sometimes, you can see on spine that maybe help you push you towards, yes, this is probably a leak versus not. Dr Smith: So, your article has a lot of great examples and detail about kind of advanced imaging to, like, find the fistula and what not. I guess I'm thinking most of our listeners are probably practicing in a location where they don't have a team that really focuses on that. So, let's say we do the imaging of the spine and you don't find a clear cause. Is the next step to just do a blood patch? Do you send them to someone like you? What's the practical next step? Dr Rau: Yeah, if your- regardless of whether you find a leak or not, if your clinical acumen is such that you think this patient has a leak or I've treated them for everything else and it's not working and I have at least a high enough suspicion that I think the risk of getting a patch is lower than the benefit that if they got a patch and it worked, I do send my patients for non-directed blood patches, because it currently does take a long time to get them to a center that can do CT myelograms or any kind of advanced imaging to look for sort of a CSF venous fistula or to get treated outside of a nondirected patch. You know, sometimes nondirected patches are beneficial for patients, and there's some good papers out there that sort of explain the low risks of doing these if done properly versus the extreme benefit for patients when it works. And, I mean, I can't tell you how many people come in and tell me how their lives are changed because they finally got a blood patch. And sometimes it works. And it's life-changing for those people. You know, they go back to work. They can interact with their kids again. Before, they didn't know what was wrong, just had this headache that started. So it's worth doing if you have a strong clinical suspicion. Dr Smith: Yeah. I mean, that was great. And, you know, to go back to where we began, this is severe. It's something like 60% of patients with this problem have thought about suicide, right? And you take this patient and cure the problem. I feel really empowered having read the article and talked to you today. And so, I'm ready to go out and look for this. Thank you so much for a really engaging conversation. This has been terrific. Dr Rau: Thank you. I appreciate it. I enjoyed being here. Dr Smith: Again, today I've been interviewing Dr Jill Rau about her article on clinical features and diagnosis of spontaneous intracranial hypotension---which I guess I should say hypovolemia after having talked to you---which she wrote with Dr Jeremy Cutsworth-Gregory. This article appears in the most recent issue of Continuum on disorders of CSF dynamics. Please be sure to check out Continuum Audio episodes from this really interesting issue and other interesting issues. And thank you, our listeners, again for listening to us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Ayman Al-Hendy, MD, PhD, FRCSC, FACOG, CCRP In addition to heavy menstrual bleeding, patients with uterine fibroids often deal with many other considerable effects on their physical and mental wellbeing. To provide optimal care, it's important to recognize the full impact of fibroids, communicate carefully about treatment options, and promote equitable access to care. Dr. Charles Turck sits down with Dr. Ayman Al-Hendy to learn more about how we can address the multifaceted burden of uterine fibroids. Dr. Al-Hendy is a Professor of Obstetrics and Gynecology and the Director of Translational Research at the University of Chicago Pritzker School of Medicine.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Ayman Al-Hendy, MD, PhD, FRCSC, FACOG, CCRP Despite longstanding reliance on surgery, recent advancements have reshaped our approach to uterine fibroids. However, common myths and misconceptions have limited the adoption of newer therapies, leaving many patients unaware of their available options. Join Dr. Charles Turck and Dr. Ayman Al-Hendy as they explain shifting treatment paradigms and patient education strategies in uterine fibroid care. Dr. Al-Hendy is a Professor of Obstetrics and Gynecology and the Director of Translational Research at the University of Chicago Pritzker School of Medicine.

In today's episode, we spoke with Matthew Galsky, MD, about the FDA approval of neoadjuvant durvalumab (Imfinzi) plus gemcitabine and cisplatin followed by adjuvant durvalumab monotherapy after radical cystectomy for the treatment of adult patients with muscle-invasive bladder cancer (MIBC). Dr Galsky is a professor of medicine (hematology and medical oncology), a professor of urology, director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, and director for Translational Research at The Tisch Cancer Institute in New York, New York. In our exclusive interview, Dr Galsky discussed the significance of this approval, key efficacy and safety data from the pivotal phase 3 NIAGARA trial (NCT03732677), and the role of this regimen in the MIBC treatment paradigm, including for cisplatin-eligible patients with mild renal impairment.

In this episode of SHE MD, Dr. Thaïs Aliabadi and Mary Alice Haney welcome melanoma specialist Dr. Omid Hamid. They explore the rising incidence of melanoma in young people, debunk common misconceptions, and discuss groundbreaking treatments. Dr. Hamid explains the different stages of melanoma and the revolutionary immunotherapy treatments that are changing patient outcomes. The hosts and guest discuss real-life cases, including those of celebrities Khloe Kardashian and Teddy Mellencamp, to illustrate the importance of awareness and regular skin checks. The conversation also touches on melanoma during pregnancy and genetic predisposition to the disease - learn why genetic testing is crucial, even without family history.Access more information about the podcast and additional expert health tips by visiting SHE MD Podcast and Ovii. Sponsors: Myriad: Knowing your family's history of cancer is the first step to understanding your own cancer risk and may qualify you for the MyRisk Hereditary Cancer Test with RiskScore hereditary cancer test. It's easy, accurate and covered by most insurers. Learn more at GetMyRisk.comCymbiotika: Go to Cymbiotikia.com/SHEMD for 20% off your order + free shipping today.Purely Elizabeth: Visit purelyelizabeth.com and use code SHEMD at checkout for 20% off. Purely Elizabeth. Taste the ObsessionEquip: To learn more about Equip treatment, visit equip.health/sobermomlife.Strivektin: Discover the Science Behind Great SkinDavid's Protein: David is giving my listeners an exclusive offer – buy four cartons and get the fifth free at davidprotein.com/shemdCure Hydration: Cure is offering 20% off your first order! Stay hydrated and feel your best by visiting curehydration.com/SHEMD and using promo code SHEMD at checkout. Dr. Omid Hamid's Key Takeaways:1. Reduce Sun Exposure: Limit time spent in direct sunlight, especially during peak hours. Use protective clothing, hats, and sunglasses to shield your skin from harmful UV rays.2. Schedule Regular Skin Checks: Schedule routine visits with a dermatologist for comprehensive skin examinations. Self-examine your skin monthly for any new or changing moles or lesions.3. Use Effective Sunscreen: Apply broad-spectrum sunscreen with at least SPF 30 daily, even on cloudy days. Reapply every two hours when outdoors, and after swimming or sweating.4. Get Genetic Testing Done: If you have a family history of melanoma or other cancers, consider genetic testing to assess your risk. Tests like the MYRIS can identify melanoma-related gene mutations.5. Avoid Tanning Beds: Steer clear of tanning beds, as they significantly increase the risk of developing melanoma and other skin cancers.6. Be Your Own Health Advocate: Stay informed about your health, ask questions, and seek second opinions if necessary. Advocate for yourself and your loved ones by being proactive about potential health concerns.In This Episode: (00:00) Intro: Melanoma Awareness Month(02:40) Dr. Omid Hamid: Melanoma specialist introduction(6:58) Surgery for melanoma explained(10:49) Immunotherapy revolutionizes melanoma treatment(14:57) Genetic testing for melanoma risk(23:25) Importance of advocating for yourself(32:22) Teddy Mellencamp's stage 4 melanoma journey(50:51) Hormonal changes and melanoma risk(57:00) Two key melanoma prevention tipsRESOURCES:Melanoma Research Alliance: https://www.curemelanoma.org/blog/omid-hamid-mdMelanoma Research Foundation https://melanoma.org/Myriad Genetics: https://myriad.com/ GUEST BIOGRAPHY:Omid Hamid, MD, is the Chief of the Translational Research and Immuno-Oncology Department at The Angeles Clinic and Research Institute and serves as the Co-Director of the Melanoma and Phase I Programs. Academic Title as Professor, Department of Medicine at Cedars-Sinai Medical Center. His areas of expertise include immunotherapy and Phase I drug development.Dr. Hamid has published extensively and has been at the forefront of the development of paradigm-shifting breakthroughs including BRAF/MEK targeted agents, AntiCTL4A, antiPD1, and PDL1 therapies. His current interests include new immunotherapeutic options for patients including bi-specific antibodies, Adoptive T-cell Therapy, and oncolytic therapies with a focus on combinatorial approaches resulting in potentially great patient benefit.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

This episode originally aired on December 2nd, 2021. Drs. Julie Bastarache and Katie Wick sit down to discuss non-invasive sampling of the lungs in translational research.

In this episode of Conversations in Lung Cancer Research, A/Prof Mel Moore speaks with Prof Wendy Cooper, a leading pathologist in cancer research. They discuss Wendy's journey into pathology, the evolution of lung cancer diagnostics, the impact of AI and liquid biopsies, and the importance of international collaboration in research. Wendy shares insights on the challenges of equitable access to cancer diagnostics and the pressures faced by pathologists in multidisciplinary meetings. The conversation concludes with advice for junior clinicians on career development and involvement in professional organisations.(00:00) Introduction and Acknowledgements(00:36) Introducing Prof Wendy Cooper(01:32) Wendy's Path to Pathology(04:42) The Evolution of Lung Cancer Pathology(08:18) The Role of AI in Pathology(10:30) Translational Research and International Collaboration(14:09) Molecular Testing Guidelines in Australia(18:05) Challenges and Future Directions in Pathology(26:52) The Impact of Lung Cancer Screening Programs(29:08) Final Thoughts and Advice 

In this episode of the Onc Now Podcast, host Jonathan Sackier is joined by Joan Carles, Head of Section for the Genitourinary, Central Nervous System, Sarcomas and Tumours of Unknown Origin Unit at Vall d'Hebron University Hospital. Carles discusses breakthroughs in genitourinary cancer and sarcoma treatment, including anti-angiogenic therapies, overcoming resistance, and the role of genetic polymorphisms in personalised medicine.  Timestamps:     00:00 – Introduction   01:56 – Anti-angiogenic therapies  05:03 – Treatment resistance  07:53 – Genetic polymorphisms  09:02 – Sarcoma treatments  11:16 – Novel drugs  15:22 – Oncology societies  18:00 – Carles' three wishes for healthcare 

Send us a textIn this episode of Causes or Cures, Dr. Eeks chats with Dr. Amir Baniassadi about how indoor temperature affects the aging brain.Dr. Baniassadi shares what we know so far about the relationship between temperature and cognitive function, and explores the theories behind how temperature might influence cognition as we age. He discusses the findings of his recent study on temperature and cognition, including what surprised his team most. He also touches on an earlier study he conducted on temperature and sleep, and offers practical tips for optimizing your home environment. Is there a “sweet spot” for room temperature that supports both clear thinking and better sleep?Dr. Baniassadi is an instructor of medicine at Harvard Medical School and a scientist at the Marcus Institute for Aging Research. His work focuses on the aging brain and how environmental factors affect health and well-being in older adults. He holds a PhD in Civil, Environmental, and Sustainable Engineering from Arizona State University and an undergraduate degree in Mechanical Engineering from the University of Tehran. He also completed postdoctoral training in Translational Research in Older Adults, as well as a fellowship at the Harvard Graduate School of Design.Learn more about his work here. You can contact Dr. Eeks at bloomingwellness.com.Follow Eeks on Instagram here.Or Facebook here.Or X.On Youtube.Or TikTok.SUBSCRIBE to her monthly newsletter here.Support the show

Today, Lisa G. is diving deep into the science of aging, longevity, and muscle health with a true pioneer—Dr. Robert Wolfe, Co-founder and Lead Scientist at The Amino Co. A former Harvard professor, Director of the Center for Translational Research in Aging and Longevity, and one of the most cited researchers in the field, Dr. Wolfe has published over 500 studies funded by NASA, the NIH, the Department of Defense, and even the Olympic Committee.

