Podcasts about Cart

Today's Story is about a pony named Clover. She belonged to a farmer and she would pull his cart to the market in the glen each weekend. Follow along as Clover has a hard time pulling an extra heavy cart to the market, laden down with practically the whole fall harvest.Draw us a picture of what you think any of the characters in this story look like, and then tag us in it on instagram @storiespodcast! We'd love to see your artwork and share it on our feed!!If you would like to support Stories Podcast, you can subscribe and give us a five star review on iTunes, check out our merch at storiespodcast.com/shop, follow us on Instagram @storiespodcast, or just tell your friends about us!See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Marino. Cartógrafo, un hombre digno de estar en los lugares privilegiados del recuerdo y que sin embargo pocos españoles conocen. Para remediar esto, Antena Historia en directo desde el salón de actos del excelentísimo ayuntamiento de Santoña, honrando a uno de sus paisanos señalado por la gloria. Conferencia-programa: Julio Valle, Rafael Palacio Ramos y Francisco Mellén Blanco Produce Antonio Cruz Edita ANTENA HISTORIA 🔊Antena Historia (podcast) forma parte del sello iVoox Originals 🌐web……….https://antenahistoria.com/ 📧correo.....info@antenahistoria.com 🔵Facebook…..https://www.facebook.com/antenahistoria1 🔴Twitter…...https://twitter.com/AntenaHistoria ⚪Instagram...https://www.instagram.com/antenahistoria/ 🔷Telegram…...https://t.me/foroantenahistoria Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

Diffuse large B-cell lymphoma is a fast-growing cancer of the lymphatic system. A new Cochrane Review from September 2021 looks at the evidence on the effects of one treatment, chimeric antigen receptor (CAR) T-cell therapy for people whose disease relapses or does not respond to other treatments. We asked the lead author, Moritz Ernst from the Faculty of Medicine and University Hospital Cologne in Germany to tell us what they found.

The gals share strange stories of Christmas tree theft, a wicked wedgie, a trapped cat, menstrual cup mayhem, some Taco Bell that didn't sit well, a fudge-loving thief, and perhaps the most blunt obit in history. Tune in for this month's Gossip at the Corpse Cart!

La Navidad nos tiene a TODOS emocionados; pero al momento de planificar...debemos pensar en crear un plan de contingencia ante cambios o situaciones que puedan ocurrir. En este episodio te doy 3 claves para crear tu plan de contingencia. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com  

Starring . . . MOM! Yes indeed. Susan Blackwell Ramsey herself has come to guest star. Thanksgiving arrived and Kate had the brilliant notion that she and Betsy should take advantage of their #1 fan and finally do one of her favorite picture books (the one they've always avoided). So, if you've ever listened to our podcast and thought to yourself, "These two ladies sound too similar. I wish there was a THIRD voice that sounded a lot like both of them to join in," then your prayers have been answered! In short, if you'd like to hear two daughters ribbing their mom, this is the podcast episode for YOU! Show Notes: Mom and Betsy discuss a Slate article that provides a rather magnificent rundown of the history of Donald Hall's poem and its transformation into a book. It does not, however, include the info about his Caldecott Room loo: https://slate.com/culture/2018/07/how-donald-hall-changed-ox-cart-man-from-the-poem-to-the-childrens-book.html Here's the Reading Rainbow episode where Lorne Green reads Ox-Cart Man: https://www.youtube.com/watch?v=tXHZARNpBZM For the full Show Notes please visit: https://blogs.slj.com/afuse8production/2021/11/29/fuse-8-n-kate-ox-cart-man-by-donald-hall-ill-barbara-cooney/

Brad and Josh invite Duke Weskamp back to the podcast to talk about the new Ketch cart. He gives us the details of the production and testing to ensure the high quality Ketch is known for. Waypoint TV- https://waypointtv.com Patreon-https://www.patreon.com/paddlenfin Podcast & Website- www.paddlenfin.com YouTube- https://www.youtube.com/paddlenfin Email- paddlenfin@gmail.com Social Media- @paddlenfin Yak Gadget- www.yakgadget.com Pelican Professional- www.pelican.com Rocktown paddlesports - rocktownadventures.com JigMasters Jigs- https://jigmasters.com Learn more about your ad choices. Visit megaphone.fm/adchoices

We'll break down the blowback of affairs and uncover some of the hurts beyond the affair itself, tracing the origin of the feelings leftover even months and years after the initial affair. Our Relationship's Residual Effects The accumulation of lost dreams, broken promises, disillusionment, regret, emotional setbacks, disenchantment, with the past romantic partners, and unrealistic expectations all make up your ex-factor. Consider the following: The cycle of despair and desperation Emotional histories repeating themselves Setting yourself for failure The hardest part of creating a new relationship is stopping the old, negative emotional patterns and antiquated styles of intimacy and connection. --- Support this podcast: https://anchor.fm/thebarbershopgroup/support

Tu Tienda Online debe prepararse visualmente para la mejor temporada del Ecommerce. Objetivo: Queremos que el cliente entre, viva la experiencia de la temporada y se “exploten” sus emociones. Por que las EMOCIONES son LO QUE VENDE. ¿Cómo lo hacemos posible? En este episodio te cuento TODO. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com

Welcome to another installment of The Reigning Champs Podcast! Also, be sure to use the email below if you're interested in us doing a sponsorship, promo, and anything else! Make sure to follow on Spotify and 5 star on Apple Podcast. ! Kick back and enjoy. #RAISETHEBANNER Adrian's Playlist: https://t.co/Qq5xfJWoRB?amp=1 For all inquires : thereigningchampspod@gmail.com Adrian- Twitter/Instagram: @AD_Lite15 Javonn-Twitter/Instagram: @J_Easyy Boostz21 Twitch: https://www.twitch.tv/boostz21 JGLove5 Twitch: https://www.twitch.tv/jglove5/ Mix By: Dar @ntve_grvs NEW Atlantic Ave. Cruise Tape Vol. II https://soundcloud.app.goo.gl/WmkoUKT4y2ttzp2S6 Beat Made By: https://soundcloud.com/dkgbeats

- Rock the Rittenhouse  - On the couch - How to deal with your unvaxxed fam  Kyle Rittenhouse acquitted on all charges having a seizure on the Kenosha Courthouse steps Croiss Talk “Cart Narcs” Founder Accused of Publicly Shaming Customers For Not Returning Shopping Carts How to deal with unvaccinated family members this Christmas     Podcast; iTunes - https://podcasts.apple.com/au/podcast/the-daily-boogie/id1437957774 https://boogiebumper.podbean.com/ https://www.streamlabs.com/boogiebumper Merchandise; https://teespring.com/stores/boogiebumper "BoogieBumper Tonight" theme music written, performed and produced by Irrational Times Stream music provided by Epidemic Sounds

Comedian Dean Stanfield joins Shannon and Matty to talk Skankfest highlights, a massive barfight, a naked roast, a date with food poisoning, and flipping a truck six times! Leave a Voicemail for Scary Things/Bad Things at (732) 997 - 7066...Air Date: 11/16/21Support Our Sponsors!Promescent.comYoKratom.comThe Thing Is... Airs every Tuesday, at 5:30pm ET on the GaS Digital Network! The newest 15 episodes are always free, but if you want access to all the archives, watch live, chat live, access to the forums, and get the show five days before it comes out everywhere else - you can subscribe now at gasdigitalnetwork.com and use the code TTI to save 15% on the entire network.Follow the show on social media:instagram:https://www.instagram.com/shannonlee6982https://www.instagram.com/jesterskullsWant some merch? https://podcastmerch.com/collections/the-thing-isSubscribe On YouTube: https://www.youtube.com/channel/UC87Akt2Sq_-YEd_YrNpbS2QShannon Lee and Matty Jesterskulls get together weekly with interesting guests in comedy, reality TV, porn and every other walk of life to find out about their nightmare date stories, paranormal experiences and street fight stories! It gets crazy, hysterical, scary and shocking as they uncover stories you won't hear on other podcasts.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

In this episode, Cymulate's Co-founder & CTO Avihai Ben-Yossef will discuss continuous automated red teaming (CART), how to get to the crown jewels of an organization, and more. Cymulate's breach and attack simulation platform enables companies to challenge, assess and optimize their cybersecurity posture against threat evolutions, simply and continuously. To learn more about our sponsor, Cymulate, visit https://cymulate.com/

Vamos analisar a prestação do Sporting até à jornada 11 da Liga, antevisão da Taça de Portugal, a Selecção Nacional, Cartão do Adepto e a restante actualidade Leonina.

