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Normal pressure hydrocephalus (NPH) is a clinical syndrome of gait abnormality, cognitive impairment, and urinary incontinence. Evaluation of CSF dynamics, patterns of fludeoxyglucose (FDG) uptake, and patterns of brain stiffness may aid in the evaluation of challenging cases that lack typical clinical and structural radiographic features. In this episode, Katie Grouse, MD, FAAN, speaks with Aaron Switzer, MD, MSc, author of the article “Radiographic Evaluation of Normal Pressure Hydrocephalus” in the Continuum® June 2025 Disorders of CSF Dynamics issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Switzer is a clinical assistant professor of neurology in the department of clinical neurosciences at the University of Calgary in Calgary, Alberta, Canada. Additional Resources Read the article: Radiographic Evaluation of Normal Pressure Hydrocephalus 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 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 Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Aaron Switzer about his article on radiographic evaluation of normal pressure hydrocephalus, which he wrote with Dr Patrice Cogswell. This article appears in the June 2025 Continuum issue on disorders of CSF dynamics. Welcome to the podcast, and please introduce yourself to our audience. Dr. Switzer: Thanks so much for having me, Katie. I'm a neurologist that's working up in Calgary, Alberta, Canada, and I have a special interest in normal pressure hydrocephalus. So, I'm very happy to be here today to talk about the radiographic evaluation of NPH. Dr Grouse: I'm so excited to have you here today. It was really wonderful to read your article. I learned a lot on a topic that is not something that I frequently evaluate in my clinic. So, it's really just a pleasure to have you here to talk about this topic. So, I'd love to start by asking, what is the key message that you hope for neurologists who read your article to take away from it? Dr. Switzer: The diagnosis of NPH can be very difficult, just given the clinical heterogeneity in terms of how people present and what their images look like. And so, I'd like readers to know that detailed review of the patient's imaging can be very helpful to identify those that will clinically improve with shunt surgery. Dr Grouse: There's another really great article in this edition of Continuum that does a really great job delving into the clinical history and exam findings of NPH. So, I don't want to get into that topic necessarily today. However, I'd love to hear how you approach a case of a hypothetical patient, say, where you're suspicious of NPH based on the history and exam. I'd love to talk over how you approach the imaging findings when you obtain an MRI of the brain, as well as any follow-up imaging or testing that you generally recommend. Dr. Switzer: So, I break my approach down into three parts. First, I want to try to identify ventriculomegaly and any signs that would support that, and specifically those that are found in NPH. Secondly, I want to look for any alternative pathology or evidence of alternative pathology to explain the patient's symptoms. And then also evaluate any contraindications for shunt surgery. For the first one, usually I start with measuring Evans index to make sure that it's elevated, but then I want to measure one of the other four measurements that are described in the article, such as posterior colossal angle zed-Evans index---or z-Evans index for the American listeners---to see if there's any other features that can support normal pressure hydrocephalus. It's very important to identify whether there are features of disproportionately enlarged subarachnoid space hydrocephalus, or DESH, which can help identify patients who may respond to shunt surgery. And then if it's really a cloudy clinical picture, it's complicated, it's difficult to know, I would usually go through the full evaluation of the iNPH radscale to calculate a score in order to determine the likelihood that this patient has NPH. So, the second part of my evaluation is to rule out evidence of any alternative pathology to suggest another cause for the patient's symptoms, such as neurodegeneration or cerebrovascular disease. And then the third part of my evaluation is to look for any potential contraindications for shunt surgery, the main one being cerebral microbleed count, as a very high count has been associated with the hemorrhagic complications following shunt surgery. Dr Grouse: You mentioned about your use of the various scales to calculate for NPH, and your article does a great job laying them out and where they can be helpful. Are there any of these scales that can be reasonably relied on to predict the presence of NPH and responsiveness to shunt placement? Dr. Switzer: I think the first thing to acknowledge is that predicting shunt response is still a big problem that is not fully solved in NPH. So, there is not one single imaging feature, or even combination of imaging features, that can reliably predict shunt response. But in my view and in my practice, it's identifying DESH, I think, is really important---so, the disproportionately enlarged subarachnoid space hydrocephalus---as well as measuring the posterior colossal angle. I find those two features to be the most specific. Dr Grouse: Now you mentioned the concept of the NPH subtypes, and while this may be something that many of our listeners are familiar with, I suspect that, like myself when I was reading this article, there are many who maybe have not been keeping up to date on these various subtypes. Could you briefly tell us more about these NPH subtypes? Dr. Switzer: Sure. The Japanese guidelines for NPH have subdivided NPH into three different main categories. So that would be idiopathic, delayed onset congenital, and secondary normal pressure hydrocephalus. And so, I think the first to talk about would be the secondary NPH. We're probably all more familiar with that. That's any sort of pathology that could lead to disruption in CSF dynamics. These are things like, you know, a slow-growing tumor that is obstructing CSF flow or a widespread meningeal process that's reducing absorption of CSF, for instance. So, identifying these can be important because it may offer an alternative treatment for what you're seeing in the patient. The second important one is delayed onset congenital. And when you see an image of one of these subtypes, it's going to be pretty different than the NPH because the ventricles are going to be much larger, the sulcal enfacement is going to be more diffuse. Clinically, you may see that the patients have a higher head circumference. So, the second subtype to know about would be the delayed onset congenital normal pressure hydrocephalus. And when you see an image of one of these subtypes, it's going to be a little different than the imaging of NPH because the ventricles are going to be much larger, the sulcal enfacement is going to be more diffuse. And there are two specific subtypes that I'd like you to know about. The first would be long-standing overt ventriculomegaly of adulthood, or LOVA. And the second would be panventriculomegaly with a wide foramen of magendie and large discernomagna, which is quite a mouthful, so we just call it PAVUM. The importance of identifying these subtypes is that they may be amenable to different types of treatment. For instance, LOVA can be associated with aqueductal stenosis. So, these patients can get better when you treat them with an endoscopic third ventriculostomy, and then you don't need to move ahead with a shunt surgery. And then finally with idiopathic, that's mainly what we're talking about in this article with all of the imaging features. I think the important part about this is that you can have the features of DESH, or you can not have the features of DESH. The way to really define that would be how the patient would respond to a large-volume tap or a lumbar drain in order to define whether they have this idiopathic NPH. Dr Grouse: That's really helpful. And for those of our listeners who are so inclined, there is a wonderful diagram that lays out all these subtypes that you can take a look at. I encourage you to familiarize yourself with these different subtypes. Now it was really interesting to read in your article about some of the older techniques that we used quite some time ago for diagnosing normal pressure hydrocephalus that thankfully we're no longer using, including isotope encephalography and radionuclide cisternography. It certainly made me grateful for how we've come in our diagnostic tools for NPH. What do you think the biggest breakthrough in diagnostic tools that are now clinically available are? Dr. Switzer: You know, definitely the advent of structural imaging was very important for the evaluation of NPH, and specifically the identification of disproportionately enlarged subarachnoid space hydrocephalus, or DESH, in the late nineties has been very helpful for increasing the specificity of diagnosis in NPH. But some of the newer technologies that have become available would be phase-contrast MRI to measure the CSF flow rate through the aqueduct has been very helpful, as well as high spatial resolution T2 imaging to actually image the ventricular system and look for any evidence of expansion of the ventricles or obstruction of CSF flow. Dr Grouse: Regarding the scales that you had referenced earlier, do you think that we can look forward to more of these scales being automatically calculated and reported by various software techniques and radiographic interpretation techniques that are available or going to be available? Dr. Switzer: Definitely yes. And some of these techniques are already in development and used in research settings, and most of them are directed towards automatically detecting the features of DESH. So, that's the high convexity tight sulci, the focally enlarged sulci, and the enlarged Sylvian fissures. And separating the CSF from the brain tissue can help you determine where CSF flow is abnormal throughout the brain and give you a more accurate picture of CSF dynamics. And this, of course, is all automated. So, I do think that's something to keep an eye out for in the future. Dr Grouse: I wanted to ask a little more about the CSF flow dynamics, which I think may be new to a lot of our listeners, or certainly something that we've only more recently become familiar with. Can you tell us more about these advances and how we can apply this information to our evaluations for NPH? Dr. Switzer: So currently, only the two-dimensional phase contrast MRI technique is available on a clinical basis in most centers. This will measure the actual flow rate through the cerebral aqueduct. And so, in NPH, this can be elevated. So that can be a good supporting marker for NPH. In the future, we can look forward to other techniques that will actually look at three-dimensional or volume changes over time and this could give us a more accurate picture of aberrations and CSF dynamics. Dr Grouse: Well, definitely something to look forward to. And on the topic of other sort of more cutting-edge or, I think, less commonly-used technologies, you also mentioned some other imaging modalities, including diffusion imaging, intrathecal gadolinium imaging, nuclear medicine studies, MR elastography, for example. Are any of these modalities particularly promising for NPH evaluations, in your opinion? Do you think any of these will become more popularly used? Dr. Switzer: Yes, I think that diffusion tract imaging and MR elastography are probably the ones to keep your eye out for. They're a little more widely applicable because you just need an MR scanner to acquire the images. It's not invasive like the other techniques mentioned. So, I think it's going to be a lot easier to implement into clinical practice on a wide scale. So, those would be the ones that I would look out for in the future. Dr Grouse: Well, that's really exciting to hear about some of these techniques that are coming that may help us even more with our evaluation. Now on that note, I want to talk a little bit more about how we approach the evaluation and, in your opinion, some of the biggest pitfalls in the evaluation of NPH that you've found in your career. Dr. Switzer: I think there are three of note that I'd like to mention. The first would be overinterpreting the Evans index. So, just because an image shows that there's an elevated Evans index does not necessarily mean that NPH is present. So that's where looking for other corroborating evidence and looking for the clinical features is really important in the evaluation. Second would be misidentifying the focally enlarged sulci as atrophy because when you're looking at a brain with these blebs of CSF space in different parts of the brain, you may want to associate that to neurodegeneration, but that's not necessarily the case. And there are ways to distinguish between the two, and I think that's another common pitfall. And then third would be in regards to the CSF flow rate through the aqueduct. And so, an elevated CSF flow is suggestive of NPH, but the absence of that does not necessarily rule NPH out. So that's another one to be mindful of. Dr Grouse: That's really helpful. And then on the flip side, any tips or tricks or clinical pearls you can share with us that you found to be really helpful for the evaluation of NPH? Dr. Switzer: One thing that I found really helpful is to look for previous imaging, to look if there were features of NPH at that time, and if so, have they evolved over time; because we know that in idiopathic normal pressure hydrocephalus, especially in the dash phenotype, the ventricles can become larger and the effacement of the sulci at the convexity can become more striking over time. And this could be a helpful tool to identify how long that's been there and if it fits with the clinical history. So that's something that I find very helpful. Dr Grouse: Absolutely. When I read that point in your article, I thought that was really helpful and, in fact, I'm guessing something that a lot of us probably aren't doing. And yet many of our patients for one reason or other, probably have had imaging five, ten years prior to their time of evaluation that could be really helpful to look back at to see that evolution. Dr. Switzer: Yes, absolutely. Dr Grouse: It's been such a pleasure to read your article and talk with you about this today. Certainly a very important and helpful topic for, I'm sure, many of our listeners. Dr. Switzer: Thank you so much for having me. Dr Grouse: Again, today I've been interviewing Dr Aaron Switzer about his article on radiographic evaluation of normal pressure hydrocephalus, which he wrote with Dr Patrice Cogswell. This article appears in the most recent issue of Continuum on disorders of CSF dynamics. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.
In this episode of the Dr. Geo Prostate Podcast, Dr. Geo welcomes Dr. Alberto Vargas, Vice Chair of Oncologic Imaging at NYU Langone Health and expert in prostate cancer imaging.They dive deep into the evolving world of diagnostic tools—MRI, PET, CT, and PSMA scans—and how these technologies help detect, monitor, and guide treatment for prostate cancer. Dr. Vargas explains the difference between imaging modalities, when to use them, and how PSMA PET scans are changing the game in identifying recurrent and metastatic disease earlier than ever before.Key topics covered:MRI vs. PET vs. CT: what each scan shows and when it matters mostThe rise of PSMA PET for finding prostate cancer at extremely low PSA levelsWhy not all PET scans are the same, and how tracers like FDG, Axumin, and PSMA workThe potential future of prostate cancer diagnosis: fewer biopsies, more imagingLimitations, false positives, and how imaging results are interpretedThe role of imaging in both first-time diagnosis and recurrenceWhether you're a patient, caregiver, or clinician, this episode offers valuable insight into how imaging helps guide smart, proactive decisions in prostate cancer care.----------------Thank you to our partnersThe ProLon 5-Day Fasting Mimicking Diet is a plant-based meal program designed to provide fasting benefits while allowing food intake. Developed by Dr. Valter Longo, it supports cellular renewal, fat loss, and metabolic health through low-calorie, pre-packaged meals that maintain the body in a fasting state.Special Offer: Thank you for listening, you can purchase the ProLon kit for just $148 by using this link.We'd also like to thank our partner AG1 by Athletic Greens. AG1 contains 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, nervous system, immune system, energy, recovery, focus, and aging. All the essentials in one scoop. Enjoy AG1 by Athletic Greens.----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how you can live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook, Instagram Click here to become a member of Dr. Geo's Health Community.Improve your urological health with Dr. Geo's formulated supplement lines:XY Wellness for Prostate cancer lifestyle and nutrition: Mr. Happy Nutraceutical Supplements for prostate health and male optimal living.You can also check out Dr. Geo's online dispensary for other supplement recommendations Dr. Geo's Supplement...
