Podcasts about prognostic

Commentary by Dr. Jian'an Wang.

Listener discretion is advised! References: Buttner & Arlanger. (May 3, 2022). ST depression does not localise. Available: https://litfl.com/st-depression-does-not-localise/ Cannon, J. W., Khan, M. A., Raja, A. S., et al. (2017). Damage control resuscitation in patients with severe traumatic hemorrhage. Journal of Trauma and Acute Care Surgery, 82, 605-617. Kabra, R., Acharya, S., Kamat, S., & Kumar, S. (2022). ST-Segment Elevation in Lead aVR With Global ST-Segment Depression: Never Neglect Left Main Coronary Artery (LMCA) Occlusion. Cureus. Lee, G.-K., Hsieh, Y.-P., Hsu, S.-W., Lan, S.-J., & Soni, K. (2019). Value of ST‐segment change in lead aVR in diagnosing left main disease in Non‐ST‐elevation acute coronary syndrome—A meta‐analysis. Annals of Noninvasive Electrocardiology, 24. Morrison, C. A., Carrick, M. M., Norman, M. A., et al. (2011). Hypotensive Resuscitation Strategy Reduces Transfusion Requirements and Severe Postoperative Coagulopathy in Trauma Patients With Hemorrhagic Shock: Preliminary Results of a Randomized Controlled Trial. Journal of Trauma: Injury, Infection & Critical Care, 70, 652-663. Rossaint, R., Afshari, A., Bouillon, B., et al. (2023). The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Critical Care, 27. Tamura, A. (2014). Significance of lead aVR in acute coronary syndrome. World Journal of Cardiology, 6(7), 630. Uthamalingam, S., Zheng, H., Leavitt, M., Pomerantsev, E., Ahmado, I., Gurm, G. S., & Gewirtz, H. (2011). Exercise-Induced ST-Segment Elevation in ECG Lead aVR Is a Useful Indicator of Significant Left Main or Ostial LAD Coronary Artery Stenosis. JACC: Cardiovascular Imaging, 4, 176–186. Weymouth, W., Long, B., Koyfman, A., & Winckler, C. (2019). Whole Blood in Trauma: A Review for Emergency Clinicians. The Journal of Emergency Medicine, 56, 491-498. Wang, A., Singh, V., Duan, Y., Su, X., Su, H., Zhang, M., & Cao, Y. (2020). Prognostic implications of ST‐segment elevation in lead aVR in patients with acute coronary syndrome: A meta‐analysis. Annals of Noninvasive Electrocardiology, 26.

With Edoardo Conte and Daniele Andreini, Galeazzi-Sant'Ambrogio Hospital IRCCS, Milan - Italy and Gal Tsaban, Mayo Clinic, Rochester - USA. Link to paper Link to editorial

Commentary by Dr. Katsuhiko Imai.

In this episode of the NCS Podcast Hot Topics series, host Richard Choi, DO, FNCS, is joined by Katharina Busl, MD, MS, to discuss the article "Infratentorial Pressure Monitoring in Cerebellar Stroke: Feasibility and Prognostic Utility," recently published in Neurocritical Care. Their conversation examines why pressure in the posterior fossa may differ from supratentorial measurements in patients with cerebellar stroke and why that distinction may matter clinically. They discuss the physiologic basis for compartmentalized intracranial pressure, the challenges of posterior fossa management and the potential implications for monitoring and treatment. Dr. Busl reviews the study's design and key findings, including evidence of a significant pressure gradient between infratentorial and supratentorial compartments and an early signal that higher infratentorial pressures may be associated with worse outcomes. She also discusses important limitations, including the study's small sample size, single-center nature and unanswered questions about surgical variables such as decompression size. The discussion further considers how this proof-of-concept work could inform future studies on monitoring, prognostication and treatment selection in cerebellar stroke. The views expressed on the NCS Podcast are solely those of the hosts and guests and do not necessarily reflect the opinions or official positions of the Neurocritical Care Society.

Melanoma prognostic gene expression profiles - with Dr. Doug Grossman! [article, article]Tranexamic acid in Mohs surgery [article]Large-spot PDL works better for port wine stains [article]Learn about Dr. Grossman's work here! - https://healthcare.utah.edu/find-a-doctor/douglas-grossmanCheck out Luke's Urticaria CME experience! aaaaicsu.gathered.com/invite/KQe1wPZbJY Learn more about the U of U Dermatology ECHO model! physicians.utah.edu/echo/dermatology-primarycare Want to donate to the cause? Do so here!Donate to the podcast: ⁠uofuhealth.org/dermasphere⁠Check out our video content on YouTube:⁠www.youtube.com/@dermaspherepodcast⁠and VuMedi!: ⁠www.vumedi.com/channel/dermasphere/⁠The University of Utah's DermatologyECHO: ⁠⁠physicians.utah.edu/echo/dermatology-primarycare⁠ -⁠ Connect with us!- Web: ⁠⁠dermaspherepodcast.com/⁠⁠ - Twitter: @⁠DermaspherePC⁠- Instagram: dermaspherepodcast- Facebook: ⁠www.facebook.com/DermaspherePodcast/⁠- Check out Luke and Michelle's other podcast,SkinCast! ⁠⁠healthcare.utah.edu/dermatology/skincast/⁠⁠ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at:- ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge)- ⁠⁠www.levelex.com/games/top-derm⁠⁠ (A free dermatology game to learn more dermatology!

In the final episode of this series, Dr. Justin Abbatemarco and Dr. Shreya Louis discuss the study results and their implications for improving clinical practice.  Read more about this abstract on the AAN website. 

In part two of this series, Dr. Justin Abbatemarco and Dr. Shreya Louis discuss how this technology was developed and how it has evolved.  Read more about this abstract on the AAN website. 

Podcast Host and Interviewee:  Host: John Fortunato Interviewee: Bob Jenkins  Podcast Description: Dr. John Fortunato interviews Dr. Bob Jenkins on his recent manuscript, titled "DNA copy number patterns reveal prognostic markers and elucidate mechanisms of evolution in IDH-mutant astrocytoma."

In the first part of this series, Dr. Justin Abbatemarco and Dr. Shreya Louis discuss the background and evolving terminology around circulating tumor DNA, cell‑free DNA and CSF‑based testing in neurology.  Read more about this abstract on the AAN website. 