Ya tu sabes….¡que estamos en la mejor temporada del año! El Ecommerce es el negocio perfecto y la parte VISUAL es lo que provocará que tu cliente lleve ese producto al carrito y complete su órden. En este episodio hablamos de cómo preparar tus artes promocionales tanto para la tienda online como las redes. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com  

In this video, Eric shares his best practices around Ecommerce Website Tips and Tricks: Post-purchase CRO, Customer Support, and Email Marketing.Eric built a tool called ReConvert ​that helps people drive more sales on the customer thank you page.Here are a few of his best tips and tricks:- It's super important that you optimize your thank you page. We've taken customers from 0 to as high as a 10% conversion on thank you pages. Transactional emails drive traffic to thank you page and based on our data, customers visit the thank you pages on average 2.7 times per order.- A great way to upsell and cross-sell products is by offering same product purchased at additional discount, only now for the next few minutes. If they decline, offer the same product with even bigger discount.- Offer multiple types of offers since different customers respond differently to various offers.- We've seen the following be super effective: On the thank you page, display a popup with time sensitive offer on entire store, where the discount auto applies.- Cart recovery is the most powerful automation for ecommerce stores. Make sure you keep testing and optimizing. You can learn more about ReConvert here: https://www.reconvert.io/BeProfit is the #1 profit calculator app that helps you leverage your business data to optimize your profit & grow your store. Get an all-in-1 analytics dashboard to stay on top of your numbers.They're hooking you up w/15% off - just use the code CD15Visit: BeProfit.co

Truly Inconsequential - Not all characters are created equal. Mr. Greer and Brimstone of The Grindhouse Radio debate this week's zeroes in front of a live audience. It'll be determined in real time who will remain inconsequential, and who may be liberated back into the hero's category. This week they argue a four way dance between legendary secondary characters. The combatants are Luigi (Nintendo's Mario Bros) vs. Knuckles (Sonic) vs. Toad (Mario Bros) vs. Tailz (Sonic). This will be one wild ride of game console mayhem pitting Nintendo classics against Sega classics - only one can be victorious. Question is, who will remain truly inconsequential.

You are about to enter....the Wordplay Zone! A place where kids get to share their story ideas for Sheila and her gang...and we get to bring them to life with our crazy voices, sounds fx, and nonsense! So...WELCOME to our first episode of the Wordplay Zone. In this episode you get to hear the script of 11 year old Buttons & Figs kid Noah. He come up with a crazy library book cart race for Sheila, Max and Jimmy...not to mention a chipmunk, Robot and Spring-Heeled Jack! Get ready to enter the...Wordplay Zone: The First Annual Library Book Cart Race, by Noah If you enjoyed this crazy story, then be sure to check out Noah's inspiration: Mr. Lemoncello's Library book series, by Chris Grabenstein. If you have a story idea for Sheila and her friends, be sure to email pamela@buttonsandfigs.com If you'd like to add your voice to the Wordplay Zone, find a grownup and ask them to record you saying: Welcome to the Wordplay Zone! This episode was written by Noah, with support from Buttons & Figs Sheila, Max, Jimmy, Spring-heeled Jack voiced by Mark Pena Robot, Chipmunk, Wordplay Zone musical introduction by Noah Writing support and production by Pamela Rogers Audio engineering by Blaise Collins

Special Guest: @Estevan J. (Chuy) ZarateEstevan J. (Chuy) Zarate is an actor/director/coach from San Antonio TX that has been improvising for audiences for 31 years. He is a member of The Big Bash at The Hideout Theatre, The Known Wizards (Merlinworks faculty troupe), Luby' Bingo Hall and more duos than he can count. He teaches all styles and formats being that he has a very eclectic tool belt to reach into. If there is a scenario to be performed in, he has probably performed it. With specialties in improv singing and grounded/character-driven scenework, Chuy has coached hundreds of kids, teens, students and adults for years to multiple successesTopics:- Shows about bad people- School Board Politics- Working in Retail or Service- Spotters and CondimentsScenes:- Summer Improv Camp Meeting- Burger King "Assault"- The Best Cart Runners- Cardinal Rules of CondimentsWe have opinions and you're gonna hear them! Follow our characters down rabbit holes in our fast-paced improv shows.Hosted by Amechi Ngwe, Antoine W.B, Jon Myles, and Tandiwe Kone.Edited by Antoine W.BHosted on Mocking Bird Network

The world is your oyster, and it is up to you to take chances in life and make things happen. Life is short as Omair Tariq has been reminded by the near-death experiences that have prompted him to go big rather than remain stagnant. His venture, Cart.com has raised funding from top-tier investors like Sebastian Rymarz, Moonshots Capital, Oaks HC/FT, and Clearco.

In this week's episode, Travis and Josiah go through the steps they would take to create and launch a brand new print on demand store from scratch. While it may seem obvious to some, each step builds on the previous ones so it's smart to have a plan going into the process. Even if you are already doing POD, there are always opportunities to build new stores that you can capitalize on. Plus, in this week's Point Of Interest, the guys talk about a free option to start a store that may work for you if you're OK with using Printful as your provider. Check out Launch Cart! Enjoy the show! http://printondemandcast.com http://printondemandcast.com/shop http://printondemandcast.com/facebook http://printondemandcast.com/youtube Links from the show: https://printondemandcast.com/launchcart https://printondemandcast.com/vexels

Featuring perspectives from Dr Jonathon Cohen, including the following topics: Chimeric antigen receptor (CAR) T-cell therapy for non-Hodgkin lymphomas (0:00) Case: A woman in her mid-60s with relapsed diffuse large B-cell lymphoma (DLBCL) after R-CHOP and maintenance rituximab (27:20) Case: A man in his late 50s cured of DLBCL but with long-term toxicities related to CAR T-cell therapy (32:43) Case: A man in his early 60s with progressive mantle cell lymphoma after CAR T-cell therapy (38:36) CME information and select publications

Dr Jonathon Cohen from the Winship Cancer Institute of Emory University in Atlanta discusses recent advances and future directions in the use of CAR T-cell therapy for the management of non-Hodgkin lymphoma. CME information and select publications here (http://www.researchtopractice.com/OncologyTodayCARTLymphoma21).

Ya sabes que el email marketing es VIDA en tu tienda online. Una excelente manera ara conectar en estas temporadas donde fluye las emociones. Aquí te brindo unos consejos para que hagas un email marketing efectivo en esta temporada. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com

Chaque soir, Olivier Delacroix vous ouvre la Libre antenne. Pas de jugements ni de tabous, une conversation franche mais aussi des réponses aux questions que les auditeurs se posent. Un moment d'échange et de partage propice à la confidence pour repartir le cœur plus léger.

We discuss the spending bill and which representatives are voting.  Our guests are: Boris Epshteyn, Jack Posobiec, Dr. Peter Navarro, Ben Bergquam Stay ahead of the censors - Join us warroom.org/join Aired On: 11/05/2021 Watch: On the Web: http://www.warroom.org On Podcast: http://warroom.ctcin.bio On TV: PlutoTV Channel 240, Dish Channel 219, Roku, Apple TV, FireTV or on https://AmericasVoice.news. #news #politics #realnews

Listen to the full show for Friday, November 5th, 2021! -The River Rock N' Roll Machine: AC/DC's “Moneytalks” -What's On Your Mind: Jury Duty Update -How Joe Is Feeling -The Cart Narc -This Just In -What The Fact! -Dog Interviews Joe & Dana -What To Watch TheDog, Joe and Dana Show is live Monday-Friday 5:45am-10:00am on 93.7 The River in Sacramento, CA!