The inflammatory and infectious optic neuropathies are a broad, heterogeneous, and common group of diseases producing visual loss. Although many now-distinct syndromes have been previously combined as “typical or atypical optic neuritis,” recent developments highlight the importance of precision terminology as well as an individualized evaluation and treatment approach. In this episode, Gordon Smith, MD, FAAN speaks with Eric Eggenberger, DO, MS, FAAN, author of the article “Optic Neuritis” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Eggenberger is a professor of ophthalmology, neurology, and neurosurgery at the Mayo Clinic in Jacksonville, Florida. Additional Resources Read the article: Optic Neuritis Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith. Today I'm interviewing someone who really needs no introduction, Dr Eric Eggenberger, about his article on optic neuritis, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Eric, welcome to the podcast, and maybe you can introduce yourself to our audience. Dr Eggenberger: Thank you. Thanks for having me. So, my name is Eric Eggenberger. I work at Mayo Clinic Florida, and I am involved exclusively in neuro-ophthalmology. Dr Smith: I just had the pleasure, Eric, of talking yesterday with Lindsey De Lott about non-optic neuritis causes of optic neuropathy. And so, I'm going to kind of reference a little bit what I learned yesterday. She was great. I wonder if you might begin by talking a little bit about nomenclature. You talk about the need for use of precise terminology in your article. And yesterday she taught me a lot about the risk of misdiagnosis and other causes of optic neuropathy, and the two seem related. So, I wonder if you can maybe lay the foundation for our conversation by talking about terminology? Dr Eggenberger: I think that's a great point. So, we are in an era now where, instead of lumping all these different diagnoses together, we have learned to split apart some of these clinical entities. And so, I think it's really important that we focus on precise terminology and recognize that all optic neuritis is not the same. And we have very different, distinct clinical pathways for these imaging pathways, treatment pathways, for these different types of optic neuritis, whether that's MS related, whether it's MOG related or aquaporin-4 related. Dr Smith: So, I wonder maybe we can begin by just, you know, giving our listeners wisdom, pearls, and pitfalls about, how do you recognize when someone with a suspected optic neuropathy has optic neuritis versus a noninflammatory optic neuropathy? Dr Eggenberger: So, that's a really important issue because there's a lot of clinical overlap in terms of exam findings. So, for instance, in any optic neuropathy, let's say it's unilateral, you typically are going to see decreases in acuity and field and color, and you're going to see a relative afferent pupillary defect. And then it's really the context that that occurs in that helps us distinguish different disease entities. So, with optic neuritis, typically you're going to have pain. And that's oftentimes going to be in the younger populations compared to some of the other common optic neuropathies we see, like ischemic optic neuropathy, for instance. Dr Smith: Right. So maybe we can talk a little bit about, kind of, your overall diagnostic approach, right? A lot of this is, of course, based on age and context, but young people get ischemic lesions and older people can have inflammatory lesions. So, what's your overall approach to the patient you just described? Let's say it's a forty-eight-year-old woman who comes to the emergency department with subacute unilateral vision loss and there's dyschromatopsia, APD, reduced acuity. And, you know, let's just say a fairly, you know, benign-looking fundoscopic exam. What do you do to evaluate that patient? Dr Eggenberger: In that particular context, I think we're looking at other contextual clues. Is there other vascular risk factors or other things to point you in one direction or the other? One of the important parts you mentioned was the fundus exam. So, we know with ischemic optic neuropathy, 100% of the time with AIOM, you're going to see disc edema. And so, in the context of that story, we want to confirm on our exam an optic neuropathy, and then we can kind of focus on the retrobulbar courses or different types of optic neuropathies. From an exam perspective, in that particular patient we'd be looking to measure the acuity, quantify that. And in the ER, you're not going to be able to do a perfect field, but you'll get some sense of the field and how much field loss there is. And then as you mentioned, the afferent pupillary defect is critical. And we're going to get a little bit of the historical features in terms of pain. With typical retrobulbar optic neuritis, most of those patients are going to experience some pain, and usually it's pain on eye movements. And those would be the clinical things to focus on. Other exposures the patient may or may not have had, any other concomitant conditions, would all help point you in different directions, perhaps, and then we're probably on towards imaging. Dr Smith: Yeah, maybe you can talk a little bit about that? What's the appropriate use of imaging? I mean, presumably the patients, like the one I just threw out there, are pretty much all going to get neuroimaging. What's your approach to that? How do you protocol the study? What should we be looking for? Dr Eggenberger: In our clinic, we would typically be ordering an MRI orbit and brain, and each of those has a specific purpose. The orbit is going to show us the extent of the optic neuropathy. So, we're particularly looking for a longitudinally extensive optic nerve lesion or more than half of the optic nerve involved. And most patients acutely, if it isn't an “itis" situation, we'll see enhancement. And then the MR brain is going to be useful for looking for other evidence of demyelination within the central nervous system. We may at some point get down to doing an MR cord, but I think acutely it's going to be brain and orbit that most of our patients are getting. Dr Smith: Let's say that we did the scan and, sure enough, there's sort of a shorter segment, so less than half the length of the nerve region of enhancement. What's the rest of your diagnostic evaluation look like for that patient? Dr Eggenberger: So, in that particular case, we would look at the remainder of the brain. So, we're looking for other evidence of demyelination and any other contextual clues, systemically that would point you one direction or another. But with a shorter segment involved, one of the more common things we might encounter would be multiple sclerosis-related optic neuritis. Dr Smith: Would you look for aquaporin-4 and MOG in a patient with what appears to be an isolated, uncomplicated short segment optic neuritis? Dr Eggenberger: So, I think it really depends a bit on the context. I would never fault anybody for looking at MOG or an aquaporin-4 in that context because those are really treatment-altering diagnoses, but the yield in this particular case with a short segment involved and depending on the acuity and other features is probably going to be pretty low. Dr Smith: I really liked as an aside- I wasn't going to go there next, but you kind of got me thinking about it, you have a really nice section in your article. Which, all of it's great, but talking about how to manage low titer MOG antibodies. I wonder if you could talk about that because I think that's a lesson, maybe, that is transferable to a lot of other testing that we do. in terms of pre-prior probability and titer and so forth. Dr Eggenberger: Yeah, that's really an important point. So, we've seen this come up a number of times where the MOG antibody is a very good test, but in low titer it has a relatively low positive predictive value, perhaps 50%. In those cases, particularly without a classic clinical context, you have to be extremely alert for some other diagnosis that could mimic what you think is inflammatory demyelinating optic neuritis, but in fact is infectious or some other cause. Dr Smith: Yeah, super, super important and helpful. In terms of aquaporin-4, how does that compare in terms of predictive values, lower titer positive results? Dr Eggenberger: So aquaporin-4, the test has a very high specificity. So, it's quite useful if positive. You have to keep in mind there can be some false negatives, but the test otherwise is quite specific. And that is a diagnosis, you know, we never want to miss. It's a vicious disease. It tends to be a blinding disease, particularly without treatment. Bad things happen when we miss that, and we want to get on that diagnosis early and do pretty aggressive early and prophylactic treatment. Dr Smith: Your article covers not only the common causes of optic neuritis and, you know, MS, isolated optic neuritis, MOGAD NMO, you talk about a bunch of other things. I wonder, in this patient that we've been discussing, in the absence of any other historical information that seems relevant---or maybe you can define what would seem relevant---would you do other evaluation in that individual, other serologic evaluation and so forth, just in terms of diagnosis? Dr Eggenberger: In that particular case, without other red flags, I don't think I would initially. And follow-up is going to give you a lot of this context. So, you'd be on the lookout for other systemic conditions. So, if the patient had some arthropathy, if the patient had any pulmonary disease hints, if there was anything else that could lead you on a broader expedition. But I think in the context of this case, acutely in the ER, I probably wouldn't do a big lab plug for this. I probably would kind of go down the most likely road and start our treatments, and then follow that patient up. Dr Smith: Yeah, I know your article does a really great job, I think, of outlining when do you need to think about some of these less common causes. Well, can we talk about treatment, Eric? Because I want to move on to some other things. But- so, we've got a patient with isolated optic neuritis, nothing else, you know, in terms of the other antibodies we've talked about. What state-of-the-care- or, state-of-the-art treatment for that patient? Dr Eggenberger: So, the acute treatment for these inflammatory, optic neuritis-type cases is very similar Initially. High dose steroids remains kind of the standard. And then, in MS-related optic neuritis, we may or may not see a taper. So many times it's just an acute treatment of three to five days high dose. Whether that's oral or PO, we could institute either depending on the particular case. And then the taper would depend on the potential cause. So, for instance, with these antibody-driven diseases---so with MOG- or particularly with aquaporin-4---if it's a longitudinally extensive region of optic nerve involved, we tend to use a longitudinally extensive taper. And so, we use prednisone in those cases for several months while we're getting everything else set and deciding what the overall course is going to bring. Dr Smith: What about IV versus oral? There must be something about my practice. I was telling this to Lindsey. Every time on our hospital service, we seem to have at least two patients with optic neuropathies, which I always enjoy, but I find it's a little weird to admit someone who's doing just fine otherwise to the hospital with three days of IV SOLU-MEDROL. So, I'm always trying to figure out, like, how can I get this patient home? And your article had the best term I've heard in a long time, which is “SOLU smoothies.” I mean, are there other strategies that you sometimes use, other than just high-dose IV methylprednisolone? Dr Eggenberger: So, I agree with you. It's sometimes hard to admit somebody for just an IV therapy. And we'll do this as an outpatient, high-dose IV, but we'll also use high-dose orals. And in times in the past when there's been methylprednisolone shortage, we've used high-dose oral or IV dexamethasone as well. I think the IV form, although it's the gold standard, the high-dose oral forms have pretty equivalent bioavailability and are pretty tolerable in my experience. And certainly more convenient. Dr Smith: I wonder if we should switch and maybe talk a little bit about aquaporin-4, I mean, you emphasized that this is a vicious disease---I love the way you describe that---and often blinding. What updates do you have in terms of our therapeutic approach to NMO? That's been rapidly evolving of late. Dr Eggenberger: Right, so these are cases we're always going to share with neuroimmunology. And it requires kind of a multidisciplinary approach, in my opinion, for ideal or for best outcomes. And so, all of these patients are going to get put on prophylactic medications. So, this is a disease you just can't leave untreated. Bad stuff will happen for sure. And we now, fortunately, have some approved, FDA-approved medications that can positively impact the course of this disease. So, that's been a welcome addition. Dr Smith: What are the FDA-approved medications at this point for NMO? Dr Eggenberger: So, there are several at this point, and this is an area that's in growth, fortunately. And again, these are cases we're going to be sharing with our neuroimmunology colleagues. So, these are IV medications typically aimed at complement or CD19. And they all are relatively effective at quieting the course of the disease. Dr Smith: Maybe we can talk a little bit about MOG? I think that most of our listeners are probably pretty familiar with aquaporin-4 and NMO, what- maybe you could describe MOG a little bit and the therapeutic approach for patients with MOG-associated disease? Dr Eggenberger: So, MOG has been a real interesting kind of condition to learn more about. We certainly see a lot of MOG, and I'm sure we saw MOG before it was formally described, but I think we just thought it was kind of a benign, maybe monophasic MS type of presentation. But MOG tends to come in with a loss of acuity that kind of rivals aquaporin-4. So, the acuity tends to be pretty, pretty depressed, but it's very steroid-responsive. So, a lot of times these are the patients, you'll see that their vision will start to improve even when they're on the initial few days of the high-dose steroids. And many times we can get their vision back to 20/20 or very close to that. Dr Smith: And do these patients need chronic management? Dr Eggenberger: So, that's an area of controversy to some degree. About 50% of the optic neuritis MOG-related cases are going to have a relapsing course. And because the disease is steroid-responsive, many times we'll follow these patients after a first attack to see if this is the condition that's going to declare itself to be relapsing or if this is just going to be a monophasic kind of presentation of optic neuritis. We don't have great biomarkers to separate patients who are going to be in that 50% monophasic course versus the other half. It'll be relapsing. And so, it depends on the patient. If there's somebody that's, as many of these patients are, been very steroid responsive, they get back to 20/20, we can teach them about the disease so that if they do have a relapse, we can get them high-dose steroids in a relatively rapid fashion and they're otherwise healthy, we're probably going to watch that patient. And if it's somebody that doesn't recover 100%, there's other issues with treating them with high-dose steroids potentially in the future, then we may learn more towards an earlier prophylactic approach in that patient. Dr Smith: And what would that approach look like? Is it different from NMO or using more IVIG or B cell depletion as opposed to complement inhibition, for instance? Dr Eggenberger: In MOG, we know that the B cell depletion strategies don't work as well. And so most times we're turning to IVIG, and we found that pretty effective. That's kind of our go-to at this point. Dr Smith: Eric, it's a joy talking to you and I'd love to keep going about content, but I'll refer our listeners to your outstanding article. I mean, you're such a highly regarded neuro-ophthalmologist and educator. I wonder if you could talk to us about why you've done neuro-ophthalmology, and maybe this is an opportunity for you to convince all of our great residents that are listening or students what's great about being a neuro-ophthalmologist. Dr Eggenberger: I think neuro-ophthalmology is by far the most interesting part of neurology. So, it's an area that I think a lot of general neurologists, in my view, don't get enough of in their residency. But it's kind of the essence of neurology, where in neurology you're localizing down to the millimeter and in neuro-ophthalmology,  we're localizing down to the micron level. We have several new emerging diseases like these varieties of optic neuritis we're focused on. We're learning lots about those. You get to be involved in lots of different areas of neurology. So, we'll see not just demyelinating conditions, we'll see trauma as it relates to the visual system. And we'll see tumor, and we see all different flavors, stroke, and in any piece of neurology, commonly we'll have some vision aspect that we that we get involved in. So, we see a wide variety of conditions. So, I think it's been a really exciting place to be within neurology. And it's rapidly changing at this point. We're getting new therapeutics. So, it's, I think it's a great time to be a neuro-ophthalmologist. Dr Smith: Yeah, listening to you talk and just reflecting on it, it's really true. Neuro-ophthalmology does cover the entire span of neurology, right? I'm a neuromuscular guy and we see a lot of ocular myasthenia, which is another super exciting area. But we've been talking about optic neuritis, and your article talks about infectious causes and the paraneoplastic and a whole host of things. So, you're a great advocate and salesperson for your field. You convinced me. Dr Eggenberger: Efferent neuro-ophthalmology we love, we could talk about ocular myasthenia and other aspects for another hour. And we get involved in all kinds of cases: third nerve palsies, ocular myasthenia, trauma that involves the efferent system, all different aspects. It's really a great subspecialty, and you get to see a bit of all of neurology. Dr Smith: I'm trying to remember who it was, Eric. It was an attending of mine at medical school. I went to medical school at the Mayo Clinic in Rochester, and I want to say it was Manny Gomez, who was a very famous tuberous sclerosis person, who told me that neuro-ophthalmology was the most elegant specialty within neurology. That stuck with me. Thank you so much for joining me today. I really appreciate it. Dr Eggenberger: Thank you. I appreciate it as well. Dr Smith: So again, today I've been interviewing Dr Eric Eggenberger about his really wonderful article on optic neuritis, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum audio episodes from the neuro-ophthalmology and other issues. And listeners, thank you very much for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Optic neuropathies encompass all congenital or acquired conditions affecting the optic nerve and are often a harbinger of systemic and central nervous system disorders. A systematic approach to identifying the clinical manifestations of specific optic neuropathies is imperative for directing diagnostic assessments, formulating tailored treatment regimens, and identifying broader central nervous system and systemic disorders. In this episode, Gordon Smith, MD, FAAN speaks with Lindsey De Lott, MD, MS, author of the article “Optic Neuropathies” in the Continuum® April 2025 Neuro-ophthalmology issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. De Lott is an assistant professor of neurology and ophthalmology at the University of Michigan in Ann Arbor, Michigan. Additional Resources Read the article: Optic Neuropathies Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @lindseydelott Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: Hello, this is Dr Gordon Smith. Today I'm interviewing Dr Lindsey De Lott about her article on optic neuropathies, which appears in the April 2025 Continuum issue on neuro-ophthalmology. Lindsey, welcome to the podcast, and perhaps you can introduce yourself to our audience. Dr De Lott: Thank you, Dr Smith. My name is Lindsey De Lott and I am a neurologist and a neuro-ophthalmologist at the University of Michigan. I also serve as the section lead for the Division of Neuro-Ophthalmology, which is actually part of the ophthalmology department rather than the neurology department. And I spend a good portion of my time as a researcher in health services research, and that's now about 60% of my practice or so. Dr Smith: I'm super excited to spend some time talking with you. One, I'm a Michigan person. As we were chatting before this, I trained with Wayne Cornblath and John Trobe, and it's great to have you. I wonder if we maybe can begin- and by the way, your article is outstanding. It is such a huge topic and it was actually really fun to read, so I encourage our listeners to check it out. But you begin by talking about misdiagnosis as being a common problem in this patient population. I wonder if you can talk through why that is and if you have any pearls or pitfalls in avoiding it? Dr De Lott: Yeah, I think there's been a lot of great research looking at misdiagnosis in specific types of optic neuropathies; in particular, compressive optic neuropathies and optic neuritis. A lot of that work has come out of the group at Emory and the group at Washington University. But a lot of neuro-ophthalmologists across the country really contributed to those data. And one of the statistics that always strikes me is that, you know, for example, in patients with optic nerve sheath meningiomas, something like 70% of them are actually misdiagnosed. And a lot of those errors in diagnosis, whether it's for compressive optic neuropathy or some other type of optic neuropathy, really comes down to the way that physicians are really incorporating elements of the history in the physical. For example, in optic neuritis, we know that physicians tend to anchor pretty heavily on pain in general. And that often tends to lead them astray when optic neuritis was never the diagnosis to begin with. So, it's really overindexing on certain things and not paying attention to other features of the physical exam; for example, say presence of an afferent pupillary defect. So, I think it just really highlights the need to have a really relatively structured approach to patients that you think have an optic neuropathy when you're trying to sort of plan your diagnostic testing and your treatment. Dr Smith: I do maybe five or six weeks on our hospital service each year, and I don't know if it's just a Richmond thing, but there's always at least two people in my week who come in with an optic neuropathy or acute vision loss. How common is this in medical practice? Or neurologic practice, I should say? Dr De Lott: Optic neuropathies themselves… if you look across, unfortunately we don't have any great data that puts together all optic neuropathies and gives us an actual sort of prevalence estimate or an incidence estimate from year to year. We do have some of those data for specific types of optic neuropathies like optic neuritis and NAION, and you're probably looking around five-ish per one hundred thousand. So, these aren't that common, but at the same time they do get funneled to- often to emergency rooms and to neurologists from our ophthalmology colleagues and optometry colleagues in particular. Dr Smith: So, one other question I had before kind of diving into the topic at hand is how facile neurologists need to be in recognizing other causes of acute visual loss. I mean, we see acute visual loss as neurologists, we think optic neuropathy, right? Optic neuritis is sort of the go-to in a younger patient, and NAION in someone older. But what do neurologists need to know about other ophthalmologic causes? So, glaucoma or acute retinal disorders, for instance? Dr De Lott: Yeah, I think it's really important that neurologists are able to distinguish optic neuropathies from other causes of vision loss. And so, I would really encourage the listeners to take a look at the excellent article by Nancy Newman about vision loss in this issue where she really kind of breaks it down into vision loss that is acute and chronic and how you really think through distinguishing optic neuropathies from other causes of vision loss. But it is really important. For example, a patient with a central retinal artery occlusion may potentially be eligible for treatments. And that's very different from a patient with optic neuritis and acute vision loss. So, we want to be able to distinguish these things.  Dr Smith: So maybe we can pivot to that a little bit. Just for our listeners, our focus today is going to be on- not so much on optic neuritis, although obviously we need to talk a little bit about how we differentiate optic neuritis from non-neuritis optic neuropathies. It seems like the two most common situations we encounter are ischemic optic neuropathies and optic neuritis. Maybe you can talk a little bit about how you distinguish these two? I mean, some of it's age, some of it's risk factors, some of it's exam. What's the framework, of let's say, a fifty-year-old person comes into the emergency room with acute vision loss and you're worried about an optic neuropathy? Dr De Lott: The first step whenever you are considering an optic neuropathy is just making sure that the features are present. I think, really going back to your earlier question, making sure that the patient has the features of an optic neuropathy that we expect. So, it's not only vision loss, but it's also the presence of an apparent pupillary defect in a patient with a unilateral optic neuropathy. In a person who has a bilateral optic neuropathy, that apparent pupillary defect may not be present because it is relative. So, you really would have to have asymmetric vision loss between the two eyes. They should also have impairment of their color vision, and they're probably going to have some kind of visual field defect, whether that's central scotoma or an arcuate scotoma or an altitudinal defect that really respects the horizontal meridian. So, you want to make sure that, first and foremost, you've got a patient that really meets most of those- most of those features. And then from there, we're looking at the other features on their history. How acute is the onset of the vision loss? What is the progression over time? Is there pain associated or not associated with the vision loss? What other medical issues does the patient have? And you know, one of the things you already brought up, for example, is, what's the age of the patient? So, I'm going to be much more hesitant to make a diagnosis of optic neuritis in a much older patient or a diagnosis on the other side, of ischemic optic neuropathy, in a much younger patient, unless they have really clear features that push me in that direction. Dr Smith: I wonder if maybe you could talk a little bit about features that would push you away from optic neuritis, because, I mean, people who are over fifty do get optic neuritis- Dr De Lott: They do. Dr Smith: -and people who get ischemic optic neuropathies who are younger. So, what features would push you away from optic neuritis and towards… let's be broad, just a different type of optic neuropathy? Dr De Lott: Sure. We know that most patients with optic neuritis do have pain, but that pain is accompanied---within a few days, typically---with vision loss. So, pain alone going on for a number of days without any visual symptoms or any of those other things I listed, like the afferent papillary defect, the visual field defect, would push me away from optic neuritis. But in general, yes, most optic neuritis is indeed painful. So, the presence of optic disc edema is unfortunately one of those things that an optic neuritis may be present, may not be present, but in somebody with ischemia that is anterior---and that's the most common type of ischemic optic neuropathy, would be anterior ischemic optic neuropathy---they have to have optic disc edema for us to be able to make that diagnosis, and that is a diagnosis of NAION, or nonarteritic ischemic optic neuropathy. An APD in this case, again, that's just a feature of an optic neuropathy. It doesn't really help you to distinguish, individual field defects are going to be relatively similar between them. So then in patients, I'm also looking, like I said, at their history. So, in a patient where I'm entertaining a diagnosis of ischemic optic neuropathy, I want to make sure that they have vascular risk factors or that I'm actually doing things like measuring their blood pressure in the office if they haven't seen a physician recently or checking a lipid panel, hemoglobin A1c, those kinds of things, to look for vascular risk factors. One of the other features on exam that might push me more- again, in a patient with ischemic optic neuropathy, where it might suggest ischemia over optic neuritis, would be some other features on exam like a crowded optic disc that we sometimes will see in patients with ischemic optic neuropathy. I feel like that was a bit of a convoluted answer. Dr Smith: I thought that was a great answer. And when you say crowded optic disc, that's the- is that the “disc at risk”? Dr De Lott: That is the “disk at risk,” yes. So, crowded optic disk is really a disk that is smaller than what we see in the average population, and the average cup to disk ratio is 0.3. So, I think that's where 30% of the disk should be. So, this extra wiggle room, as I sometimes will explain to my patients. Dr Smith: And then, I wonder if you could talk a little bit about more- just more about exam, right? You raised the importance of recognizing optic disc edema. Are there aspects of that disc edema that really steer you away from optic neuritis and towards ischemia-like hemorrhages or whatnot? And then a similar question about the importance of careful visual field testing? Dr De Lott: So, on the whole, optic disc edema is optic disc edema. And you can have very severe optic neuritis with hemorrhages, cotton wool spots, which is essentially just an infarction of the retinal nerve fiber layer either overlying the disc or other parts of the retina. And ischemia, you can have some of the same features. In patients who have giant cell arteritis, which is just one form of anterior ischemic optic neuropathy, patients can have a pallid optic disc edema where the optic disc is swollen and white-looking. But on the whole, swelling is swelling. So, I would caution anyone against using the features of the optic nerve swelling to make any type of, sort of, definitive kind of diagnosis. It's worth keeping in mind, but I just- I would caution against using specific features, optic nerve swelling. And then for visual field testing, there are certain patterns that sometimes can be helpful. I think as I mentioned earlier, in patients with ischemic optic neuropathy, we'll often see an altitudinal defect where either the top half or, more commonly, the bottom half of the vision is lost. And that vision loss in the field corresponds to the area of swelling on the disk, which is really rewarding when you're actually able to see sectoral swelling of the disk. So, say the top half of the disk is swollen and you see a really dense inferior defect. And other types of optic neuropathy such as hereditary optic neuropathies, toxic and nutritional optic neuropathies, they often cause more central field loss. And in patients who have optic neuropathies from elevated intracranial pressure, so papilladema, those folks often have more subtle visual field loss in an arcuate pattern. And it's only once the optic nerves have sustained a pretty significant injury that you start to see other patterns of field loss and actual decline in visual acuity in those patients. I do think a detailed visual field assessment can often be pretty helpful as an adjunct to the rest of the exam. Dr Smith: So, we haven't talked a lot about neuroimaging, and obviously, neuroimaging is really important in patients who have optic neuritis. But how about an older patient in whom you suspect ischemic optic neuropathy? Do those patients all need a MRI scan? And if so, is it orbits and brain? How do you- how do you protocol it? Dr De Lott: You're asking such a good question, totally controversial in in some ways. And so, in patients with ischemic optic neuropathy, if you are confident in your diagnosis: the patient is over the age of fifty, they have all the vascular, you know, they have vascular risk factors. And those vascular risk factors are things like diabetes, hypertension, high blood pressure, hyperlipidemia, obstructive sleep apnea. They have a “disc at risk” in the fellow eye. They don't have pain, they don't have a cancer history. Then doing an MRI of the orbits is probably not necessary to rule out another cause. But if you aren't confident that you have all of those features, then you should absolutely do an MRI of the orbit. The MRI of the brain probably doesn't provide you with much additional information. However, if you are trying to distinguish between an ischemic optic neuropathy and, say, maybe an optic neuritis, in those patients we do recommend MRI orbits and brain imaging because the brain does provide additional information about other CNS demyelinating disorders that might be actually the cause of a patient's optic neuritis. Dr Smith: I wonder if you could talk a little bit about posterior ischemic optic neuropathy. That's much less common, and you mentioned earlier that those patients don't have optic disk edema. So, if there's a patient who has vision loss that- in a similar sort of clinical scenario that you talked about, how do you approach that and under what circumstances do we see patients who have posterior ischemic optic neuropathy? Dr De Lott: So, you're going to most often see patients with posterior ischemic optic neuropathy who, for example, have undergone a recent surgery. These are often associated with things like spinal surgeries, cardiac surgeries. And there are a number of risk factors that are associated with it. Things like blood pressure, drain surgery, the amount of blood loss, positioning of patient. And this is something that the surgeons and anesthesiologists are very sensitive to at this point in time, and many patients are often- this can be part of the normal informed consent process at this point in time since this is something that is well-recognized for specific surgeries. In those patients, though… again, unless you're really certain, for example, maybe the inpatient neurology attending and you've been asked to consult on a patient and it's very clear that they went into surgery normal, they came out of surgery with vision loss, and all the rest of the features really seem to be present. I would recommend that in those cases you think about orbital imaging, making sure you're not missing anything else. Again, unless all of the features really are present- and I think that's one of the themes, definitely, throughout this article, is really the importance of neuroimaging in helping us to distinguish between different types of optic neuropathy. Dr Smith: Yeah, I think one of the things that Eric Eggenberger talks about in his article is the need to use precise nomenclature too, which I plan on talking to him about. But I think having this very structured approach- and your article does it very well, I'll tell our listeners who haven't seen it there's a series of really great tables in the article that outline a lot of these. I wonder, Lindsey, if we can switch to talk about arteritic optic neuropathy. Is that okay? Dr De Lott: Sure. Yeah, absolutely. Dr Smith: How do you sort that out in an older patient who comes in with an ischemic optic neuropathy? Dr De Lott: Yeah. In patients who are over the age of fifty with an ischemic optic neuropathy, we always need to be thinking about giant cell arteritis. It is really a diagnosis we cannot afford to miss. If we do miss it, unfortunately, patients are likely to lose vision in their fellow eye about 1/3 to 1/2 the time. So, it is really one of those emergencies in neuro-ophthalmology and neurology. And so you want to do a thorough review systems for giant cell arteritis symptoms, things like headache, jaw claudication, myalgias, unintentional weight loss, fevers, things of that nature. You also want to check their inflammatory markers to look for evidence of an elevated ESR, elevated C-reactive protein. And then on exam, what you're going to find is that it can cause an anterior ischemic optic neuropathy, as I mentioned earlier. It can cause palette optic disc swelling. But giant cell arteritis can also cause posterior ischemic optic neuropathy. And so, it can be present without any swelling of the optic disc. And in fact, you know, you mentioned one of my mentors, John Trobe, who used to say that in a patient where you're entertaining the idea of posterior ischemic optic neuropathy, who is over the age of fifty with no optic disc swelling, you should be thinking about number one, giant cell arteritis; number two, giant cell arteritis; number three, giant cell arteritis. And so, I think that is a real take-home point is making sure that you're thinking of this diagnosis often in our patients who are over the age of fifty, have to rule it out. Dr Smith: I'll ask maybe a simple question. And presumably just about everyone who you see with a presumed ischemic optic neuropathy, even if they don't have clinical features, you at least check a sed rate. Is that true? Dr De Lott: I do. So, I do routinely check sedimentation rate and C-reactive protein. So, you need to check both. And the reason is that there are some patients who have a positive C-reactive protein but a normal sedimentation rate, so. And vice versa, although that is less common. And so both need to be checked. One other lab that sometimes can be helpful is looking at their CBC. You'll often find these patients with giant cell arteritis have elevated platelet counts. And if you can trend them over time, if you happen to have a patient that's had multiple, you'll see it sort of increasing over time. Dr Smith: I'm just thinking about how you sort things out in the middle, right? I mean, so that not all patients with GCF, sky-high sed rate and CRP…. And I'm just thinking of Dr Trobe's wisdom. So, when you're in an uncertain situation, presumably you go ahead and treat with steroids and move to biopsy. Maybe you can talk a bit about that pathway? Dr De Lott: Yeah, sure. Dr Smith: What's the definitive diagnostic process? Do you- for instance, the sed rate is sky-high, do you still get a biopsy? Dr De Lott: Yes. So, biopsy is still our gold-standard diagnosis here in the United States. I will say that is not the case in all parts of the world. In fact, many parts of Europe are moving toward using other ancillary tests in combination with labs and exam, the history, to make a definitive diagnosis of giant cell arteritis. And those tests are things like temporal artery ultrasound. We also, even though we call it temporal artery ultrasound, we actually need to image not only the temporal arteries but also the axillary arteries. The sensitivity and specificity is actually greater in those cases. And then there's high-resolution imaging of the vessels and the- both the intracranial and extracranial distributions. And both of those have shown some promise in their predictive values of patients actually having giant cell arteritis. One caution I would give to our listeners, though, is that, you know, currently in the US, temporal artery biopsy is still the gold standard. And reading the ultrasounds and the MRIs takes a really experienced radiologist. So, unless you really know the diagnostic accuracy at your institution, again, temporal artery biopsy remains the gold standard here. So, when you are considering giant cell arteritis, start the patient on steroids and- that's high dose, high dose steroids. In patients with vision loss, we use high dose intravenous methylprednisolone and then go ahead and get the biopsy. Dr Smith: Super helpful. And are there other treatments, other than steroids? Maybe how long do you keep people on steroids? And let's say you've got a patient who's, you know, diabetic or has other factors that make you want to avoid the course of steroids. Are there other options available? Dr De Lott: So, in the acute phase steroids are the only option. There is no other option. However, long term, yes, we do pretty quickly put patients on tocilizumab, which is really our first-line treatment. And I do that in conjunction with our rheumatology colleagues, who are incredibly helpful in managing and monitoring the tocilizumab for our patients. But when you're seeing the patients, you know, whether it's in the emergency room or in the hospital, those patients need steroids immediately. There are other steroid-sparing agents that have been tried, but the efficacy is not as good as tocilizumab. So, the American College of Rheumatology is really recommending tocilizumab as our first line steroid-sparing agent at this point. Dr Smith: Outstanding. So again, I will refer our listeners to your article. It's just chock-full of great stuff. This has been a great conversation. Thank you so much for joining me today. Dr De Lott: Thank you, Dr Smith. I really appreciate it.  Dr Smith: The pleasure has been all mine, and I know our listeners will be enjoying this as well. Again, today I've been interviewing Dr Lindsey De Lott about her article on optic neuropathies, which appears in the most recent issue of Continuum on neuro-ophthalmology. Be sure to check out Continuum Audio episodes from this and other issues. I already mentioned Dr Eggenberger and I will be talking about optic neuritis, which will be a great companion to this discussion. Listeners, thank you for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In the build to the International Festival of Neuroscience being held in Liverpool from the 27th to 30th of April, 2025. We spoke to Dr. Dorothy Tse of Edge Hill University about her incredible research aimed at understanding memory, preventing dementia and promoting healthy ageing. We speak about the Tse Lab's work in understanding how prior knowledge can help in developing new memories and the importance of public input in all their research activities.Episode in collaboration with the British Neuroscience Association, Liverpool Neuroscience Group and The Brain Charity.Public Events run by LNG: https://meetings.bna.org.uk/BYOBLiverpool/BNA Festival of Neuroscience: https://meetings.bna.org.uk/bna2025/ Dr. Dorothy Tse: https://www.edgehill.ac.uk/person/dr-dorothy-tse/staff/Support the showSupport us and reach out!https://smoothbrainsociety.comhttps://www.patreon.com/SmoothBrainSocietyInstagram: @thesmoothbrainsocietyTikTok: @thesmoothbrainsocietyTwitter/X: @SmoothBrainSocFacebook: @thesmoothbrainsocietyMerch and all other links: Linktreeemail: thesmoothbrainsociety@gmail.com