In this episode of the Dr. Geo Prostate Podcast, Dr. Geo welcomes Dr. Alberto Vargas, Vice Chair of Oncologic Imaging at NYU Langone Health and expert in prostate cancer imaging.They dive deep into the evolving world of diagnostic tools—MRI, PET, CT, and PSMA scans—and how these technologies help detect, monitor, and guide treatment for prostate cancer. Dr. Vargas explains the difference between imaging modalities, when to use them, and how PSMA PET scans are changing the game in identifying recurrent and metastatic disease earlier than ever before.Key topics covered:MRI vs. PET vs. CT: what each scan shows and when it matters mostThe rise of PSMA PET for finding prostate cancer at extremely low PSA levelsWhy not all PET scans are the same, and how tracers like FDG, Axumin, and PSMA workThe potential future of prostate cancer diagnosis: fewer biopsies, more imagingLimitations, false positives, and how imaging results are interpretedThe role of imaging in both first-time diagnosis and recurrenceWhether you're a patient, caregiver, or clinician, this episode offers valuable insight into how imaging helps guide smart, proactive decisions in prostate cancer care.----------------Thank you to our partnersThe ProLon 5-Day Fasting Mimicking Diet is a plant-based meal program designed to provide fasting benefits while allowing food intake. Developed by Dr. Valter Longo, it supports cellular renewal, fat loss, and metabolic health through low-calorie, pre-packaged meals that maintain the body in a fasting state.Special Offer: Thank you for listening, you can purchase the ProLon kit for just $148 by using this link.We'd also like to thank our partner AG1 by Athletic Greens. AG1 contains 75 high-quality vitamins, minerals, whole-food sourced ingredients, probiotics, and adaptogens to help you start your day right. This special blend of ingredients supports your gut health, nervous system, immune system, energy, recovery, focus, and aging. All the essentials in one scoop. Enjoy AG1 by Athletic Greens.----------------Thanks for listening to this week's episode. Subscribe to The Dr. Geo YouTube Channel to get more content like this and learn how you can live better with age.You can also listen to this episode and future episodes of the Dr. Geo Podcast by clicking HERE.----------------Follow Dr. Geo on social media. Facebook, Instagram Click here to become a member of Dr. Geo's Health Community.Improve your urological health with Dr. Geo's formulated supplement lines:XY Wellness for Prostate cancer lifestyle and nutrition: Mr. Happy Nutraceutical Supplements for prostate health and male optimal living.You can also check out Dr. Geo's online dispensary for other supplement recommendations
En 2010, certains éditeurs cherchent encore à se faire une place au soleil des AAA en mettant de plus gros moyens dans de nouvelles licences. C'est le cas de THQ, qui mise sur le studio Vigil Games et son premier jeu : Darksiders. Mené par Joe Madureira, le projet vient se frotter à Kratos et Link, en proposant un jeu d'aventure rythmé par des combats sanglants et des puzzles plus ou moins pesants. Efficace, bien habillé par sa reprise des 4 cavaliers de l'apocalypse, il convainc largement à l'époque. Malheureusement, la licence connaitra un destin chaotique, prise dans les déconvenues de son éditeur. FDG profite de l'aventure de Guerre pour revenir sur la chute de THQ.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAME pour soutenir l'émission Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.
Vampire Survivors est de ces jeux qu'on n'a pas vus venir mais qu'on voit partout depuis. Développé d'abord comme un projet de framework, son créateur, Poncle, s'est tellement amusé dessus qu'il a fini par le sortir en tant que jeu solo. Et s'il aura fallu quelques vidéos de Youtubers célèbres pour lancer la vague, elle ne s'est jamais calmée. Sa formule qui consiste à enchainer les récompenses et les choix pour maximiser ses DPS n'a besoin que de quelques minutes pour démontrer son efficacité et accrocher le chaland. Et ses multiples défis sont là pour nous engager sur la durée. A moins de se porter sur un de ses nombreux clones, qui profitent des faiblesses assez évidentes du titre pour se tailler une part du gâteau. Retour sur la recette originale (ou presque) dans cet épisode de FDG.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAME pour soutenir l'émission. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.
Dans cet épisode, l'escouade de FDG plonge dans Helldivers 2, l'immense succès populaire du début de l'année 2024. Un deuxième opus qui reprend texto la formule du jeu d'origine sorti 10 ans plus tôt, mais en la transposant dans un TPS moderne. Il s'agit toujours de massacrer des bestioles et autres automatons sur l'autel de la Liberté, en évitant au possible les pertes alliées dues à des obus plus ou moins perdus. Un jeu pensé pour la coopération et le grind, qui brille moins par sa profondeur que par son sens du burlesque et de la pyrotechnie. Ce n'est pas la grande satire qu'on a pu faire de lui, mais le meilleur simulateur de stormtrooper ? Probablement.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAME pour soutenir l'émission. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.
Après la sortie compliquée du premier Alan Wake, il aura fallu 13 ans pour que Remedy remonte sa licence à la surface. La recette reste la même : un TPS classique pris entre le surnaturel et l'horreur psychologique. Mais cette suite va bien plus loin formellement, en usant (et abusant) de très nombreuses séquences filmées, des pubs, des concerts, des vlogs et autres superpositions d'images pour narrer son histoire. Le tout convoquant des références incessantes, à Lynch comme aux précédents titres du studio. Un méli-mélo qui peut rendre le titre attachant mais qui embourbe son gameplay déjà convenu dans un rythme laborieux et laisse finalement peu de place à celle ou celui qui tient la manette. Et qui en donne beaucoup, beaucoup à Sam Lake. FDG revient sur cet égo-trip à l'équilibre bien précaire.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAME pour soutenir l'émission. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.
Avant de passer en 2025, le trio de FDG remonte dans le temps de 30 années pour revenir sur Chrono Trigger. Un jeu qui tenait presque du fantasme à l'époque de sa sortie, puisqu'il réunissait les créateurs de Final Fantasy, Dragon Quest et Dragon Ball. Une “dream team” qui a donné vie à un J-RPG ambitieux et avant-gardiste, par sa structure construite autour du voyage dans le temps, son rythme ou son traitement des combats, intégrés directement dans l'espace de jeu. Une grande épopée à travers le temps qui nous mettait face aux conséquences de nos choix, et ce, même après l'avoir terminé une première fois. Pas étonnant qu'il soit devenu culte, et même considéré encore aujourd'hui comme un des meilleurs représentants de son genre. Une bien belle façon de terminer l'année.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAME pour soutenir l'émission. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.
Sometimes, fluctuating disabilities mean you have to pivot plans, and that's okay x 00:00 – Intro 03:52 – Arevya played Super Market Simulator, Botany Manor 05:30 – Steven Spohn and Mark Barlet are leaving AbleGamers 08:40 – FDG 2025 will have the theme "Accessible Worlds, United Through Play" 10:35 – Laura and Arevya have consulted on Sorry, We're Closed 12:05 – Arevya consulted on Life Below 14:43 – Lauras take on the PS5 PRO 19:15 – Laura has played Mario & Luigi Brothership, Super Mario Party Jamboree, Dragon Age: The Veilguard, and LEGO Horizon Adventures 36:25 – Where to find us
In today's episode, we delve into the world of PET scans and other imaging modalities crucial for accurate diagnosis and staging of breast cancer. We are joined by two incredible guests: Dr. Kiser, the Medical Director of Molecular Imaging for Carilion Clinic, and Pam Kohl, a patient advocate living with metastatic breast cancer.Dr. Kiser provides an in-depth explanation of PET scans, particularly focusing on FDG and FES (also known as Cerianna) PET scans. FDG-PET scans use radioactive glucose to highlight cancerous tissues, while FES-PET scans target estrogen receptors, making them highly specific for ER-positive breast cancer. Dr. Kiser emphasizes the revolutionary impact of these imaging techniques in both diagnostics and therapeutics.Pam shares her personal experience with breast cancer, highlighting the importance of advocating for oneself. Diagnosed with early-stage breast cancer in 2009, Pam experienced a recurrence in 2017, which led to a stage 4 metastatic diagnosis. Her story underscores the critical role of PET scans in detecting metastasis early and informing effective treatment plans. Pam's experience with FES-PET scans has been particularly transformative, allowing her medical team to tailor her treatment precisely to her cancer's characteristics.SURVIVINGBREASTCANCER.ORGAttend a free virtual SurvivingBreastCancer.org event:https://www.survivingbreastcancer.org/eventsFollow us on InstagramSurvivingBreastCancer.org: https://www.survivingbreastcancer.org/Breast Cancer Conversations: https://www.instagram.com/breastcancerconversations/About SurvivingBreastCancer.org: SurvivingBreastCancer.org, Inc. (SBC) is a federally recognized 501(c)(3) non-profit virtual platform headquartered in Boston with a national and global reach. Through education, community, and resources, SurvivingBreastCancer.org supports women and men going through breast cancer. We provide a sanctuary of strength, compassion, and empowerment, where those diagnosed with cancer unite to share their stories, learn invaluable coping strategies to manage wellness and mental health, and find solace in the unbreakable bond that fuels hope, resilience, and the courage to conquer adversity.Support the Show.
A new study finds insulin resistance and reduced glucose uptake in the heart is linked with early-onset atherosclerosis and heart issues. Sponsored: Support your Workout Sessions and Healthy Hydration with the Electrolyte + Creatine Combo by MYOXCIENCE: https://bit.ly/electrolyte-stix *Save 12% with code podcast at checkout Link to Video and Research: https://bit.ly/3UXLhal Research Mentioned: Devesa, A. et al. Cardiac Insulin Resistance in Subjects With Metabolic Syndrome Traits and Early Subclinical Atherosclerosis. Diabetes Care 46, 2050–2057 (2023). Time Stamps: 00:00 FDG = Fluorodeoxyglucose 00:30 Reduced glucose uptake in the heart is tethered to atherosclerosis. 01:20 LDL levels are not strongly associated with poor outcomes. 02:00 Your heart becomes insulin resistant. 03:05 Those with no glucose uptake in the heart had higher fasting glucose. 03:45 Those with more cardiovascular risk factors had lower LDL. 04:35 The heart can generate energy from fatty acids, carbs, and ketones. 05:00 Cardiac abnormalities are associated with metabolic syndrome. 07:00 Insulin resistance changes muscle and heart muscle. 09:16 Insulin resistance is associated with a progressive decrease of myocardial FDG uptake. 09:50 Cardiovascular risk increases with the decline of FDG uptake. 11:30 Your heart loses the ability to pump blood effectively as it loses ability to utilize different energy substrates. 12:40 Support your heart by supporting your metabolism.
Help us with a DONATION You can support and help the FDG With TC Dj (Live) Help us with a DONATION You can support and help the FDG by making a donation via bank transfer to the following coordinates: UNICREDIT Bank IT 87 S 02008 44101 000004613369 Reason: "donation to help young diabetics". Aiutaci con una DONAZIONE Puoi sostenere e aiutare la FDG facendo una donazione tramite bonifico bancario alle seguenti coordinate: Banca UNICREDIT IT 87 S 02008 44101 000004613369 Causale: “donazione per aiuto ai giovani diabetici”. https://www.fdgdiabete.it/
This audio is brought to you by Endress and Hauser, a leading supplier of products, solutions and services for industrial process measurement and automation. State-owned electricity utility Eskom will reduce planned maintenance to 3 000 MW during the upcoming winter season and will seek to keep unplanned breakdowns to below 14 000 MW in a bid to navigate the high-demand period with limited loadshedding. During the summer period, from September to the end of March, the utility set a target of restricting unplanned breakdowns to 14 500 MW during the high-maintenance summer months, when average planned maintenance levels of 7 000 MW were targeted. During those periods when breakdowns exceeded the target, loadshedding was typically implemented, at times at high levels of intensity of between Stage 4 and 6. While the winter outlook was still being finalised, Eskom Generation's Eric Shunmagum confirmed during a briefing on the implementation of the Energy Action Plan that it should be released later this month. He also confirmed that the diesel budget for the 2024/25 financial year would be below the R30-billion set aside for the operation of the Eskom and independent power producer open-cycle gas turbines in 2023/24; a budget that he confirmed had been marginally exceeded, without providing specifics. The diesel budget for the current financial year, meanwhile, would be communicated at a future briefing. Speaking amid a sustained period during which Eskom had not resorted to loadshedding, Shunmagum stressed that the winter plan, as with previous plans, would contain three scenarios, with the base scenario likely to indicate only limited loadshedding for the period from April to the end of August. He also insisted that Eskom Generation would work to ensure that breakdowns were kept below the 14 000 MW level to further reduce the threat of loadshedding. However, the coal fleet remained unreliable with intense recovery work still under way at six priority stations, including Majuba, Matla, Duvha, Kendal, Tutuka and Kriel, which had replaced Kusile on the list after Kusile's performance was deemed to have recovered following the introduction of temporary stacks. EAF TARGET MISSED Meanwhile, Electricity Minister Kgosientsho Ramokgopa confirmed that the Eskom fleet failed to achieve the 65% energy availability factor (EAF) target set by the board for the end of March, coming in at only 54.6%. The performance was even below the 56% EAF reported by Eskom in its previous financial year. Nevertheless, Shunmagum described the target as non-negotiable and insisted that the 65% to 70% target remained intact for the current financial year. Ramokgopa attributed the failure to achieve the EAF target to "aggressive planned maintenance" efforts, which he said were prioritised ahead of lifting the EAF to closer to 60%. "Planned maintenance increased from 9.3% in FY2023 to 12.0% in FY2024 reinforcing the commitment to execute the recovery plans and reduce plant risks," he said. The Minister also insisted that various additional capacity was scheduled to be added or returned to service over the coming five months, including: Medupi Unit 4 in August, where a second-hand generator was being installed after a unit was crippled by a fire incident in August 2021; Koeberg Unit 2, which is currently scheduled to return from an extended outage in September; and Kusile Unit 6, which is also currently scheduled to be synchronised to the grid in September. "In the next five months, we should be able to get 2 583 MW of new generation capacity [from Eskom]," Ramokgopa said. He also played down concerns that up to 2 100 MW of Kusile capacity would be unavailable from November, when the three units that are currently bypassing the flue-gas desulphurisation (FGD) plant using temporary stacks, were scheduled to start being reconnected to the FDG through the west stack. The west stack was rendered inoperable when Kusile's Unit 1 flue duct collapsed because of an unco...