Hearts be still, meet Meredith Quill! In this week's episode, we talk with Meredith Quill about her new jewelry brand, Becket + Quill. Meredith's been designing jewelry since she was a teenager and launched her growing  brand with Alli Webb just under a year ago. Meredith tells us about the inspiration behind her company, her process and her favorite pieces. She describes how making jewelry is her Nirvana, and so much more. Amy reviews her favorite new product and Meredith gives us a secret product reco during our 5 minute flow discussion. Get your holiday list started as Meredith gives us the scoop on her latest jewelry launches and a sneak peak of what's to come. About Meredith Quill:At the age of three, Meredith wore her mother's engagement ring to preschool and told the teachers that she had gotten married. This was the start of a lifelong passion for jewelry. As a teenager, she started making her own pieces, learning how to solder and set stones using a variety of metals.  After getting married and having 3 kids, Meredith saw a hole in the marketplace for reasonably priced, beautiful jewelry.  She started beading bracelets and necklaces for her family and friends and through word of mouth, the business quickly took off.  Her line of well priced, classic pieces could be seen on celebrities like Busy Philips and also on regular moms like herself!   She recently joined forces with Dry Bar founder and entrepreneur Alli Webb to form Beckett and Quill, an affordable, luxurious brand of jewelry that brings a little sparkle to everyone.  Follow Becket + Quill @becketandquill on IG.Follow us @nirvanasisters on InstagramSay hi at hello@nirvanasisters.comPlease subscribe, rate, review and share

Do you find the idea of email automation daunting? Well, you shouldn't! Because the right email campaigns can help you get awesome results in your business. This week on the podcast we chatted to Chelsea Martinus from Black Girl Boss Collective, who shared the best cart abandonment emails and tips to help you retarget your audience and increase your sales. Ready to find out Chelsea's best-kept secrets? SOME EPISODE HIGHLIGHTS: (3:46) Does Chelsea really watch the same three movies every New Year's Eve? (7:45) What is email automation? (9:46) Email marketing isn't something you do TO your subscribers. (11:35) What is a retargeting sequence? (13:20) What can an abandoned cart email sequence do for your and your subscribers? (16:18) Why timeliness is important in abandoned cart emails. (17:22) Why you need to personalise your email campaigns. (18:35) Why you want to 'nudge' your subscribers. (19:50) How to create the best cart abandonment emails for each of your products. (23:05) Subject line of the week with Chelsea Martinus. What is email automation?For Chelsea, automation is the key to a seamless client journey. When you're looking to connect with people who are a great fit for your community, you're not just sending them emails to convince them to buy, right? (Right?) Email marketing is a way of creating a connection with your audience. And the easiest way to do that is through automation. Why? Because email automation helps you foster a relationship with your subscribers and connect with them in a way that's authentic. It also helps you produce high-quality content that will get them to reach their goals. In other words, email automation allows you to build relationships that surpass a transaction and the exchange of money for services and goods. You can use email automation to let your community know they're not alone. This is you showing them they have someone in their corner they can turn to when they don't know what to do in a particular area of their business or life. Have we convinced you about the benefits yet? Email marketing isn't something you do TO your subscribersUnfortunately, a lot of people think of email marketing as a thing they do TO their subscribers. But it's not like that at all! It's about the subscribers' journey and their path through your email system - that's the big difference. Creating automated campaigns allows you to take all your customers on the same journey. Isn't that amazing? And the key to achieve this is to make your emails so good that your subscribers will want to be on our list because they're genuinely looking forward to our emails, rather than being there because they downloaded a cool lead magnet once. What is a retargeting sequence?A retargeting sequence is a campaign that gets sent when a subscriber has clicked on a product but hasn't bought it yet. We have a specific email sequence about this that we teach inside our membership, https://get.emailmarketingheroes.com/league/ (The League). We call it the Tell Me More sequence, and as Chelsea put it, it's probably one of the most underrated email automation campaigns for service providers. Because a lot of people think the automation stops when the subscriber buys. Or when they don't. And that's not quite the case. Chelsea explains that if you're running a campaign and presenting an offer you believe in – one that's going to help people solve problems - then you need to take a moment to re-engage and retarget those people. Chelsea refers to these campaigns as retargeting sequences or click sequences. If you work in e-commerce, you've probably heard the phrase abandoned cart sequence. What can an abandoned cart email sequence do for your business?Your retargeting  (or abandoned cart) campaign allows you to check in with any subscribers who clicked on your link but didn't buy. Do they have any questions? Why didn't they go ahead and purchase? Asking these types of questions...

Dr. Shah discusses the FDA approval of brexucabtagene autoleucel in relapsed/refractory B-cell acute lymphoblastic leukemia, key findings from the pivotal ZUMA-3 trial, and next steps with CAR T-cell therapy in the field.