Host: Peter Buch, MD, FACG, AGAF, FACP Guest: Aasma Shaukat, MD, MPH While fecal immunochemical testing and multitarget stool DNA testing are commonly used to screen for colon cancer, screening rates remain low throughout the United States. With the introduction of blood-based testing modalities, noninvasive colon cancer screening is becoming more accessible than ever. Join host Dr. Peter Buch and Dr. Aasma Shaukat as they discuss the effectiveness of current and emerging methods as well as best practices for screening patients. Dr. Shaukat is the Robert M. and Mary H. Glickman Professor of Medicine at the NYU Grossman School of Medicine and the Co-Director of Translational Research, Education, and Careers and the Director of Outcomes Research in the Division of Gastroenterology and Hepatology at NYU.

In this episode of Absolute Gene-ius, Dr. C. Dustin Rubinstein takes us inside the world of advanced genome editing, where cutting-edge tools like CRISPR and digital PCR are helping shape the future of biomedical research.As the Director of the Advanced Genome Editing Laboratory at the University of Wisconsin-Madison, Dr. Rubinstein shares how his lab develops genetically engineered pig models to study diseases like neurofibromatosis and cancer, providing researchers with more clinically relevant models than traditional small animals. He explains how digital PCR plays a crucial role in confirming genome edits with absolute precision, eliminating the ambiguity that often comes with qPCR and sequencing alone. The discussion dives into the advantages of dPCR for copy number variation analysis and gene editing confirmation, emphasizing the importance of multiple complementary technologies in modern molecular biology.Beyond the science, Dr. Rubinstein reflects on his career path, the value of mentors, and the unpredictable nature of scientific discovery. He also joins in on some lighthearted lab humor and shares his most embarrassing (and proudest) moments in research. Tune in for an insightful and entertaining look at the intersection of gene editing, career evolution, and the future of molecular biology.Visit the Absolute Gene-ius pageto learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

In this episode, Dr. Ken Cohen, Executive Director of Translational Research at Optum Health, discusses the impact of value-based care models on patient outcomes. He shares key findings from his recent research, including how Medicare Advantage patients in value-based arrangements receive superior care and how these benefits extend to traditional Medicare patients.

In this episode, Dr. Ken Cohen, Executive Director of Translational Research at Optum Health, discusses the impact of value-based care models on patient outcomes. He shares key findings from his recent research, including how Medicare Advantage patients in value-based arrangements receive superior care and how these benefits extend to traditional Medicare patients.

Well, here we are—the final episode of Informatics in the Round (we think!). After five incredible years, 38 episodes, and thousands of listeners, we've decided it's time to wrap up this journey. But first, we're taking a minute (or maybe two hours) to reflect on this wild ride—and we've brought some people you might recognize! In this episode, we pull some clips from the archive to help us look back at our best moments, favorite topics, and silliest slip-ups over the years. We take you through our “Top 5” topics that we loved to talk about the most: electronic health records, patient privacy, public health, health equity, and AI. We will also share some stories you didn't hear (like that time we forgot to hit records—oops), how the pandemic reshaped our personal and professional lives, and the lessons that will stick with us. To lead us through our Top 5, we invited back some of our favorite guests to reflect and discuss the future of the field:  Dr. Yaa Kumah-Crystal, MD, MPH, MS, is an Associate Professor of Biomedical Informatics and Pediatric Endocrinology at Vanderbilt University Medical Center whose research focuses on documentation in healthcare communication. Dr. Ellen Wright Clayton, JD, MD, is a professor of Pediatrics, Law, and Health Policy at Vanderbilt University Law School and Vanderbilt University Medical Center. Her research focuses on the ethical, legal, and social implications of genomics research. Dr. Melissa McPheeters, PhD, MPH, is the Senior Director for Analytics at RTI International, as well as an esteemed epidemiologist and public health informatician. Her work focuses on building interdisciplinary teams to address complex problems across health, public health, and data modernization processes. Dr. Consuelo H. Wilkins, MD, is the Senior Vice President and Senior Associate Dean of Health Equity at Vanderbilt University Medical Center and the Associate Director of the Vanderbilt Institute for Clinical and Translational Research. Her work attempts to bring together community stakeholders and create collaboration initiatives to improve community health and biomedical research. Dr. Chris Callison-Burch, PhD, MS, is a Professor of Computer and Information Science at the University of Pennsylvania. His research focuses on natural language processing and generative AI. So, is this really goodbye? Maybe, maybe not. We can never sit still for long. But for now, let's raise a glass, share a few laughs, and remember the good ol' times! We can't leave without saying thank you to all of you for being part of the ride, for listening to us on your jog or your commute, and for engaging critically with all we've had to say. It's been an honor. Thank you to all the guests who have joined us throughout the last five years. Thank you for contributing your expertise, your lived experiences, and your unfiltered thoughts. Thank you to the musicians who bravely stepped into conversations about topics they knew little about and for offering up their questions. You ensured we spoke to everyone, and your music said the rest of what our words couldn't convey. To all our guests, your generosity with your time and your knowledge is what made this podcast what it was. Our mission was always to make informatics intelligible so that you and all your friends and family can engage confidently with the topic. We hope you now have the language to feel empowered navigating this crazy, awesome, flawed, fascinating healthcare system.  For now, this is Kevin Johnson, Harris Bland, and Ellie Shuert signing off! Mentioned in the episode: -Hidden Brain podcast -Scott Scovill and Moo TV, plus his appearance on episode 4: “Automated Resilience: Biomedical Informatics as a Safety Net for Life” -Nancy Lorenzi in “Informatics and Anti-Black Racism: What We Need to Do” (Jun. 2020) -Trent Rosenbloom in “21st Century Cures: Curing our Anxiety or Causing It?” (May 2021) -Hey Epic! -Brad Malin in “Data Privacy: Possible, Impossible, or Somewhere In Between?” (Aug. 2020) -Moore v. Regents of the University of California (1990) -”Learning Health Care and the Obligation to Participate in Research” by Ruth R. Faden and Nancy E. Kass (Hastings Center Report) -”The Right to Privacy” by Samuel D. Warren II and Louis Brandeis (Harvard Law Review) -Revenge of the Tipping Point: Overstories, Superspreaders, and the Rise of Social Engineering by Malcolm Gladwell -Colin Walsh in “COVID and the Hidden Data Gap” (Feb. 2021) -Bryant Thomas Karras in “Get Your Dose of Data! An Introduction to Public Health Informatics” (Jul. 2024) STE and public health highway? -Consuelo Wilkins in “Clinical Trials: Are We Whitewashing the Data?” (Nov. 2023) -Where Do We Go from Here: Chaos or Community? by Martin Luther King Jr. -Michael Matheny and Tom Lasko in “AI and Medicine: The Slippery Slope to an Uncertain Future” (Feb. 2020) -Lyle Ungar and Angela Bradbury in “Chatbots in Healthcare: The Ultimate Turing Test” (Aug. 2024) -“A Textbook Remedy for Domain Shifts: Knowledge Priors for Medical Image Analysis” by Yue Yang, Mona Gandhi, Yufei Wang, Yifan Wu, Michael S. Yao, Chris Callison-Burch, James C. Gee, Mark Yatskar (NeurIPS) -Google DeepMind -OpenAI's Deep Research -The Thinking Game (2024) dir. by Greg Kohs -“Dolly the Sheep: A Cautionary Tale” by Robin Feldman and Vern Norviel (Yale Journal of Law & Technology) -Who, Me? Children's book series -The Influencers Substack Follow our social media platforms to stay up to date on our new projects!