Bewegungskomplexität – noch nie gehört? Dann wird es Zeit. Denn wie komplex Du Dich bewegst, entscheidet darüber, wie gut Dein Gehirn altert. Und die meisten Trainingspläne ignorieren das komplett.Am Ende dieser Folge weißt Du, warum vielfältige, kognitiv fordernde Bewegung Dein Gehirn besser schützt als jedes Standardprogramm – und was eine Langzeitstudie mit über 8.600 Menschen über den Zusammenhang von Sportwahl und Lebenserwartung herausgefunden hat.Außerdem: Warum chronische Anspannung Dich blind für die Warnsignale Deines Körpers macht. Bock auf eine kleine Challenge? Dann erfährst Du, wie Du Deinen Körper in wenigen Minuten am Tag sofort fühlbar resilienter bekommst – in 30 Tagen oder weniger.____________*WERBUNG: Infos zum Werbepartner dieser Folge und allen weiteren Werbepartnern findest Du hier.____________Vertiefende InhalteFolge 551: Das Weber-Fechner-GesetzSquat Challenge – 10 Min. Hocken/Tag × 30 TageTiefe Hocke, "Stoppuhr" läuft nur im HockenÜber den Tag verteilen (z.B. 10×1 Min.)Anfangs festhalten erlaubt, Fersen dürfen abhebenEinstieg: 2–3 Min./Tag, langsam steigernZiehen okay – Schmerz nichtHanging Challenge – 7 Min. Hängen/Tag × 30 TageAn Stange hängen, über den Tag verteilenWer nicht frei hängen kann: Füße am Boden lassenProgression: Mit Fußstütze → Frei passiv → Aktiv → EinarmigNicht direkt nach dem AufstehenBei Schulterproblemen vorsichtig startenLiteratur:Schnohr P et al. (2018). Various Leisure-Time Physical Activities Associated With Widely Divergent Life Expectancies: The Copenhagen City Heart Study. Mayo Clin Proc 93(12):1775-85.Rehfeld K et al. (2017). Dancing or Fitness Sport? The Effects of Two Training Programs on Hippocampal Plasticity and Balance Abilities in Healthy Seniors. Front Hum Neurosci 11:305.Rehfeld K et al. (2018). Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly. PLoS ONE 13(7):e0196636. ← NEUVerghese J et al. (2003). Leisure activities and the risk of dementia in the elderly. N Engl J Med 348:2508-16.Proske U, Gandevia SC (2012). The proprioceptive senses. Physiol Rev 92(4):1651-97.Schiftan GS et al. (2015). The effectiveness of proprioceptive training in preventing ankle sprains. J Sci Med Sport 18(3):238-44.Raichlen DA et al. (2020). Sitting, squatting, and the evolutionary biology of human inactivity. PNAS 117(13):7115-21.Rojas-Jaramillo A et al. (2024). Impact of the deep squat on articular knee joint structures. Front Sports Act Living.Hartmann H et al. (2013). Analysis of the load on the knee joint and vertebral column with changes in squatting depth. Sports Med 43(10):993-1008.Sikirov D (2003). Comparison of straining during defecation in three positions. Dig Dis Sci 48(7):1201-5.Leong DP et al. (2015). Prognostic value of grip strength: findings from the PURE study. Lancet 386(9990):266-73.García-Hermoso A et al. (2018). Muscular Strength as a Predictor of All-Cause Mortality. Arch Phys Med Rehabil 99(10):2100-13.____________Shownotes und Übersicht aller Folgen.Trag Dich in Marks Dranbleiber Newsletter ein.Entdecke Marks Bücher.Folge Mark auf Instagram, Facebook, Strava, LinkedIn. Hosted on Acast. See acast.com/privacy for more information.

https://www.tadeclinicagem.com.br/guia/Confira a promoção especial para o plano anual do Guia TdC: Receba em casa o Card de Consulta Rápida no Plantão, com os temas: IOT, ACLS, ATB, ECG, trombólise e reposição eletrolítica.Receba em casa o porta-crachá (tirante para crachá) do TdC.Ganhe R$ 50 OFF (de 449 por 399,00)7 primeiros dias inteiramente grátisUse o CUPOM: GUIADZEROAline Campos e Pedro Magno convidam João Pedro Noronha para discutir o novo Guideline de Tromboembolismo Pulmonar da AHA/ACC 2026. Referências: 1. Writing Committee Members* et al. “2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.” Circulation, 10.1161/CIR.0000000000001415. 19 Feb. 2026, doi:10.1161/CIR.00000000000014152. Meyer, Guy et al. “Fibrinolysis for patients with intermediate-risk pulmonary embolism.” The New England journal of medicine vol. 370,15 (2014): 1402-11. doi:10.1056/NEJMoa13020973. Konstantinides, Stavros V et al. “2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).” European heart journal vol. 41,4 (2020): 543-603. doi:10.1093/eurheartj/ehz4054. Zhang, Robert S et al. “Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism.” Circulation. Cardiovascular interventions vol. 17,8 (2024): e014088. doi:10.1161/CIRCINTERVENTIONS.124.0140885. Barco, Stefano et al. “Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis.” European heart journal vol. 40,11 (2019): 902-910. doi:10.1093/eurheartj/ehy8736. Kjaergaard, J et al. “Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism.” Cardiovascular research, cvag038. 29 Jan. 2026, doi:10.1093/cvr/cvag0387. Dudzinski, David M et al. “Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism.” Academic emergency medicine : official journal of the Society for Academic Emergency Medicine vol. 24,3 (2017): 337-343. doi:10.1111/acem.13108

Dr. John Fortunato interviews Dr. Stefania Picariello and Dr. Enrico Opocher on their manuscript, entitled "Visual morbidity, long-term outcome, and prognostic factors in infants and young children with optic pathway low-grade glioma."

In this episode, we dive deep into ASH 2025 updates on myeloid malignancies with Dr. Curtis Lachowiez. From the plenary halls of ASH 2025 to long-term follow-up of Aza/Ven/Gilteritinib, we unpack what the latest evidence means for the future of AML management.1. PARADIGM Trial (Plenary Session, Abstract 6)Fathi A, Perl A, Fell G, et al. Results from PARADIGM – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia. Blood 2025;146(Suppl 1):6.https://doi.org/10.1182/blood-2025-6ClinicalTrials.gov: NCT048017972. VICEROY Study – Aza/Ven/Gilteritinib Triplet (Abstract 654)Venetoclax (VEN) and azacitidine (AZA) with gilteritinib (GILT) in patients with newly diagnosed FLT3mut+ AML ineligible for intensive induction chemotherapy: Interim results from the phase 1/2 VICEROY study. Blood 2025;146(Suppl 1):654.ClinicalTrials.gov: NCT055205673. Long-Term Follow-Up of Aza/Ven/Gilteritinib in FLT3-Mutated AML (Abstract 45)Azevedo RS, et al. Long-term follow-up of azacitidine, venetoclax, and gilteritinib in patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Blood 2025;146(Suppl 1):45.Original publication: Short NJ, Daver N, DiNardo CD, et al. J Clin Oncol 2024;42:1499–1508. https://doi.org/10.1200/JCO.23.01911ClinicalTrials.gov: NCT041404874. PRISM-AML Score (Abstract 453)Lachowiez CA, et al. Prognostic risk integration for survival modeling (PRISM) in newly diagnosed acute myeloid leukemia treated with venetoclax: A multinational retrospective cohort study. Blood 2025;146(Suppl 1):453.Interactive Calculator: https://prism-aml.com5. Additional Studies Referenced in Discussion•       VIALE-A Trial: DiNardo CD, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020;383:617–629. (NCT02993523)•       VERONA Trial: Randomized study of Aza-Ven vs. Aza vs. placebo in MDS (discussed as a negative study)•       4-Gene Classifier (mPRS): Bataller A, et al. Prognostic risk signature in patients with AML treated with HMA and venetoclax. Blood Adv 2024;8(4):927–935. https://doi.org/10.1182/bloodadvances.2023011757•       LACEWING Trial: Azacitidine plus gilteritinib vs. azacitidine plus placebo in FLT3-mutated AML (discussed as a negative study) 