An interview with Dr. Bryan Schneider from the University of Michigan Health System and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center, co-chairs of the Management of Immune-Related Adverse Events Guideline Expert Panel. They discuss an overview of the “Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update” in Part 1 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and I want to introduce you to our series on the Management of Immune-Related Adverse Events. ASCO has developed two guidelines for the management of immune-related adverse events, one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. Today, we'll be focusing on an overview of the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. And we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy and an episode to discuss the management of immune-related adverse effects in patients treated with CAR T-cell therapy. Today, I am joined by Dr. Bryan Schneider from the University of Michigan Health System in Ann Arbor, Michigan, and Dr. Kathryn Bollin from Scripps MD Anderson Cancer Center in San Diego, California, co-chairs on Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy, ASCO Guideline Update and authors of the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy, ASCO Guideline. Thank you for being here, Dr. Schneider and Dr. Bollin. BRYAN SCHNEIDER: Thank you, Brittany. KATHRYN BOLLIN: Thank you for having us. BRITTANY HARVEY: I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Schneider, do you have any relevant disclosures that are related to this guideline? BRYAN SCHNEIDER: I have research funding to my institution from Bristol Myers Squibb and Genentech Roche at the time of panel formation. BRITTANY HARVEY: Thank you. And, Dr. Bollin, do you have any relevant disclosures that are directly related to this guideline? KATHRYN BOLLIN: No disclosures. BRITTANY HARVEY: Thank you. Then, let's talk about this guideline. So first, Dr. Schneider, what prompted this update to the Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy Guideline last published in 2018? BRYAN SCHNEIDER: Yeah. The previous guideline was widely used and consistently one of the top read articles of the JCO over the last couple of years. And since the original guideline publication in 2018, new data have emerged on the management of immune checkpoint inhibitor toxicities. So our goal was to build on the original guideline with more treatment options, especially for patients who fail initial steroid treatment. New strategies have developed for the management of many toxicities, especially GI, cardiac, and heme toxicities. And ASCO and the panel felt it was important to present these new options to the providers in the community. We also wanted to add sections that the providers would find valuable, including a table with many of the immunosuppressive agents used with typical dosages and schedules. We also added a table of commonly conducted testing while patients are on high-dose steroids as this is something many medical oncologists may not be used to handling as we typically do not have patients on steroids at high doses for several weeks or even months. BRITTANY HARVEY: Understood. Then, in addition to those updates that Dr. Schneider just mentioned, Dr. Bollin, what is the general scope and purpose of this guideline? KATHRYN BOLLIN: Yes. So the immune-related adverse event management guideline update and the CAR T-cell toxicity guideline serve to provide physicians that are prescribing these therapies with an understanding of the wide range of known potential toxicities of these agents and the best available evidence-based and expert opinion recommendations for their management. So up to 70% of patients treated with immune checkpoints will experience some form of immune-related adverse event, and nearly all patients getting CAR T-cell therapies experience toxicity. So recognition of the occurrence of these toxicities and appropriate management are essential for optimizing patient outcomes. BRITTANY HARVEY: Definitely, those are key points. So then, Dr. Schneider, what are the overarching recommendations for the management of immune-related adverse events irrespective of the affected organ? BRYAN SCHNEIDER: I think early recognition of the side effect is critical. So the guideline has typical signs and symptoms of each toxicity to help clinicians decide if this is occurring in their patients. Second, I think it's critical to grade the toxicity. We often don't do that with side effects related to traditional chemotherapy outside of clinical trials. So for example, if a patient has a platelet count of 75, I can't think off the top of my head what grade that is. I just know I'm going to hold chemotherapy for a week or two. But grading of the toxicity of these immune checkpoint therapies really is very important to decide whether patients can just be watched, whether they need to start steroids or whether they need to be admitted. I think still corticosteroids and dose holds are the first steps that clinicians will do. The majority of these toxicities-- although it would be nice if we could personalize the treatment based on the particular side effect and what we see under the microscope if the particular affected organ is biopsied, I think, in broad strokes, corticosteroids can be implemented easily, and a lot of our oncologists can be comfortable doing this potentially without subspecialty help. Having said that, I think multidisciplinary care is a must for the higher-grade side effects as, in oncology, we can't pretend to also be cardiologists, gastroenterologists, neurologists, dermatologist, and so on. And although there may be varying degrees of comfort from our subspecialists regarding the management of these toxicities, we do need their help for shared decision making, especially for the steroid refractory toxicities. We always want to emphasize a slow steroid taper oftentimes over at least four to six weeks. We get into trouble when we try to get them off the steroid quickly because they do have side effects that the patient may not enjoy. But oftentimes, we try to taper them quickly, and the side effect comes roaring back. And then, finally, to escalate immunosuppression quickly if no improvement with high-dose steroids is observed, oftentimes, that's done even within just a few days. But commonly, in practice, there's still hope that the steroid will kick in two or three weeks down the road, and that's not a good strategy. If the patient's having significant symptoms and steroids aren't helping, they do need to go on to a more important immunosuppressant. BRITTANY HARVEY: Those are important notes on the overarching management, particularly on how the adverse effects are different than those in patients treated with chemotherapy and the importance of multidisciplinary care. So then, Dr. Bollin, in your view, how will this guideline impact clinical practice? KATHRYN BOLLIN: So the impact of this guideline update is actually very broad. As with the previous guideline, as Dr. Schneider alluded to earlier, it's been very frequently accessed by readers since it offers symptom outlines and algorithmic recommendations for early identification and the management of immune-related adverse events based on the severity and organ system involved. What's really important to understand is that while initially, as hematology-oncology physicians prescribing these agents, we're doing so in the setting of early phase clinical trials. We were learning about the toxicities, and those physicians were often managing the toxicities themselves. But now, with the exponential increase and the therapeutic indications for immune checkpoint therapies in cancer, the experience with the toxicities and their management and the questions have also followed suit with an exponential rise. With this guideline update, we have experts among all of the internal medicine subspecialties that are now guiding the hematology-oncology physicians in immune-related adverse event management. We enlisted the experts in crafting this guideline update. So in summary, this serves not only as a tool for the prescribing hematology-oncology physicians but also for all of the subspecialists in the community and within academic centers for optimizing patient outcomes in the setting of immune-related adverse events. BRITTANY HARVEY: Great. Yeah, it sounds like this update will be hugely important for practicing clinicians. So then, in addition to those points raised by Dr. Bollin, Dr. Schneider, what are the implications for patients receiving immune checkpoint inhibitor therapy? BRYAN SCHNEIDER: So we really hope this will be an essential tool to help providers quickly treat patients when these toxicities present. Often, this is unexpected, and busy clinicians may be blindsided by these issues. So these guidelines will provide a quick resource to guide the workup and formulate a treatment plan that will expedite patient recovery. And ultimately, this should help promote quality of life for patients on these therapies and may help reduce trips to the emergency department, hospitalizations, and potentially allow the safe rechallenge of immune checkpoint therapy after resolution of the side effect. Many centers have the advantage of subspecialty support with experience in managing these toxicities. But for providers who may not have immediate access to, say, hepatology or endocrinology, we hope these guidelines will help the oncology providers provide the best treatment to facilitate the optimal clinical outcome. BRITTANY HARVEY: Absolutely, those are key for optimal care. Then, finally, Dr. Bollin, looking toward the future, what are the important outstanding questions and developing areas of research for the management of immune-related adverse events? KATHRYN BOLLIN: So while our recognition of immune-related adverse events, the testing for them, and management strategies have greatly improved with the expanded use of and experience with these therapies, large gaps in our knowledge remain. Translational and basic science research efforts are underway to understand these gaps, such as with the intrinsic and extrinsic drivers of autoimmunity, such as those with HLA allelic variations and the microbiomes interplay with our immune systems. There are also research efforts underway to develop rapid diagnostic tests to deploy early in the onset of irAE signs and symptoms and for the development of biomarkers and modeling tools that will aid us in predicting which patients are likely to experience immune-related adverse events. There have also been some interventional protocols that have attempted to prevent these immune-related adverse events by incorporating immune suppressants along with therapeutic agents. But so far, promising results with this strategy remain elusive. In regard to treatment for immune-related adverse events, investigators are working to learn the best strategies for selective immune suppression rather than just the use of glucocorticoids that will control immune-related adverse events while maintaining the clinical benefit of these incredible anticancer therapies. BRITTANY HARVEY: Thank you for highlighting those research gaps and both of you for your efforts to lead this guideline update. We'll be joined by authors on the guideline over the next episodes to review the key recommendations for organ-specific management in patients treated with immune checkpoint inhibitors and to review the recommendations for patients receiving CAR T-cell therapy. Stay tuned for these episodes highlighting the sections of the guidelines. And thank you for your time today, Dr. Schneider and Dr. Bollin. KATHRYN BOLLIN: Thank you so much. BRYAN SCHNEIDER: Thank you. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center and Dr. Monalisa Ghosh from the University of Michigan Health System, authors on “Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline.” They discuss recommendations for management of irAEs in patients treated with CAR T-Cell Therapy in Part 2 of this 13-part series. For more information visit www.asco.org/supportive-care-guidelines   TRANSCRIPT [MUSIC PLAYING] SPEAKER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING]   BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network. A collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today we're continuing our series on the management of immune-related adverse events. ASCO has developed two guidelines for the management of immune-related adverse events-- one for patients treated with immune checkpoint inhibitor therapy and a second for patients treated with CAR T-cell therapy. In our last episode, you heard an overview of the Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Today, we'll be focusing on the Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline, and we'll have authors join us for future episodes to discuss the key recommendations for organ-specific management for patients treated with immune checkpoint inhibitor therapy. Today, I am joined by Dr. Monalisa Ghosh, from the University of Michigan Health System in Ann Arbor, Michigan and Dr. Bianca Santomasso from Memorial Sloan Kettering Cancer Center in New York, New York, authors on both Management of Immune-Related Adverse Events in Patients Treated with Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline and Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. Thank you both for being here, Dr. Ghosh and Dr. Santomasso. In addition, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with the publication of the guidelines in the Journal of Clinical Oncology. Dr. Ghosh, do you have any relevant disclosures that are directly related to this guideline? MONALISA GHOSH: No. I do not have any relevant disclosures. BRITTANY HARVEY: Thank you. And, Dr. Santomasso, do you have any relevant disclosures that are directly related to this guideline? BIANCA SANTOMASSO: Yes. I'd like to disclose that I've served as a paid consultant for Celgene, Janssen Pharmaceutical, and Legend Biotech for advising them on the topics of CAR T-cell therapy side effects. BRITTANY HARVEY: Thank you. Then, getting into these immune-related adverse events-- first, Dr. Ghosh, can you give us an overview of the scope and purpose of this guideline? MONALISA GHOSH: Sure. The purpose of this guideline is to offer expert guidance and recommendations on the management of immune-related adverse events in patients treated with chimeric antigen receptor or CAR T-cell therapy. This guideline offers guidance on the diagnosis, evaluation, and management of the most common toxicities of CAR T-cell therapy, which includes Cytokine Release Syndrome-- or CRS-- and immune effector associated neurologic syndrome-- or ICANS. As well as other potential, but less common toxicities, such as Hemophagocytic Lymphohistiocytosis-- or HLH-- B-cell aplasia, prolonged and recurrent cytopenias, Disseminated Intravascular Coagulation-- or DIC-- and infections. BRITTANY HARVEY: Great. Thank you. Then, Dr. Santomasso-- looking at this guideline, there's a few overarching recommendations. So, what are those general recommendations for the management of immune-related adverse events in patients receiving CAR T-cell therapy? BIANCA SANTOMASSO: Yes. The overarching recommendations are, really, first to recognize that these side effects exist. And that, as such, it's important to recognize that patients who develop these toxicities or side effects after CAR T-cell therapy need to be evaluated, or managed in, or transferred to a specialty center that has experience with the management of these toxicities. They're new toxicities. This is a new therapy. And patients are increasingly going to be managed in, or treated in, the outpatient setting, and, as such, they need to remain within a short distance of the treating center for about four to eight weeks post-therapy, and they should then return to their treating center upon experiencing any toxicities. Finally, as its flu season and infection season, it is recommended that inactivated influenza and COVID-19 vaccination be performed on patients and also family members as well. And any patient who does have an active infection, the CAR T-cell infusion should be delayed until that infection has been successfully treated or controlled. I often make a final point, which is that the immunogenicity of and efficacy of COVID-19 vaccines is uncertain in these patients with these agents, but the potential benefits outweigh the risks and uncertainties for most patients. BRITTANY HARVEY: Thank you. Those are important points for patients and treating clinicians. So then, Dr. Ghosh-- as you mentioned, this guideline addresses the seven most common CAR-T-related toxicities, and I'd like to review the key recommendations for each of those. So let's start with, what are the key recommendations for identification, evaluation, and management of cytokine-release syndrome? MONALISA GHOSH: Well, Cytokine Release Syndrome is one of the two major toxicities that occur immediately or within a short time period after infusion of CAR T-cells. We have defined Cytokine Release Syndrome, or CRS, as an immune-mediated phenomenon that's characterized by various symptoms that are indicative of immune activation and inflammation. And patients may experience signs and symptoms that could include fever, hypotension, hypoxia, tachycardia, shortness of breath, rash, nausea, headache, and various other symptoms that are a little less common. These symptoms are caused primarily by the release of cytokines. Cytokines are the messengers of the immune system, and most of them are released by bystander immune and non-immune cells. We know that the onset of Cytokine Release Syndrome is variable depending on the CAR T-cell product that's used, as well as the patient population that's treated. But it generally occurs anywhere from two to seven days after infusion of CAR T-cells, and in some rare cases can occur even a little bit later. A standard grading system has been developed and grade CRS, or Cytokine Release Syndrome, based on three parameters-- fever, hypotension, or low blood pressure; and hypoxia or low oxygen levels. CRS is primarily managed with IL-6 antagonists because IL-6 is an inflammatory cytokine that has been shown to mediate a lot of the systemic effects that we see from Cytokine Release Syndrome. And one of the treatments is the monoclonal antibody tocilizumab, which acts against-- or blocks-- the IL-6 receptor. CRS that is refractory to tocilizumab is generally treated with steroids. Then there's limited experience with additional therapies, especially in the setting of CRS, that does not respond to tocilizumab or steroids. There are other anti IL-6 therapies available. For example, siltuximab, which binds to IL-6 itself rather than the IL-6 receptor. However, there have been no direct comparative studies of these agents. Anakinra, which is also an IL-1 receptor antagonist has also been shown to mitigate CRS in some CAR T-cell recipients that have high grade CRS. BRITTANY HARVEY: OK. Thank you for reviewing those management strategies. So, following that-- Dr. Santomasso, what are key recommendations for identification, evaluation, and management of immune effector cell-associated neurotoxicity syndrome? BIANCA SANTOMASSO: Sure. Immune Effector Cell-associated Neurotoxicity Syndrome-- also known as ICANS-- is the second most frequent severe toxicity that can be seen after CAR T-cell therapy. So, what is ICANS? These are transient neurological symptoms that occur in the days after infusion, most commonly with CD19 CAR T-cell therapy. And the clinical manifestations of ICANS include encephalopathy, which is confusion, behavioral changes, expressive aphasia, or other language disturbance, change in handwriting or other fine motor impairment or weakness, and tremor and headache can also be seen. In more severe cases, patients can become obtunded with a depressed level of consciousness or even develop seizures, and they may require a higher level of ICU care, such as intubation for airway protection. And in very rare cases, malignant cerebral edema may develop, which may be fatal. ICANS can occur at the same time as Cytokine Release Syndrome, or can also occur several days after or shortly after CRS resolves, so it's important to have a high index of suspicion even after Cytokine Release Syndrome has resolved, but typically the side effects are self-limited and occur within the one month after infusion. Most symptoms lasts between 5 and 17 days, and the time of onset duration and severity of ICANS may really vary depending on the CAR T-cell product used or the disease state of the patient. So, what do I mean by that? Patients with high disease burden seem to be at increased risk for severe ICANS, so kind of knowing the disease that the patient has and the burden of disease is important. And then also there may be product-specific differences as well, so reviewing the product label is important as well because each may have its own risk evaluation and mitigation strategies that inform both the duration and the frequency of monitoring for ICANS after infusion. For evaluation of ICANS, we recommend, again, the ASTCT ICANS grading system. These allow for monitoring of several different aspects of neurologic function in these patients. Mental status changes are really what define the onset of ICANS. So for CRS, it's fever; for ICANS, it's mental status changes. And the severity of the mental status change can be determined by a standardized score known as the ICE score, which stands for Immune Effector Cell-associated Encephalopathy score. This is a simple 10-point scoring metric where points are assigned for orientation to year, month, city, hospital, ability to name three objects, ability to follow simple commands, write a standard sentence, and count backwards from 100 by tens. And for children younger than age 12 or those with developmental delay, The Cornell Assessment of Pediatric Delirium, also known as the CAPD, can be used in placement of the ICE assessment. Prior to CAR infusion, patients should be evaluated, including with an ICE score, for their baseline neurologic status. And what's nice is that this ICE assessment can be used as a daily screen after CAR infusion for the onset of ICANS during at-risk period. Then, other than the ICE score, there are four other neurologic domains that contribute to ICANS grading, and that's level of consciousness, seizures, severe motor weakness, and signs and symptoms of elevated intracranial pressure or cerebral edema, and patients are graded according to the most severe symptom in any of the five domains. So for patients who develop ICANS, it's recommended that they have workup, including blood work, CRP, CBC, comprehensive metabolic panel, fibrinogen, and coagulation tests. Neuroimaging with a non-contrast CT of the brain should be done and considering MRI of the brain in patients who are stable enough. In addition, electroencephalogram and lumbar puncture should be considered. And the electroencephalogram is really to rule out subclinical seizures, and the lumbar puncture is to assess the opening pressure-- or the pressure within the central nervous system-- and also to send studies to rule out infection. And again, these all have to be considered on an individual case by case basis, but are things to keep in mind. So for treatment of ICANS, the mainstay of treatment is, really, supportive care and corticosteroids. Tocilizumab, while it seems to rapidly resolve Cytokine Release Syndrome and most symptoms, actually does not resolve ICANS and may worsen it, so steroids are really typically used. The typical steroid is dexamethasone at a dose of 10 milligrams, and the interval really depends on the grade of the ICANS. Because of the possibility that tocilizumab may worsen neurotoxicity, ICANS really takes precedence over low grade CRS when the two occur simultaneously. And patients who don't show improvement within 24 hours after starting steroids or other supportive measures should have CSF evaluation and neuroimaging. Often treatment of seizures-- many patients are put on Keppra and levetiracetam or other anti-seizure medicine if they develop ICANS, and patients with grade 3 or greater ICANS may need an ICU level of care and escalation of steroid doses. The steroids are continued until ICANS improves to grade 1 and then tapered as clinically appropriate. And the most important thing to remember is that ICANS just needs to be monitored very closely as patients may worsen as some steroids are tapered. They also may improve rapidly after steroids are started, so steroids should be tapered quickly as patients improve. And, again, as with CRS, there's limited experience with other agents, such as Anakinra and siltuximab, but those could be considered in severe or refractory cases. BRITTANY HARVEY: Understood. I appreciate you going through when and how clinicians should screen for ICANS and those key management points. So, in addition to that-- Dr. Ghosh, what are the key recommendations regarding cytopenias? MONALISA GHOSH: So cytopenias can occur post-CAR T-cell infusion, and they can occur either in the early phase or in the later phase after CAR T-cell infusion. Meaning that they can occur early within the first few days to weeks post-CAR T-cell therapy or could even occur months to years later. These cytopenias include anemia, thrombocytopenia, leukopenia, neutropenia. Many patients may present with fatigue, weakness, shortness of breath, lightheadedness, frequent infections, fevers, bruising, and bleeding, and the symptoms usually are consistent with how they would present otherwise with anemia, thrombocytopenia, or neutropenia. Acute cytopenias within three months of CAR T-cell therapy are more common. This is due to usually the lymphodepleting chemotherapy that is administered prior to CAR T-cell therapy. Most patients receive a combination of fludarabine and cyclophosphamide prior to CAR T-cell infusion, or they may receive another agent, such as bendamustine. Most patients also come into CAR T-cell therapy with low lymphocyte counts from previous therapies. Early