In this episode, Jonathan Sackier welcomes Andrew Blauvelt, a distinguished dermatologist and leading expert in immunodermatology. They discuss groundbreaking advancements in psoriasis treatment, including the role of high-dose biologics in achieving deep remission and how IL-23 inhibition is transforming long-term disease management. Timestamps: (00:00) – Introduction (02:25) – A recent knockout study (17:22) – The wider applications of biologic treatments (19:40) – Deep remission in psoriasis (27:20) – The next frontier in psoriasis research (32:36) – Barriers to research breakthroughs (36:11) – What's on the horizon for dermatology research? (41:37) – Andrew's three wishes for healthcare

Genetic testing plays a key role in the evaluation of epilepsy patients. With the expanding number of choices for genetic tests and the complexity of interpretation of results, genetic literacy and knowledge of the most common genetic epilepsies are important for high-quality clinical practice. In this episode, Gordon Smith, MD, FAAN speaks Sudha Kilaru Kessler, MD, MSCE, author of the article “Epilepsy Genetics,” in the Continuum February 2025 Epilepsy issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Kessler is an associate professor of neurology and pediatrics at Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia in Philadelphia, Pennsylvania. ADDITIONAL RESOURCES Read the article: Epilepsy Genetics Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com SOCIAL MEDIA facebook.com/continuumcme @ContinuumAAN  Host: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr Sudha Kessler about her article on epilepsy genetics, which appears in the February 2025 Continuum issue on epilepsy. Sudha, welcome to the podcast and please introduce yourself to our audience. Dr Kessler: Oh, thank you so much. I'm Sudha Kessler. I am a pediatric epileptologist here at the Children's Hospital of Philadelphia and the University of Pennsylvania. Dr Smith: Tell us a little bit about yourself. Are you a geneticist too, or how did you get into this particular topic? Dr Kessler: Yes, I want to emphatically say that I am not a geneticist. I'm not an expert in epilepsy genetics at all. I take care of all sorts of patients with epilepsy. I actually do mostly epilepsy surgery-related care. But this part of epilepsy is, every year, increasingly important to our everyday practice. And I think it's fascinating, often a little daunting. I think I was asked to get involved with this article as a non-expert to help translate from the experts to the rest of us. Dr Smith: We're going to get there, because one of the things you do a really good job of in the article is talking about genetic concepts that are germane to everything we do. And I think you're an expert. You do it in a way that I understood. So, I'd like to get there, but- and this is a really hot area. For instance, I really loved your figure that shows the arc of discovery of genetic causes for epilepsy. It's really breathtaking, something we wouldn't have thought possible that long ago. And it's also a lot to digest. And so, I wonder if maybe we can begin by thinking about a framework and, for instance, you talk about these different groups of disorders. And one that seems to be particularly impacted by this unbelievable A-rated discovery. Our developmental and epileptic encephalopathies, or DEEs. What can you tell our listeners about that group of disorders? Dr Kessler: Sure. I think that, you know, most of what we think about in epilepsy genetics now has to do with disorders that are attributable to changes in a single gene. Genetics is obviously much more complicated than that, but that's still where we are in the stage of discovery. And the graph in the article is definitely one to take a look at because it represents the explosion that we've had in our understanding of single gene disorders leading to epilepsy and related manifestations. The DEEs are a group of disorders where any individual disorder is fairly rare, but as a group they are not that rare, and very impactful because they often cause epilepsy at a very young age. And either as a consequence of seizures or as a consequence of the underlying pathophysiology of that gene change, they are typically associated with really significant developmental impairments for a child 's entire life. Dr Smith: My understanding is that there's therapeutic development going on in this space. So, the early recognition of these genetic testing offers the promise of very impactful treatment---like we now do for SMA, for instance---early in the disease course. Dr Kessler: I think that's right. That's one of the most exciting parts of this field is that so much, just around the corner, for drug development, therapy development in this area. And as you can imagine, with a lot of these disorders, earlier intervention is likely to be much more impactful than later intervention when a lot of the developmental consequences are sort of… you know, when the cat 's already out of the bag, so to speak. Dr Smith: Yeah. So, this is really transformational and something that everyone who takes care of kids with epilepsy needs to know about, it seems. So on the other extreme, I guess, there are the self-limited epilepsies. I didn't really know about this in terms of genetic discovery, but can you talk about those disorders? Dr Kessler: Yeah, sure. I mean, I think some of these are the classic childhood epilepsy syndromes that we think about like childhood absence epilepsy or what we used to call benign romantic epilepsy and now call self-limited epilepsy of childhood with centrotemporal spikes. It's a mouthful, shortened to SeLECTS. Those are the epilepsies that occur typically in previously healthy children, that affects them for a few years and often remits so that epilepsy is just age-limited and doesn't continue for life. They clearly have genetic influences because they tend to run in families, but the genetics of them is not generally single gene associated. And so, we haven't actually explained why most of those kids actually get epilepsy. I think that'll be sort of another interesting area of discovery that will help us even understand some really fundamental things about epilepsy, like, why does this syndrome start at this age and tend to resolve by adolescence? Dr Smith: And the other thing I found interesting is disorders that I might have thought going into it would have a defined genetic cause or some of the disorders that there are not. So JME, for instance, or childhood absence, which is a little counterintuitive. Dr Kessler: It's completely counterintuitive. We call them genetic generalized epilepsies, and we know that they run in families, but we still know so little. I would say of all of the disorders that are mentioned in this article, that is the group where I think we have explained the genetic underpinnings the least well. Dr Smith: Yeah. Isn't that interesting? It's… wasn't it Yogi Berra who said, it's hard to predict things, particularly the future? So… Dr Kessler: Yes. Dr Smith: Who would have thought? So, we've talked a lot about kids. What about adults? You know, what role does genetic testing play in adults who have unexplained epilepsy? Dr Kessler: Yeah, I think that that is also a really important emerging area of knowledge. I think many epileptologists may think of genetic epilepsy as being solely pediatric. There are definitely not how many of these disorders can manifest for the first time in adulthood. Not only that, many of our children with childhood onset epilepsy that is due to a genetic problem grow up to become adults and will then need adult epilepsy care. In order to take care of both of those groups, it's really important for all epileptologists, including those that take care of adults, to have some knowledge of the potential impact of genetic testing. And how do you even approach thinking about it? Dr Smith: The message I guess I'm getting is if our listeners take care of patients with epilepsy, no matter how old those patients are, they need to be familiar with this. And the other message I'm getting is, it sounds like there are a lot of patients who really need genetic testing. And this came through in one aspect of your article that I found really interesting, right? So, what are the recommendations on genetic testing? So, the National Society of Genetic Counselors, as I understand it, said everyone needs genetic testing, right? Which I mean, they're genetic counselors, so. Which is great. In the International League Against Epilepsy, they recommended a more targeted approach. So, what's your recommendation? Should we be testing anyone with unexplained epilepsy, or should we be focusing on particular populations? Dr Kessler: Well, I guess I think about it as a gradation. There are certain populations that really deserve genetic testing, where it is going to be absolutely critical. You know, it's very likely that it will be critical knowledge to their care. If you diagnose somebody with epilepsy and you do imaging and that imaging does not reveal an answer, meaning you don't see a tumor or you don't see an old stroke or some other sort of acquired lesion, the next pillar of testing for understanding underlying etiology is genetic testing. That is the point at which I typically send my patients, and that's whether they're refractory or not. I think in the past some people felt that only patients with refractory epilepsy deserve or require testing. I think the reason why not to limit it to that population is that what's on a person's mind with epilepsy, or a family's mind with epilepsy, is what's going to happen to my child or to me in the future? And if genetic testing can shed some light on that, that will have a huge impact on that person's life. Dr Smith: You've got great cases in your article, which, I just want to give you a compliment. The information and entertainment, frankly, for per page: off the charts. It's not a long article, packed with useful information. And, I mean, some of your cases are great examples of patients who are heading down the surgical epilepsy path and you discovered, nope, there's a genetic cause that really impacted their care. What's the yield, right? The number of patients that you send genetic testing on for epilepsy, what percentage come back positive for a relevant sequence variant that you think is either causing or contributing to their epilepsy? Dr Kessler: That's a great question. I think that is actually still in flux because it depends on the population of patients that are being sent for testing, obviously, and then also on what testing is being done. So, I know in at least one large recent meta-analysis, the overall yield was 17%. And somebody hearing that number might think, oh, that's not very high, but it's actually very comparable to the yield for imaging. And we all do MRIs and patients that have new-onset epilepsy where the yield of MRI testing is about 20%  or so. So, quite comparable. And then with children with DEEs, the yield is much, much higher than that. Dr Smith: So, 17% is actually a really great diagnostic yield. When I think of my yield and doing genetic testing on patients who have an axonal CMT phenotype, right? I mean that's better than what I get. So, good for you. That's exciting. Dr Kessler: It's interesting. I think that maybe an assumption might be that you're working somebody up. You do a genetic test, it reveals a difference, and thus surgery is off the table. It's actually quite different than the head, which is that some results may make surgery be even more “on the table” because you might find a gene that is known to be associated with a propensity to vocal cortical dysplasia, for example. And you may take a good second look at that person's MRI imaging or do other imaging to reveal the MRI invisible vocal cortical dysplasia. Dr Smith: Outstanding point. Let's talk a little more about the genetic testing itself. So, we've got all these genes. We understand when to test. What do you do? For instance, last night I just looked at the company that we use for most of our neuromuscular testing and they have a genetic epilepsy next gen panel with, I don't know, three hundred and twenty genes, right? Do you use that kind of panel? Do you go directly to a whole EXO? What's the right approach? Dr Kessler: Yeah, I think that that is quite dynamic right now, meaning that recommendations seem to change often enough that I rely on help. I have the enormous good luck of working here at CHOP where there is a fantastic epilepsy genetics group that I can easily refer to, and I know not everyone has that resource. The current recommendation is to start with an exome if that is available and is covered by that patient's insurance. When exome is not available, then the next best thing is a gene panel. You know, in recent years there have been a lot of sponsored gene panels, meaning free to the patient, administered by a company that then, you know, has other uses for compiled or grouped genetic data. And I think that as long as all of that can be clearly explained to a patient, and- along with all of the other things so you have to explain to a patient before doing genetic testing, about the pluses and minuses of doing it, I think that you sort of go for the best test you can that's available to that patient. Dr Smith: The sponsored programs can be very, very helpful, particularly from a payer or a patient payment perspective. And so, I guess the lesson there is it's great if you got the resources and CHOP to help you decide, but better to get whatever panel you can get than to do nothing; or, of course, refer to a center if you're not comfortable. Dr Kessler: And also, just know that these things change often enough that if it's been a couple of years and you might want to recheck whether the EXO is available to that patient or whether a gene panel can be sent that includes more than they had eight years ago. Dr Smith: So, are there situations to go to the other extreme where you just do targeted sanger sequencing? Like, just sequence the specific gene of interest?  Dr Kessler: Yeah, absolutely. I'm still a big proponent of thinking clinically about a patient. If there are clues in that patient's history, exam, imaging, anything that gives you some sense of the disorder that this patient might have. And I think a classic example would be tuberous sclerosis. If you see an infant who has new onset spasms, you see hypopigmented macules on their skin and their MRI shows a tuber, you know, also known as a focal cortical dysplasia, then sure, send the targeted sequencing for the TSC1 and TSC2 genes. Dr Smith: And Rett syndrome?  Dr Kessler: And Rett syndrome would be another example. And there are many examples where, if you feel like you have a good sense of what the disorder is, I think it's completely acceptable to send the targeted testing.  Dr Smith: So, I'm going to get further down the rabbit hole and get to from easier to harder. I always get confused about things like chromosomal microarrays or, like, karyotypes and rings and stuff like that. What role do these tests play and what do our listeners need to know about them? Dr Kessler: Yeah, I think that it is really important to have at least some knowledge of what each test can't tell you. I tell my medical students at my residence that all the time. With anything in medicine, you should know what you're asking of a test and what answers a test can tell you and can't tell you. It is baseline knowledge before requesting anything. And if you don't know, then it's best to ask. So, chromosomal microarray is used when you think that there is a large-scale derangement in a bunch of genes, meaning there is a whole section of a chromosome missing---that would be deletion, or that that information is duplicated or is turned around in a, you know, in a translocation. That is what- the kinds of things that that test can tell you. I think of doing a microarray when a child has not just epilepsy and intellectual disability, but also has, for example, other organ systems involved, because sections of chromosome can include many, many, many different genes and it can affect the body in larger ways. That's often when I think about that. So, a child with multiple congenital anomalies. Karyotype, which we think of as the most old-fashioned way of looking at our genes, still has some utility because it is useful for looking at a specific situation where the ends of arm of a chromosome get cut off and get sticky and then stick to each other and make a ring. For example, ring chromosome 20 is a disorder which can cause epilepsy, particularly hard-to-treat frontal lobe epilepsy, and that sometimes doesn't show up until adolescence or even early adulthood. That's just one example of something that karyotype can tell you.  Dr Smith: And it goes without saying, but just to emphasize, these are things that you would miss completely on a next generation panel or a next genome? Dr Kessler: That's correct. Because this isn't about sequencing. This is about large structures. You know, with my patients, it's sometimes, I think, very hard to explain. It's hard enough to explain it to other physicians who aren't in genetics, but it's a whole other undertaking to explain it to families who may not have a lot of literacy about cell biology or genetics or, you know, anything related to that. So, I often rely on analogies. And one analogy I use is that if you're- all of your genetic information is like a book, that book is split into chapters and those are the chromosomes. And you can be missing entire paragraphs or have paragraphs duplicated. And that would be the kind of thing that we would be looking for with the chromosomal microarray with sequencing or, you know, with sequencing, we're looking for spelling of words, and we can look at one word at a time. That would be targeted sequencing. Or we can look at many, many words at a time. And that would be next gen sequencing.  Dr Smith: I just want to say that you are the genetic whisperer. You know, translator. I love it.  Dr Kessler: You can continue using it down to the level of explaining the possibility of a variant of unknown significance, which I think is sometimes difficult to explain. So, I often will say, I know how the word color is spelled: C O L O R. But sometimes in other places it will be spelled C O L O U R and that's still the same word, that's still color. That's just what we would call a population variant. If it is spelled C O M O R, that changes meaning; that is not a word, and that is probably a pathogenic variant. But if it gets misspelled and it's K O L O R, then I'm not sure. Could that be a variant that means something different or not. And so that I would call that a variant of unknown significance, meaning its impact is to be determined. Dr Smith: So, I was going to ask you about variant calling, but you'd beat me to the punch. And that's a great metaphor that I will definitely remember. All right, here's another concept that I think people often find challenging, which is read depth. Can you tell us about reading depth or sequence depth?  Dr Kessler: Yes, hopefully I can. Again, not an expert here, but as I understand it, the way next gen sequencing works is that pieces of DNA are getting read. And the number of times any given nucleotide is read in this process is the read depth. It basically just translates to the number of times the processor, the machinery of doing this, pays attention to anyone site. The reason it's important is that the process by which this reading is done can sometimes result in errors. The greater your depth, the more times something is read, the less likely you are to have a mistake.  Dr Smith: In either direction. So, you're presumably less likely to have a false positive or false negative. Yep, again, very well explained. You know, I've got a lot of other questions I want to ask you, but I do want to be respectful of our listeners' time. I wonder if we could pivot a little bit and just let's go back to where we began. Really exciting time, right? Amazing. And you've been doing this long enough. I'm sure you didn't think when you started that it was going to look like this. What does the future look like? I mean, we talked a little bit about therapeutics, but the world's changing fast. Five, ten years from now, what's your hope for that?  Dr Kessler: Oh, that's such a great question. You know, we are at the point with genetic epilepsies that gene-based therapies, either antisense oligonucleotide-based therapies or viral vector-based gene therapies, are actually now being developed and administered in trial situations to actual patients. And so, it always feels like we're on the cusp, but I think actually now we really are on the cusp of having gene-based therapies for genetic epilepsies. I think that there is still so much to sort out, both from basic scientific point and from a practical administering these things to patients and what are the potential long term consequences.For example, unlike medications, which are therapies that you can stop if there are adverse effects, often administering a gene therapy is a one-and-done thing that can't be retracted. Thinking even about the ethical framework of that and the framework of explaining to patients that we don't know the ten, twenty-year consequences of that, is part of the informed consent process, for example. So, there's still so much work that is going to be transformational, not just from the, you know, the big picture, but from developing all, you know, from going through all of these steps to really make these kinds of therapies a reality. Dr Smith: Well, it's really amazing. And, you know, we're seeing this in multiple different areas in neurology. So, well done. You run the child neurology residency program there, I understand. I try to snoop on people before I talk to them because we haven't met before this. And you're obviously a very a very good educator. Thank you so much for talking with me today. I don't spend a lot of time in epilepsy, but every time I do one of these, I kind of want to go back and do something different because it's such a neat field. Thank you.  Dr Kessler: You're welcome. It was my pleasure.  Dr Smith: Again, today I've been interviewing Dr Sudha Kessler about her article on epilepsy genetics, which is truly outstanding. This article appears in the most recent issue of Continuum on epilepsy. Be sure to check out Continuum audio episodes from this and other issues. And thank you, listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In today's episode, we had the pleasure of speaking with Rachna Shroff, MD, MS, FASCO, about the phase 3 SWOG S1815 trial (NCT03768414) evaluating the addition of nab-paclitaxel (Abraxane) to gemcitabine and cisplatin in patients with newly diagnosed, advanced biliary tract cancer. Dr Shroff of the interim clinical affairs director, the associate director of Clinical Investigations, and co-lead of the Gastrointestinal Clinical Research Team, at The University of Arizona Cancer Center. She is also a professor in the Department of Medicine, chief of the Division of Hematology/Oncology, medical director for the Oncology Service Line, and associate dean for Clinical and Translational Research at The University of Arizona College of Medicine in Tucson. In our exclusive interview, Dr Shroff discussed the rationale for this research, key efficacy and safety data from the trial, and the potentially wide-reaching future implications of these findings.

Send us a text In this episode of Causes or Cures, Dr. Eeks chats with Dr. Timothy Yeatman about  the connection between diet, inflammation, and colon cancer. He'll explain why cancer can be thought of as a "poorly healing chronic wound" and describe his recent study highlighting how chronic inflammation, fueled by dietary choices, plays a key part in the progression of colorectal cancer. We'll explore the alarming rise of colon cancer in adults under 50 and any common patterns he's observed in this population. Dr. Yeatman will shed light on the immune tumor microenvironment, how it influences colon cancer, and its potential role in future treatments. Plus, we'll discuss natural approaches to prevention and treatment, including key lifestyle interventions, such as achieving the right balance of omega-3s and omega-6s.  Dr. Yeatman is the Associate Center Director for Translational Research and Innovation at Tampa General Hospital Cancer Institute and a Professor of Surgery at the University of South Florida. With a career spanning leadership roles at Intermountain Healthcare, the Huntsman Cancer Institute, and Moffitt Cancer Center, he has spearheaded groundbreaking research in colorectal cancer, genomics, and biomarker development. He founded the Guardian Research Network, led a $100M Moffitt-Merck collaboration, and co-founded M2Gen, a biotech company. His work has been funded by the National Cancer Institute since 1993, and he continues to advance cancer research and clinical innovation. You can contact Dr. Eeks at bloomingwellness.com.Follow Eeks on Instagram here.Or Facebook here.Or X.On Youtube.Or TikTok.SUBSCRIBE to her monthly newsletter here.Support the show

Our podcast is back! And with a new name chosen by you! "The Phelan-McDermid Podcast: Sharing Research, Progress, and Hope". In this episode, Dr. Lauren Schmitt, the Chief Science Officer of the Phelan-McDermid Syndrome Foundation (PMSF), restarts the podcast with the first of three interviews with our 2023 Grant Awardees. Lauren is joined by Dr. Julia Dallman, an Associate Professor at Miami University, whose project titled, “Validation of a Novel, Inexpensive, Home-Based Gastrointestinal Transit Test among People with Phelan-McDermid Syndrome” won the 2023 PMSF Translational Research Award. They discuss how Dr. Dallman got into the Phelan-McDermid syndrome field, how basic scientists can use zebra fish to study motility issues, and the latest on Julia's project! Plus, you'll have to tune in to know why they are talking about blue poop!To find out more about Julia Dallman's lab and research: https://dallmanlab.weebly.com/To hear more about the latest in GI research, check out Dr. Bennet, Still, and Dallman present at the 2024 PMSF Family Conference: https://youtu.be/IP4eaimpKM0?feature=sharedHave ideas for a future podcast? Email your recommendations to info@pmsf.org!