This study of 801 multiple myeloma patients found that atrial fibrillation occurred in 5.5% within 90 days after autologous stem cell transplantation—nearly double previously reported rates—indicating disease‑specific risks. AF strongly predicted mortality from non‑relapse causes and may serve as a marker of physiological vulnerability, emphasizing the value of expanded pre‑transplant cardiac assessment and monitoring.

Angenommen, Dein Personalausweis sagt, Du bist 46. Dann erzählt Dein Körper vielleicht die Geschichte einer 55-Jährigen – oder die eines 37-Jährigen. Der Unterschied? Dein biologisches Alter. Und das kannst Du beeinflussen.Am Ende dieser Folge weißt Du, was biologisches Alter wirklich bedeutet, wie Du es messen kannst – von DNA-Tests bis Wearables – und welche drei Hebel auf Basis aktueller Forschung am effektivsten sind. Mark teilt seine eigenen WHOOP-Daten aus 2025: vom Bestwert im Sommer über Bundeswehrübung und USA-Jetlag bis zum Buchlaunch-Stress. Das Ergebnis? Trotz allem netto jünger geworden.Du lernst, warum VO₂max der stärkste Prädiktor für Deine Lebenserwartung ist, warum Schlafkonsistenz wichtiger ist als Schlafdauer – und warum 90 Minuten Krafttraining pro Woche Dich um fast 4 Jahre verjüngen können.____________*WERBUNG: Infos zum Werbepartner dieser Folge und allen weiteren Werbepartnern findest Du hier.Nur diese Woche: Sichere Dir Dein #DRNBLBR Gym Towell – solange vorrätig: drnblbr.de.____________Erwähnte Tools und Ressourcen:Fitnesstracker:WHOOP (Fitness-Tracker mit umfassendem Healthspan-Feature) – 1 Monat gratis über diesen Link.Cerascreen Genetic Age Test (epigenetischer Test, Horvath-Uhr)Polar Loop (kein Abo, weniger Funktionen)Amazfit Helio Strap (kein Abo, Basisfunktionen)Waage:Withings Body ScanBücher:„Looking Good Naked – Die Gesamtausgabe“ von Mark Maslow (2025)Podcast und Artikel:Folge 466: Die neue Wissenschaft vom Schlaf – mit Dr. Peter SporkArtikel: Genetic Age Test: Die Wahrheit über Dein biologisches Alter?Testbericht:c't Fitnessarmband-Vergleichstest (Helio Strap, Polar Loop, WHOOP)Forschungseinrichtung:Buck Institute for Research on Aging (Whoop-Forschungspartner)Literatur:Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115.Fitzgerald, K.N. et al. (2021). Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging, 13(7), 9419–9432.Mandsager, K. et al. (2018). Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open, 1(6), e183605.Windred, D.P. et al. (2024). Sleep regularity is a stronger predictor of mortality risk than sleep duration. SLEEP, 47(1), zsad253.Leong, D.P. et al. (2015). Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. The Lancet, 386(9990), 266–273.Tucker, L.A. (2024). Telomere Length and Biological Aging: The Role of Strength Training in 4814 US Men and Women. Biology, 13(11), 883.c't Magazin (2025). Fitnessarmbänder ohne Display im Test: Helio Strap, Polar Loop, WHOOP MG. Ausgabe 25, S.102.Produktlinks sind Affiliate-Links.____________Shownotes und Übersicht aller Folgen.Trag Dich in Marks Dranbleiber Newsletter ein.Entdecke Marks Bücher.Folge Mark auf Instagram, Facebook, Strava, LinkedIn. Hosted on Acast. See acast.com/privacy for more information.