cytopenias, as I mentioned, are generally due to lymphodepleting chemotherapy or other recent therapies. There also could be an immune-mediated process due to the CAR T-cells. Usually prolonged cytopenias which occur beyond three months post-CAR T-cell infusion can be seen in a small number of patients. And the mechanism of prolonged cytopenias is really unclear at this time, but likely multifactorial. Most recipients of CAR T-cells who have prolonged cytopenias beyond three months post-CAR T-cell infusion should have a standard workup to rule out other common causes, such as vitamin or nutritional deficiencies. They should also have testing such as bone marrow biopsy and scans to rule out relapse disease-- relapse lymphoma or leukemia, for instance, that could be causing these cytopenias. Other examples would be myelodysplastic syndrome or other bone marrow failure syndromes. So cytopenias are generally managed with supportive care including growth factor and transfusion support. This applies to both cytopenias in the early period post-CAR T-cell therapy or more delayed prolonged cytopenias. In patients who have prolonged cytopenias of unclear cause that could be immune-mediated, other interventions such as high dose IVIG or even steroids could be considered depending on the situation. For those that have cytopenias in the first few months post-CAR T-cell therapy, generally they are monitored and treated with supportive care, and these cytopenias eventually resolve in the majority of patients. BRITTANY HARVEY: Great. Those are important considerations. Then, Dr. Santomasso, what are the key recommendations regarding Hemophagocytic Lymphohistiocytosis? BIANCA SANTOMASSO: The major recommendations for the identification, evaluation, and management of Hemophagocytic Lymphohistiocytosis, or HLH-- this is also known as macrophage activation syndrome. First, let's just start by saying that this is a dysfunctional immune response, and it's basically characterized by macrophages which are revved up and hyperactive and also possibly lymphocytes as well. There are high levels of pro-inflammatory cytokines during this state and tissue infiltration, and hemophagocytosis, and organ damage. This can occur outside of the context of CAR T-cell therapy, either as a primary HLH or secondary HLH that can be either triggered by infections, or autoimmune disease, or cancer-- especially hematological malignancies, but HLH has also been observed as a rare complication of CAR T-cell therapy. And outside of the setting of CAR T-cell therapy, HLH is defined by fever, cytopenias, hyperferritinemia-- or high ferritin level-- as well as bone marrow hemophagocytosis. And what's interesting is that this is very similar to what's seen during Cytokine Release Syndrome, and that can make it difficult for patients who have moderate to severe CRS to distinguish that from HLH. The laboratory results may be very similar. So the key to recognizing HLH is really to have it on your differential even though it occurs rarely after CAR T-cell therapy. It may occur with slightly different timing and may require more aggressive treatment. The lab alterations can include, again, as I mentioned, these elevated levels of several cytokines, such as interferon gamma. We can't normally send those in the hospital or the clinic, but sometimes soluble IL-2 receptor alpha can be sent and serum ferritin can be sent, and that's an especially useful marker. There have been diagnostic criteria for CAR T-cell-induced HLH that have been proposed, and these conclude very high ferritin levels-- over 10,000-- and at least two organ toxicities that are at least grade 3, such as transaminitis, increased bilirubin, renal insufficiency or oliguria, or a pulmonary edema, or evidence of hemophagocytosis in bone marrow or organs. Unlike other forms of HLH that occur outside of the context of CAR T-cell therapy, the patients may not have hepatosplenomegaly, lymphadenopathy, or overt evidence of hemophagocytosis. So just because a patient may not show those yet doesn't mean that HLH shouldn't be considered. If we see patients that have a persistent fever without an identified infection source or worsening fever, we basically should be considering HLH and doing the appropriate workup and treatment. Patients with HLH often have low fibrinogen, high triglycerides, and also cytopenias as well. The treatment-- just as there's an overlap kind of in the signs and symptoms, the treatment and the clinical management overlaps as well with CRS, so tocilizumab is typically administered. But corticosteroids should really be added for these patients, especially if there's clinical worsening or grade 3 or greater organ toxicity. And if there's insufficient response after 48 hours of corticosteroid therapy plus tocilizumab, many centers consider adding another medication such as Anakinra. I'll finally make a comment that, outside of the context of CAR T-cell therapy, HLH is sometimes treated with cytotoxic chemotherapy, such as etoposide. This approach generally is not used as a first line for patients undergoing CAR T-cell therapy due to etopiside's documented toxicity to T lymphocytes. And generally, the corticosteroids, plus the anti IL-6 agent, plus Anakinra is considered the first line of management. BRITTANY HARVEY: Got it. That's an important note on the management of HLH, and a great note on distinguishing CRS and HLH. So in addition, Dr. Ghosh-- what are the recommendations for management of B-cell aplasia? MONALISA GHOSH: B-cell aplasia, it's a disorder that's caused by low numbers or absent B-cells. And this is particularly relevant to CD19 directed CAR T-cell therapy, which is what most of the CAR T-cell therapies that are available right now target. They target CD19, and CD19 is present on normal as well as malignant B-cells. So most patients who receive anti-CD19 CAR T-cell therapy will develop B-cell aplasia at some point, and B-cell aplasia may be temporary or prolonged. It usually does, on one hand, indicate ongoing activity of the CD19 CAR T-cells and can be used as a surrogate marker. And increase in CD19 CAR T-cells could, in some patients, signal impending relapse, or dysfunction, or absence of activity of CD19 CAR T-cells. B-cell aplasia in CAR T-cell recipients is really due to, as I mentioned, an on-target, off-tumor effect. It can be prolonged and there is variability in rates of prolonged B-cell aplasia. The most significant consequence of B-cell aplasia is that it can lead to low immunoglobulin production. And immunoglobulin production is a very important part of the immune response by providing antibody-mediated immunity, so patients may present with frequent infections and low immunoglobulin levels. For most CAR T-cell recipients, this can be managed with infusions of Intravenous Immunoglobulins-- IVIG. However, the presence of B-cell aplasia can also present other challenges-- especially during this current pandemic, as Dr. Santomasso alluded to earlier, that it is unclear if patients will be able to mount a sufficient enough antibody response to the COVID-19 vaccines available since they cannot produce significant amounts of antibodies. This is an active area of research. However, we do advise that all CAR T-cell recipients do get the COVID vaccine and also other seasonal vaccines, such as the influenza vaccine. So it remains to be seen. We need some more long-term follow-up studies on how many people who receive CD19-directed CAR T-cell therapy will have prolonged B-cell aplasia and what the consequences will be. At this time, it is suggested that patients have their IgG levels monitored and-- if possible-- their actual B-cell numbers monitored. And if their IgG levels drop below a certain number, then they may receive IVIG infusions intermittently. We recommend in this guideline using 400 as a possible cutoff for IgG levels prior to administering IVIG. However, if patients have higher IgG levels and they have recurrent or life threatening infections, infusion of IVIG is recommended as a consideration to help boost the antibody response. BRITTANY HARVEY: OK. As you mentioned, those challenges are particularly relevant now. So then, Dr. Santomasso, what are the key recommendations regarding Disseminated Intravascular Coagulation? BIANCA SANTOMASSO: Disseminated Intravascular Coagulation is a disorder that's characterized by systemic pathological activation of blood clotting mechanisms, which results in both clot formation throughout the body and also bleeding. There's an increased risk of hemorrhage as the body is depleted of platelets and other coagulation factors. So it's basically important for clinicians to be aware that DIC-- or Disseminated Intravascular Coagulation-- can occur after CAR T-cell therapy, and it can occur either with or without concurrent Cytokine Release Syndrome. The treatment is primarily supportive care and replacing the factors, such as fibrinogen-- based on the levels-- and also replacing factors based on partial thromboplastin time and bleeding occurrences. But corticosteroids and IL-6 antagonist therapy can be used if there is concurrent CRS or in the setting of severe bleeding complications. There is limited evidence for other interventions. BRITTANY HARVEY: Great. Appreciate you reviewing those. So then, the last category of toxicity addressed in this guideline-- Dr. Ghosh, what are the key recommendations for identification, evaluation, and management of infections? MONALISA GHOSH: So a variety of infections can be seen after CAR T-cell therapy. And there are many factors that can lead to infection after CAR T-cell therapy including the presence of cytokines, such as neutropenia or leukopenia and B-cell aplasia that we earlier discussed-- leading to low immunoglobulin production and protection. As well as the increased risk of infection due to use of high-dose steroids to treat CAR T-cell-related toxicities, such as ICANS or CRS. Early after the infusion of CAR T-cell therapy-- that is, within three months-- patients often develop neutropenia due to lymphodepleting chemotherapy and/or the CAR T-cells themselves. And these patients are particularly susceptible to infection, so most of the infections that occur early on tend to be bacterial infections, and a few fungal infections have been observed as well. Patients who receive high-dose steroids for high grade CRS or ICANS have been shown to have increased serious infectious complications including bacterial infections, fungal infections, as well as viral reactivations. Infectious complications that occur later are often due to hypogammaglobulinemia due to B-cell aplasia and reduced production of immunoglobulins. And treatment is typically directed at the infectious source, as it would be even if these patients did not have CAR T-cell therapy. There are some prophylactic antimicrobials that are recommended for CAR T-cell recipients who have prolonged cytopenias. Especially those with prolonged neutropenia should be on some sort of bacterial and/or fungal prophylactic antimicrobials. Patients should also be monitored for hypogammaglobulinemia long term and should receive intravenous immunoglobulins as needed. As we have mentioned a couple of times already, being very aware that these patients are also more susceptible to seasonal infection, such as influenza, is important, and so vaccinations are very important for this patient population. Vaccinating against influenza and vaccinating against COVID-19. BRITTANY HARVEY: Thank you both for reviewing those key points for the most common CAR T-related toxicities. So, just to wrap us up-- Dr. Santomasso-- in your view, how will this guideline impact both clinicians and patients? BIANCA SANTOMASSO: Well, I think we've seen now that cell therapy is really one of the major advances in cancer treatment in the past decade. And I think it's reasonable to expect more of these cell therapies to be developed, and we'll hopefully see their use extend beyond very specialized centers. But CAR T-cell therapy side effects are manageable if they're recognized, so I think this guideline helps that, and they're reversible with proper supportive care. They can be serious and they require close vigilance and prompt treatment. But, again, we believe this guideline and recommendations will help members of clinical teams with both the recognition and management of all of these toxicities, and that will help patients by increasing their safety. BRITTANY HARVEY: Great. That's important to note that these toxicities can be severe, but are also manageable. So I want to thank you both for your work on these guidelines and for taking the time to speak with me today, Dr. Santomasso and Dr. Ghosh. BIANCA SANTOMASSO: Our pleasure. MONALISA GHOSH: Absolutely. It was my pleasure. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. Stay tuned for additional episodes on the management of immune-related adverse events in patients treated with immune checkpoint inhibitors. To read the full guidelines, go to www.asco.org/supportive care guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