Join Dr. Andy Cutler as he talks with Dr. Jeffrey Strawn about how clinicians can determine the appropriate scenarios for benzodiazepine deprescribing, best practices for benzodiazepine tapering, and how to balance patient preferences to ensure best outcomes.  Jeffrey R. Strawn, MD is a Professor and Associate Vice Chair of Research in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati (UC) College of Medicine, the Assistant Director of Clinical and Translational Research in the Center for Clinical & Translational Science and Training at UC, and an Associate Professor in the Department of Pediatrics at UC and Cincinnati Children's Hospital Medical Center.   Andrew J. Cutler, MD is a distinguished psychiatrist and researcher with extensive experience in clinical trials and psychopharmacology. He currently serves as the Chief Medical Officer of Neuroscience Education Institute and holds the position of Clinical Associate Professor of Psychiatry at SUNY Upstate Medical University in Syracuse, New York.  Save $100 on registration for 2025 NEI Spring Congress with code NEIPOD25  Register today at nei.global/spcongress25p  Never miss an episode!

In this episode of our special pediatric psychopharmacology series, Dr. Jeffrey Strawn and Dr. Katherine Dahlsgaard review how psychiatric prescribers can incorporate cognitive behavioral therapy (CBT) practices into medication checks with pediatric patients who have anxiety disorders. Specifically, they discuss the importance of using exposures to reduce avoidance behaviors that are characteristic of and feed anxiety disorders. Jeffrey R. Strawn, MD is a Professor and Associate Vice Chair of Research in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati (UC) College of Medicine, the Assistant Director of Clinical and Translational Research in the Center for Clinical & Translational Science and Training at UC, and an Associate Professor in the Department of Pediatrics at UC and Cincinnati Children's Hospital Medical Center. Katherine Dahlsgaard, PhD, ABPP is a licensed clinical psychologist in Philadelphia, Pennsylvania with expertise in CBT for children, adolescents, and adults. Dr. Dahlsgaard specializes in evidence-based assessment and treatment of anxiety and related disorders.   Save $100 on registration for 2025 NEI Spring Congress with code NEIPOD25 Register today at nei.global/spcongress25a   Never miss an episode!

Dr. Hunter Champion received his training in Cardiovascular Disease, Heart Failure and Transplant Cardiology at Johns Hopkins where he later directed the Bernard Laboratory for the Study of Cardiovascular Disease.  Thereafter he was recruited to the University of Pittsburgh to join the faculty of the Divisions of Pulmonary, Allergy and Critical Care Medicine and the Cardiovascular Institute as an Associate Professor of Medicine where he directed Translational Research for the University of Pittsburgh Vascular Medicine Institute. He is a Heart Failure trained specialist and a Pulmonary Hypertension trained specialist and treats patients with hypertension, coronary artery disease, heart rhythm issues, and valvular disease. Dr. Champion joins Mark Immelman on the #OntheMark podcast to introduce 5 lifestyle changes that are sure to lead to a healthier, happier existence - habits which will also set you on the path to better physical performance and, by extension, better golf. Dr Champions elaborates on: Healthy body movement High quality sleep Morning sunlight, fresh air and breathwork The practice of gratitude, and Healthier eating involving protein and green vegetables. He also talks about the 'mind-body connection', alcohol consumption, managing stress, hydration, dietary supplements, meditation, hot and cold water therapy and grounding. Download this podcast or watch it on YouTube - search and subscribe to Mark Immelman.  

Informal care partners are essential to the care of people living with dementia, but they often experience significant burden and receive minimal training, support, and resources. Multicomponent interventions can mitigate burden and other negative consequences of caregiving. In this episode, Gordon Smith, MD, FAAN speaks with Angelina J. Polsinelli, PhD, ABPP-CN, author of the article “Care Partner Burden and Support Services in Dementia” in the Continuum® December 2024 Dementia issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Polsinelli is an assistant professor of clinical neurology at the Indiana University School of Medicine in Indianapolis, Indiana. Additional Resources Read the article: Care Partner Burden and Support Services in Dementia Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Angelina Polsinelli about her article on care partner burden and support services in dementia. This article appears in the December 2024 Continuum issue, which is on dementia. Ange, welcome to the podcast. And maybe you can begin by just introducing yourself to our audience?  Dr Polsinelli: Yeah. Well, thank you for having me. I'm very excited to be here. I'm Ange Polsinelli. I'm a neuropsychologist at Indiana University School of Medicine, where I work in the Department of Neurology. I also work with the Longitudinal Early Onset Alzheimer's Disease study that's led by Liana Apostolova. And I also do some work with the Outreach, Recruitment and Engagement Core of the Indiana Alzheimer's Disease Research Center. This topic that we're going to talk about today is extremely near and dear to my heart. Dr Smith: Well, thanks for joining me. And of course, IU is a powerhouse for Alzheimer's and basketball, in that order. So, we're really excited to have you. I'd like to get right into it. I'll emphasize, we were chatting a little bit about this, Ange, before we started recording, that your topic today is so important for all of us. And I think, you know, this is a podcast that not only neurologists listen to, but students and, and I think increasingly members of the lay public. And this conversation is going to be very important for neurologists and our neurology learners. But I lost my grandmother to Alzheimer's disease. I lost my uncle just in the last week. So, this touches all of us. So, I'm really excited. And then with that in mind, I wanted to begin with a statistic that- you can correct me if I misunderstood it, but it really blew my mind. And that is across the world, as I understand it, care partners provide one hundred and thirty three billion hours of care for people living with dementia yearly, which is pretty staggering. But what's really amazing is that by 2030 that number is expected to go to one point four trillion hours, which I couldn't grab my mind around it. So, I figured I'd try and determine how many years of person work is that and if my math is right, that's almost a hundred and sixty million person years of worth caring for people with dementia yearly across the world. One, are those numbers right? Did I get it right? And then, assuming so, can you put a human face or experience to these numbers?  Dr Polsinelli: Yeah, unfortunately those numbers are correct. And with our increasing aging population across the world, that's why you're getting that, you know, exponential increase in care per hours, compounded by the fact that the majority of the caregiving that happens is not done by doctors, physicians, but it's done by these informal care partners, these family members, these friends, these siblings, children, who are providing these really important services and unfortunately not being trained to do this, doing it largely on their own in a lot of respect. But again, these are people who are loved ones of the person living with dementia. There are a variety of kinships, as I mentioned, siblings, children, spouses, friends; and all sorts of age ranges as well. A large majority of them being spouses, and then the second largest majority being children. So, kind of a sandwich generation of people who are caring for parents with Alzheimer's or dementia and then caring for children as well. Dr Smith: Yeah, I was actually struck by the statistic that a quarter of caregivers or so called sandwich caregivers; in other words, they're taking care of a parent and a child. But listen to what you said. But just to call it out, two-thirds of care partners are women, which is a striking statistic.  Dr Polsinelli: Absolutely. Women are not only more likely to have dementia, but they are also more likely to be the care partners of somebody who has dementia. And so, the research shows, too, that if you're a care partner, you're at higher risk of developing dementia yourself. So, there's a lot of risk for women when it comes to dementia, development of dementia, but also that the burden and the majority of care needs that are that are supported by women as well. Dr Smith: Right. And there's a lot to unpack in that observation, and maybe we can come back to that. But I wonder if you might talk to us a little bit about the risk of dementia in women caregivers. That's really striking. Is there any thought regarding mechanism for that? Why is that the case? Is it a shared risk factor? Is it cause and effect? What's the story?  Dr Polsinelli: So, there are - this is kind of a dissociable or different - kind of two aspects to this, this question. There's the fact that women are at higher risk for developing dementia in general. I think the researchers feel sort of out about why exactly that is. It's not just that women are at higher risk or more likely to develop dementia because they're living longer than men, but there's probably some hormonal aspects of their higher risk factor for dementia. But then there's the other aspect of it too, is that as caregivers, caregivers are at higher risk of developing dementia. And because caregivers tend to be women, that increases or compounds the risk for women as well. We know with caregiving, particularly with someone who's living with dementia, there's more risk of developing things like depression, high stress, health problems, psychological distress, and all of these things increase somebody 's risk for developing dementia as well. Dr Smith: So, I wonder if you might talk a little more, Ange, about what you mean by burden? I think we have in our mind what that is. But in reading your article, there's a lot of- a lot more to it than may meet the eye. Dr Polsinelli: Yeah, it is a more complicated, I guess, topic or terminology that's gone through several iterations over the course of doing research into burden. But when we think about burden, it's really a kind of a combination of both objective experiences and subjective experiences. And these objective, subjective experiences fall into the categories of physical burden, emotional burden, psychological burden. So, there's a lot of different areas of life in which someone can experience burden. But really, it's a combination of factors of both the objective experience, lived experience, and the person 's perception of that experience or what they're dealing with. I should also mention that it appears to be more of that subjective experience or that perception that people have of their objective experience of stressors or burden. That really does determine the person's response to that, if whether they actually perceive their lived experience as being burdensome.  Dr Smith: One of the things I found really interesting was the societal and cultural context surrounding this, that there are different cultural expectations and societal dynamics, both in the nature of the burden care partners may feel and how they're viewed. I wonder if you could talk about that? I think it's something that it would seem all of us need to be attuned to as we're working with our patients and their families.  Dr Polsinelli: Yeah, this is a topic we could talk for a very long time on. I will try and- I will try not to kind of provide too much of a, or too lengthy of a response. But what we know now is basically that our models of stress and burden that we have typically used or historically used do not incorporate a lot of factors of cultural identity of social and structural determinants of health factors. And so, what we understand now is that stress and the way that people perceive burden is influenced by so many other factors than just kind of an experience and a perception. Because that perception is influenced by so many factors, including, as you mentioned, cultural factors that include how society's familial expectations for us, cultural expectations for us, as well as what our resources are that are determined by, again, structural and social determinants of health, what our community resources are. They're just a lot of different factors that go into how somebody perceives their ability to cope with, again, this kind of life-altering diagnosis that their loved one has received and them being the person who is caring for them through that. Dr Smith: Your article actually goes through in some detail the types of burdens and what drives the burden. And that changes over time. And so I wonder if maybe you can talk a little bit about what the specific natures of the burden are from the caregiver perspective. I mean, what  sort of tasks there are, you know, from the many of us who take care of patients, we still don't know unless we've been in the room or in the home watching this happen. So maybe you can describe that for those of our listeners who maybe haven't lived through this?  Dr Polsinelli: Yeah, absolutely. I will say upfront that the caregiving experience is going to be different for every single person. And again, kind of dependent on some of those factors that I mentioned before. So, it's going to look different for most people. It's also going to look different through the dementia journeys. The experiences and the requirements earlier on in dementia are going to be a vastly different than what occurs later on when dementia is in the more late stage, moderate or severe stages of the disease. Those care responsibilities absolutely change over the spectrum of that time as well. We know that early on the stage of disease, primary care partner might be spending forty plus hours a day. So, a full-time- or not a day. I'm sorry, a week. So, a full time job carrying it. But that number increases up to a hundred and fifty or so hours per week once the person is more advanced in their disease. So, I say that because the number of hours, I think, make all, like- putting that into perspective of somebody having a full time, multiple full time jobs, basically providing care, I think is really important. But the responsibilities of the care partner are going to range from everything from just helping the person early on in terms of managing finances or managing them, making sure they're reminding them to take their medications, scheduling their medical appointments for them, maybe taking over all of the driving to get them to their appointments or to get them to family outings and things like that. They're going to be the ones that's going to be the most responsible for reminding people to do something: to eat, to maybe stay on track for a recipe or something that they are making. So, kind of being the eyes and ears for this person right away, basically right at the beginning, even early stages. And then that progresses over time to the person who is caregiving, who is doing potentially everything for this person. So that means helping them use the restroom when they need to, helping them shower. So, there's a physical component to the caregiving as well as that- sort of what we call instrumental support in terms of organizing medical appointments and things like that. They're just basically doing it all for that person.  Dr Smith: So, what about a busy clinician who has half an hour to see a dementia patient follow up? Kind of hard to- in these days, you know, we've got, you know, these new therapies to think about as well. What advice do you have to neurologists and other professionals caring for patients? Dr Polsinelli: Yeah. And I think neurologists, I mean, we all have limited time. And I know neurology in particular is like primary care, has even more constrained time. I think one of the biggest things that neurologists can do is really check in with the care partner. So, take a moment to check in with the care partner who's there with the person with dementia to see how are they doing. You're looking for signs of burden or stress, so things like physical complaints like headaches or stomach ache, mentioning feeling burnt out or overwhelmed, maybe feeling depressed or something like that. There's also some short kind of questionnaires that you could give care partners prior to an appointment that they could fill out. You could kind of get a sense of where is this person at this point and then help connect them potentially to some resources that might be available. And I would refer people to that article that has a list of resources in there that you could just basically print out and give to somebody.  Dr Smith: Yeah, I was going to make the same point, Ange. Your article is a treasure trove of information. And you know, I'm certainly, I keep all of these on file, as you might imagine, but I'm keeping it in hand for future use. One of the things you talk about that really hit home for me among many is the idea of self-care, and I think sometimes the best care partners are susceptible to burnout because they they're so dedicated. You made the airplane oxygen mask metaphor, which I love. So maybe you can talk about what airplane oxygen masks have to do with dementia care and what advice you have for us and helping our patient's care partners take care of themselves? Dr Polsinelli: Yeah, absolutely. Self-care is the number one thing I tell care partners to do. It's also one of the hardest things for care partners to do. Like you mentioned, there is a deep, generally speaking, a deep love and caring for the person with who is living with dementia. And the focus becomes on them. And understandably so, the care partners sort of loses focus on themselves and making sure that they're doing okay. So I oftentimes use this oxygen airplane metaphor for people, which is basically, you know, when you're in an airplane and if there's some kind of pressure change in an airplane, they always tell you, put your oxygen mask on first before you help somebody else because you're not going to be any good to anybody if you're passed out. In the airplanes, the pressure changes, you know. You need to be available. you need to be getting what you need in order to help somebody else. So, I think that metaphor, that analogy really works well in dementia care is you need to be- the care partner needs to be caring for themselves and replenishing themselves in order to be the best care partner they can be for their loved one.  Dr Smith: Another challenge that, it strikes me as shared between people living with dementia and their care partner is that of social isolation and loneliness, right? If you're working a hundred and fifty hours a week doing anything, you don't have time to care for yourself or very hard to engage in social connections. And one of the loud messages I think I heard from your article is the power of social connectedness, both in terms of resilience and in many different ways. I wonder if you can talk a little bit about loneliness? And I just reflect that in a postpandemic world, this is probably a bigger issue than it was four years ago or four years and three months ago. Dr Polsinelli: Yeah, absolutely. Loneliness and social isolation was a big problem before, and it's even worse now is when I'm hearing from my patients. What I'm seeing in the literature is this postpandemic time is even more has been even more isolating and more problematic for people, but this social network cannot be, as you said, it cannot be overstated in terms of the importance for people. So that social network is important for not only providing potential instrumental care - so that practically care that care partners can use can lean on other people to come into the home to do things for the person living with dementia so the care partner can go practice self-care or go do those errands that need to be done - but also the emotional support as well that social networks can provide for people. And also, you know, social networks for not just the person, the care partner, but for the person living with dementia as well. We know that social engagement in particular is really good for brain health. I mean, we don't think about it, but social engagement is a very cognitive activity. And so, it helps give the brain a bit of a workout. So that social network is important for a lot of different reasons, and understandably a lot harder to maintain in this sort of postpandemic world as well. Dr Smith: As our time starts to come to- close to a close, we're not done yet, but I think we're probably going to have to start winding up. I wonder if we could pivot to something positive and then talk about the joy in this. And by that, I mean you describe and I think we've witnessed relationships and caring, caregiving situations that, as challenging as they are, provides fulfillment and the connection one has with a loved one or sort of that social aspect. Are there things that- predictive of that kind of positivity, and are there ways that we as professional caregivers for patients and their families can facilitate that? Dr Polsinelli: Yeah, there are. There are a couple of things. So, one of which is basically the quality of relationship between the care partner and the person living with dementia already. So that's the quality of that relationship. The better the quality of that relationship, the more likely it is that the care partner will experience more meaning and fulfillment and joy associated with caregiving, kind of outweighing that burden. But the additional piece of that is the more resources, the more mastery they feel about their caregiving or care partnering abilities, the more competent they feel and their ability to do good by the person, their loved one, the person living with dementia, the more likely they are to find that role fulfilling and meaningful. And I think that's where neurologists and other providers can kind of come in as helping people make sure that they have those resources that they are connecting to places where they can learn skills for giving appropriate care so that they can feel confident in what they're doing. There's the preexisting relationship piece that matters a lot. But I think that there's a lot of modifiability that neurologists have, too, in making a positive impact on the care partner and the person living with dementia. Dr Smith: That's really great advice, Ange. And I definitely will refer our listeners yet again to your article, which is a compendium of useful advice about this, both in terms of the text itself and in tables that provide lists of resources, websites, books, organizations, good case examples. It's a home run and I hope all of our listeners check it out. I'd like to wind up by talking a little bit about your work. And as I understand it, you obviously are very passionate about this topic, but you have specific interests in caregiver burden and underserved and marginalized communities. And then, we've touched on this, but this is a huge percentage of our population. And when you look out globally, it's even bigger than that. Tell us about what you're working on. And then maybe following that, what's the future look like? Where are we going to see advances in this in the coming years?   Dr Polsinelli: So just a really quick kind of brief history is that I've worked in dementia for almost twenty years or so now. And what I've consistently seen is when you give care partners good supports and education and resources, there are better outcomes for them and their families. The unfortunate thing is, a lot of these really great interventions and things that we have are not necessarily really accessible by a lot of people, but particularly not accessible by those living in underserved communities. The last few years in particular, I've really shifted into wanting to better understand that and better understand how do we provide culturally and socially appropriate interventions and education for these care partners and their families. With the current research project that I'm working on, we're looking at better understanding the needs of care partners of people who have early onset Alzheimer's disease, specifically from Black and African American individuals and other underrepresented groups. Again, the idea of this is to understand the needs before building an intervention for these groups, and I'm very excited about it. I know that there are lots of really great people who are working in this area, including Dr Dilworth Anderson and Kalisha Bonds Johnson, doing really fabulous work in this area. So, and building on what they're doing as well. In terms of what the future holds, one, I think we absolutely need to, we have lots of really great care partner interventions out there that have been lots of research going on, but it's not really transitioning into the clinical sphere. It's really kind of staying in that research sphere. So, I think it's really important that we get some implementation scientists who are taking those interventions and moving them into the clinical sphere, into the sort of like everyday, how do these actually work for people sphere. And then similar to some of this conversation we're having in terms of serving, making sure our interventions and making sure that our resources are appropriate and accessible for underserved communities, we really need to be taking a look at what these communities need rather than kind of saying, this is what's available. Kind of, hopefully this works for you. Speaking with these communities, engaging stakeholders and understanding what are the needs in these groups so that we can provide the appropriate resources, the appropriate interventions, the appropriate supports for care partners and people living with dementia. Dr Smith: And I'm just thinking, imagine what this looks like with effective treatments for Alzheimer's disease, that slow progression. And you know, that's going to make the caregiving even more important, it seems to me. But there's an opportunity to make it a better rewarding and a better-supported system as we develop these new therapies. So, this is a, like a Clarion call for learners listening that they should all become dementia neurologists and neuropsychologists like here. Thank you. That was outstanding. Say, Ange, I want to thank you a lot for a really engaging conversation. This fulfilled every hope I had coming into it. I was really excited to talk to you. I always love talking to neuropsychologists, but I think again, this is really useful for neurologists, learners, people who are nonneurologists everyone. And so, thank you very much. I've learned a lot and I really would encourage everyone to check out the article.  Dr Polsinelli: Well, thank you so much for having me on and giving me the opportunity to talk about the stuff that is really important to me and, I think, to most of us out there. So, hopefully people find the article and the resources in there useful and, and thanks again for having me.  Dr Smith: I'm sure they will. Again, today I've been interviewing Dr Angelina Polsinelli, whose article on care partner burden and support service in dementia appears in the most recent issue of Continuum, which is on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thanks to you, our listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Dr. Gee returns to the discussion of his involvement in a university report on the Black Community Experience at the University of Wisconsin–Madison. In episode 188 he discussed the upcoming report with UW-Madison Chancellor Jennifer Mnookin and now that the report is public, he is joined by fellow board members on the ad hoc committee. Dr. Angela Byers-Winston and Ray Allen discuss the difference between good intentions and intentionality, when it comes to identifying and creating real change? The ad hoc study group worked to present their critical findings and strategic recommendations aimed at addressing the long-standing challenges faced by Black students, faculty, and staff on university campus. They discuss the question, “What is the systemic inertia to follow through on the recommendations?” Hear the unfiltered conversation about the report conducted by the UW by those that served on the board. All three speak honestly about the process, offering what made them angry or frustrated, and the hopes they have for change. They talk about how creating programs only can't change the DEI issues, but it takes institutional and organizational change. Also, be sure to catch a double portion of the Black Ice Breakers segment. Dr. Angela Byars-Winston is a tenured faculty member in the Division of General Internal Medicine within the Department of Medicine. She is also the inaugural Chair of the University of Wisconsin Institute for Diversity Science, associate director in the Collaborative Center for Health Equity, and faculty lead in the Center for the Improvement of Mentored Experiences in Research. Dr. Byars-Winston has received numerous awards for her research on advancing diversity goals and mentorship in STEM fields. In 2011, Dr. Byars-Winston was selected as a Champion of Change by the White House through President Obama's Winning the Future initiative for her research efforts to diversify science fields. In 2022, she was the recipient of the Innovation in Mentorship Research award from the Association of Clinical and Translational Research. Dr. Byars-Winston chaired the National Academies of Sciences' 2019 consensus study report, The Science of Effective Mentorship in STEMM. She is an elected Fellow in the American Psychological Association and is currently an appointed member of the NIH National Advisory General Medical Sciences Council. Over a career spanning nearly 50 years, Ray Allen has worked at the John Deere Company and served in a number of leadership roles in state government, including Secretary of the Wisconsin Department of Workforce Development. He was elected to three terms on the Madison School Board from 1995 to 2004, has served as chair of the Madison Area Technical College Board, and is the former publisher and owner of weekly newspaper The Madison Times. In 2016 Allen was honored with the Outstanding Alumni of Color Award from the UW–Madison Division of Diversity, Equity & Educational Achievement. He currently serves on more than 10 corporate and community boards, including 100 Black Men, the Overture Center, UMOJA Magazine's board of directors, United Way of Dane County, American Red Cross, Downtown Madison Inc., and Madison College. Read the Report: Black Community Experience on the University of Wisconsin – Madison Campus- AD Hockey Study Group alexgee.com Support the Show: patreon.com/blacklikeme Join the Black Like Me Listener Community Facebook Group