This audio is brought to you by Endress and Hauser, a leading supplier of products, solutions and services for industrial process measurement and automation. State-owned electricity utility Eskom will reduce planned maintenance to 3 000 MW during the upcoming winter season and will seek to keep unplanned breakdowns to below 14 000 MW in a bid to navigate the high-demand period with limited loadshedding. During the summer period, from September to the end of March, the utility set a target of restricting unplanned breakdowns to 14 500 MW during the high-maintenance summer months, when average planned maintenance levels of 7 000 MW were targeted. During those periods when breakdowns exceeded the target, loadshedding was typically implemented, at times at high levels of intensity of between Stage 4 and 6. While the winter outlook was still being finalised, Eskom Generation's Eric Shunmagum confirmed during a briefing on the implementation of the Energy Action Plan that it should be released later this month. He also confirmed that the diesel budget for the 2024/25 financial year would be below the R30-billion set aside for the operation of the Eskom and independent power producer open-cycle gas turbines in 2023/24; a budget that he confirmed had been marginally exceeded, without providing specifics. The diesel budget for the current financial year, meanwhile, would be communicated at a future briefing. Speaking amid a sustained period during which Eskom had not resorted to loadshedding, Shunmagum stressed that the winter plan, as with previous plans, would contain three scenarios, with the base scenario likely to indicate only limited loadshedding for the period from April to the end of August. He also insisted that Eskom Generation would work to ensure that breakdowns were kept below the 14 000 MW level to further reduce the threat of loadshedding. However, the coal fleet remained unreliable with intense recovery work still under way at six priority stations, including Majuba, Matla, Duvha, Kendal, Tutuka and Kriel, which had replaced Kusile on the list after Kusile's performance was deemed to have recovered following the introduction of temporary stacks. EAF TARGET MISSED Meanwhile, Electricity Minister Kgosientsho Ramokgopa confirmed that the Eskom fleet failed to achieve the 65% energy availability factor (EAF) target set by the board for the end of March, coming in at only 54.6%. The performance was even below the 56% EAF reported by Eskom in its previous financial year. Nevertheless, Shunmagum described the target as non-negotiable and insisted that the 65% to 70% target remained intact for the current financial year. Ramokgopa attributed the failure to achieve the EAF target to "aggressive planned maintenance" efforts, which he said were prioritised ahead of lifting the EAF to closer to 60%. "Planned maintenance increased from 9.3% in FY2023 to 12.0% in FY2024 reinforcing the commitment to execute the recovery plans and reduce plant risks," he said. The Minister also insisted that various additional capacity was scheduled to be added or returned to service over the coming five months, including: Medupi Unit 4 in August, where a second-hand generator was being installed after a unit was crippled by a fire incident in August 2021; Koeberg Unit 2, which is currently scheduled to return from an extended outage in September; and Kusile Unit 6, which is also currently scheduled to be synchronised to the grid in September. "In the next five months, we should be able to get 2 583 MW of new generation capacity [from Eskom]," Ramokgopa said. He also played down concerns that up to 2 100 MW of Kusile capacity would be unavailable from November, when the three units that are currently bypassing the flue-gas desulphurisation (FGD) plant using temporary stacks, were scheduled to start being reconnected to the FDG through the west stack. The west stack was rendered inoperable when Kusile's Unit 1 flue duct collapsed because of an unco...
À la fin des années 2000, le cover shooter domine le jeu vidéo mainstream et son roi s'appelle Gears Of War 2. Après un premier épisode qui a posé toutes les bases, cette suite vient parfaire la formule conçue par Cliff Blezinski et les équipes d'Epic Games. Un shooter pensé pour une console grand public, où on prend ses positions, on vide ses chargeurs et on tronçonne du locuste en lâchant de punchlines plus ou moins élégantes. Et si ça paraît un peu désuet aujourd'hui, ce Gears 2 nous rappelle que ça ne fait pas si longtemps que les gros jeux s'appuient sur différents piliers de gameplay pour se renouveler. FDG revient sur l'Epic Games pré-Fortnite, mais bien pro-Lanzor.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAMERejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkN
En à peine 2 opus, la série Little Nightmares s'est déjà imposée comme une référence dans le genre "jeu d'aventure court, abordable et spooky". Bon. C'est vrai que la catégorie n'est pas encore bien chargée mais c'est aussi que les jeux du studio Tarsier proposent une formule calibrée, entre des puzzles légers, des séquences de cache-cache avec des monstres maladroits mais bien affreux et des courses-poursuites qui font monter l'adrénaline. Le tout dans des décors qui viennent chercher le petit gosse apeuré qui sommeille en chacun et chacune de nous. Et si ça reste perfectible, sur les mécaniques comme sur la narration, on ne peut nier l'efficacité de ces petits contes vidéo-ludiques macabres, surtout quand on voit leurs chiffres de ventes. On attend maintenant de voir la suite pour Tarsier, et comment Bandai Namco va exploiter la licence à l'avenir. L'équipe FDG sort son plus beau k-way jaune et s'engouffre dans ces petits cauchemars.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameSi vous réalisez un achat sur Top Achat, vous pouvez entrer le code créateur FINDUGAMERejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkN
Soluce, c'est le nouveau podcast JV co-créé par Hugo de la team FDG et Lucie Ronfaut, journaliste spécialisée dans les nouvelles technologies. C'est une mini-série de 5 épisodes, qui tente de replacer le Jeu Vidéo au sein de nos vie quotidiennes. C'est dispo partout et si vous aimez FDG, allez écouter ça ! https://shows.acast.com/soluce
Drs. Diwakar Davar and Ben Boursi discuss the role of the gut microbiome in the outcome of cancer immunotherapy and the prevention of immunotherapy-related adverse events, as well as compelling research on nutritional interventions to improve response to immune checkpoint inhibitors. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar. 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. Researchers have shown that microorganisms in the gut can impact the effectiveness of immunogenic chemotherapy for patients with cancer. Although microbial therapies for cancer are still at a very early stage of clinical development, compelling research in recent years has shown that changing the gut microbiome can help improve outcomes in patients receiving treatments for cancer enduring immune checkpoint inhibition. My guest today is Dr. Ben Boursi, a GI medical oncologist at the Sheba Medical Center at Tel Aviv University in Israel. Dr. Boursi is also an adjunct professor at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania. He joins me today to discuss his pivotal research on the role of the gut microbiome in mediating its effects on immunotherapy. And again, I want to highlight that we're recording this on October 9th, and as you may well know, many recent events over the last couple of days have happened in Israel, and so Dr. Boursi has joined us at a very difficult time. So, we're very grateful for him taking time out of his suddenly very busy schedule to join us at a time that is fraught for all. You'll find our disclosures in the transcript of this episode. You'll also find the disclosures of all guests on the podcast at asco.org/DNpod. Ben, it's great to have you on the podcast today. Thank you for being here at such a difficult time, sharing what will, I think, be a great episode. Dr. Ben Boursi: Thanks for having me, Diwakar. Dr. Diwakar Davar: Ben, the gut microbiome and its role in terms of mediating effects and side effects of cancer immunotherapy has gotten a lot of interest recently. You've done some fundamental work in this space. Why don't you briefly summarize for the audience, firstly, what is the gut microbiome and what are the major themes in relation to cancer immunotherapy? Dr. Ben Boursi: Well, the microbiome is the ecosystem of microorganisms, bacteria, phages, fungi, that are crucial for immunologic, metabolic and hormonal homeostasis of the host. In the last decade, we began to understand the central role of the gut and tumor microbiome in tumorigenesis, metastasis, treatment efficacy and toxicities, and in 2022, polymorphic microbiomes became one of the hallmarks of cancer, in addition to previous hallmarks that focused mainly at the cellular/genetic levels. The initial studies in mice models showed that therapeutic efficacy of immunotherapy depends on both the presence and composition of the microbiota (In germ-free or antibiotic treated mice, immunotherapy is ineffective), and following these studies, three observational studies in human patients showed that the gut microbiome can predict response to immunotherapy and that response to immunotherapy could be transferred to germ-free mice by fecal microbiota transplantation (FMT) from responding patients. These studies helped us to define three main research questions regarding the possible role of microbial modulation in cancer treatment. First, can microbial modulation overcome resistance to immunotherapy, both primary and secondary resistance? And this question was the focus of the initial proof of concept studies. Second, can microbial modulation improve response to immunotherapy in treatment-naive patients? And third, can microbial modulation prevent or treat immune related adverse events? The initial positive results of clinical trials also led to additional questions. For example, can microbial modulation induce anti-tumor immune response even in non-immunogenic tumors? And it is important to note that there are many ways to modulate the microbiota, but so far, the only reliable way that showed positive results is fecal microbiota transplantation that allows the transfer of the entire microbiota both in terms of composition and relative abundance. Dr. Diwakar Davar: That's great. Essentially with the trials that I think the data sets that you're referencing of course, are papers by Jennifer Wargo, Thomas Gajewski, and Lawrence Zitvogel, looking at the role of gut microbiota in several different cancers, primarily immune checkpoint sensitive tumors such as melanoma, non-small cell lung cancer and kidney cancer. And then the work from several different groups showing that essentially proof of concept experiments can be done to try to change this, certainly preclinically, and now we know that that can be done clinically. So, I guess the failure rates of immunotherapy in some patients are quite high. And we know that the microbial composition can change the likelihood to respond to immunotherapy based on all these trials. And actually, even going back to 2015, we had two seminal papers that looked at the role of CTLA-4 blockade as well. But subsequently, many years after that, 7 years after 2015, and certainly 3 years after 2018, when the three observational PD-1 papers were published, there were 2 pivotal trials in PD-1 advanced or refractory melanoma. They demonstrated that changing the gut microbiome can reprogram the immune system to attack tumors. So, there were 2 separate trials, both published the same issue of Science. One trial was led by your group at Sheba, and another one's led by us, the University of Pittsburgh. Why don't you summarize both studies for our audience. Dr. Ben Boursi: So, both studies were Phase I clinical trials of FMT in metastatic melanoma patients who failed immunotherapy. Recipients were metastatic melanoma patients that progressed on at least one line of anti PD-1 and in BRAF mutated patients, BRAF inhibitors as well. Donors in the Sheba study were metastatic melanoma patients with durable complete responses to immunotherapy for at least one year, and in the Pittsburgh study, you also included patients with durable partial responses of more than two years as donors. It is important to note that each fecal transplant in both studies was composed of a single donor. Prior to transplantation, we performed a microbiome depletion phase using a combination of two antibiotics, vancomycin and neomycin. The goal of this phase was to assist in engraftment (by avoiding colonization-resistance by recipient bacteria) and to “reset” the immune system, which may remind some people of the logic behind bone marrow transplantation. In the Pittsburgh study, there was no bacterial eradication with antibiotics, mainly because of studies showing that response to immunotherapy is lower following antibiotic treatment. Both studies performed FMT through colonoscopy. At Sheba, we also performed maintenance FMT using capsules in order to keep the donor's microbial composition. After the initial FMT, both studies reintroduced the same immunotherapy in which the patient progressed in the past. Clinically, we have seen a 30% response rate with durable, complete and partial responses, and in the Pittsburgh study, there was a 20% response rate and 40% disease control rate. Both studies showed following FMT, immune response in the gut and in the tumor, and tumors that were immune deserts prior to FMT became infiltrated with lymphocytes. Interestingly, in our study, there were no moderate to severe immune related adverse events following FMT and reintroduction of immunotherapy. And this is despite the fact that five of the patients had significant side effects during previous rounds of the same immunotherapy. Dr. Diwakar Davar: So essentially, in these very early proof of concept studies, what I think is pretty remarkable is that obviously the sample sizes were very small, but remarkably, patients that appeared to respond, responded in a setting in which they were not expected to respond. So, the probability of a patient responding to attempt at giving PD-1 in patients who were PD-1 relapse refractory is on the order of about 7%, based on an FDA analysis by Viva et al. And here, two separate studies, two independent studies, investigators had not known that each paper was being published, remarkably similar results clearly demonstrating that this is perhaps one of the best pieces of evidence to suggest that microbiome modulation may actually truly be effective in reversing PD-1 refractoriness. More recently, our colleague Dr. Bertrand Routy at University of Montreal has done a proof of concept trial in evaluating the use of healthy donor fecal microbiota transplant in addition to anti PD-1 monotherapy in PD-1 naive metastatic melanoma. In this study, published in Nature Medicine a few weeks ago, his group reported an objective response rate of 65%. What are your thoughts about this study? And specifically, what are your thoughts about some of the pharmacodynamic and translational results that were demonstrated? Dr. Ben Boursi: This is a very interesting question, because in both the Sheba and the University of Pittsburgh studies we chose responding patients as donors. We thought that by using these patients, we provide beneficial bacteria that enhance responses to immunotherapy through several mechanisms (molecular mimicry, immunomodulatory bacterial metabolites, modulation of immune checkpoint expression, and much more), and here in the Routy paper, the researchers used FMT from healthy donors without any selection for specific beneficial bacteria, and they demonstrated a similar effect on overall response rate. So maybe FMT works actually through reducing colonization by deleterious bacteria? Another question that we should ask is whether we need to choose donors differently when we use microbial modulation in treatment resistant patients compared to treatment-naive patients? Moreover, a previous meta-analysis of FMT studies across indications that was conducted by the group of Dr. Nicola Segata, demonstrated that recipients with better engraftment were more likely to experience clinical benefit, and that increased engraftment was mainly observed in individuals receiving FMTs through multiple routes, colonoscopy and capsules, as well as recipients that received antibiotics prior to FMT. But in Routy's trial, they not only used healthy donors, they performed bacterial cleansing only prior to FMT instead of bacterial eradication with antibiotics, and used FMTs through colonoscopy only, and they didn't give maintenance FMT. Of course, such an approach is much more feasible in the clinical setting and is relevant for designing future clinical trials. Dr. Diwakar Davar: So, many differences, relatively few similarities, but I guess one interesting point is that of engraftment, which is that in your paper, our