My guest today is Omair Tariq, the founder of Cart.com. He says it’s the world’s first end-to-end e-commerce platform and he’s going up against Amazon and Shopify right out of the gate. I don’t know why he’s taking them on but I appreciate the battle. I invited him here largely because the guy’s got a war chest and a track record of creating amazing e-commerce successes. I want to find out how he’s using it. Omair Tariq is the founder of Cart.com, and end-to-end e-commerce platform. Sponsored byHostGator – Ready to take your website to the next level? Whether you're a first-time blogger or an experienced web pro, HostGator has all the tools you need to create a great-looking website or online store. A wide range of options includes cloud-based web hosting, reseller hosting, VPS hosting and dedicated servers. Founded in 2002, HostGator is the perfect web partner for business owners and individuals seeking hands-on support. Visit www.hostgator.com/mixergy to see what HostGator can do for your website. More interviews -> https://mixergy.com/moreint Rate this interview -> https://mixergy.com/rateint

En este episodio hablaremos de planificar. Quien no planifica, planifica fracasar. Comencemos a vender más en BFCM pero....debemos tener un plan. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com  

Podcast 205 / Interview with Damon Cart This week is the second part of my chat with NLP Expert Damon Cart and in this part, we dive a little deeper into setting goals and making sure that whatever goal you are achieving is growing you as a person and leading you towards a greater sense of long-term fulfilment.   You can subscribe to this podcast on: Podbean | Apple Podcasts | Stitcher | Spotify | TUNEIN   Links: Email Me | Twitter | Facebook | Website | Linkedin   Damon's Website Damon's YouTube Channel Download the Annual Planning Template Evernote link for the Annual Planning Template More about the Time And Life Mastery Course The FREE Beginners Guide To Building Your Own COD System Carl Pullein Learning Centre Carl's YouTube Channel Carl Pullein Coaching Programmes The Working With… Podcast Previous episodes page   Episode 205 | Script Hello and welcome to episode 205 of the Working With Podcast. A podcast to answer all your questions about productivity, time management, self-development and goal planning. My name is Carl Pullein and I am your host for this show. This episode is part two of my chat with Damon Cart. Damon Cart is an NLP specialist who has studied NLP or Neuro-Lingustic Programming for over ten years. Damon has a very successful YouTube channel, which I have linked to in the show notes, as well as a thriving coaching business where he helps senior executives and high achievers build fulfilling lives.  There's a lot of valuable information in this episode, so get your notebooks ready and let's go.   Well, there you go. I hope you got a lot of valuable information from this episode. Thank you so much to Damon for doing this with me and … It just remains for me now to wish you all a very very productive week.   