******Support the channel****** Patreon: https://www.patreon.com/thedissenter PayPal: paypal.me/thedissenter PayPal Subscription 1 Dollar: https://tinyurl.com/yb3acuuy PayPal Subscription 3 Dollars: https://tinyurl.com/ybn6bg9l PayPal Subscription 5 Dollars: https://tinyurl.com/ycmr9gpz PayPal Subscription 10 Dollars: https://tinyurl.com/y9r3fc9m PayPal Subscription 20 Dollars: https://tinyurl.com/y95uvkao   ******Follow me on****** Website: https://www.thedissenter.net/ The Dissenter Goodreads list: https://shorturl.at/7BMoB Facebook: https://www.facebook.com/thedissenteryt/ Twitter: https://twitter.com/TheDissenterYT   This show is sponsored by Enlites, Learning & Development done differently. Check the website here: http://enlites.com/   Dr. Luana Colloca is Professor in Pain and Translational Symptom Science, Director of the Placebo Beyond Opinions Center, MPower Professor, and Adjunct Professor in the Department of Anesthesiology (School of Medicine) at the University of Maryland, Baltimore. She is co-editor of Placebo Effects Through the Lens of Translational Research.   In this episode, we focus on Placebo Effects Through the Lens of Translational Research. We start by discussing what a placebo is, how placebos work, and the goals of the book. We talk about placebo-based clinical interventions, expectations and culture in a clinical context, individual variation in the placebo effect, and we explore the example of the placebo effect in alcohol use disorder. We discuss when a placebo effect becomes a treatment effect, the patient-clinician relationship, and whether psychotherapy is an open-label placebo. Finally, we discuss why placebos matter for research quality. -- A HUGE THANK YOU TO MY PATRONS/SUPPORTERS: PER HELGE LARSEN, JERRY MULLER, BERNARDO SEIXAS, ADAM KESSEL, MATTHEW WHITINGBIRD, ARNAUD WOLFF, TIM HOLLOSY, HENRIK AHLENIUS, FILIP FORS CONNOLLY, ROBERT WINDHAGER, RUI INACIO, ZOOP, MARCO NEVES, COLIN HOLBROOK, PHIL KAVANAGH, SAMUEL ANDREEFF, FRANCIS FORDE, TIAGO NUNES, FERGAL CUSSEN, HAL HERZOG, NUNO MACHADO, JONATHAN LEIBRANT, JOÃO LINHARES, STANTON T, SAMUEL CORREA, ERIK HAINES, MARK SMITH, JOÃO EIRA, TOM HUMMEL, SARDUS FRANCE, DAVID SLOAN WILSON, YACILA DEZA-ARAUJO, ROMAIN ROCH, DIEGO LONDOÑO CORREA, YANICK PUNTER, CHARLOTTE BLEASE, NICOLE BARBARO, ADAM HUNT, PAWEL OSTASZEWSKI, NELLEKE BAK, GUY MADISON, GARY G HELLMANN, SAIMA AFZAL, ADRIAN JAEGGI, PAULO TOLENTINO, JOÃO BARBOSA, JULIAN PRICE, EDWARD HALL, HEDIN BRØNNER, DOUGLAS FRY, FRANCA BORTOLOTTI, GABRIEL PONS CORTÈS, URSULA LITZCKE, SCOTT, ZACHARY FISH, TIM DUFFY, SUNNY SMITH, JON WISMAN, WILLIAM BUCKNER, PAUL-GEORGE ARNAUD, LUKE GLOWACKI, GEORGIOS THEOPHANOUS, CHRIS WILLIAMSON, PETER WOLOSZYN, DAVID WILLIAMS, DIOGO COSTA, ALEX CHAU, AMAURI MARTÍNEZ, CORALIE CHEVALLIER, BANGALORE ATHEISTS, LARRY D. LEE JR., OLD HERRINGBONE, MICHAEL BAILEY, DAN SPERBER, ROBERT GRESSIS, IGOR N, JEFF MCMAHAN, JAKE ZUEHL, BARNABAS RADICS, MARK CAMPBELL, TOMAS DAUBNER, LUKE NISSEN, KIMBERLY JOHNSON, JESSICA NOWICKI, LINDA BRANDIN, GEORGE CHORIATIS, VALENTIN STEINMANN, PER KRAULIS, ALEXANDER HUBBARD, BR, JONAS HERTNER, URSULA GOODENOUGH, DAVID PINSOF, SEAN NELSON, MIKE LAVIGNE, JOS KNECHT, LUCY, MANVIR SINGH, PETRA WEIMANN, CAROLA FEEST, MAURO JÚNIOR, 航 豊川, TONY BARRETT, BENJAMIN GELBART, NIKOLAI VISHNEVSKY, STEVEN GANGESTAD, AND TED FARRIS! A SPECIAL THANKS TO MY PRODUCERS, YZAR WEHBE, JIM FRANK, ŁUKASZ STAFINIAK, TOM VANEGDOM, BERNARD HUGUENEY, CURTIS DIXON, BENEDIKT MUELLER, THOMAS TRUMBLE, KATHRINE AND PATRICK TOBIN, JONCARLO MONTENEGRO, AL NICK ORTIZ, NICK GOLDEN, AND CHRISTINE GLASS! AND TO MY EXECUTIVE PRODUCERS, MATTHEW LAVENDER, SERGIU CODREANU, BOGDAN KANIVETS, ROSEY, AND GREGORY HASTINGS!

The prospect of a minimally toxic, chemotherapy-free cure for hepatoblastoma is held out by findings from a mouse model using the small-molecule drug WNTinib that inhibits the Wnt signaling pathway involved with cancer growth. Lead author Ugnė Balaševičiūtė, a pre-doctoral researcher in Translational Research of the Hepatic Oncology Group led by Josep M. Llovet, Professor at the Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) in Barcelona, Spain, reported that the CTNNB1 (catenin beta-1 protein) gene targeted by WNTinib was expressed in 90 percent of all hepatoblastomas. Hopes were high that a safer alternative to chemotherapy in humans was on the way.

In this episode of our special pediatric psychopharmacology series, Dr. Jeffrey Strawn and Dr. Robyn Thom discuss the situations in which psychotropic medications are appropriate for children with autism spectrum disorder. They also explore strategies for managing side effects of these medications, including cases involving polypharmacy in this population.   Jeffrey R. Strawn, MD is a Professor and Associate Vice Chair of Research in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati (UC) College of Medicine, the Assistant Director of Clinical and Translational Research in the Center for Clinical & Translational Science and Training at UC, and an Associate Professor in the Department of Pediatrics at UC and Cincinnati Children's Hospital Medical Center.  Robyn Thom, MD is an Assistant Professor at Harvard Medical School and a staff psychiatrist at the Massachusetts General Hospital Lurie Center for Autism. Dr. Thom specializes in treating children and adults with autism spectrum disorder and other neurodevelopmental disorders, anxiety disorders, and mood disorders.  Save $100 on registration for 2025 NEI Spring Congress with code NEIPOD25 Register today at https://nei.global/spcongress25p Never miss an episode!

Send us a textPodcast episodes are fully available to paid subscribers on the M&M Substack and on YouTube. Partial versions are available elsewhere.About the guest: Tim Yeatman, MD is a Professor at the University of South Florida and ACD for Translational Research and Innovation at the Tampa General Hospital Cancer Institute. Ganesh Halade, PhD is an Associate Professor at the USF Health Heart Institute.Episode summary: Nick talks to Dr. Yeatman & Dr. Halade about: cancer & wound healing; inflammation; lipid (fat) biology; dietary fats, seed oils, omega-6 & omega-3 fatty acids; recent colon cancer lipidomics study; and more.Related episodes:M&M #134: Omega-6-9 Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis SimopoulosM&M #136: Seed Oils, Omega-6 PUFAs, Inflammation, Obesity, Diabetes, Chronic Disease & Metabolic Dysfunction | Chris Knobbe Special offer: Use MINDMATTERSPECIAL2 for a free 1-year premium subscription to Consensus, an AI-powered research tool that helps you find the best science, faster. ($150 value, limited-time offer).*This content is never meant to serve as medical adviceSupport the showAll episodes (audio & video), show notes, transcripts, and more at the M&M Substack Affiliates: Consensus: AI-powered academic research tool. Find & understand the best science, faster. Free 1-year premium sub with code MINDMATTERSPECIAL2 (exp 12.23.24) MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. Learn all the ways you can support my efforts...

Dr. Christoph Borchers is a Full Member in the McGill Centre for Translational Research in Cancer, Senior Investigator at the Lady Davis Institute for Medical Research, Director of the Segal Cancer Proteomics Centre, and Professor in the Department of Oncology at McGill University. In this episode, Christoph discusses his research in the area of proteomics and important applications of his work in anti-doping, including a PCC-funded research project examining quantitative proteomics longitudinally in blood to screen for blood doping. He also shares future directions for this line of research and his perspectives on important areas of opportunity in anti-doping science.

In this episode of our special pediatric psychopharmacology series, Dr. Jeffrey Strawn and Dr. Adelaide Robb explore the nuanced use of lithium in treating bipolar disorder among children and adolescents. Their discussion delves into critical aspects of lithium treatment, including carefully calibrated dosing regimens, comprehensive side effect management, and the essential role of parental involvement in treatment decisions.  Jeffrey R. Strawn, MD is a Professor and Associate Vice Chair of Research in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati (UC) College of Medicine, the Assistant Director of Clinical and Translational Research in the Center for Clinical & Translational Science and Training at UC, and an Associate Professor in the Department of Pediatrics at UC and Cincinnati Children's Hospital Medical Center.  Adelaide S. Robb, MD is a psychopharmacologist who specializes in mood disorders, anxiety, and attention deficit disorder. She is Chief of the Division of Psychiatry and Behavioral Sciences at Children's National Hospital in Washington, DC.  Never miss an episode!

Michele Pagano, Chairman of the Department of Biochemistry and Molecular Pharmacology at NYU School of Medicine, takes us through his groundbreaking research on the Ubiquitin-Proteasome System and Cullin-RING Ligases. As a leading Investigator at the Howard Hughes Medical Institute, Professor Pagano shares insights into targeted protein degradation and its potential for treating “undruggable” cancer proteins. Reflecting on the evolving dynamics within academia, he discusses the challenges and intricacies of managing a research lab and offers his perspectives on the current publishing and peer review systems in scientific journals. Don't miss this engaging conversation on the challenges and opportunities shaping the future of biomedical science. Link to the paper mentioned in the show: https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2742

In today's episode, we had the pleasure of speaking with Alan P. Venook, MD, about recent updates to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for gastrointestinal (GI) cancers. Dr Venook holds the Madden Family Distinguished Professorship in Medical Oncology and Translational Research and is a professor in the Department of Medicine (Hematology/Oncology) at the University of California San Francisco (UCSF). He is also the Shorenstein Associate Director for Program Development at the UCSF Helen Diller Family Comprehensive Cancer Center.

In the first episode of a special pediatric psychopharmacology series hosted by Dr. Jeffrey Strawn, Dr. John Walkup joins the podcast to discuss deprescribing in pediatric patients. The conversation delves into the situations that warrant deprescribing from antidepressants, selecting the right time to do so, and dealing with relapse, as well as much more!  Jeffrey R. Strawn, MD is a Professor and Associate Vice Chair of Research in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati (UC) College of Medicine, the Assistant Director of Clinical and Translational Research in the Center for Clinical & Translational Science and Training at UC, and an Associate Professor in the Department of Pediatrics at UC and Cincinnati Children's Hospital Medical Center.  John T. Walkup, MD is Head of the Pritzker Department of Psychiatry and Behavioral Health at Ann & Robert H. Lurie Children's Hospital of Chicago and a Margaret C. Osterman Professor of Psychiatry and Behavioral Science. He also serves as Director of the Division of Child and Adolescent Psychiatry in the Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine.  Never miss an episode!

Rachna Shroff, MD, is the Chief of the division of Hematology/Oncology and Associate Director for Clinical Research at the University of Arizona Cancer Center and the Associate Dean for Clinical and Translational Research at the University of Arizona College of Medicine. She is a clinical and translational investigator focused on developing novel targeted therapies and immunotherapies for pancreatic and hepatobiliary cancers and has led multiple clinical trials including the first randomized phase 3 trial in biliary cancers in the US. An internationally recognized expert, she is one of three women to achieve the prestigious 2022 Women in Oncology Award. “You have to understand your why and then let that drive you… be open-minded and try all kinds of different activities and opportunities. It's a little bit of throwing darts at a dartboard and seeing what sticks, and then going with your gut. Ask yourself, ‘What do you want your legacy to be?' Once you understand your legacy, you can create metrics for [your] success." In this episode of The Medicine Mentors, we discuss discovering our why and creating a long-lasting legacy with Dr. Rachna Shroff. Pearls of Wisdom:   1.  ‘What do you want your legacy to be?' is a different question than ‘What is your why?' Once we understand what we want our legacy to be, we can start creating the metrics for success. 2. It's essential to have the right people on board and maintain that network of mentors. One of the secrets to maintaining this network is to stay connected with them and keep them updated with what's going on in our lives. 3. If we can first learn how to take good care of patients, we'll identify the needs because the paramount questions come from the clinic. It will take a while, but our persistence, diligence, hard work, and patience will pay off.

Howie and Harlan are joined by Margaret McGovern, deputy dean for clinical affairs at the Yale School of Medicine, CEO of Yale Medicine, and chief physician executive of the Yale New Haven Health System. They discuss her path from the lab to healthcare leadership, and her efforts to better align Yale's medical school and its health system. Harlan reflects on the anniversary of the September 11 attacks; Howie provides an update on the bird flu outbreak.  Links: September 11 “60 Minutes remembers 9/11: The FDNY” Margaret McGovern “McGovern Welcomed as Yale Medicine CEO” “Margaret McGovern, MD, PhD, Appointed YSM Deputy Dean and CEO of Yale Medicine” “What is Translational Research?” “Three SBU Leaders Honored for Outstanding Service During Pandemic” “What Are Relative Value Units (RVUs)?” “You're Invited: Alignment-Focused Town Halls” “Clinically Integrated Networks” “Elevating Patient Access and the Consumer Experience” Bird Flu “Current H5N1 Bird Flu Situation in Dairy Cows” “How CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation” “5 burning questions about Missouri's mysterious H5 bird flu case” Learn more about the MBA for Executives program at Yale SOM. Email Howie and Harlan comments or questions.