paper, and certainly in Bertrand's paper, it is very interesting that engraftment appears to be a key pharmacodynamic biomarker of microbiome modulation. And certainly, the analogy that you used earlier, which is that it's very similar to what happens in a stem cell transplant, which is that if there's no take, there's probably not going to be any effect. So that's very interesting that engraftment is emerging as a key PD biomarker of essentially the success of any kind of microbiome modulation across multiple different settings. Now, we've heard of certainly defined microbial consortia, of cultivated species, as an alternative gut microbiome modulation strategy that balances the benefits of the ecological complexity of FMT with the scalability and practicality of probiotics. Do you think we are ready to design consortia? Dr. Ben Boursi: So to date there are several probiotics that use a single bacteria and several microbial consortia that were evaluated in clinical trials, and as you mentioned, they may offer more tractable solutions for widespread clinical use. If we begin with the single bacteria probiotics, two phase 2 clinical trials found that administration of the butyrate producing probiotic clostridium butyricum 588 (CBM588) to immunotherapy naive patients with metastatic renal cell carcinoma led to markedly better immunotherapy responses, although the probiotic had a minimal effect on the composition of the microbiota, and the control arm of the trial responded worse than expected. In addition, in preclinical studies, probiotic strains of lactobacillus and bifidobacterium have been shown to enhance immune control of transplanted tumors and to augment anti PD-1 activity. However, a clinical trial in patients with metastatic melanoma found that the use of lactobacillus or bifidobacterium probiotics was associated with reduced microbiota diversity and worse responses to anti PD-1. So here the conclusion is that when we try to design probiotics, we should not focus only on the composition since other factors, such as the relative abundance also matter. Too much of a beneficial bacterial species may potentially be worse than having a balanced and diverse microbiota. For example, a recent study of patients with non-small cell lung cancer receiving immunotherapy found that patients with a detectable Akkermansia muciniphila in their gut microbiota (this is a beneficial bacteria) responded well to treatment, but those with relative abundance of Akkermansia muciniphila greater than 5% responded worse than patients lacking Akkermansia, and this is due to the mucolytic effect of the bacteria. So, the use of rationally designed consortia may be better than a single probiotic strain. And there are currently 3 main microbial consortia that are being evaluated: the SER-401, a bacterial consortium enriched with clostridium, led in a randomized controlled trial to reduced response to immunotherapy compared to placebo control in first line metastatic melanoma patients, potentially due to a confounding effect of a vancomycin pretreatment; MET4 is a 30 bacteria consortium that was shown to be safe and to alter the gut microbiota and serum metabolome of immunotherapy naive patients. Here, the initial study was underpowered to determine the effect on treatment efficacy; And finally, VE800 is an immunotherapy enhancing 11-bacterial consortium that is currently being evaluated in phase 1 and 2 clinical trials, and we are looking forward to see the results with this agent. Dr. Diwakar Davar: So I guess where we are right now is that social design is clearly difficult because of all the reasons you've mentioned. The SER-401 data and the MET4-IO trials certainly give us pause for thought. Certainly, no pharmacodynamic changes that were seen with SER-401, MET4-IO did result in pharmacodynamic shifts metagenomically, but neither trial was positive. And certainly, the VE800 trial, which has been ongoing now for several years, and the lack of publicly reported data certainly doesn't suggest that there's a huge efficacy signal. So consortias, at least at this point, certainly do not appear to be having a significant effect, though we don't know what might happen in the future. Data from multiple groups has shown that gut microbial composition influences the development of immune related adverse events (irAEs) in both PD-1 and combination PD-1 and CTLA-4 treated patients. Unsurprisingly, as a result, there have been attempts made at evaluating the role of fecal microbiota transplants to treat refractory immune related adverse events and very specifically immune checkpoint associated colitis or IMC. So, Dr. Yinghong Wang, who is the chair of the Immunotherapy Toxicity Working Group at the University of Texas MD Anderson Cancer Center has been very prominent in this space, and in a recent paper published in Science Translational Medicine, which is a follow up paper to her early work in Nature Medicine, she reported that HDFMT, healthy donor fecal transplantation, was very efficacious in feeding early refractory immune checkpoint colitis. So, what are your thoughts on this approach and how important is this space and where else might it be efficacious? Dr. Ben Boursi: When I talked about the Sheba clinical study, I mentioned the possible role for microbiota modulation in the prevention of immunotherapy related adverse events in general, not only colitis. But the study by Dr. Yinghong showed that FMT can actually treat immune-related colitis refractory to steroids and anti-TNF. Now, this approach is probably relevant not only for immune related colitis, but also to other immune related adverse events. We can define certain bacterial species that may be associated with different immune related events. For example, streptococci can be associated with immune related arthritis. And maybe in the future we won't need to use FMT, but we will rather be able to target these specific immunogenic strains by narrow spectrum antibiotics or phages. The main challenge would be to develop microbiotic targeting interventions that reduce immune related adverse events without compromising therapeutic efficacy. Now, is microbial modulation relevant only for toxicity from immune checkpoint inhibitors? So, the answer is ‘no'. We know mainly from animal models of hematopoietic cell transplantation, CAR T, and immune agonist antibodies that antibiotic-treated or germ-free mice have markedly reduced immunotoxicity, such as graft versus host disease, cytokine release syndromes, and more. It is also worth mentioning that microbial modulation is relevant not only for reducing toxicity from immunotherapy, but also from chemotherapy and other anticancer modalities. And the best example is the gastrointestinal toxicity of irinotecan that is mediated by the bacterial beta-glucuronidase. And here the targeting may even be a bit less complex. Dr. Diwakar Davar: So, what we take away from that is that starting with actually your paper originally, and papers to be produced, immune-related adverse events can be prevented using microbiome modulation with FMT, and Dr. Wang's data suggesting that eventually FMT can be used to eradicate highly refractive colitis, again, this is important to keep in mind that this approach is not yet FDA-approved. It's being done under IND. It's not currently something that is a certain standard of care. One interesting area of drug development is that there's a French microbiome company named MaaT Pharma where they have an agent that is a very interestingly a pooled microbiome product from multiple different donors. Again, the trials in both Israel and Pittsburgh used individual donors. This is a pooled donor construct. The lead candidate is actually graft versus host disease. The trial is the ARES trial, A-R-E-S, as in the Roman god of war. This trial is actually ongoing in Europe, and I believe there's some effort to try to see whether or not it's going to be a trial that can be done in the United States as well. So, at this point in time, again, we don't know whether or not there are any developmental approaches from a pharmaceutical company in the United States, but certainly this is definitely an area of interest. So microbial therapies are still relatively early. It's going to be interesting to see how the advanced field of nutritional interventions provide an appealing method for modulating the gut microbiome due to the excellent safety profile, cost effectiveness and noninvasiveness. And certainly, if you are what you eat and your bacteria are what they eat, which goes down to our diet, there's enough rationale to believe that certain nutritional interventions can have an effect via the intermedial gut microbiota modulation. Holistic dietary changes and or supplementation specific nutrients such as prebiotics could therefore be utilized to specifically shape the population of beneficial microbes and shift the immune microbiota landscape. Now, we have seen in data published by several of our colleagues that in patients with cancer, high fiber intake is associated with greater microbial diversity, greater abundance in fiber fermenting microbes such as members of the Ruminococcaceae family, and these are all associated with the response to checkpoint inhibitor therapy. So, what do you think about nutritional interventions? Do you want us to briefly summarize data regarding nutritional data and where it stands in cancer at his time? And can you speculate as to how effective this might be in the context of patients with cancer? Dr. Ben Boursi: So, let's begin with diet. A growing number of clinical and preclinical studies suggest that specific dietary interventions such as a high fiber diet can not only improve response to immune checkpoint blockers, but also reduce immunotoxicity such as graft versus host disease. And there are many other diets that are being tested such as ketogenic diets and intermittent fasting. And the effects of diet may be mediated by both microbiota-dependent and microbiota-independent mechanisms. The limitation of this approach is that changes to the microbiota induced by diet are generally quite variable between patients and can depend on an individual's microbiota prior to intervention. And patient compliance is also a concern, particularly in the very strict diets. Now, regarding high fiber diets, several large cohorts of melanoma patients from the US, Australia, and the Netherlands demonstrated how a high fiber diet modulates the microbiome and results in a better response to immunotherapy, better progression-free survival. Additional studies that were presented at AACR in 2023 showed that high fiber dietary interventions, in which patients received a fiber-enriched diet for six weeks, was feasible and that the high fiber diet resulted in a rapid shift in the gut microbiota toward fiber-responsive short chain fatty acid-producing taxa and a shift of the metabolome, with increase in the short chain fatty acid acetate, Omega-3, Omega-6, polyunsaturated fatty acid, and tryptophan metabolites. Prebiotics can also promote the growth of beneficial microbial species in the gut by providing targeted nutrition. And one example of a prebiotic that was shown to enhance immunotherapy efficacy in mouse models is castalagin, which is isolated from the camu-camu berry. Castalagin directly binds the outer membrane of ruminococci and promotes their growth, which has been shown to increase the CD8-positive T-cell activity and anti-PD-1 efficacy. Now, since prebiotics rely on the presence of beneficial taxa already in the host microbiota, symbiotics, which refers to the administration of the appropriate prebiotic and probiotic together, may prove in the future to be more effective than using either separately. Dr. Diwakar Davar: Certainly, these dietary interventions can be very exciting and certainly we do know of several colleagues who are doing these diet interventions, though compliance with any kind of dietary intervention may be a challenge that decides how effective such an approach is going to be. So microbial therapies in general are still at a relatively early stage of development. And it'll be exciting to see how they advance. What approaches are you excited about? What is on your radar? Dr. Ben Boursi: There are many exciting works that are currently ongoing, and to emphasize just a few: there are many clinical trials in immunogenic tumors, in addition to melanoma, for example, renal cell carcinoma, and non-small cell lung cancer, that also evaluate different modulation protocols. We should remember that one size does not fit all, and different tumors have different microbiomes. We have a project in collaboration with MD Anderson in MSI-high patients with exciting initial results. Another study that was initiated at Sheba is using microbial modulation in order to improve TIL therapy (to overcome resistance to TIL and T-cell exhaustion). There are also studies that try to change the pharmaco-microbiome, for example, to eradicate bacteria that inactivates the chemotherapy agent, gemcitabine, in pancreatic cancer patients. And there are groups that try to identify recipients that will respond to microbial modulation and to generate better donor-recipient matching algorithms. There are already signatures like TOPOSCORE that was presented at ASCO 2023 that try to predict response to immunotherapies through the ratio between harmful and beneficial bacteria. Now, there's also more basic science work, for example, bacterial engineering. There was a wonderful study from the Fischbach group in Stanford that demonstrated how Staphylococcus epidermidis engineered to express melanoma tumor antigens was able to generate a systemic tumor-specific response in mice models when applied topically; functional imaging of the microbiome, for example, FDG uptake in the colon can reflect microbial diversity and response to immunotherapy; works that characterizes other microbiomes such as the urinary and skin microbiomes, and their interaction with the gut microbiome; and studies of the nonbacterial component of the microbiome, mainly phages and fungi. But for me, the most important word should probably be collaboration, because without joining forces internationally, we won't be able to understand the human metaorganism, the variations according to geography, ethnicity, lifestyle, diets, and much more in the microbiome. And this is crucial in order to really understand the complex tumor ecological niche within the human host. Dr. Diwakar Davar: I think one of the key points that you just mentioned is collaboration. That's going to be very, very critical as we move this forward for many reasons, including the unexpected impact of geography upon the composition of the gut microbiome in work that has been published by many groups, but also including ours in a paper that we published about a year ago now. So, Dr. Boursi, thank you for your great work in this area. Thank you for sharing your insights with us today on the ASCO Daily News Podcast. This is a very difficult time for all of you and your colleagues in Israel, and we thank you so much for taking such a great deal of time out of your busy workday to spend some time with us. Dr. Ben Boursi: Thank you very much. Dr. Diwakar Davar: Thank you to all our listeners today. This is a very exciting area. This is an area where we are discovering more every day than we knew just up until the day prior. You will find the links to the studies that were discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take the time to rate, review, and subscribe wherever you get your podcast. 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. Guests' 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 Dr. Ben Boursi Follow ASCO on social media: @ASCO on Twitter 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. Ben Boursi: No relationships to disclose.
El Maestro Speaks with Freddie of @Fdg stages. Freddie is a vlogger/content creator who focuses on creating content that highlights Igorot cultures and tradition. He also owns the #badthewrong cafe in La Trinidad Benguet #igorotPodcast #kankanaeyPodcast #podcast #elmaestrspeaks #torogitalks #FDGSTAGES Don't forget to check the Sponsors of this Podcast by clicking the Link below.. This podcast is sponsored by the following. Check them out by clicking the link: 1. Millennial TECH. https://www.facebook.com/melltech/ 2. Cyspace Tech https://www.facebook.com/cyspacetech/ 3. MONAPHLORE's EGG POULTRY https://www.facebook.com/MonaPhloreEggPoultry/ 4. BMEP damdamag/local https://www.facebook.com/igorotlocalfilmmaker/ 5. Joemar P. Sacpa https://www.facebook.com/joemar.pasuli 6.Frederick Wallang https://www.facebook.com/frederick.wallang 7. CarlTech Repairs https://www.facebook.com/CarlNgalides. 8. Dem's Auto Performance +639503867369 --- Send in a voice message: https://podcasters.spotify.com/pod/show/el-maestro-speaks/message
On vous attend ce samedi 6 mai au Reset Bar à Paris (Châtelet) à partir de 17h ! Le lieu est réservé, il suffit de dire que vous venez pour la soirée FDG. A bientôt !