Clinicians and patients are in a state of prognostic uncertainty when they are unsure about the future course of an illness. By embracing uncertainty while cultivating prognostic awareness, neurologists can serve the critical role of supporting patients and families through the living and dying process. In this episode, Casey Albin, MD, speaks with Robert G. Holloway, MD, MPH, FAAN, author of the article "Managing Prognostic Uncertainty in Neurologic Disease" in the Continuum® December 2025 Neuropalliative Care issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Holloway is the Edward and Alma Vollertsen Rykenboer Chair and a professor of neurology in the department of neurology at the University of Rochester School of Medicine and Dentistry in Rochester, New York. Additional Resources Read the article: Managing Prognostic Uncertainty in Neurologic Disease 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: @caseyalbin 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 Albin: Hello, this is Dr Casey Albin. Today I'm interviewing Dr Bob Holloway about his article on managing prognostic uncertainty in neurologic disease, which appears in the December 2025 Continuum issue on neuropalliative care. Welcome to the podcast, and please introduce yourself to our audience. Dr Holloway: Hi, Casey, and thank you. Again, my name is Bob Holloway. I'm a clinician and neurologist up in Rochester, New York, and I've been doing both neurology and palliative care for many years. Dr Albin: Well, that's fantastic. And I really wanted to emphasize how much I really enjoyed reading this article. I know that we're going to get into some of the pearls that you offer, but I really want to tell the listeners, like, this is a great one to read because not only does it have sort of a philosophical take, but you also really provide some pragmatic tips of how we can help our patients manage this prognostic uncertainty. But maybe just tell us a little bit, what is prognostic uncertainty? Dr Holloway: Yes, thank you. Well, I think everyone has a sense of what prognostic uncertainty is. And it's just the uncertain futures that we as clinicians and our patients face. And I would just say that a way to summarize it is just, how do we manage the "not yet" of neurologic illness? Dr Albin: I love that. In neurologic illness, there is so much "not yet" and there are so many unknowns. And what I thought was really helpful about your article is you kind of give us three buckets in which we can think about the different types of uncertainty our patients are facing. What are those? Dr Holloway: This is, I think, an area that really is of interest to me, thinking about how to organize the prognostic "not yet" or that landscape. And one way I've tried to simplify it is to think about it as data-centered. And that's the world that we mostly live in as neurologists. That's the probability distributions. We also have kind of system-level uncertainties, and that's the uncertainties that our health system affords for our patients. And then we have, also, the patient-centered uncertainties and the uncertainties that those two prior categories cause for our patients. And that's a big uncertainty that we often don't address. Dr Albin: In reading the article, I was really struck by, we spend a lot of time thinking about data uncertainty. Can we get population-based research? Can we sort of look at prognostication scoring? I live in the ICU, and so we think a lot about these, like, scoring metrics and putting patients into buckets and helping us derive their care based on where their severity index is. And I'm sure that is true in many of the divisions of neurology. But what I did not really appreciate---and I thought you did a really fantastic job of kind of drawing our attention to---is there's a lot of system-centered uncertainty. Can you give us a little bit of examples, like, what is system-based uncertainty? Dr Holloway: I think system-level uncertainties just encompass the practical information gaps that may arise during our healthcare encounter. And a lot of, I think, the uncertainty that our patients face and families, they actually describe it as they feel captive by the uncertainty. And it's just the unknowns, not just what affords from the actual information about the disease and its prognosis in the future, but actually the level of the system, like, who's going to take care of them? How do you manage arranging for nurses to come into the home or all those practical-level uncertainties that the system provides that sometimes we don't do a good job of road-mapping for patients. Dr Albin: Absolutely. Because I feel like we have a little bit of a gap in that often as physicians. Like, the family asks, what will hospice at home look like? Well, you know, that's a question for case management. I think they'll come in and they'll tell you. But it strikes me that that's a real gap of my being able to walk patients through. Will they get home health care? Will they have transportation set up? Will there be a nurse who comes in to check? How often are they available? What's the cost going to be? All of these practical aspects of dealing with an illness that are beyond sort of our scope of knowledge, but probably have a huge practical impact to the patient. Dr Holloway: Without question, every encounter patients wonder about, that kind of future wish landscape that we- all our future-oriented desires and hopes. And so much of that is the practical aspects of our health system, which is often fragmented, kind of unknown, uncertain. And that's a huge source of uncertainty for our patients and families. And then that leads to many other uncertainties that we need to address. Dr Albin: Absolutely. I think another one that we, again, maybe don't spend quite as much time thinking about is this patient-level uncertainty. What's going on there? Dr Holloway: Yeah. So, I think patient-level uncertainty is that uncertainty that they experience when confronted with the two other types of uncertainty: the actual data-centered uncertainty and the system-level uncertainty. And that's that, kind of, very huge kind of uncertainty about what it means for them and their family and their future futures. And that's a source of huge stress and anxiety, and often frankly bordering on dread and fear for our patients and families. That actually gets into very levels of uncertainty that I would call maybe over even in the existential realm. Patient-level uncertainty in the actual existential questions or the fear and the dread or the kind of just unnerving aspect of it is actually even more important to patients than the scientific or data-centered uncertainty that we focus most of our attention on. Dr Albin: Yeah, I think this is, to me, was getting towards that, like, what does the patient care about and how are they coping with what is in many times a really dramatic shift in their life expectancy or morbidity expectations and this sort of radical renegotiation about what it means to have a neurologic illness? And how does that shift their thinking about who they are and their priorities in the world? Is that right? Dr Holloway: One thousand percent, and in fact, I will say---and I think is one of the main take home messages is that, you know, managing prognostic certainty is not an end in itself. It really is to help patients and families adaptively cope to their new and often harsh new reality, that we could help them adapt to their new normal. I think that is one of our main tasks as neurologists in our care teams is to help patients find and ultimately maybe achieve existential or spiritual or well-being even in their new health states. You know, that you certainly often see in the intensive care unit, but we often always see in the outpatient realm as well, and all our other diseases. Dr Albin: I think that's really hard to do. I think those conversations are incredibly difficult and trying to navigate where patients want to be, what would bring meaning, what would bring value. I think many of us struggle to have these pretty real and intense conversations with families about what really is important. And one of the things I really liked about this article is you kind of walk us through some steps that we as clinicians can take to get a little bit more comfortable. Maybe just walk us through, what are some of the things that you have found most helpful in trying to get families and patients to open up about what brings them meaning? How are they navigating this new, really uncertain time in their life? Dr Holloway: Yeah, so I do kind of have a ten-point recommendations of how to help cultivate a more integrated awareness of an uncertain future. I mean, I think the most important thing is actually just recognizing that embracing uncertainty as an amazingly remarkable cognitive tool. I mean, let's face it, uncertainty, when it happens with neurologic illness and disease, is often fearful. It's scary. It kind of changes our world. But on the flip side of it, it's a remarkable cognitive tool that actually can help us find new ways and new paths and new creativity. And I think we can use that kind of opposites to help our patients find new meaning in very difficult situations. So, thinking about uncertainty, kind of being courageous, leaning into it and recognizing that it does create anxieties and fear, but it also can kind of help create new solutions and new ideas to help people navigate. Dr Albin: I was hoping that maybe you could give us an example of, like, how would you do that? If a patient comes in and they're dealing with, you know, a new diagnosis and they're navigating this new uncertainty, what are some of the things that you ask to help them reframe that, to kind of take some of the good about that uncertainty? How do you navigate that? Dr Holloway: One of the other recommendations is actually just resetting the timeline and expectations for these conversations. That it shouldn't be expected that patients should accept their harsh new reality immediately, that it takes time in a trusted environment. And that there's this, like, oscillating nature of hopes and fears and dread, and you've just got to work with them over time. And with time, and once you understand who the patient and family are and understand where they find meaning and where they find, actually, joy in their life, or what actually brings them meaning, you can start recasting their futures into credible narratives in their kind of future landscape in ways that I think can help them enter into their new realities within the, you know, framework of disease management that you can offer them within your healthcare team or your healthcare