Autoimmune cerebellar ataxia and other autoimmune movement disorders encompass a broad spectrum of different clinical syndromes, antibodies, and immunopathophysiologic mechanisms. Given the overlap between phenotypes and antibodies, panel testing in serum and CSF is recommended. In this episode, Gordon Smith, MD, FAAN, speaks with Bettina Balint, MD, author of the article “Autoimmune Movement Disorders,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Balint is an assistant professor for clinical research on complex movement disorders and Parkinson's diseases, a consultant neurologist, the head of the Department of Movement Disorders, and co-lead for the Centre for Movement Disorders and Functional Neurosurgery in the Department of Neurology at the University Hospital Zurich in Zurich, Switzerland. Additional Resources Read the article: Autoimmune Movement Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Smith: This is Dr Gordon Smith. Today, I'm interviewing Dr Bettina Balint about her article on ataxia and other autoimmune movement disorders, which appears in the August 2024 Continuum issue on autoimmune neurology, which is a highly anticipated and exciting issue. Dr Balint, welcome to the podcast, and, perhaps, you can just introduce yourself to our audience and tell us a little bit about your practice and how you became interested in this topic.   Dr Balint: Thank you, Gordon, for having me. I am an assistant professor for clinical research in complex movement disorders and Parkinson's disease at the University of Zurich and the Head of the Movement Disorders Department at the University Hospital in Zurich. So while I'm originally German (from Heidelberg), I have now been to Switzerland since end of 2021.   Dr Smith: So, you know, how many movement disorder chiefs have a focus on autoimmune movement disorders? I found that really interesting. Most of the movement disorder folks I interact with, their primary interest is in neurodegeneration.   Dr Balint: Very good question. Even so, I never asked myself that question, really, but I think I'm the only one with this designated focus as such. Many people come from the neurology angle - most of them. Even so, movement-disorder people really welcome this field and are interested, but I think somebody who has dedicated their interest and time to it? I think I can't actually think of many other people.   Dr Smith: Yeah, I think it's really cool, and, of course, autoimmune neurology is the flavor of the day these days, right? I mean, I remember when I was at the University of Utah, we were recruiting Stacy Clardy (who I think many of our listeners will know). I remember thinking, you know, she's never going to be busy. How many of these autoimmune problems are there, really? And she was, like, deluged when she came. These are really common problems. I guess that was one question I had for you. You know, we think of these as rare disorders, and when we look at the article, you have these tables of these antibodies, and a lot of them are pretty uncommon – but, cumulatively, how common are autoimmune movement disorders?   Dr Balint: It's a very difficult question, because we don't have good epidemiological data. And if you look at series, I mean, most papers addressing this issue come actually from the ataxia field. And then, depending on where you look at, you might find varying numbers, and they might be also influenced by the fact that they come from ataxia centers with own certain biases. Even so, it's very close to my heart, but, I also still think it's overall very rare. So, in my practice, I see all sorts of movement disorders, and overall, they're still quite rare, but the point is that they are treatable and have important management implications, so you want to be sure not to miss any of them.   Dr Smith: Well, maybe we can go to that next. Part of the challenge here, of course, is there's just so many of these different syndromes and antibodies. Are there pearls that you can provide our listeners that would help them guide when they should be thinking about these disorders when they confront a patient with a particular phenotype? Like ataxia, for instance - you know, there are certain aspects of the clinical scenario that should trigger, “Wow, this might be an autoimmune problem”.   Dr Balint: So, in general, I would say there are certain scenarios where you would want to think of an autoimmune etiology in your differential. One is a very characteristic phenotype. So, speaking broadly in terms of movement disorders, stiff-person spectrum disorders have a very characteristic phenotype which you need to recognize, and then you will be able to see it when a patient enters. Important phenotypes to know which are very characteristic are faciobrachial dystonic seizures, for example, with anti-GA1 antibodies, or pseudofinalistic movements in non-REM sleep is IgLON5 antibodies, leg myoclonus is CASPR2 antibodies. I don't want to necessarily enumerate all the scenarios. The point here is there are some characteristic phenotypes where you would think of autoimmune neurology. Another scenario where you would think of autoimmune, for example, the context of late-onset paroxysmal movement disorders. So, classically, when we think of paroxysmal dyskinesia, we think of a group of genetic disorders, but if somebody develops a paroxysmal movement disorder later in life in adulthood, then you would think of autoimmune neurology, and this applies also in the context of episodic ataxias. Another red flag might be a propensity to autoimmunity. For example, somebody with type one diabetes and vitiligo coming in for cerebellar ataxia, of course, you would think of anti-GAD ataxia. And, similarly, if somebody has recently been diagnosed with a cancer and develops a rapidly disabling syndrome, of course, then you would think of a paraneoplastic autoimmune disorder. And with autoimmune syndrome, there are some symptoms which are also like tell-tale signs. So, for example, somebody with a stiff-person spectrum disorder, an ataxia with long-lasting diarrhea over months, losing weight - investigations haven't found anything, then you would think of DPPX antibodies or celiac disease. Or, if you have, like, a neuropathic pain which is otherwise not explained, then you might think of CASPR2 antibodies in somebody with a cerebellar ataxia. So, there are some features of some antibodies. (Again, I will not now list all of them which might point you to a diagnosis.) Then, of course, another scenario which is important, I think, is if you have a hemisyndrome without a structural lesion on imaging. Classically, neurologists are trained to think of a hemisyndrome - we look for a lesion on the contralateral side. But if you have, like, for example, a hemichorea without a lesion or a hemiataxia without a lesion, one should also think of an autoimmune disorder with antibodies. And then, more generally, of course, if you have changes on brain MRI or information on CSF, of course, if the clinical cause is more rapidly progressive - and last, but not least, if somebody does not really fit into our categories of the degenerative symptoms or metabolic syndromes or functionality disorders, then, of course, one should just take a step back and think, could it be something autoimmune? Having said that, if I may, I just want to say that, I mentioned that rapid disease course, and on the other hand, it's important to stress that a slowly progressive disease cause does not exclude an autoimmune etiology.   Dr Smith: So, that was a great summary. Thank you. I don't know if you're familiar with the term “Aunt Minnie” (something I learned in medical school and radiology). There are certain findings that are “Aunt Minnie”, you know what “Aunt Minnie” looks like, and if you see these particular findings, you should really think about a specific disease - and I think you gave a lot of pearls in that answer, so I appreciate that. This may seem like a bit of a random question, but it's interesting that there are some of these phenotypes that do replicate genetic phenotypes, and you used episodic ataxia, which, in a younger individual, we think of a spectrum of various genetic disorders. Is that random, or are there instances where the underlying mutation in a genetic disorder actually serves as a target for autoimmunity in a later-onset autoimmune problem? Not that the mutation causes autoimmunity, but are there shared targets - in one disease it's the mutation, and another, there's an antibody that binds to the protein, for instance?   Dr Balint: That's an excellent topic, and even though it's not addressed in the Continuum article, I actually covered this in an article in Brain from 2018, where we also discuss parallels (immunogenetic parallels) with targets seen in genetic disease or in autoimmune disease, and there are actually some examples for cerebellar ataxia, and some of the targets are, indeed, the same for the antibodies and mutation. And some targets are a little bit more difficult, because for those, the antibodies would probably not be pathogenic, but it's more like an autoimmune overall target but it's T-cell mediated. But, for example, water-gated, um, calcium channels - we have antibodies and we have mutations. Or, another example would be glycine receptor antibodies give you acquired hyperekplexia, whereas the mutations give you hereditary hyperekplexia. So, there is, indeed, a bit of an overlap between autoimmune and genetic disorders, but often, also, like, the age at onset (because that might be the next question, the age at onset), and maybe family history and associated features, should help to distinguish the two. I think more from the pathophysiological point interesting, rather than clinically too confusing.   Dr Smith: Wow, that's really cool. So, another question I have is regarding antibody panels, right? And so, I think, oftentimes (at least around here), folks confronting an unusual phenotype will send the Mayo panel - they'll send autoimmune encephalitis or a paraneoplastic panel – and, you know, I think one of the challenges I have thinking about the spectrum of phenotypes that you described, I mean, if you recognize “Aunt Minnie”, then you know where to go, but it seems to me that there's a lot of these that maybe folks don't recognize “Aunt Minnie”. What is the diagnostic utility and pearls and pitfalls of ordering these panels when you're not really certain? In other words, is there a risk of a false positive if the pretest probability is low? So, I guess that's a long question, but do you have guidance about when we should and maybe when we should not be ordering these panels? So, you know, undifferentiated ataxia that's chronically progressive - should we be sending a panel or not? Patients who are later-onset acute, maybe so. So, what's the guidance on when to order the panel?   Dr Balint: It's a tricky topic also for many people in our practice, because, of course, as you said, we don't want to miss something, but, indeed, with any test which you order with a low pretest probability and which is not quite appropriate, you might have false positives, and that might cause much additional trouble in security, or maybe unnecessary and invasive immunotherapy with adverse effects – so, it's really important to think well about antibody testing. And, generally speaking, like always in medicine, we shouldn't order random tests, and antibody panels and neuronal antibodies are not designed as a screening test, so you need to have a phenotype and a reasonable suspicion - and clinical acumen is really key, and that's why also the article is so much focused on the phenotype. It's clearly not that any movement disorder patient who enters the outpatient clinic should get a blood test for antibodies that will likely cause harm, and it has been shown that these antibodies can be falsely positive, both in other diseases but also in healthy controls, and much depends also on which tests you use (but, let's not go into too much detail over here) - so, generally speaking, I would say if you have a suspicion of an autoimmune disease clinically (I mentioned some scenarios where you would think of an autoimmune disorder). And then, ataxias are, of course, a bit tricky, because often, we don't have too many other handles there, and there's still also a significant number of acquired late-onset ataxia where we don't know what the cause is. I think in the ataxia scenario, if I don't have a good answer or explanation, I would order antibody tests a bit more freely - I mean, if you do it properly, you do the serum and the CSF, and that also increases your sensitivity but also the specificities, so I wouldn't then just do the serum, but then go for serum and CSF. In other movement disorders, it depends also a little bit on the phenotype. So, somebody with a phenotype fitting well with Parkinson's disease, I wouldn't do any testing. Somebody with clear PSP phenotype without any red flags or not-fitting features, it is very unlikely to have an antibody finding, and this has been shown also in cohorts. But, if you have something which is not fitting in the phenotypes - for example, you have somebody where you think it might be a PSP phenotype with predominantly axial Parkinsonism falls, but you notice that the oculomotor disturbance is not a vertical gaze palsy, but a horizontal gaze palsy – so, it's not really fitting phenotype as you know it. That's a scenario where would probably think of antibody testing. Then, if you do the testing theorem - and CSF, in general, is gold standard - there are some antibodies where theorem is good enough (like, for example, with aquaporin-4 antibodies), but the reason why we do serum and CSF, as I mentioned, is the increased sensitivity and specificity. And nowadays, in the antibody world, we have something similar to the genetics - we have the variant of unknown significance and in the neurology world, we coin the term “antibody of unknown significance” to also give a name to the problem that, sometimes, we get a test result and it is difficult to interpret. Another handle over there would be to try to confirm the test result in another test method. So for example, if you have a cell-based assay with an antibody finding, you would like to confirm that on immunohistochemistry - the staining pattern is in keeping with that.   Dr Smith: So, Bettina, that was a really great and comprehensive answer to the question with a lot of pearls packed into it, and I think the idea that, you know, oftentimes, it's helpful to do both serum and CSF testing is important - also looking for staining to further confirm the diagnosis. And, I think one of the things that I was struck by in your response was the example of a PSP patient who instead of vertical gaze palsy had horizontal gaze palsy as a red flag, and I think a lot of our listeners are probably familiar with the idea that maybe hyperkinetic movement disorders might be autoimmune, or certainly rapidly progressive ataxia, but at least I don't think of Parkinsonian syndromes as often. I know there are some that we need to consider. Maybe you can give us some pearls about when we should consider antibody testing in a patient who has a Parkinson syndrome?   Dr Balint: So, I will not cover now the paraneoplastic Parkinsonian syndromes (because they typically develop as rapidly that you would anyway think about it, hopefully), but go more into those conditions which might mimic degenerative disease - and one of the most interesting antibodies in this regard is IgLON5, and you will be aware that it has been discovered in 2014 in patients who shared a characteristic sleep movement disorder (non-REM parasomnia). The spectrum has broadened a lot, and one possible manifestation is that it could come into the differential of Parkinsonian syndromes - so, for example, if you have axial Parkinsonism and a gaze palsy, you are in a PSP phenotype, but the red flag would be maybe if the eye movement disorders are not really fitting with the PSP phenotype. Also, in PSP patients, we don't expect parasomnias at night. If the bed partner is, for example, complaining that the patient is moving in his sleep and doing movements, then this would be a red flag, and in this context, you would think of IgLON5. IgLON5 could also give you Parkinsonism and cerebellar ataxia, and they might have dysautonomia, and, of course, with a sleep movement disorder, you are now in the ballpark of MSA phenotypes; however, if there are additional features (like, for example, fasciculations) which you don't expect in MSA, that would be, again, the red flag. So, typically, even in those differentials, there are some red flags on handles which would point you to the diagnosis - it is not that it completely mimics the phenotype of our default degenerative disease, but, sometimes, you need to hunt a little bit for those handles.   Dr Smith: So, Bettina, that's really interesting. I wanted to ask you about IgLON5, and in particular, the sleep phenotype, but, you know, I wonder whether there's a risk of just confusing this with REM sleep behavior disorder and a chronic Parkinsonian syndrome - what's the time course of this, and any other wisdom in terms of how to differentiate it from, you know, a more common neurodegenerative problem?   Dr Balint: So, the spectrum of sleep disorders in IgLON5 is actually a bit broad. The characteristic thing is the non-REM sleep parasomnia with the finalistic fine movements, but classic REM sleep behavior disorder has also been reported in these patients. And one of the tricky things is IgLON5 is a slowly progressive disease (some patients had symptoms for a decade prior to diagnosis), so it's really an important differential of autoimmune disease - but as mentioned, the features not fitting in, and they are typically also the cardinal features. So, gaze palsies are very frequent, ptosis, bulbar symptoms, vocal cord palsy, sleep movement disorders which might not fit to the original phenotype, and breathing problems (for example) so severe that they require a tracheostoma – so, these are some red flags which would alert you to this diagnosis of anti-IgLON5 disease.   Dr Smith: I'm curious, Bettina, how do you keep up on all of this and keep it all straight? Right, there's a lot of information, and as I was reading your article, you've got these wonderful tables - and in fact, this whole issue for our listeners feels that way. I've read several of these articles now, and I'm just curious what your strategy is to stay up to date and stay organized. You have to be very organized to be an autoimmune neurologist, it seems to me.   Dr Balint: And having a little bit of OCD helps clearly, as always, in neurology. I think it is just that I started to be interested in this area for a while and I have in my head the clinical phenotype to most important associated antibodies, and as the field continues, I just add up on that panel. But, I don't want people to be discouraged - you're right, many antibodies, but I think the point is not to know each and every antibody but to know in which scenario to think of an autoimmune syndrome and then to know where to look it up.   Dr Smith: Well, I think that's a great way of ending our conversation, Bettina. I think your article does a great job of that, and one of the things I love about Continuum is these articles serve as point-of-care tools. I think our conversation will also serve as a useful framework, because I think you've talked a lot about how to organize your thinking, and, you know, pearls for when we should be thinking about these disorders which are uncommon, but you certainly don't want to miss one because the therapy can be very effective. So, Bettina, thank you so much for joining me. This has been a really great conversation.   Dr Balint: Thank you so much, Gordon. Thank you very much for your good questions.   Dr Smith: So, again, today, I've had the great pleasure of interviewing Dr Bettina Balint, whose article on ataxia and other autoimmune movement disorders appears in the most recent issue of Continuum, which is on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thanks to our listeners for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. Growing availability of effective treatment options will lead to personalized therapies and improved outcomes. In this episode, Gordon Smith, MD, FAAN speaks with Elia Sechi, MD, author of the article “NMOSD and MOGAD,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Sechi is a neurology consultant in the neurology unit of the Department of Medical, Surgical and Experimental Sciences at the University Hospital of Sassari in Sassari, Italy. Additional Resources Read the article: NMOSD and MOGAD Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @EliaSechi Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Smith: Hello. This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Elia Sechi about his article on aquaporin-4 antibody-positive NMOSD and MOGAD, which appears in the August 2024 Continuum issue on autoimmune neurology. Dr Sechi, before we dig into this really exciting topic about NMOSD and MOGAD, perhaps you can tell our listeners a little bit about yourself, where you practice, how you got interested in this topic.   Dr Sechi: Hi, Dr Smith, and thank you for having me. So, my story begins here in Italy, actually - I did my med school and residency in neurology at the University Hospital of Sassari here in Sardinia. And after residency, I was lucky enough to be accepted at the Mayo Clinic in Rochester, Minnesota for a research fellowship - and that's where I spent the next three-and-a-half years, approximately. My fellowship was focused on autoimmune neurology, specifically demyelinating diseases of the CNS associated with antibodies – so, of course, NMOSD and MOGAD mostly, but also myelitis, MS, and autoimmune encephalitis – so, there's where I built most of my expertise in the field. And then, it was at the beginning of the pandemic (of the COVID pandemic) that I came back here to Italy to practice. And now, I work mostly as a neurohospitalist, and I also have my subspecialty outpatient service for patients with autoimmune neurological diseases.   Dr Smith: I wonder if you might just give us a minute or two about what it was like training in Mayo? I went to medical school there, and, you know, at the time, I thought that was just normal healthcare and normal training, and, you know, it was only later that I realized how amazing that was. I mean, this is where aquaporin-4 was discovered - I mean, what was that like? It must have been really cool training there with that team.   Dr Sechi: Yeah. You know, it's the temple of autoimmune neurology. It's fantastic. It's a great environment, very stimulating. You know, I think the great strength is that they see many patients with rare diseases, so, you get really confident with MRI features and clinical features with the history of the diseases, and this is important to recognize the typical features and differentiate from MS to do a good differential. And, of course, you know, the team is fantastic - superstars in the field. It's very, very stimulating. So, it's something that I definitely recommend. It was a fantastic experience.   Dr Smith: Well, you know what's great is, I don't know if you follow sports, but, you know, like, in the United States and college football, people refer to Gator Nation – right, these are all people who are fans of the Florida Gators. Or, maybe it's AC Milan nation in Italy. I don't want to get there (Roma, whatever), but there are all these people who've trained at Mayo, and, uh, what's great is it's a small world, right? So, I'm super excited to meet you and talk about this, because - I'm going to add you to my Rolodex, because when I see these patients (I'm a neuromuscular guy, but I do a fair bit of inpatient time), I'm always calling a small number of people, so I'm really pleased to meet you so I can put you on speed dial and ask you questions about these patients. I wonder if, maybe, we can begin? You know, in our preparatory discussions, I shared that I just came off our hospital service, and we had several of these patients, you know, where we were thinking about NMO or MOGAD as a cause for their problem - and I wonder if you just have any pearls or pitfalls in when we should suspect this, right? Most of us recognize bilateral optic neuritis, longitudinally extensive myelitis - we need to be thinking about these. Any pearls or pitfalls for when we should or should not be looking for these disorders?   Dr Sechi: Yeah, I think this is a great question. I think the first thing to pay attention is the phenotype. So, the clinical MRI phenotype that are typically associated with NMOSD and MOGAD, they are quite characteristic - and it's important to be aware of those phenotypes and how they differ from MS, because in my experience, one of the common misinterpretation (misconception) in clinical practice is just to test for AQP-4 and MOG antibodies in any patient with new-onset demyelinating disease of the CNS, even if it's typical MS. And, this is quite wrong, because MS is way more common in clinical practice - it's sixty, eighty times more common than NMO and MOGAD - and so, if you test all those patients without filter (indiscriminately) for antibodies, you increase the risk of false positivity exponentially, even if you have a highly specific test. So, first of all, I think it's good to select the right patients to test. As you said, patients with LTM, extensive involvement of the optic nerves on MRI, ADEM - there's also patients with cortical encephalitis phenotype (which is a rare phenotype of MOGAD), but not definitely good to test the typical MS patients. This is the first thing.   Dr Smith: Yeah, I mean, that's an issue in all of neurology, isn't it, right? I mean, it's an issue in sort of just sending, you know, the Mayo panel, the autoimmune encephalitis panels - you need to select patients carefully, but I think this attention to prior probability is something that we need to really focus on in multiple areas. So, I wonder if you might expand a little bit on assays. I do a lot of work in myasthenia and I know which labs do a really good job with, you know, acetylcholine receptor antibody testing and those that maybe do not, and there are different methodologies for testing - do you have any wisdom in terms of how to select a lab, what to look for, and how to interpret the results you see based on the particular assay that's being used?    Dr Sechi: Yeah, that's a critical point. I agree. And especially if you work in myasthenia, you're very well aware of the differences between different assays, and nowadays, most of the high-quality assays are cell-based assays (either fixed or live) - it's the same in myasthenia, and people need to pay attention to some of the less-specific assays. Let's say ELISA, for instance - testing AQP-4 and MOG antibodies with ELISA is quite dangerous, because the risk of false positivity is quite high. So, it's good to know what assays to trust most and also good to know what's the right specimen to send for antibody test. For instance, with AQP-4, we know that serum testing is recommended only, and the CSF doesn't add much, but with MOG, we know that approximately 10% of patients have an isolated positivity in the CSF, which is interesting, because it means that when you have a patient with a strong diagnostic suspicion as a phenotype that is highly suggestive for MOGAD and the serum testing is negative, you may consider testing the CSF to increase your sensitivity. So, this is very important.   Dr Smith: So, I have a question for you that may seem a little naïve, but I bet other people are thinking it - can you tell us why it is that these disorders affect optic nerve and spinal cord preferentially? And I think, for NMO, the whole area postrema thing seems awfully specific to me. What's the deal? Why are these areas preferentially affected by these antibody-mediated disorders?   Dr Sechi: This is a tough question. For NMO, we know, probably, there is higher expression of some of the isoforms. Let's say there is a higher density of AQP-4 molecules that target the most affected regions - so, of course, AQP-4 is preferentially expressed in the subependymal regions around the ventricles and in the spinal cord and optic nerves, but you may have, also, solutions along the cortical spinal tracts in case of the brain involvement. The area postrema is kind of a different explanation, because there is a sort of permeability - increased permeability - of the blood-brain barrier there. So, there are several factors in MOGAD - this is not very clear, so, this is a great topic to study in the future, I think.   Dr Smith: This is a really interesting area, and one that's really benefited by significant therapeutic development. I wonder if you might look a little bit in the future and tell us, maybe, the agent, or perhaps the target, that you're most excited about therapeutically that's coming down the road these days?   Dr Sechi: There are trials ongoing for MOGAD, which is the real need in terms of treatment, because for NMO, we already have three, four drugs that have been approved and which efficacy have been demonstrated by randomized clinical trials, and those are B-cell depleting agents, IL-6 inhibitors, and complement inhibitors. For MOGAD, this is still a gray zone, because the optimal treatment strategies remains to be defined. There are ongoing trials that are quite promising on IL-6 inhibitors and the inhibitors of the neonatal Fc receptor (which is also used in myasthenia gravis as you know). And something that seems to be quite effective - a good option for long-term treatment in these patients and relapse prevention - is also the periodic administration of IVIG (intravenous immunoglobulin), which is a nice option, for instance, in the children where you want to avoid immunosuppressants of other types. So, I think IL-6 is going to show to be very effective in the end. We'll see. We'll see.   Dr Smith: So, I wonder if I might just give you a vignette and get your thoughts about, kind of, acute management, right? I just took care of a patient who had a longitudinally extensive myelitis and she was essentially paraplegic and actually came in progressing fairly rapidly, and we, of course, started her on IV methylprednisolone, sent off the proper diagnostic testing - the question I have is, how quickly do you advance therapy and go to IVIG or plasma exchange when you're encountering these, right? It takes, you know, I think the turnaround time is, you know, often about a week to get these tests back (at least several days) - I mean, should we be going very quickly to plasma exchange in someone who has a severe phenotype? Is it okay to do three to five days of IV methylprednisolone and wait for the results to come back? What's the right approach?   Dr Sechi: I think this is a great question, actually. You know, management of the acute attacks probably is the most important thing, you know, to allow a good recovery, and I think timing of PLEX administration should be very short - so, the threshold for PLEX should be low, especially when the attack is severe, and this has to be done regardless of antibody testing results, which is typically not available before one or two weeks (at least a year in Italy), I think, in many hospitals. So, I think the risk-benefit ratio of administering PLEX is in favor of treatment in these patients, because the side effects (the potential side effects) are very rare and can be prevented. Some diseases, they can mimic NMO or MOGAD - they're very rare, and they can really worsen with PLEX. As an example, we can say spinal cord infarction can worsen, maybe, because of hypotension due to PLEX. Or some very rare infections, like one case, a bad case of intramedullary spinal cord abscess that looked really similar to an AQP-4 IgG-related LTM - and it was bad, because the patient had no fever, no signs of infection, the CSF culture was negative initially, so we ended up doing a biopsy after failure of PLEX and steroids. So, it is recommended to start within the first three to five days, preferentially, in severe cases, and this is great for the outcome of the patient, so, I do recommend PLEX as a second treatment option. And I'm not sure about IVIG acutely. There is some data on MOG, but it's still controversial - it works a lot when PLEX fails, but it can be considered after PLEX, of course. And there are some very rare patients that do not improve, even after IV methylprednisolone, PLEX, or IVIG, and so, you need to consider some rescue therapies. In those patients, it's kind of complicated, because there are some options, like IL-6 inhibitors seem to be quite effective and quite fast-acting for MOGAD attacks, and also eculizumab and complement inhibitors can be an option in patients with AQP-4 - but maybe less in patients with MOG. So, these are the possibilities (very quickly).   Dr Smith: So, you mentioned FcRn inhibitors a moment ago, and I wonder, do you see a future where - and I think you were mentioning them as maybe more chronic therapy? Correct me if I'm wrong.   Dr Sechi: Yeah, yeah.   Dr Smith: Do you foresee a role for these agents in acute management? I mean, there are some that, you know, very quickly lower immunoglobulin levels, though just looking out in the future, you think that these sort of infusion therapies that we think about chronic therapy (you mentioned, you know, complement inhibitors) are going to be useful in acute management?   Dr Sechi: Yeah, it depends. It's a good option to try. I'm not sure about the time to action. It's very dependent on that, because IL-6 inhibitors and complement inhibitors are very fast-acting (I think they can be effective already within twelve hours, 24 hours, which is good), but it's reasonable that, also, Fc inhibitors can be an alternative in the future. As far as I know, there is not much in the literature, but it's good to try in the future in case, acutely.   Dr Smith: Well, exciting times indeed. Elia, thank you so much for a great discussion. I thoroughly enjoyed this. I look forward to visiting you soon, and I want to congratulate you on a really great article that's very interesting and very clinically useful.   Dr Sechi: Well, thank you, Dr Smith. This is my pleasure, and thank you for great questions. I had a great time and hope the readers of Continuum will like the article and the nice figures we have put together. So, thank you, thank you very much.   Dr Smith: Well, again, congratulations. And for our listeners today, I've been interviewing Dr Elia Sechi, whose article on aquaporin-4 antibody-positive NMOSD and MOGAD appears in the most recent issue of Continuum, which is on autoimmune neurology. It's a very exciting issue. Please check out Continuum Audio episodes from this and other issues of Continuum. And thanks to you all for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