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.13.528352v1?rss=1 Authors: Inibhunu, H., Chameh, H. M., Skinner, F., Rich, S., Valiante, T. A. Abstract: Discerning the contribution of specific ionic currents to complex neuronal dynamics is a difficult, but important, task. This challenge is exacerbated in the human setting, although the widely-characterized uniqueness of the human brain as compared to preclinical models necessitates the direct study of human neurons. Neuronal spiking frequency preference is of particular interest given its role in rhythm generation and signal transmission in cortical circuits. Here, we combine the frequency-dependent gain (FDG), a measure of spiking frequency preference, and novel in silico analyses to dissect the contributions of individual ionic currents to key FDG features of human L5 neurons. We confirm that a contemporary model of such a neuron, primarily constrained to capture subthreshold activity driven by the hyperpolarization-activated cyclic nucleotide gated (h-) current, replicates key features of the in vitro FDG both with and without h-current activity. With the model confirmed as a viable approximation of the biophysical features of interest, we applied new analysis techniques to quantify the activity of each modeled ionic current in the moments prior to spiking, revealing unique dynamics of the h-current. These findings motivated patch-clamp recordings in analogous rodent neurons to characterize their FDG, which confirmed that a biophysically-detailed model of these neurons captures key inter-species differences in the FDG. These differences are correlated with distinct contributions of the h-current to neuronal activity. Together, this interdisciplinary and multi-species study provides new insights directly relating the dynamics of the h-current to neuronal spiking frequency preference in human L5 neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.25.525587v1?rss=1 Authors: Peters-Founshtein, G., Gazit, L., Naveh, T., Domachevsky, L., Korczyn, A., Bernstine, H., Groshar, D., Marshall, G., Arzy, S. Abstract: Orientation is a fundamental cognitive faculty, allowing the behaving self to link his/her current state to their internal representations of the external world. Once exclusively linked to knowledge of the current place and present time, in recent years, the concept of orientation has evolved to include processing of social, temporal, and abstract relations. Concordantly with the growing focus on orientation, spatial disorientation has been increasingly recognized as a hallmark symptom of Alzheimers disease (AD). However, few studies have sought to explore disorientation along the AD continuum beyond the spatial domain. 51 participants along the AD continuum performed an orientation task in the spatial, temporal and social domains. Under functional magnetic resonance imaging (fMRI), participants determined which of two familiar places/events/people is geographically/chronologically/socially closer to them, respectively. A series of analyses revealed disorientation along the AD-continuum to follow a three-way association between (1) orientation domain, (2) brain region, and (3) disease stage. Specifically, participants with MCI exhibited impaired spatio-temporal orientation and reduced task-evoked activity in temporoparietal regions, while participants with AD dementia exhibited impaired social orientation and reduced task-evoked activity in frontoparietal regions. Furthermore, these patterns of hypoactivation coincided with Default Mode Network (DMN) sub-networks, with spatio-temporal orientation activation overlapping DMN-C and social orientation with DMN-A. Finally, these patterns of disorientation-associated hypoactivations coincided with patterns of fluorodeoxyglucose (FDG) hypometabolism and cortical atrophy characteristic to AD-dementia. Taken together, our results suggest that AD may constitute a disorder of orientation, characterized by a biphasic process as (1) early spatio-temporal and (2) late social disorientation, concurrently manifesting in task-evoked and neurodegenerative changes in temporoparietal and parieto-frontal brain networks, respectively. We propose that a profile of disorientation across multiple domains offers a unique window into the progression of AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Exserv, Hugo et Maxime vous présentent le programme de FDG pour 2023 ! Au menu : un revirement pour la chaîne Twitch, un nouveau palier à atteindre pour la saison 6, l'annonce de la Blackliste III et une surprise pour fêter les 100 épisodes en Mai. On vous explique tout ça rapidement, merci de nous soutenir sur Patreon pour faire vivre l'émission jusqu'à l'épisode 200 ! Le lien du formulaire pour la 100ème : https://docs.google.com/forms/d/e/1FAIpQLSccVTB--mWbMUlV1E_9lbXy0oNOhcW2uanoYZ8mdf3WcnezlA/viewform Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkN
Diffuse Large B-Cell Lymphoma or DLBCL is the most common type of lymphoma. Much progress has been made in treatment of the disease lately, particularly with emergence of CAR T-cell therapy, but not all patients are benefiting from it. This episode of Cancer Topics features Drs. Loretta Nastoupil and Chijioke Nze exploring treatment approaches for two cases of refractory DLBCL: a 60-year-old man with no comorbidities (1:30) and a 39-year-old woman with HIV (18:35). The guests also discuss improving patient access to CAR T-cell therapy and managing its toxicities (10:35), as well as emerging therapies for DLBCL (14:30). To learn more about management of refractory DLBCL, check out the ASCO course linked bellow. Guest Disclosures:Loretta Nastoupil, MD: Honoraria – Gilead Sciences, Novartis, Bayer, Janssen Oncology, TG Therapeutics, Bristol-Myers Squibb, ADC Therapeuitcs, Morphosys, Epizyme, Genmab, Takeda, Genentech/Roche; Research Funding – Janssen Biotech, Celgene, Genentech/Roche, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Chijioke Nze, MD, MPH: No Relationships to Disclose Resources: ASCO Course: Second-line Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma (Free to Full and Allied ASCO Members) ASCO Podcast: Cancer Topics - New Therapies for Lymphoma (Part 1) ASCO Guideline: Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor (CAR) T-Cell Therapy ASCO Article: Navigating the Evolving Treatment Landscape of Diffuse Large B-Cell Lymphoma If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Loretta Nastoupil: So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing a refractory disease, and potentially succumbing to the lymphoma. Hello, my name is Dr. Loretta Nastoupil, I'm an Associate Professor and Deputy Chair of the Department of Lymphoma and Myeloma, at the University of Texas MD Anderson Cancer Center. Welcome to this ASCO Education podcast episode. It's my pleasure to welcome Dr. Chijioke Nze. Dr. Chijioke Nze: Hello, everyone. I'm Dr. Chijioke Nze, a Hematology/Oncology fellow at MD Anderson, I'll be co-hosting this episode with Dr. Nastoupil. Dr. Loretta Nastoupil: We've seen notable advances in diffuse large B-cell lymphoma research lately, with novel treatments including CAR T-cell therapy, offering the prospect of long-term remission for some patients, yet many patients are not even receiving second-line or later therapy, and even fewer are treated beyond the second line. How do you approach a patient with refractory diffuse large B-cell lymphoma? In today's episode, we'll explore strategies for management of refractory diffuse large B-cell lymphoma through two patient cases. So, Dr. Nze, walk us through our first case. Dr. Chijioke Nze: Our first case is Frank. Frank is 60 years old and has no comorbidities. He presented with severe back pain in September 2021, and was evaluated locally. He had a CT scan that showed retroperitoneal mass, prompting further evaluation. He had a biopsy of the left retroperitoneal mass in November 2021, which was consistent with diffuse large B-cell, germinal center B-cell of phenotype Ki-67 of 90%. He had a subsequent PET-CT scan, which showed a large conglomerate, and invasive left retroperitoneal hypermetabolic mass with satellite nodularity and contiguous bulky retroperitoneal adenopathy. He had bulky, FDG-avid metastatic retrocrural and intrathoracic adenopathy as well. He was treated with R-CHOP for six cycles, and at the end, achieved complete remission. He had a PET-CT a year later that showed new and worsening intensely FDG-avid abdominal adenopathy. This was new from a PET scan he'd had in January 2022 of the same year. He had a biopsy of this retroperitoneal adenopathy, which was consistent with relapsed diffuse large B-cell germinal center phenotype, also Ki-67 of 90%. Locally, he was treated with ICE, times five cycles, and had a follow-up CT scan at the end, which showed persistent bulky nodal disease with periaortic regional nodes with double 5, consistent with persistent disease. He also was found to have new and more conspicuous nodes in other areas as well. He presented for his first visit at MD Anderson in September 2022. Dr. Nastoupil, when you see a patient like this coming into your clinic, what's your typical approach? Dr. Loretta Nastoupil: For a diffuse large B-cell lymphoma, we are always hoping for cure with frontline rituximab, containing anthracycline-based chemotherapy. And so, it's always a gross disappointment when patients experience relapse. The timing of that relapse right now informs our current approach. And the reason I mention that, is because there have been three large randomized studies conducted and reported out just in the last year demonstrating that CAR T-cell therapy is the preferred option for patients who experience either primary refractory disease, or relapse within 12 months. And that is because they resulted in better outcomes than standard salvage-based chemotherapy and high-dose therapy autotransplant in the setting of chemosensitive disease. I have to acknowledge, of the three studies that were done, two were positive trials, so that's why currently, we have axi-cel or Axicabtagene ciloleucel, or Lisocabtagene maraleucel, and not tisa-cel or Tisagenlecleucel, as CAR T-cell therapy options. And again, that's because two of the three studies were positive trials. Now, the challenge is why would we have two positive studies in one negative trial? There are a lot of caveats to how those studies were conducted, but I think one of the biggest important lessons to be gained is that if you're going to consider CAR T for these high-risk patients, you want to do it as soon as possible, because that delay from identifying CAR T as a preferred option to actually infusing cells in a disease-- in a case particularly like this, where patients may have bulky, aggressively-behaving disease - that prolonged time may actually have an impact on outcomes. Dr. Chijioke Nze: Excellent. Thank you. So, you've mentioned he had an early relapse. How would you define early relapse in this patient population? Dr. Loretta Nastoupil: Thinking back to how we've been approaching diffuse large B-cell lymphoma over the last two decades, the PARMA study, which was done prior to Rituximab, suggested that for patients who had chemosensitive disease to a platinum-based salvage chemotherapy, which generally, was at least a partial response on CT, if they went on to high-dose therapy autologous stem cell transplant, 50-60% of those patients could anticipate cure. Whereas for the folks who continued on salvage chemotherapy, 10-20% of those patients had favorable outcome. So, we generally do try salvage-based chemotherapy, and for patients with chemosensitive disease, go on to high-dose therapy autotransplant. However, in the modern era where we've approached patients who've had rituximab as part of their frontline therapy, at least two studies - the ORCHARD study, and the CORAL study suggested that only 20% of patients who relapse in the post-rituximab era, particularly within 12 months, were successfully salvaged with platinum-based chemotherapy and high-dose therapy autologous stem cell transplant. Now, fortunately for patients who fail salvage, we have had CAR T-cell therapy as an option based off of three pivotal phase II studies, demonstrating about 40% of patients could anticipate a cure with CAR T-cell therapy. So, it only made sense to try and move that therapy up into second line, and the preferred population was those that had progressed within 12 months of frontline rituximab and anthracycline-based chemo. Now, to qualify for those studies, patients had to be considered fit for the control arm, which was salvage and auto transplant. Nonetheless, I do think for a patient like this, who's 60, without any other significant comorbidities, whose biggest challenge to longevity of life is his aggressive lymphoma, CAR T-cell therapy should be considered as soon as possible for this patient. Dr. Chijioke Nze: Is there still a role for high-dose therapy and autologous transplant in the new era, given the efficacy shown with CAR T-cell therapy? Dr. Loretta Nastoupil: I think there is. And the reason why I say that is, the trials that were done really did focus on the highest-risk patients, which were those with primary refractory disease or those who progress within 12 months of frontline. Now, there are patients that will have later relapse. And so, I do think for those patients, particularly those who are young and otherwise fit, should be approached first with a platinum-based salvage chemotherapy, in the setting of chemosensitive disease, proceed onto high-dose therapy and autologous stem cell transplant. Now, what do we do for those patients who have a late relapse but are otherwise older, or who have comorbidities that would make them suboptimal candidates for the high-dose therapy preceding stem cell transplant? I have a couple other options for those patients - so, there was a trial done with liso-cel for patients who were otherwise older, or not fit for intensive therapy. It's a single-arm phase II without a randomized comparison, but also demonstrated that liso-cel in second-line, later relapsed patients who are not fit for intensive therapy, resulted in comparable outcomes to what we would anticipate on that third-line or later setting. We also have other non-CAR T-cell therapy options, such as tafasitamab, which is a naked CD19 antibody, which has been combined with lenalidomide in the L-MIND study, again, for patients without primary refractory disease and who would not be appropriate candidates for intensive therapy. So, I do think we have alternative options, it's just when we look at the totality of the data right now, my conclusion is that CAR T-cell therapy, particularly for high-risk patients, is the most likely chance to result in cure. Dr. Chijioke Nze: Excellent. In a patient who we are considering CAR T-cell therapy, what are some of the short-term and long-term consequences, or toxicities that we should worry about? Dr. Loretta Nastoupil: One of the challenges right now with CAR T, and why it's still only available in specialized centers, is the acute toxicity, which is really a derivative of its mechanism of action. We take patients' own T-cells, we use a viral vector to introduce extracellular receptor, but also a co-stimulatory molecule. So, once these cells engage their antigen, sort of prime to react to that, and that can lead to pretty rapid T-cell expansion, release of cytokines, recruitment of other inflammatory cells to that tumor bed, and as a result, a large portion of patients can anticipate to experience cytokine release syndrome, which again, is the result of the activation of these T-cells, the expansion and the recruitment of other inflammatory cells. Fortunately, for most patients, this results in fever