system or wherever you are in the world and the available resources that you have to offer patients and families. Dr Albin: So, this sounds like a lot to me like active listening and really trying to get to know what is important to the family, what is important to the patient. And I guess probably just creating that space even in that busy clinical environment. Do I have that right? Dr Holloway: You can absolutely do that, right. You know, and honestly, active listening, we are challenged in our busy healthcare system to do this, but I think with the right listening skills and the appropriate ways of paying attention, you can definitely illuminate these possible, kind of future-oriented worlds for patients and help them navigate those new terrains with them. Frankly, I think that's a real new space for us in neurology. We don't think about and train how to create credible narratives for patients and families. We do it on the fly, but I think there's so much more work to do. How do you actually keep, you know, that best-case, worst-case, most likely credible narratives for patients that can help them adapt to their new realities and support them on their new journeys? Dr Albin: I love that best-case, worst-case, most likely case. I find that framework really helpful. But you talk in your article, it's not just about using that best case or worst case or most likely, but it's actually building some forecasting into that and having some real data to kind of support what you're saying. And there's a lot of growth towards actually becoming good as a medical forecaster. Can you describe a little bit, what did you mean by that? Dr Holloway: You're absolutely right. I think, actually, one of the skillsets of becoming and managing prognostic uncertainty is actually becoming a skilled medical forecaster. And it's a really tall order. So, we've got to be both good medical forecasters as well as helping patients adaptively cope to their new reality. But the good medical forecasting is actually now going more quantitative in thinking about the data that's available to help think about the important outcomes for patients and families and then predicting what their probabilities are so you can shape those futures around. So, yes, we do have to have an open mindset. We do have to actually look at the data that's available and actually think about, what are those long-term probabilities and outcomes? And we can be honest about those and even communicate them with families. But it's a really good skill set to have. Dr Albin: Yeah. This to me was a little bit about, how do you bring in the data knowledge that we try to get over time as we develop our expertise? You're developing not just a reliance on population-based data, but in my experience, I have seen this. And that sort of ability to kind of look at the patient in front of you, think about the big picture, but also a little bit about their unique medical comorbidities or prior life experiences. So, some of that database knowledge, and then bringing in and getting to know what is important to the patient. And so, sort of marrying that data-centric/patient-centric mindset. Dr Holloway: I love it. I guess the other way of saying that, too, is we need to think with precision, but communicate in narratives. And it's okay to gently put more precise estimates on our probability predictions with patients and families, what we think is the most likely case, best and worst case. Because patients and families want us to be more precise. We often shy away from it, but- so, it's okay to think in precisions, but we've got to put those in narratives in the most likely, best-, and worst-case scenarios. And don't be afraid if you think in terms of ninety percents, ten percents, fifty percents; most patients and families don't mind that. And what they're telling us is they actually want to hear that, if you are comfortable talking in those terms. Dr Albin: Yeah, absolutely. And giving a sense of the humility to say, like, this is my best guess based on medical data and my experience, I would say, but again, none of us have a crystal ball. And I do think families, as long as you're sort of couching your expectations into the sort of imperfect, but I'm doing my best, really appreciate that. Dr Holloway: They totally do all the time. Just say, I simply don't know for certain, but these are my best estimates. That's a good way of just phrasing that. Dr Albin: Yeah. So powerful. I don't know for certain. And then I wanted to just kind of close out, because there's this one term that you use that I thought was so interesting. And I wanted you to kind of tell our listeners a little bit about what you mean here, which is that, when you're actively open-minded, you're using this, quote, "dragonfly eyes." What do you mean by that? Dr Holloway: So, the dragonfly eyes, as you know, they can look at three sixty around them and they just, they move in all directions. Being actively open minded, I guess the biggest example I would say is, I don't like the term prognostic discordance, which means that there's a difference of subjective estimates of prognosis between patients and families. Being openly minded is actually embracing the potential information that the family has about prognosis and incorporating that into your estimates. So, I wouldn't say it's discordances, per se; I think being really actively open-minded is taking that all in and utilizing that as, you know what, they know more than you do about the patient and their loved ones, and they may have insights that can inform your best estimates of prognosis. So, the true dragonfly prognosticator actually is one who embraces and doesn't consider it discord, but considers it kind of new, useful information that I just need to weigh in so I can help the family in my best professional way in terms of developing a prognosis, whatever the condition may be. Dr Albin: I can imagine this is just so challenging and something that takes a long time to sort of perfect all of this. I think you say right below that, you need a growth mindset to do this because it is hard, and it's going to take an active participation and an active desire to get better at these conversations with our families. Dr Holloway: One thousand percent. You are so right that it takes time, effort, and not feeling like you're being challenged, but that actually you are including them in your entire body of knowledge, that you're just- it's part of all you're collecting. And even, I was on service last week, and I talked to residents and students about that very issue. It's like take their prognosis. And someone who came in, we thought CJB, very sad, tragic case, but we were thinking about what the future may look like and how do we actually work with the family who had very what we thought was unrealistic expectations. I said, well, no, this is not discordance. This is just useful information that we can take understand where they're coming from and incorporate that into the ways we want to build relationships, build trust, and over time we'll get to a point where we hopefully can work with them and have them have that fully integrated awareness of their future. Dr Albin: Yeah, that's beautiful. It really is this ongoing negotiation that really requires so much listening, understanding, and then obviously information and expertise about the data that we're presenting and the likelihood outcome, recognizing that there's a lot of uncertainty in all of this. Which, you know, again, this is kind of a 360 talk. At every level there is uncertainty, and that's what makes it so hard. Dr Holloway: Yeah, you're absolutely right. And actually, even in the article I kind of used the term radical uncertainty as that, no matter how resolvable all this uncertainty is, there will always still remain that radical element of our existence which we have to actually incorporate and be prepared for. And actually, not only of ourselves, but actually for patients and families and helping manage that. Using narratives and credible narratives and kind of ranges of possibilities is the best way to do that in a personalized way. Dr Albin: Well, this has been a fantastic conversation, and I know that we are running a bit short on time. So, as we wrap up and you think about this topic, are there any key take-home messages that you hope our listeners will walk away with? Dr Holloway: I think one main emphasis is that despite all the successes we feel we have in neurology, is that we all have to recognize that prognostic uncertainty is just going to increase in the future. But this is going to be for several reasons. One is that, just, the illness uncertainty of all of our great therapies are just going to be creating more uncertainty for the future. And precision medicine is paradoxical, and that actually it creates more uncertainty. So, I think we need to be prepared that we have to manage prognostic uncertainty better, because it's definitely going to increase. And two, it's what I said earlier, is that actually managing prognostic uncertainty is not an end to itself. It's actually helping patients and families adapt to their new and sometimes harsh new reality and actually help them to ultimately get to a place where maybe either their condition is neither dreaded, but actually they can accept it as their new reality and actually achieve some sort of existential well-being and existential health. I think that we have a lot more to emphasize in this area. And for far too long, we've focused on the certainty aspect of our field and not enough on the uncertainty in the world of medicine to help our patients and families. Dr Albin: And gosh, isn't there just so much uncertainty? And I think this has been beautiful. So, thank you again for coming and sharing your expertise. Dr Holloway: Thank you very much. It's been a pleasure. Dr Albin: For all of our listeners out there, this is a truly fantastic article, and I would just like to direct you to going to read the cases because not only do the cases offer a little bit of practical advice, but there's one that's actually sort of a philosophical discussion about, what does it mean to be alive and confront death? There's some beautiful artwork that's featured as well. So this is just a really unique article, and I'm excited for our listeners to have a chance to check it out. So again, today I've been interviewing Dr Bob Holloway about his article on managing prognostic uncertainty in neurologic disease, which appears in the December 2025 Continuum issue on neuropalliative care. Be sure to check out Continuum Audio episodes from this and other issues. 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.