In this episode of The Glioblastoma AKA GBM Podcast, Dr. Ashish Shah, Assistant Professor of Neurological Surgery at the University of Miami Miller School of Medicine and Director of Clinical Trials and Translational Research within the University of Miami Brain Tumor Initiative, dives deep into his groundbreaking research on glioblastoma. Dr. Shah discusses a fascinating study revealing how fragments of a retrovirus, integrated into the human genome millions of years ago, are implicated in the proliferation and progression of glioblastoma, the most aggressive primary brain tumor. This episode explores how these findings from Dr. Shah's research at the Sylvester Comprehensive Cancer Center could revolutionize our understanding of glioblastoma and lead to novel treatment strategies. We also delve into the potential of antiretroviral agents and gene therapy as innovative approaches to target these viral fragments, opening new avenues for combatting this challenging cancer. Episode Sponsor: Novocure. Visit https://www.novocure.com/ to learn more. Trigger Warning: This episode includes discussions on medical conditions, cancer treatments, and genetic research. Visit to Learn More: For more information and support resources, visit GBMResearch.org. Disclaimer: The content discussed on The Glioblastoma AKA GBM Podcast is based on personal stories and experiences. It is not intended as medical advice. Always consult with healthcare professionals for medical guidance and treatment options.

Matt Waning's cancer journey began in 2021, at the age of 34, when he wasdiagnosed with testicular cancer. The aggressive nature of his illness led to surgery that removed a tumor the size of a watermelon, along with his left testicle and kidney, as the tumor had reached his aorta. Following surgery, he underwent two months of preventive chemotherapy known as VIP treatment and celebrated being in remission by August 2021. However, the VIP treatment came with a rare side effect—a potential risk of developing acute myeloid leukemia (AML). Unfortunately, in January 2023, Matt was diagnosed with AML as a result of the chemotherapy he had previously received. Matt is an avid Boston sports fan, with a particular passion for the Bruins. Musicis another love of his, offering solace and joy throughout his journey. As the oldest of three siblings, he shares a special bond with his family, including his dog Mogley, named after the main character from "The Jungle Book." Dr. Stone is currently the Director of the Adult Acute Leukemia Program atDana-Farber Cancer Institute, serves on the Medical Oncology Board of the American Board of Internal Medicine, and is vice chair of the Leukemia Core Committee for the national cooperative trials group Cancer and Leukemia Group B. As the Senior Leukemia Protocol Research Nurse Practitioner at Dana-FarberCancer Institute, Ilene Galinsky practices autonomously and in collaboration withphysicians and other members of the multidisciplinary team in the diagnosis, treatment, and management of patients with acute and chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), myelofibrosis, and other bone marrow failure diseases.

“It was nothing to worry about,” Andrew was repeatedly told, when he visitedurgent care twice for pain in his pelvis area. But the discomfort wouldn't go away, so he met with his primary care physician who referred him to a urologist for an ultrasound. The scans led to a testicular cancer diagnosis in early 2023. It was caught early enough, and he was told there was a good prognosis. The cancer had only spread very lightly to his lymph nodes. Adam works as the director of data analytics for a pharmaceutical company. Heloves vacationing with his family, watching his children play their sports (soccer for his son Jacob and gymnastics for his daughter Julia) and caring for his 2004 BMW. He hopes to help normalize conversations around testicular cancer for other men so they can overcome stigmas and shame around it. Today, he and his wife Kara arecelebrating their wedding anniversary. Dr. Atish Choudhury is a medical oncologist and clinical/translational investigatorwithin the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, and currently serves as Chair of the Gelb Center for Translational Research. He also serves as an Assistant Professor of Medicine at Harvard Medical School. His research interests include investigation of genetic and epigenetic biomarkers from circulating free DNA from patients with metastatic cancer, biomarker studies from other banked human specimens from patients participating in clinical trials, and clinical investigation in novel therapeutics for genitourinary malignancies. According to the American Cancer Society, testicular cancer is not common. About 1 of every 250 males will develop testicular cancer at some point during their lifetime. The American Cancer Society's estimate for testicular cancer in the United States for 2024 is about 9,760 new cases of testicular cancer diagnosed. The average age of males when first diagnosed with testicular cancer is about 33. This is largely a disease of young and middle-aged men, but about 6% of cases occur in children and teens, and about 8% occur in men older than 55.

After six years of medical school in Romania, Mioara Manole, MD, came to the U.S. and discovered her passion for pediatric emergency medicine and the unique challenges it can bring. In addition to seeing patients in our emergency department, she is also the director of Basic and Translational Research in the Division of Pediatric Emergency Medicine. Learn about Dr. Manole's journey to emergency medicine and how her research translates to her clinical work, including the creation of the FLO2 NeuroCap, a noninvasive device that measures brain oxygenation and neuronal activity in children after cardiac arrest or other brain injuries.

In the 20th installment of the Inside JABA Series, I'm joined by Drs. Brennan Armshaw, Manish Vaidya, and Sachen Mehta. As always, I'm also joined by JABA Editor in Chief, Dr. John Borerro. In this episode we discuss a fantastic paper that is out in the summer issue of JABA titled, “Surface electromyography-based biofeedback can facilitate recovery from total knee arthroplasty.” In brief, this study that examined a novel treatment approach for rehabilitating patients following knee replacement surgery. And guess what, they used simple behavioral techniques to radically improve physical therapy outcomes! Orthopedics is something that's been on my mind lately as I am recovering from a broken metacarpal bone in my hand. It's probably something of interest to others who have either had orthopedic problems themselves, or who have taken care of hose who have. However, even if you're not interested in orthopedics, I encourage you to really dig into this episode because it's just a great case study of applying our science to a novel problem that affects millions of people . As always, there are no advertisements in the Inside JABA Series shows, but I will mention that if you would like to get a CEU for listening to this episode an answering series of questions related to its content, you can find out how to do just that by clicking here. So if you would like to learn from your favorite podcast guests, especially while you're on the go, check out what we have to offer over. I should also mention that there are discounts available for multiple event purchases. I recently crunched some numbers and found out that CEU customers, on average, save almost $100 when they leverage these discount codes. Here are the links to resources mentioned in the podcast: Armshaw, Vaidya, and Mehta (2024). Surface electromyography-based biofeedback can facilitate recovery from total knee arthroplasty. Vaidya and Armshaw (2021). Surface electromyography and gamification: Translational research to advance physical rehabilitation. Inside JABA 9: Applied and Translational Research in Healthcare. The Institute for Behavior Science and Technology in Rehabilitation. Comprehensive Orthopedics and Rehabilitation. Brennan's WVU faculty page and LinkedIn. Manish's LinkedIn page.  

View This Week's Show NotesStart Your 7-Day Trial to Virtual Mobility CoachJoin Our Free Weekly Newsletter: The AmbushDr. Emily Kraus is a Clinical Assistant Professor at Stanford Children's Orthopedic and Sports Medicine Center trained in the specialty of Physical Medicine and Rehabilitation. She has research and clinical interests in endurance sports medicine, injury prevention, running biomechanics, prevention of bone stress injuries, and the promotion of health and wellness at any age of life. Dr. Kraus is the director of the FASTR Program, which stands for Female Athlete Science and Translational Research. The FASTR program seeks to help close the gender gap in sports science research with an emphasis on early identification and interventions to prevent injury and identify ways to optimize performance in female athletes. Dr. Kraus is also a member of the U.S. Olympic and Paralympic Committee Women's Health Task Force and is the medical director of the Stanford Children's Motion Analysis and Sport Performance Lab. She has completed nine marathons including the Boston Marathon twice and one 50k ultramarathon. With running and staying physically active as one of her personal passions, she recognizes the importance of fitness for overall wellbeing and the prevention of chronic medical conditions.Dr. Kraus joins us to talk about the state of youth sports, RED-S in males and females, and actionable advice for keeping developing athletes healthy.SPONSORSThis episode of The Ready State Podcast is brought to you by Momentous, a leading high-performance lifestyle company making the best supplements and sports nutrition products for individuals looking to optimize all parts of their lives. If you feel overwhelmed by the amount of supplements out there, just focus on the basics. We find PR Lotion to be one of the most foundational products that Momentous offers. You just rub it on the major muscle groups that you worked, and you'll find that you are WAY less sore and WAY more ready to do it all again tomorrow. Go to livemomentous.com/TRS and use code TRS for 20% OFF your first purchase.This episode of The Ready State Podcast is brought to you by LMNT, a tasty electrolyte drink mix with everything you need and nothing you don't. That means lots of salt — with no sugar. We are still abuzz about LMNT Sparkling now available to everyone. All the electrolytes you need, in the MOST festive beverage you've ever tasted. If you love LMNT, this is going to blow your mind. Go to DrinkLMNT.com/TRS and check it out!This episode of The Ready State Podcast is brought to you by Sleepme. The Chilipad bed cooling system is your new bedtime solution. It lets you customize your sleeping environment to your optimal temperature, ensuring you fall asleep, stay asleep and wake up refreshed. Kelly credits the Chilipad mattress topper with revolutionizing his sleep. Go to sleep.me/TRS and use code TRS and save up to $315!This episode of The Ready State Podcast is brought to you by Cockpunch Coffee. Here at The Ready State we are OBSESSED with coffee, and we can't get enough of this coffee with a cause. Created by our friend Tim Ferriss, Cockpunch Coffee is roasted on a Bellwether Roaster, creating the lowest carbon footprint coffee available today. If that isn't enough, all proceeds from the sale of Cockpunch Coffee go to Tim's nonprofit foundation, Saisei, focused on cutting-edge scientific research that explores treating conditions that are widely considered “untreatable”. If you want to get some delicious coffee that gives back, go to cockpunchcoffee.com/TRS and use code TRS for 20% OFF your first purchase.