alone that can be managed with supportive measures. Occasionally, they'll have concomitant hypoxia or hypotension, and unfortunately, few patients will have significant or severe toxicity. The other toxicity that's less easily manageable or less predictable is the neurotoxicity that can vary according to patient-specific characteristics, such as age, and the amount of tumor burden, their performance status going into CAR, but even more importantly, the construct that's utilized, with highest rates of neurotoxicity associated with axi-cel. Again, likely speaking to its construct and the CD28 costimulatory domain that is unique to axi-cel. As a result of these acute toxicities, patients are required to stay within two hours of their treating center for the first four weeks, and they're also discouraged from operating heavy machinery, such as driving, for the first eight weeks following CAR T. So, I do you think this creates some barriers to access to this therapy, particularly the patients that are treated in community settings that may reside long distances from these certified CAR centers. Dr. Chijioke Nze: So, you mentioned that obviously, given the specialized care needed for the CAR T therapy, that they're kind of localized in certain sites. What are some of these issues with access that you're noticing both in the logistics of giving CAR T, and also in patient access? Dr. Loretta Nastoupil: I'm hoping we're going to address one of those issues right now, which is, education and awareness, because we've had these three randomized studies, and two being positive readouts just in the last year. It's important to get the message out that CAR T-cell therapy for high-risk early relapsed refractory large cell lymphoma patients can result in a significant improvement in event-free survival and progression-free survival over the standard of care. And so, being aware that this therapy can result in more favorable outcomes is step one. Step two is, we have to ensure that there are minimal barriers to getting those patients into these treating centers as quickly as possible. So, recognizing who delivers the care - is it your traditional stem cell transplant physician? Is it a lymphoma doctor? What centers are certified? Some of these issues can be addressed with quick internet searches. So, for instance, in our center, we have a 1-800 number for anyone who's interested in CAR T-cell therapy that connects them directly to a CAR T coordinator who can help them understand do they meet the FDA-approved indication? Would they be interested in seeking consult? And we try and prioritize getting those patients in the door as soon as possible since time likely does have an impact on outcomes. And then, partnering with our community oncologist - you're going to be the primary oncologist for these patients leading up to CAR, and then after that four-week window, when we're keeping the patients in close proximity to our centers, we often send them back. And so, making sure that they're comfortable knowing what potential late toxicities to be on the lookout for, which include B-cell aplasia and risk for infection, or prolonged cytopenias, beyond just lymphopenia. And so again, there's a need for education and partnering with our community sites to make sure that there is successful handoff of these patients back after they've completed the monitoring for the acute toxicity. And then, really trying to explore opportunities to utilize some of the better tolerated CAR T, such as liso-cel, in your non-traditional academic centers. Those that are equipped to handle phase I studies or stem cell transplant, for instance, may not be affiliated with the university. So, I think those are all types of strategies that could be employed to try and improve access for patients. Dr. Chijioke Nze: And then, you mentioned the liso-cel, but in some of the toxicities, are there ways of predicting which patients will do better or worse? Are there ways to reduce toxicities? And is there any hope for things such as outpatient administration of CAR T? Dr. Loretta Nastoupil: So, my answer today may improve over time as we get larger numbers and more experience, but what we currently understand is that the patient performance status, their degree of tumor, how quickly that tumor is increasing, LDH and some inflammatory markers such as CRP or ferritin pretreatment can provide some insight into a higher risk of toxicity. And then obviously, the construct that's utilized. Again, axi-cel has higher rates of neurotoxicity. All will have some form of cytokine release syndrome, generally speaking, but rates of grade three or higher are quite infrequent, particularly with liso-cel and tisa-cel. So, it's multifactorial. That then raises the question, can we do anything to alter those modifiable risk factors? Can we reduce the disease burden? Can we improve the performance status? Can we do anything to reduce the inflammatory markers pre-treatment? And so, those are strategies that are being discussed, and I think in general, as we get more effective therapies that enter into the treatment landscape, it's probably some of the best ways to try and reduce some of those risk factors. Dr. Chijioke Nze: Rounding that up, are there any exciting developments or things to look out for, for exciting therapies in the relapse setting? Dr. Loretta Nastoupil: A couple of things beyond CAR T that I think we should all be aware of and anticipate to be in our toolkit relatively soon; probably, one of the most exciting, is the development of the bispecific antibodies. So, another challenge with CAR T is the requirement to collect these patients' own T-cells and send them off to a central manufacturing site, and the turnaround time can be anywhere from 3-4 weeks. And again, in a situation where you have an aggressive disease, that can be a long time to wait. And so, is there any treatments that are more readily available, that again, will be effective at reducing disease burden? And so, by specifics kind of fit those unmet needs to some extent - you have essentially two heads; one head is going to bind the endogenous T-cells that eliminates the need to leukapherese these patients and manufacture, and then the other head is going to generally engage CD20, which we know is an effective targeted antigen, particularly in B-cell lymphomas. And there are a number that are under development. We saw preliminary phase II data with glofitamab, epcoritamab, as well as combination strategies with mosunetuzumab. So, I do have optimism that the bispecific antibodies will potentially enter into the treatment landscape. I anticipate they'll probably be used first post-CAR T, but will likely move their way into earlier lines of therapy. I've already mentioned tafasitamab in combination with lenalidomide, which is an effective non-chemotherapy option. We have antibody-drug conjugates, such as Loncastuximab, which is a CD19 antibody-drug conjugate. It's essentially targeted delivery of chemotherapy, and it looks to have a pretty promising activity as a single agent in that third-line or later space, and then polatuzumab, which is a CD79b antibody drug conjugate, in the relapse setting has been combined with bendamustine and rituximab, but also demonstrated significant improvement in the frontline setting in the POLARIS study where vincristine was replaced with polatuzumab. So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing refractory disease, and potentially succumbing to the lymphoma. Dr. Chijioke Nze: And then, one additional question: How do you approach a patient who is not quite as fit, in thinking about what their options are for later-line therapies? You already mentioned some of these, but which of those would you prioritize in this setting? Dr. Loretta Nastoupil: Again, as we get more experience, we develop skills that help us sort of navigate all these different options. In my practice, if I'm even considering CAR T, I'm going to delay bendamustine until after I've collected those cells. I think that's one caveat that-- we do get nervous about the quality of those autologous CAR Ts if they're generated in someone who's had recent exposure to bendamustine. So, that may help me sequence that later on. We have questions right now about what's the optimal sequencing of CD19-directed therapy because we have several options beyond just CAR T-- As I mentioned, we have Lonca, we've got tafasitamab and lenalidomide. Currently, we don't have prospective data that really informs that question, and there's a number of research studies underway to try and help us understand if there is a preferred sequence, or even if it matters how we handle CD19 targeting. For my older, frailer patients where I'm really worried, they're not going to be able to tolerate something like liso-cel, or they're not going to be able to have that caregiver, and they're uncomfortable relocating to an area where CAR T might be available, my general approach right now is to consider tafasitamab and lenalidomide first in that relapse setting, followed by either Lonca or Pola-BR. Selinexor is another option. It's an oral agent, though again, in my opinion, if we look at the totality of the data, may be less effective than the other options. So, I might reserve that as a last option for someone, again, with relapsed/refractory large cell. Dr. Chijioke Nze: Excellent. Thank you. This has been very helpful. Dr. Loretta Nastoupil: All right. So, Dr. Nze, now I'm going to turn the table and ask you some questions. I'm going to change this up a little bit - she's now a 39-year-old female. She has significant comorbidities. She has HIV, and again, large cell lymphoma. So, let me walk you through her case, and then we'll discuss some of the challenges, again, in a very different scenario, albeit a similar disease. So, our female is, I mentioned 39, pre-existing HIV, she's treated frontline with six cycles of R-CHOP and intrathecal methotrexate for CNS prophylaxis. Because of her comorbidities, again, not well controlled HIV, she also has a poor functional status at the time of relapse. This was a couple years ago, and CAR T was not an option in second line, though she is someone who had a relapse that was beyond 12 months. So, for her second-line approach, because of her comorbidities, she actually receives rituximab in combination with high-dose cytarabine, dexamethasone, and oxaliplatin for three cycles, and actually achieves a chemosensitive disease and is referred to our stem cell transplant colleagues. Unfortunately, at that time, due to comorbidities, she was deemed not to be an appropriate candidate for high-dose therapy, and she's been monitored for signs of relapse. Despite being in the minority, she actually does not have a recurrence of her lymphoma but has a number of other, again, challenges in regards to her comorbidity, including multiple infections, resulting in recurrent hospitalizations. And so, it's always been a challenge for me in being intimately involved in her case, deciding when she's presenting, how alarmed to be about recurrent lymphoma versus infection, and how I might approach her in the setting of relapsed large cell lymphoma. So, what role does prior type and response to therapy play in treatment selection at your next line of treatment? Dr. Chijioke Nze: I think in this patient, it sounds like she got one adequate therapy on and the initial presentation with R-CHOP, and then with IT chemotherapy as well. She looked like she had a good response. I think the fact that she achieved a complete response and the duration of her response, lets me know that she likely has chemosensitive disease. This, in turn, helps me to pick what to do next. As you mentioned previously, we know how efficacious the CAR T therapy is, but in someone like her who had a long duration, trying salvage therapy and proceeding to autologous transplant might make sense. I'd be interested in your thoughts. Dr. Loretta Nastoupil: Yeah, I agree. And I think part of the challenge, particularly when we're facing patients with HIV, they're often excluded from prospective studies. And so, we're often in a scenario where we may not have the wealth of data to inform our treatment decision. But I do think in general, comorbidities play a major role-- we're navigating treatment options. Because again, traditionally, we've used intensive chemotherapy as our mainstay of treatment, and there are clear criteria that patients generally should meet that help us predict how likely they are to have significant or severe toxicity from high-dose therapy. And this is a prime example of even though she was young, her comorbidity made her a poor candidate for intensive therapy. I think the other sort of non-clinical factors that we sometimes take into consideration, because CAR T was approved off of single-arm phase II studies, again, none of which would've included someone like her, because of her HIV status, how do we extrapolate-- for instance, if she had relapsed in that third-line space, and suggesting that she did not have significant infection or other significant comorbidities, do we have experience to proceed with an autologous CAR in that setting? So, again, there've been a few cases where we have case reports where people have reported on their standard of care outcomes, particularly with CAR T in patients with active HIV disease, but one of the concerns I have in these scenarios is very selected. If you have active infection, that can make the acute toxicity with CAR significantly worse. And so again, we're trying to navigate a sort of limited data zone to try and help her and choose the right therapy. Again, you've met this patient with me, you helped care for her for some time, and you have a unique experience of also practicing in a county hospital where comorbidities, particularly, like HIV, can be much more common. What is your perception regarding barriers to accessing CAR T as it pertains to social factors, clinical factors, and again, this is a case that highlights some of those issues. Dr. Chijioke Nze: You mentioned at first that she had uncontrolled HIV. So, I think which, one, speaks to her treatment reference of her non-malignancy-related diseases, and trying to get that under control would be one of the first things I could think about. Thinking about how her care is managed and what kind of support she has are very important for us to think about as well. The other thing that's very important is, a lot of patients who we're seeing in the community may not have access to such specialized centers such as MD Anderson, where patients do have access to clinical trials and CAR T therapy. So, patients who are unlike her, who might qualify, may not actually be able to get these therapies as well. Part of the reason is, it can be insurance status, which is what we see in a lot of our patients. So, a barrier to get into the door. And then too barriers, lack of social support can be a big issue as well. And then there's also a big push in the community to improve the trust and awareness of these novel therapies, as you've mentioned. So, in a lot of the community practice, some of the community practitioners may not be comfortable with these, and a lot of the patients may not have heard of these new technologies, and also want to defer trying new therapies before having other people try new therapies before they consider them themselves. I think all these things present specific significant barriers to patients in the community. One, their ability to adhere to care, two, their insurance and their ability to get care and the financial toxicities associated with that. And then third, really understanding the options that are available. Dr. Loretta Nastoupil: And again, just to try and illustrate a couple other points. You know, we use a case here, which is a real case, with significant comorbidities such as HIV, which again, is something that is not frequently encountered, and will have a large impact on treatment selection. What if I just told you this patient has comorbidities, but she has moderate type-2 diabetes, and as a result, she has mild renal insufficiency, ejection fraction is actually adequate, would you have done anything different in this case? Dr. Chijioke Nze: No. I think in this particular case, I do think the fact that she did have a good response for a long duration of time, and did seem to have chemosensitive disease, I would probably still have tried a salvage therapy and autologous transplant in this patient. In the event that she was refractory, or had early relapse, and in that case, I would consider her to not be chemosensitive and would definitely have sought some more active therapies such as CAR T cell therapy through available products. Dr. Loretta Nastoupil: And then one last question for you: What if we just changed her age and we made her 79, but no other significant comorbidities, how would that have impacted your approach? Dr. Chijioke Nze: I'm going to turn that one over to you, I'm not exactly sure how I would treat with older patient with the same disease. Dr. Loretta Nastoupil: That's fair. So, if you have an older patient who has a late relapse, but not necessarily someone you would consider appropriate for salvage chemotherapy and high-dose therapy, then I think tafasitamab and lenalidomide would be probably my first choice in that setting, just based off of the L-MIND study. Dr. Chijioke Nze: Thank you, Dr. Nastoupil, for a great discussion of the management of diffuse large B-cell lymphoma. And thank you to all our listeners. We appreciate you tuning in to this episode of the ASCO Educational podcast. 