Commentary by Dr.  Jian'an Wang.

Featuring an interview with Dr Scott Kopetz, including the following topics:  Circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy de-escalation in the treatment of Stage III colon cancer from the ctDNA-negative cohort of the DYNAMIC-III trial (0:00) Prognostic and predictive role of ctDNA in the management of Stage III colon cancer treated with celecoxib: Findings from the CALGB (Alliance)/SWOG 80702 trial (8:01) Phase III ALTAIR study comparing trifluridine/tipiracil to placebo for patients with molecular residual disease after curative resection of colorectal cancer (CRC); a methylation-based, tissue-free ctDNA test (12:51) ctDNA with locally advanced mismatch repair-deficient/microsatellite instability-high solid tumors; real-world evidence regarding ctDNA with resected CRC (17:31) CME information and select publications

In this week's episode, Blood editor Dr. Laurie Sehn interviews three of the latest Blood authors: Drs. Vijay Sankaran, Ruud Delwel, Françoise Kraeber-Bodere. Two studies on the MECOM gene have been paired in this episode, analyzing new groundwork for potential novel myeloid differentiation therapies via repression of MECOM restoring enhancer mediated CEBPA expression. We'll also hear about the results of CASSIOPET, imaging companion study of the CASSIOPEIA trial, and how achieving negativity in PET before starting maintenance therapy is significant even in patients who still show residual disease in the bone marrow.Featured ArticlesCEBPA repression by MECOM blocks differentiation to drive aggressive leukemiasMECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed from the CASSIOPEIA trial

Commentary by Dr. Jian'an Wang.

In today's VETgirl online veterinary continuing education podcast, we dig into the latest evidence on prognostic indicators during Cardiopulmonary Resuscitation (CPR) in dogs and cats. Using data from the RECOVER registry, this 2025 JVECC study sheds light on which factors can help predict return of spontaneous circulation (ROSC) and survival to discharge, giving us practical tools to guide our decision-making in the heat of resuscitation. Tune in to hear how this data can help set realistic expectations for veterinary staff and for pet owners, and shape how we approach veterinary CPR!

In today's VETgirl online veterinary continuing education podcast, we dig into the latest evidence on prognostic indicators during Cardiopulmonary Resuscitation (CPR) in dogs and cats. Using data from the RECOVER registry, this 2025 JVECC study sheds light on which factors can help predict return of spontaneous circulation (ROSC) and survival to discharge, giving us practical tools to guide our decision-making in the heat of resuscitation. Tune in to hear how this data can help set realistic expectations for veterinary staff and for pet owners, and shape how we approach veterinary CPR!

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on Prognostic Implications of Preoperative hs-cTnT in Elective Coronary Artery Bypass Grafting.

Dr Neil Greening and Dr Hnin Aung join Diana Stanley to discuss a new multidimensional prognostic risk stratification model for COPD exacerbations.click here to read the full article: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00362-5/fulltextContinue this conversation on social!Follow us today at...https://thelancet.bsky.social/https://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

Commentary by Dr. Jian'an Wang.

Dr. Kenneth Ellenbogen, Deputy Editor of JACC: Clinical Electrophysiology, discusses Mental Disorders Following Implantable Cardioverter-Defibrillator Therapy: Incidence and Prognostic Implications in a Nationwide Cohort Study.

Commentary by Dr. Anastasios Apostolos.

Featuring an interview from Dr John Strickler, including the following topics: Prognostic value of molecular residual disease (MRD) as detected by circulating tumor DNA (ctDNA) and optimal incorporation of MRD assays into the care of patients with colorectal cancer (0:00) Potential use of MRD assays for patients with microsatellite instability (MSI)-high localized colorectal cancer or those with delayed progression or metastatic disease (16:09) Tumor-informed MRD assays under clinical development (20:36) Predictive role of ctDNA in Stage III colon cancer treated with celecoxib; effect of low-dose aspirin on response to celecoxib in patients with PI3K pathway alterations (24:19) Case: A man in his late 50s with resected Stage IIA colon cancer (30:06) Case: A woman in her late 40s with Lynch syndrome and MSI-H colon cancer with a solitary, small hepatic metastasis (34:57) MRD as a future clinical trial endpoint for solid tumors; increasing incidence of colorectal cancer in younger people (40:24) Antibody-drug conjugates in the treatment of colorectal cancer (45:13) Perspectives on promising areas of clinical research in colorectal cancer (48:23) CME information and select publications

In this week's episode we'll learn about targeting the tissue factor pathway inhibitor with a monoclonal antibody to rebalance HEMOSTASIS in hemophilia A and B. In the phase 3 BASIS trial, the monoclonal antibody marstacimab reduced bleeding events, and was generally well tolerated, with no unanticipated side effects. After that: matched-donor allogeneic CD19 CAR-T for adult B-ALL. Given after allogeneic transplantation, CAR-donor lymphocyte infusion after lymphodepleting chemotherapy was associated with favorable efficacy and a tolerable safety profile. Finally: a new prognostic index for mycosis fungoides and Sézary syndrome. Comprised of four prognostic factors, the “CLIPI” could enable more personalized treatment of cutaneous lymphomas, identifying patients who may benefit from intensified treatment.Featured ArticlesMarstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trialMatched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletionA new prognostic index (CLIPI) for advanced cutaneous lymphoma enables precise patient risk stratification

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/DPB865. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on Prognostic Implications of Preoperative N-Terminal Pro-B-Type Natriuretic Peptide Dynamics in Patients Undergoing Cardiac Surgery.

Dr. John Fleetham chats with Dr. Chris Ryerson and Dr. Yet Khor about their article, "Epidemiology and Prognostic Significance of Cough in Fibrotic Interstitial Lung Disease."

Dr. John Fleetham chats with Dr. Chris Ryerson and Dr. Yet Khor about their article, "Epidemiology and Prognostic Significance of Cough in Fibrotic Interstitial Lung Disease."