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 back! Happy New Year! Strickland in as short notice opponent in what we feel is one of the top plays on the card. We are proud to announce our partnership with Betstamp and our looking forward to brining you sharper angles and cleaner plays. We had a chance to chop it up with Damon Jackson. He is hunting a finish. FDG sounds good. Twitter: @mcgmma. @mma_breakdowns IG. - Twitter. - Youtube: @Donttappodcast https://withkoji.com/@DonttapCulture https://youtube.com/channel/UC04L_oMTKKnCZplmTg_NyrQ https://open.spotify.com/show/5CWNwtOVSMnB2dzTBxFdPg?si=Ur-xpwSiTtmMI88CctgRvQ&utm_source=copy-link
Dans une industrie où les suites sont plus un réflexe qu'une tendance, rares sont les jeux à pouvoir traiter l'idée qu'ils soient les derniers de leur licence. C'est pourtant le cas de cet Uncharted 4, qui nous présente un Nathan Drake qui n'arrive pas à raccrocher alors qu'il est clairement en bout de course. Et si l'équipe de Neil Druckmann et Bruce Straley arrive à sortir ses meilleurs séquences sur cette opus (coucou Madagascar), elle pose aussi un regard lucide sur une formule qui a fait son temps au sein du AAA moderne. FDG revient sur cet opus presque meta, oh yes yes yes yes yes. Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : https://discord.gg/YTGbSkNLa chaîne Twitch : https://www.twitch.tv/findugamejv
Lung Cancer Histology and Staging*Workup for a nodule that is concerning: **Ensure there is a dedicated CT scan of the chest to evaluate **Try to obtain old imaging; the rate of change is important **Can get PET, but even if a lesion if not FDG-avid, but growing quickly we should consider biopsy anyway**Referral to pulmonary medicine, who can assist with biopsy and also regional lymph node evaluation (important – more below)**PFTs are often ordered because it provides information about lung function in anticipation of possible surgery for treatment Lung Cancer Histology: *Non-small cell lung cancer (NSCLC)**Umbrella term for a variety of cancers**Increased risk in smokers**More common types: ***Adenocarcinoma (~50% of all lung cancers)****Most common overall; cancer of the mucus producing cells****IHC: TTF-1, NapsinA, CK7 positive***Squamous Cell Carcinoma (22.7%)****More often seen in patients with a smoking history ****IHC: p63 positive and cytokeratin pearls***Remaining ~15% are the other types of lung cancer / mixed histologies**Small cell lung cancer (SCLC)***Neuroendocrine tumor with very different pathology***Much more aggressive than NSCLC***Oncologic emergency***IHC: Chromogranin and synaptophysin positive IHC pearls: TTF-1 usually means lung cancer (but can be negative in squamous cell lung cancer). This will be important in the future (we promise :])*Staging for NSCLC:**Nodal evaluation: lymph node evaluation is part of the workup for NSCLC**Single digit = central/mediastinal nodes (higher risk)**Double digit = peripheral/hilar/intrapulmonary lymph nodes (lower risk)**“R” vs. “L” is direction *Pearl: Why is this important? If there is nodal involvement, systemic therapy is going to be necessary *Putting it all together: **T: Tumor size: T1-4**N: Nodal involvement***N0: no nodal involvement ***N1: Nodes closest to the primary tumor (double digits)****Ipsilateral peribronchial, hilar, intrapulmonary ***N2: Further away (single digit)****Ipsilateral mediastinal and/or subcarinal LN***N3: Contralateral any node or supraclavicular LN **M: Metastasis – in lung cancer, patients with certain patterns of metastatic disease are still curable! ***M0: no mets***M1a: Contralateral lobe, pleural effusion or pericardial effusion à these are generally still curable!***M1b: single site of metastatic disease à these are generally still curable!***M1c: multiple sites of metastatic disease à these are generally not curable*Staging for SCLC: **Limited stage - meaning it can fit in “one radiation field”**Extensive stage - does not fit in “one radiation field”*Once lung cancer is diagnosed:**Go to NCCN to learn the flow of ongoing management**Complete staging (if not already done):***CT C/A/P (don't necessarily need if a PET scan is done)***PET Scan***MRI brain à in general this is needed, but there are some exception to this (see NCCN)**Referral to pulmonary for nodal evaluationReferences: NCCN.orghttps://doi-org.proxy.library.vanderbilt.edu/10.1016/j.semcancer.2017.11.019-Article about IHC markers for lung cancer Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google Podcast
En guise de conclusion de cette saison 4, l'équipe de FDG monte à bord du Normandy pour revenir sur le premier opus de Mass Effect, la trilogie culte de Bioware. Après le succès de KOTOR, le studio Canadien veut développer son propre univers et au passage, sortir un RPG grand public sur console HD. Dans la peau du commandant Shepard, on explore des planètes hostiles, on drague des aliens sexy et on sauve la galaxie à coups de fusil à pompe ou de bons mots. C'est ça la SPECTRE Life. Mais malgré quelques bonnes idées sur sa gestion des dialogues, Mass Effect peine à convaincre sur les autres aspects de sa proposition ludique. Et si les épisodes suivants sauront faire quelques choix judicieux pour améliorer la formule, jamais elle n'atteindra les sommets qu'on pouvait projeter en elle. Reste plus qu'à moissonner. Et réessayer ?Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameLe lien de la chaîne Twitch : https://www.twitch.tv/findugamejvLe lien du Twitter : https://twitter.com/findugamejvRejoignez le club de lecture sur Discord : discord.gg/YTGbSkN
Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we sit down with guest pulmonologist Dr. Greta Dahlberg to discuss how she thinks about and works up lung nodules concerning for malignancy.Lung nodules: * For discussions about incidental lung nodules and lung cancer screening, check out Episode 197 from our friends, The Curbsiders (link: https://thecurbsiders.com/podcast/197) * Nodule vs. mass:** “Micronodule” is
Début 2019, le marché du Battle Royale semble déjà saturé. Après le succès explosif de PUBG, Fortnite règne en maitre et les nouveaux prétendants sont mis K.O. à peine après avoir débarqué dans l'arène. Mais chez Respawn, on a justement pris son temps avant de faire le grand saut. En plus des bases solides de Titanfall, les équipes de Vince Zampella ont tout fait pour rendre Apex Legends unique, en misant sur le jeu en équipe et des hér... légendes aux capacités variées. Résultat : après sa sortie surprise, le titre trouve immédiatement son public et s'impose comme une référence, notamment grâce au soin apporté à son UX et son fameux "Ping system". Alors qu'il entame sa 13ème saison, FDG revient sur le dernier produit star du portefeuille d'Electronic Arts.Merci à nos patreotes qui financent l'émission sur https://www.patreon.com/findugameRejoignez le club de lecture sur Discord : discord.gg/YTGbSkNMerci à notre sponsor pour cet épisode, le Game Pass : https://www.xbox.com/fr-FR/xbox-game-pass
✋ Intervista con Fabio Millevoi, Direttore ANCE FVG e Futurista
Featuring an interview with Dr Ajai Chari including the following topics: Case: A man in his early 80s with newly diagnosed multiple myeloma (MM) presenting with new anemia and an IgA monoclonal spike (0:00) Case: A woman in her early 60s with newly diagnosed MM presenting with hypercalcemia and FDG avid lytic lesions (8:02) Updates from ASH 2021 on CAR (chimeric antigen receptor) T-cell therapy for MM (29:27) Data on bispecific antibodies at ASH 2021 (36:28) CME information and select publications
This week's View highlights the use of ICD therapy in ischemic vs. non-ischemic cardiomyopathy; what are the (FDG)-positron emission tomography (PET) and MRI findings, and abnormalities in patients with COVID-19; and a meta-analysis examining oral anticoagulation in AFib.
Image of the Year Ganna Blazhenets PET scans show long covid We discuss the SNMMI image of the year for 2021 Where FDG scans showed acute changes on the brain following COVID and for some subjects these changes were not gone at 6 months. https://jnm.snmjournals.org/content/early/2021/03/31/jnumed.121.262128 https://www.nuccast.com #Nuccast.com #UniversityofMelbourne #SNMMI #NIF #COVID #PET #NuclearMedicine #Podcast #MolecularMedicine #covid #longcovid Nuccast.com ,UniversityofMelbourne ,SNMMI ,NIF ,PET ,NuclearMedicine ,Podcast ,MolecularMedicine, Covid, Lobgcovid, FDG Please let me know what you think about the video versions of the podcast.I am also looking for new material so please get in touch with me if you can contributewith an interview.Direct link to iTuneshttps://itunes.apple.com/au/podcast/the-nuclear-medicine-and-molecular-medicinie-podcast/id1444565219?mt=2Older podcastshttps://podcasts.apple.com/au/podcast/the-nuclear-medicine-and-molecular-medicine-podcast/id94286547You can get the podcast page at both http://nuccast.com and http://www.nuccast.com with the feed to put into iTunes or juice or your favourite podcast software can be found at http://molcast.com/.The cardiac subset of the podcast can be found at http://cardiac.nuccast.com/Please pass on information about this podcast to your colleagues and to your CPD provider.Link to Video Link to Video fileLink to Audio file Link to Audio fileOr you can subscribe by entering your email address below and you will be informed of new episodesEnter your email address:Delivered by FeedBurnerMost importantly of all please help this podcast by contributing your opinions, Sound files, and emailsnucmedpodcast@gmail.comAll contributions welcome, especially as sound files to nucmedpodcast@gmail.com.
SNMMI 2021 Image of the Year Ganna Blazhenets PET scans show long covid We discuss the SNMMI image of the year for 2021 Where FDG scans showed acute changes on the brain following COVID and for some subjects these changes were not gone at 6 months. https://jnm.snmjournals.org/content/early/2021/03/31/jnumed.121.262128 https://www.nuccast.com #Nuccast.com #UniversityofMelbourne #SNMMI #NIF #COVID #PET #NuclearMedicine #Podcast #MolecularMedicine #covid #longcovid Nuccast.com ,UniversityofMelbourne ,SNMMI ,NIF ,PET ,NuclearMedicine ,Podcast ,MolecularMedicine, Covid, Lobgcovid, FDG Please let me know what you think about the video versions of the podcast.I am also looking for new material so please get in touch with me if you can contributewith an interview.Direct link to iTuneshttps://itunes.apple.com/au/podcast/the-nuclear-medicine-and-molecular-medicinie-podcast/id1444565219?mt=2Older podcastshttps://podcasts.apple.com/au/podcast/the-nuclear-medicine-and-molecular-medicine-podcast/id94286547You can get the podcast page at both http://nuccast.com and http://www.nuccast.com with the feed to put into iTunes or juice or your favourite podcast software can be found at http://molcast.com/.The cardiac subset of the podcast can be found at http://cardiac.nuccast.com/Please pass on information about this podcast to your colleagues and to your CPD provider.Link to Video Link to Video fileLink to Audio file Link to Audio fileOr you can subscribe by entering your email address below and you will be informed of new episodesEnter your email address:Delivered by FeedBurnerMost importantly of all please help this podcast by contributing your opinions, Sound files, and emailsnucmedpodcast@gmail.comAll contributions welcome, especially as sound files to nucmedpodcast@gmail.com.
In this episode, Jamie E. Chaft, MD, provides her expert perspective on new data from WCLC 2020 in early-stage NSCLC, with topics including:Updated results from ADAURA on HRQoL and DFS outcomes with or without postoperative chemotherapy after adjuvant osimertinibAn analysis of the ongoing ITACA study of personalizing chemotherapy based on biomarkers of drug resistanceFDG PET/CT adaptive radiotherapy in RTOG 1106The TALENT study in Taiwan screening nonsmokers for lung cancerPresenter:Jamie E. Chaft, MDAssociate Attending PhysicianThoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew York, New YorkContent supported by educational grants from Amgen; Bristol-Myers Squibb; Ipsen Biopharmaceuticals; Janssen Pharmaceutica NV; Jazz Pharmaceuticals; Regeneron Pharmaceuticals, Inc. & Sanofi Genzyme; and Takeda Oncology.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:http://bit.ly/2NzE6X6
There's so much going on in the ETF world right now as all kinds of trends, strategies, themes and companies collide in this hotter-than-ever market which is on pace to post another record year for inflows - and volume - in 2020. Next year could be even bigger too as many ‘Big Active' mutual fund firms representing $10 trillion in assets look to make up for lost time. So what should you watch for in 2021? Rather than do another “outlook” Bloomberg Intelligence's ETF team has come out with a report that highlights 21 ETFs to watch 2021. Analysts Athanasios Psarafagis, James Seyffart and Morgan Barna join us to go over their contributions to the full list, which are as follows: DFAU, SPGP, ICVT, VXUS, GBTC, SNPE, OVL, SQQQ, ARKK, SVAL, MSOS, VTI, QQQJ, KMED, BATT, NETL, IBUY, SPAK, USMV, FDG and LQD.See omnystudio.com/listener for privacy information.
There’s so much going on in the ETF world right now as all kinds of trends, strategies, themes and companies collide in this hotter-than-ever market which is on pace to post another record year for inflows - and volume - in 2020. Next year could be even bigger too as many ‘Big Active’ mutual fund firms representing $10 trillion in assets look to make up for lost time. So what should you watch for in 2021? Rather than do another “outlook” Bloomberg Intelligence’s ETF team has come out with a report that highlights 21 ETFs to watch 2021. Analysts Athanasios Psarafagis, James Seyffart and Morgan Barna join us to go over their contributions to the full list, which are as follows: DFAU, SPGP, ICVT, VXUS, GBTC, SNPE, OVL, SQQQ, ARKK, SVAL, MSOS, VTI, QQQJ, KMED, BATT, NETL, IBUY, SPAK, USMV, FDG and LQD.