In this JCO Precision Oncology Article Insights episode, Natalie DelRocco summarizes "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma" by Roelof van Ewijk et al. published on May 29, 2025. TRANSCRIPT Natalie Del Rocco: Hello, and welcome to JCO Precision Oncology Article Insights. I'm your host, Natalie DelRocco, and today we will be discussing the original report, "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma." This original report by van Ewijk et al. describes a study of the association between 2 biomarkers and survival outcomes among patients with high-grade osteosarcoma. Osteosarcoma is a disease where not much progress has been made in risk stratification factors that could potentially help patients target lower-risk therapies, less toxic therapies, or therapies that might be more toxic but could help their high-risk osteosarcoma. So, it's important to identify risk factors that can help target therapies. The G1/G2 gene expression signature is a prognostic risk score developed by a French osteosarcoma group in 2022. They showed in a cohort of 79 osteosarcoma patients that risk score was associated with poorer event-free survival and overall survival. This considers expression of 15 individual genes. MYC amplification was shown in 2023 by a North American osteosarcoma group to be associated with poor overall survival in a cohort of 92 osteosarcoma patients, and this group validated that finding in a localized cohort in the same publication.  The goal of this particular original report was to assess the prognostic significance of each of these biomarkers in a population independent to those prior publications and, hence, to serve as an external validation of prior findings and to assess these 2 biomarkers in the same study. The investigators considered MYC amplification, defined as having greater than 7 copies; MYC expression as a continuous rather than the previously categorized variable; and G2 expression defined as a continuous variable; and then G2 expression defined as a dichotomous variable with the cut point at the median, as done in the original paper.  What the investigators found in their primary multivariable Cox proportional hazards regression model, which controlled for additional clinical risk factors such as age, tumor site, tumor size, is that G2 expression and MYC expression as continuous variables were associated with increased hazard of EFS and OS event. MYC amplification was not found to be prognostic. This is not surprising. When we have continuous variables, we have greater statistical power, we decrease the likelihood that an identified cut point in a previous study does not generalize well to either our genetic assay or our patient population. So, we don't have to worry about finding the optimal cut point in our particular patient sample. Thank you for listening to our JCO Precision Oncology Article Insights. Don't forget to give us a rating or review, and be sure to like and subscribe so that you never miss an episode. You can find all ASCO shows at asco.orgpodcasts. 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.  

In this JCO Precision Oncology Article Insights episode, Natalie DelRocco summarizes "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma" by Roelof van Ewijk et al. published on May 29, 2025. TRANSCRIPT Natalie Del Rocco: Hello, and welcome to JCO Precision Oncology Article Insights. I'm your host, Natalie DelRocco, and today we will be discussing the original report, "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma." This original report by van Ewijk et al. describes a study of the association between 2 biomarkers and survival outcomes among patients with high-grade osteosarcoma. Osteosarcoma is a disease where not much progress has been made in risk stratification factors that could potentially help patients target lower-risk therapies, less toxic therapies, or therapies that might be more toxic but could help their high-risk osteosarcoma. So, it's important to identify risk factors that can help target therapies. The G1/G2 gene expression signature is a prognostic risk score developed by a French osteosarcoma group in 2022. They showed in a cohort of 79 osteosarcoma patients that risk score was associated with poorer event-free survival and overall survival. This considers expression of 15 individual genes. MYC amplification was shown in 2023 by a North American osteosarcoma group to be associated with poor overall survival in a cohort of 92 osteosarcoma patients, and this group validated that finding in a localized cohort in the same publication.  The goal of this particular original report was to assess the prognostic significance of each of these biomarkers in a population independent to those prior publications and, hence, to serve as an external validation of prior findings and to assess these 2 biomarkers in the same study. The investigators considered MYC amplification, defined as having greater than 7 copies; MYC expression as a continuous rather than the previously categorized variable; and G2 expression defined as a continuous variable; and then G2 expression defined as a dichotomous variable with the cut point at the median, as done in the original paper.  What the investigators found in their primary multivariable Cox proportional hazards regression model, which controlled for additional clinical risk factors such as age, tumor site, tumor size, is that G2 expression and MYC expression as continuous variables were associated with increased hazard of EFS and OS event. MYC amplification was not found to be prognostic. This is not surprising. When we have continuous variables, we have greater statistical power, we decrease the likelihood that an identified cut point in a previous study does not generalize well to either our genetic assay or our patient population. So, we don't have to worry about finding the optimal cut point in our particular patient sample. Thank you for listening to our JCO Precision Oncology Article Insights. Don't forget to give us a rating or review, and be sure to like and subscribe so that you never miss an episode. You can find all ASCO shows at asco.orgpodcasts. 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.  

Welcome to the Part Time Pilot Audio Ground School Podcast! This podcast takes our free podcast to a whole new level by providing students with every single lesson included in the Part Time Pilot Private Pilot & IFR Ground Schools without a single Ad! On top of that, VIP podcast students get BONUS episodes like Mock Checkrides, Checkride Prep, Expert Interviews and more!   The #1 reason student pilots never end up becoming a private pilot is NOT due to money. The real reason is actually deeper than that. Yes, flight training is expensive. But every student pilot knows this and budgets for it when they decide to do it.   The actual #1 reason a student pilot fails is because they do not have a good, fundamental understanding of the private pilot knowledge they are meant to learn in ground school.   You see when a student does not have a good grasp of this knowledge they get to a point in their flight training where their mind just can't keep up. They start making mistakes and having to redo lessons. And THAT is when it starts getting too expensive.   This audio ground school is meant for the modern day student pilot... aka the part time student pilot. Let's face it, the majority of us have full time responsibilities on top of flight training. Whether it is a job, kids, family, school, etc. we all keep ourselves busy with the things that are important to us. And with today's economy we have to maintain that job just to pay for the training. The modern day student pilot is busy, on the go and always trying to find time throughout his or her day to stay up on their studies. The audio ground school allows them to consume high quality content while walking, running, working out, sitting in traffic, traveling, or even just a break from the boring FAR/AIM or ground school lecture.   Did I meant high quality content? The audio ground school is taken straight out of the 5-star rated Part Time Pilot Online Ground School that has had over 2000 students take and pass their Private Pilot & IFR exams with only 2 total students failing the written. That's a 99.9% success rate! And the 2 that failed? We refunded their cost of ground school and helped them pass on their second attempt. We do this by keeping ground school engaging, fun, light and consumable. We have written lessons, videos, audio lessons, live video lessons, community chats, quizzes, practice tests, flash cards, study guides, eBooks and much more.   Part Time Pilot was created to be a breath of fresh air for student pilots. To be that flight training provider that looks out for them and their needs. So that is just what we are doing with this podcast.     IFR Section 4 Lesson 18: In this Free IFR Ground School lesson we talk about more helpful weather charts, and in particular significant weather prognostic charts such as surface, low-level and high-level which can give use significant weather event forecasts.   Links mentioned in the episode: Scholarships: https://parttimepilot.com/scholarships/  Private Pilot Online Ground School: PPL Ground School - Part Time Pilot Checkride Prep: PPL Checkride Prep - Part Time Pilot IFR Online Ground School: IFR Ground School – Part Time Pilot   PPL study group: https://www.facebook.com/groups/parttimepilot  IFR study group: https://www.facebook.com/groups/parttimepilotifr/   Recommended Products & Discounts:  https://parttimepilot.com/recommended-products-for-student-pilots/   

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News 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. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Please visit answersincme.com/URZ860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in esophageal carcinoma (EAC) discusses novel tests to predict the risk of progression from Barrett's esophagus (BE) to EAC. Upon completion of this activity, participants should be better able to: Identify the clinical rationale for using novel prognostic stratification tests to predict the risk of progression from BE to EAC, Review the clinical support for prognostic tests that provide actionable information for identifying patients with BE who are at risk of progression to EAC; and Outline strategies to integrate novel prognostic tests into the surveillance algorithm for patients with BE who may be at risk of progression to EAC.