State-owned electricity utility Eskom has issued a no-obligation request for information (RFI) in a bid to gain insight into what flue gas desulphurisation (FGD) technologies are currently available and to assess their potential suitability for deployment at the Medupi power station, in Limpopo. In a public notice, Eskom said the installation of FGD at Medupi by June 2025 formed part of a legal covenant with the World Bank, which loaned the South African utility $3.75-billion in 2010 largely for the purposes of building the 4 800-MW power station. The technology would be used to lower the coal-fired power plant’s sulphur dioxide (SO2) emissions in line with South Africa’s tightening minimum emissions standards. It has been widely reported that Eskom has been seeking to persuade the World Bank to allow it to pursue alternatives to the installation of FDG across Medupi’s six units, owing to the fact that the installation was expected to cost more than R40-billion and add to its already unsustainable debt burden. Eskom’s current debt stands at about R480-billion. The utility has also argued that retrofitting the units with FDG technology would dramatically increase the power station’s water consumption in a region that is already water stressed. Eskom said the RFI responses, which should be delivered to it by November 3, would be used to assist it in further developing its strategy for reducing SO2 emissions at Medupi. Consideration could also be given to using the technologies outlined at other coal stations in the utility’s generation fleet. “Eskom is currently in pursuit of the latest available information on the FGD technologies that will enable compliance to the relevant environmental legislation in a cost-effective and timeous manner, whilst being cognizant of the requirement for water conservation,” the RFI documentation states. Respondents could suggest more than one FGD technology option, provided that the specific limits that each technology was capable of achieving were outlined, along with the costs. The baseline unabated SO2 emissions for reduction were stated as being 4 367.03 milligrams per cubic metre (mg/Nm3). The current limit for Medupi was 3 500 mg/Nm3 and, by 2025, the limit would be 1 000 mg/Nm3. Eskom said submissions should aim to provide technology solutions to meet an emission limit of 200 mg/Nm3.
Pour cet épisode estival, Fin Du Game ouvre une faille spatio-temporelle et retourne en 1998 à Black Mesa, pour aller au bout d'Half-Life. A cette époque, les FPS sont encore des Doom/Quake-Likes et 2 anciens de Microsoft veulent rafraichir le genre. Gabe Newell et Mark Harrington fondent Valve et s'entourent de talents pour créer un shooter qui deviendra beaucoup plus que ça. Car si l'aventure de Gordon Freeman comporte de nombreuses fusillades réussies, c'est aussi son univers inspiré, sa narration avant-gardiste et ses mises en jeu toujours surprenantes qui la feront entrer dans la légende du medium. Et son pied-de-biche, évidemment. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.08.192872v1?rss=1 Authors: Viswanath P. Sudarshan, Shenpeng Li, Sharna D. Jamadar, Gary F. Egan, Suyash P. Awate, Zhaolin Chen Abstract: Functional positron emission tomography (fPET) imaging using continuous infusion of [18F]-fluorodeoxyglucose (FDG) is a novel neuroimaging technique to track dynamic glucose utilization in the brain. In comparison to conventional static PET, fPET maintains a sustained supply of glucose in the blood plasma which improves sensitivity to measure dynamic glucose changes in the brain, and enables mapping of dynamic brain activity in task-based and resting-state fPET studies. However, there is a trade-off between temporal resolution and spatial noise due to the low concentration of FDG and the limited sensitivity of multi-ring PET scanners. Images from fPET studies suffer from partial volume errors and residual scatter noise that may cause the cerebral metabolic functional maps to be biased. Gaussian smoothing filters used to denoise the fPET images are suboptimal, as they introduce additional partial volume errors. In this work, a post-processing framework based on a magnetic resonance (MR) Bowsher-like prior was used to improve the spatial and temporal signal to noise characteristics of the fPET images. The performance of the MR guided method was compared with conventional Gaussian filtering using both simulated and in vivo task fPET datasets. The results demonstrate that the MR guided fPET framework reduces the partial volume errors, enhances the sensitivity of identifying brain activation, and improves the anatomical accuracy for mapping changes of brain metabolism in response to a visual stimulation task. The framework extends the use of functional PET to investigate the dynamics of brain metabolic responses for faster presentation of brain activation tasks, and for applications in low dose PET imaging.Competing Interest StatementThe authors have declared no competing interest.View Full Text Copy rights belong to original authors. Visit the link for more info
Entre l'essai, la blague et la méta-fiction, The Stanley Parable est peut-être le jeu le plus atypique sur lequel Fin Du Game est revenu. Il nous enferme dans un dialogue interactif avec un narrateur sarcastique auquel on pourra choisir d'obéir ou non. Et si les nombreuses fins qui découlent de ces choix peuvent sembler très différentes les unes des autres, elles nourrissent toutes une même réflexion sur la liberté et les contraintes que nous offrent les jeux vidéo. 7 ans après sa sortie finale, le jeu de Davey Wreden et William Pugh est toujours aussi pertinent. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136838v1?rss=1 Authors: Meadowcroft, M. D., Purnell, C. J., Wang, J.-L., Karunanayaka, P., Yang, Q. Abstract: Cerebellar involvement in Alzheimers disease (AD) has not been studied to the extent that cortical neuropathological changes have. Historical and recent histopathological literature demonstrate cerebellar AD pathology while functional investigation has demonstrated disrupted intrinsic cortical-cerebellar connectivity in AD. Additionally, olfactory deficits occur early in AD, prior to the onset of clinical symptoms. The neurological basis for the involvement of the cerebellum and olfactory system in the disease course remain unclear. 18F-fludeoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimers Disease Neuroimaging Initiative (ADNI) were analyzed to characterize metabolism in the cerebellum and olfactory region of AD, mild-cognitive impaired (MCI), and age-matched cognitively normal (CN) controls. In contrast to known parietal and temporal lobe FDG hypo-metabolism within the default mode network in AD, a significant FDG hyper-metabolism was found in the cerebellum and olfactory cortical regions (including the piriform cortex, olfactory tubercle, anterior olfactory nucleus, and nucleus accumbens shell). The increase in cerebellum glucose utilization was shown also in late- verses early-MCI patients. The cerebellar and olfactory regions both contain inhibitory distal and inter-neuronal connections that are vulnerable to disruption in AD. The hyper-metabolism in the cerebellum and olfactory structures may reflect disruption of local and system-wide inhibitory networks due to AD neurodegeneration, suggesting a hypothetical mechanism for susceptibility of the olfactory system to early AD pathology. Copy rights belong to original authors. Visit the link for more info
Far Cry 3 marque une étape importante pour Ubisoft. Après avoir imposé sa formule du monde ouvert avec Assassin's Creed, la firme des Guillemots va chercher à la décliner sur d'autres typologies de jeu, notamment le FPS. Et le pari est réussi. Une île paradisiaque, un vilain charismatique et une myriade d'activités secondaires, le jeu s'impose comme LE shooter pop-corn de 2012. Et même si l'auteur du jeu aurait aimé qu'on y voit plus que ça, c'est bien ce fun très premier degré qui deviendra la marque de la série, avant qu'elle finisse par tourner en rond, comme beaucoup d'autres séries de l'éditeur. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
Dès ses premières apparitions, GRIS se fait remarquer par sa direction artistique hors-norme. Il la doit à son créateur, Conrad Roset, un illustrateur espagnol déjà bien installé, qui s'est lancé dans la création de jeu vidéo après une rencontre avec 2 anciens d'Ubisoft en 2015. Nomada Studio nous invite donc à redonner vie au monde brisé d'une jeune femme, où chaque nouvelle couleur qui s'ajoute et se mélange aux autres est un pas de plus vers la reconstruction. C'est une expérience onirique d'une fluidité exquise, mais qui peine parfois à dépasser ses références, ludiques ou thématiques. Fin Du Game fait son vernissage dans ce nouvel épisode. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.08.084293v1?rss=1 Authors: Zhuo, J., Zhang, Y., Liu, B., Liu, Y., Zhou, X., Bartlett, P. F., Jiang, T., the ADNI Abstract: The failure of all anti-amyloid-{beta} (A{beta}) drugs has led to a debate about the central role of amyloid in sporadic Alzheimer's disease (SAD). In order to resolve this issue, it is necessary to evaluate the impact of A{beta} biomarkers on SAD by measuring the dynamic changes in biomarkers and clinical profiles in the progression of SAD. We identified a clearer picture of the clinical and biomarker changes in the progression of SAD by aligning the clinical diagnosis of mild cognitive impairment (MCI) or AD onset. We found that changes in hippocampal volume and FDG, rather than A{beta} biomarkers, were associated with the changes in clinical measures in the progression of SAD. In addition, cognitively normal people with elevated and with normal amyloid showed no significant differences in clinical measures, hippocampal volume, or FDG. This study reveals that A{beta} is not a useful biomarker for predicting the clinical progression of patients who develop SAD. Copy rights belong to original authors. Visit the link for more info
Est-ce que le démons peuvent pleurer ? La question reste ouverte mais ce qui est sûr, c'est qu'ils savent se battre avec style. Après une pause de plus de 10 ans pour la série, Hideaki Itsuno et son équipe ont pouvé que Devil May Cry avait encore sa place dans l'ère moderne. Ce 5ème épisode est une démonstration de leur expertise du jeu d'action à la japonaise, celui où l'animation est reine et chaque nuance de gameplay est un outil d'expression pour celui ou celle qui tient la manette. Le tout servi par un trio de personnalités fortes et complémentaires, qui ne laisse jamais tomber le rythme de l'aventure. Appuyez sur le Devil Trigger, c'est parti pour un nouvel épisode de Fin Du Game. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
Our guest today is Dr. Francisco Gonzalez-Lima, a professor in the department of psychology, pharmacology and toxicology and the department of psychiatry at The University of Texas at Austin. He also is a professor at the university’s Institute for Neuroscience. We covered so much ground in our discussion with Francisco that we have split his interview into two parts. Today’s interview focuses on Francisco’s fascinating background as a youth and Cuban expatriate as well as his early research into Alzheimer’s Disease and brain metabolic mapping. The second part of our interview, which follows in a few weeks, covers two interventions Francisco has been exploring with the aim of protecting people against neurodegeneration: low-dose methylene blue and the application of near-infrared light. Francisco describes himself as a behavioral neuroscientist. He and his colleagues at the Gonzalez-Lima Lab are recognized as world leaders for their research on the relationship between brain energy metabolism, memory and neurobehavioral disorders. Although he has spent most of his academic career at the University of Texas, Francisco has been a visiting neuroscientist in Germany, England, Canada and Spain, and has delivered more than 120 lectures around the world about his brain research. He also has contributed work to more than 300 scientific publications. Over the years, Francisco’s brain research has focused on transcranial lasers, memory enhancement, neuroprotection and neurocognitive disorders. Current research in the Gonzalez-Lima laboratory focuses on the beneficial neurocognitive and emotional effects of noninvasive human brain stimulation in healthy, aging and mentally ill populations. This research primarily uses transcranial infrared laser stimulation and multimodal imaging. Show notes: [00:03:23] Dawn opens the interview mentioning that Francisco was born in Cuba where his father worked as a veterinarian. Dawn asks how Francisco’s family ended up leaving Cuba for Costa Rica when he was only ten years old. [00:04:25] Ken asks if it is true that Francisco got into a lot of fights as a child. [00:05:19] Francisco talks about his time as a child accompanying his veterinarian father to take care of cattle. [00:06:46] Dawn asks about Francisco’s time in college, two years of which he spent in Venezuela, and how he became known as an anti-communist student leader on campus. [00:08:18] Francisco tells the story of how he ended up going to school at Tulane University. [00:09:13] Dawn mentions that because Francisco’s father was a veterinarian, Francisco went to Tulane with the intent of working with animals. But after watching a professor dissect a human brain in class one day, Francisco changed his major. [00:10:17] Ken asks Francisco what lead him to decide to get a bachelor’s degree in biology and psychology. [00:11:49] Dawn asks about Francisco’s work with Nobel Prize winner Dr. Andrew Schalley during Francisco’s last summer at Tulane. [00:12:56] Francisco explains how he ended up of the University of Puerto Rico getting his doctorate in anatomy and neurobiology. [00:14:28] Dawn asks Francisco how learning about electrophysiology in his doctoral studies had an impact on him. [00:15:22] Francisco tells an interesting story of his doctoral dissertation. [00:16:21] Dawn asks about Francisco’s work with Dr. Walter Stiehl and the papers the two of them published in the European Journal of Pharmacology. [00:17:19] Dawn mentions that in 1981 Francisco met Henning Scheich, a German professor who had done a study involving the newly developed 2-deoxyglucose autoradiographic method. Francisco talks about why this neuroimaging approach to brain research fascinated him and led him to propose an ambitious collaborative research project with Dr. Scheich. [00:18:27] Dawn asks Francisco to talk about the work he did with Dr. Scheich to develop the human FDG (fluorodeoxyglucose) neuroimaging m...
We thought Jordan was the perfect guest to roll out new segments with! Jordan and his wife Katie have been building Final Drive Genetics at a rapid success rate. We talk about the history of starting FDG with one sow among his father having untraditional show livestock background. We answer questions like; Is the market flooded with "those one sow operations"? What's it like moving a sow herd from Indiana to Arkansas? $1000 Scholarship: https://stocktalk-podcast.com/stock-talk-podcast-scholarship/The Showman - Showmanship Contest: https://www.facebook.com/482290585617317/videos/515547992665099/Support the show (https://www.facebook.com/TheStockTalkPodcast/?modal=admin_todo_tour)
Héritier direct d'Alien: Isolation, Observation reprend à son compte l'exercice du huis-clos spatial, en apportant un twist inédit : nous faire incarner l'intelligence artificielle qui règne sur les systèmes et l'administration de la station. En adoptant cette perspective, en nous faisant jouer avec les interfaces et les caméras, le studio NoCode nous plonge dans un thriller certes référencé, mais qui ne pouvait être raconté que dans un jeu vidéo. Direction Saturne pour un nouvel épisode de Fin Du game, ECOUTEZ-LE. Pour soutenir Fin Du Game : https://www.patreon.com/findugame - Pour rejoindre le club de lecture FDG : https://discord.gg/SFxKYtA - Merci à notre sponsor Third Editions, maison d'édition spécialisée dans les ouvrages sur les jeux vidéo : https://www.thirdeditions.com
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