This week's episode dives into brand new research on prognostic factors for patients with nonspecific low back pain—one of the most common challenges chiropractors face every day in practice. Dr. Jeff breaks down a recent prospective study that tracked nearly 250 patients across multiple chiropractic practices, revealing what really predicts improvement, how long meaningful outcomes take, and which strategies can set your patients up for lasting success.You'll learn not only about the numbers—like the remarkable drop in pain and disability over just four weeks—but also about the power of mindset, patient expectations, and your own confidence as a provider.Episode Notes: Prognostic factors associated with improvement in patients with an episode of non-specific low back pain without radicular syndrome: a prospective observational exploratory studyThe Best Objective Assessment of the Cervical Spine- Provide reliable assessments and exercises for Neuromuscular Control, Proprioception, Range of Motion, and Sensorimotor-Integration. Learn more at NeckCare.comTurncloud EHR- Minimalist design, without being sparse. Practical, yet elegant. Turncloud's design was to find the most efficient path in a day in the life of a chiropractic office. Connect with their team at www.turncloud.com Patient Pilot by The Smart Chiropractor is the fastest, easiest to generate weekly patient reactivations on autopilot…without spending any money on advertising. Click here to schedule a call with our team.Our members use research to GROW their practice. Are you interested in increasing your referrals? Discover the best chiropractic marketing you aren't currently using right here!

Interview with Manuel Comabella, MD, author of Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome. Hosted by Cynthia E. Armand, MD. Related Content: Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome

Interview with Manuel Comabella, MD, author of Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome. Hosted by Cynthia E. Armand, MD. Related Content: Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome

Join us in this insightful episode of the Oncology Brothers podcast as we dive deep into the current treatment landscape of pancreatic cancer. Drs. Rohit and Rahul Gosain are joined by Dr. Emil Lou, a medical and neuro-oncologist from the University of Minnesota, to discuss the challenges and advancements in managing this complex disease. In this episode, we covered: •⁠  ⁠The importance of a multidisciplinary approach in treating early-stage pancreatic cancer. •⁠  ⁠The role of neoadjuvant and adjuvant therapies, including the latest insights on chemotherapy regimens like FOLFIRINOX, nal-IRI and gemcitabine. •⁠  ⁠The significance of germline and next-generation sequencing (NGS) testing in personalizing treatment plans. •⁠  ⁠The current state of clinical trials and emerging therapies, including PARP inhibitors for BRCA mutations and the implications of ctDNA testing. •⁠  ⁠Prognostic discussions around metastatic pancreatic cancer and the importance of managing side effects to improve patient quality of life. Key takeaways include the necessity of balancing treatment efficacy with adverse events, the critical role of genetic testing, and the need for vigilance regarding venous thromboembolism (VTE) in pancreatic cancer patients. Don't miss this comprehensive discussion that aims to shed light on the ongoing efforts to improve outcomes for patients battling pancreatic cancer.   YouTube: https://youtu.be/HCKQxmOqRTI   Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Subscribe to our channel for more discussions on oncology and stay updated on the latest in cancer treatment!

Chuck and Chris discuss a radial nerve palsy associated with a humerus fracture.  We discuss diagnosis, examination, and preliminary treatment options.  Part 2 will follow after the IFSSH meeting.  We also discuss upcoming, IFSSH- related episodes.Some citations1: Lieberdorfer A, Shivakumar N, Stonner MM, Brogan DM, Ray WZ, Mackinnon SE, DyCJ. Expectant Management, Tendon Transfer, or Nerve Transfer Surgery for RadialNerve Injury: A Qualitative Study Exploring Patient Expectations, Goals, andTreatment Experiences. J Bone Joint Surg Am. 2023 Apr 19;105(8):600-606. doi:10.2106/JBJS.22.01201. Epub 2023 Feb 16. PMID: 36795855. 2: Malikowski T, Micklesen PJ, Robinson LR. Prognostic values ofelectrodiagnostic studies in traumatic radial neuropathy. Muscle Nerve. 2007Sep;36(3):364-7. doi: 10.1002/mus.20848. PMID: 17587226. 3: Steenbeek ED, Pondaag W, Tannemaat MR, Van Zwet EW, Malessy MJA, Groen JL.Optimal timing of needle electromyography to diagnose lesion severity intraumatic radial nerve injury. Muscle Nerve. 2023 Apr;67(4):314-319. doi:10.1002/mus.27787. Epub 2023 Jan 22. PMID: 36625338.4.  PMID: 31714418Radial Nerve Palsy Recovery With Fractures of the Humerus: An Updated Systematic Review.Ilyas AM, Mangan JJ, Graham J.J Am Acad Orthop Surg. 2020 Mar 15;28(6):e263-e269. doi: 10.5435/JAAOS-D-18-00142.5. PMID: 32285189Radial nerve palsy associated with closed humeral shaft fractures: a systematic review of 1758 patients.Hendrickx LAM, Hilgersom NFJ, Alkaduhimi H, Doornberg JN, van den Bekerom MPJ.Arch Orthop Trauma Surg. 2021 Apr;141(4):561-568. doi: 10.1007/s00402-020-03446-y. Epub 2020 Apr 13.6.  PMID: 33335819Incidence and Management of Radial Nerve Palsies in Humeral Shaft Fractures: A Systematic Review.Hegeman EM, Polmear M, Scanaliato JP, Nesti L, Dunn JC.Cureus. 2020 Nov 15;12(11):e11490. doi: 10.7759/cureus.11490.PMID: 33335819 Free PMC article. Review.Please complete our survey:  https://bit.ly/3iHGFpDSee www.practicelink.com/theupperhand for more information from our partner on job search and career opportunities.The Upper Hand Podcast is sponsored by Checkpoint Surgical, a provider of innovative solutions for peripheral serve surgery. To learn more, visit https://checkpointsurgical.com/. Subscribe to our newsletter: bit.ly/3X0Gq89As always, thanks to @iampetermartin for the amazing introduction and concluding music.For additional links, the catalog.  Please see https://www.ortho.wustl.edu/content/Podcast-Listings/8280/The-Upper-Hand-Podcast.aspx