What we buy reveals a lot about who we are, says comedian-writer-director Kulap Vilaysack and journalist SuChin Pak, the hosts of the Add to Cart podcast. They talk to Jenn about double-cleansing, the environmental impact (and guilt) of consumerism, why SuChin still has makeup from her MTV days, and what Kulap uses to get skin like a “damp mochi ball.” Plus, Ku shares the reason she decided to grow out her gray hair and Su explains why she bought 18 types of sleeping pills on a recent trip to France.Links and sponsors: fatmascara.com/blogShop the products mentioned on this episode: myshlf.us/fatmascaraPrivate Facebook Group: Fat Mascara Raising a WandSocial media: @fatmascara, @jessicamatlin, @jenn_editSubmit a "Raise A Wand" product recommendation and be featured on the show: email info@fatmascara.com or leave a voicemail at 646-481-8182  See acast.com/privacy for privacy and opt-out information. Become a member at https://plus.acast.com/s/fatmascara.

Want to learn the future of e-commerce? What does re-envisioning the future of e-commerce operations really look like? Is there really a one-stop-shop for direct-to-consumer brands? Remington Tonar, Chief Operating Officer of Cart.com, an innovating company that is renovating the e-commerce space. Kunal and Remington discuss the process of direct to consumer and what avenues brands can take to solve the problem of expanding their brand to reach and drive acquisition. What you'll learn 2:00 what is Cart.com, what do they do, 5:30 Remington's journey to cart.com, 16:20 what lies ahead for brick and mortar, 18:00 the new name for ecommerce, 23:00 what integrating ecommerces to other platforms should look like.

@michaelsalzle. Treatment implications of cancer. Chemoprevention, and the emerging treatments of cancer, including CTLA 4 inhibitors, PD 1 inhibitors, and CAR T.

El black friday y cyber monday esta a la vuelta de la esquina. ¡Y tu sabes que YO te pondré al dia! En este episodio te presento cómo vender más en este BFCM y qué debes tomar en consideración. Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com

This month's GACC is full of magic horns, bad handwriting, a unique response to mask mandates, poop attacks, mean girls, bird romance, and one very odd obituary. Tune in for October's episode of Gossip at the Corpse Cart! For a full list of show sponsors, visit https://wineandcrimepodcast.com/sponsors/

This week, NLP Expert Damon Cart joins me to talk about how to create long-term goals that inspire you and ultimately brings you fulfilment and happiness.  You can subscribe to this podcast on: Podbean | Apple Podcasts | Stitcher | Spotify | TUNEIN   Links: Email Me | Twitter | Facebook | Website | Linkedin   Damon's Website Damon's YouTube Channel   Download the Annual Planning Template Evernote link for the Annual Planning Template More about the Time And Life Mastery Course The FREE Beginners Guide To Building Your Own COD System Carl Pullein Learning Centre Carl's YouTube Channel Carl Pullein Coaching Programmes The Working With… Podcast Previous episodes page   Episode 204 | Script Hello and welcome to episode 204 of the Working With Podcast. A podcast to answer all your questions about productivity, time management, self-development and goal planning. My name is Carl Pullein and I am your host for this show. This week, I am honoured to bring you a very special guest to help you with your 2022 goal planning and to build goals that are not only achievable but sustainable and keep you motivated.  Damon Cart is an NLP specialist who has studied NLP or Neuro-Lingustic Programming for over ten years. Damon has a very successful YouTube channel, which I have linked to in the show notes, as well as a thriving coaching business where he help senior executives and high achievers build fulfilling lives.  I am sure you are going to get a lot out of this episode, and I highly recommend you get your note books ready as there is going to be a lot of gold in this episode.    ________________________________________ Well, there you go, That's part one. Part two will be coming next week where we go a little deeper into identifying your values and you can use these to build your long-term goals and measure you achievement over time.  It just remains for me now to wish you all a very very productive week.   

Dr. Jen Fraboni is widely recognized as one of the world's top physical therapy influencers, with nearly 700,0000 followers and coverage in major outlets including Shape Magazine, Self Magazine, Men's Fitness, Muscle and Fitness, CBS, the RISE podcast and more.  Today, she offers private sports therapy, as well as online programs and workshops, global speaking events, and more.  She is also the creator of The Mobility Method program, the co-host of The Optimal Body podcast, and a member of the Women's Health magazine advisory board.  You can follow her on Instagram @docjenfit ****** When you visit www.Manscaped.com/ashley, you'll get a special 20% OFF coupon applied directly to your Cart, plus free international shipping and TWO FREE GIFTS!    Learn more about your ad choices. Visit megaphone.fm/adchoices

We're a little halfway through spooky season, but still pumping out movies reviews for all you ghouls out there. The gang watched the next chapter of the Michael Myers story in "Halloween Kills." Alex & Omar drop some Halloween franchise knowledge on everyone in this jam-packed episode

Bienvenidos a nuestra serie: Vende más en BFCM y Navidad. Una variedad de episodios para ayudarte a prepararte en la MEJOR temporada del Ecommerce. En este episodio te hablaré en base a datos de lo que ocurrió el año pasado y del por qué debes YA aprovechar este momento. Si quieres seguir avanzando, regístrate gratis en comienzatutienda.com

Margaux Alvarez is an accomplished Crossfit athlete, with nearly a decade of experience competing in the Crossfit games. In fact, But along with being a popular fitness influencer, she's also an entrepreneur and passionate winemaker, who founded G.O.A.T. wine, based out of her hometown in Las Vegas.   You can follow her on Instagram @321gaux and learn more about her business at thegoatwine.com Today on the podcast: Margaux Alvarez's Reborn story. ****** When you visit www.Manscaped.com/ashley, you'll get a special 20% OFF coupon applied directly to your Cart, plus free international shipping and TWO FREE GIFTS!    Learn more about your ad choices. Visit megaphone.fm/adchoices

The MOIF crew debate the what, where, and how of buying groceries. What even is a grocery store? Do you buy organic or conventional? Cart or basket? We answer these burning questions and many more, so much so that we have to make it a two-parter. Hosts: Dave Chang and Chris Ying Guest: Noelle Cornelio Producer: Isaac Lee Learn more about your ad choices. Visit podcastchoices.com/adchoices

We have writer Joel Jensen on and we're talking about past lives! Lyndsey sends in a video (for our eyes only) of strange lights in the woods. Steph was in Prague and saw some floating orbs. And Elias had red eyes following him! Please send us your own true paranormal experiences in either a voice memo or e-mail to funnyfeelingpod@gmail.com. BetterHelp is customized online therapy that offers video, phone and even live chat sessions with your therapist, so you don't have to see anyone on camera if you don't want to. It's much more affordable than in-person therapy and you can start communicating with your therapist in under 48 hours. Join the millions of people who are seeing what therapy is really about. See if it's for you, because you are your greatest asset. This podcast is sponsored by BetterHelp and A Funny Feeling listeners get 10% off their first month at BetterHelp.com/afunnyfeeling. Add to Cart from Lemonada Media is a fun series that explores modern day consumerism. Each week, comedian Kulap Vilaysack and journalist SuChin Pak unleash their unbiased opinions on products, fads, celebs, philosophies, and anything else on their mind. Add to Cart is all about the thing we buy and the things we buy into. Like, does Kombucha have staying power? Are we over Tik Tok yet? Is that cult we learned about on a true-crime podcast maybe-possibly our higher calling? Add to Cart from Lemonada Media has new episodes dropping each Tuesday! Subscribe to Add to Cart on Apple, Spotify, Stitcher or wherever you get your podcasts. Advertise on A Funny Feeling via Gumball.fm See omnystudio.com/listener for privacy information.

This month, the gals chat about some unusual landscaping, their love for Bloomin' Onions, a librarian's revenge, one majorly hungry juror, and a super mysterious (not at all) murder. Tune in for this month's episode of Gossip at the Corpse Cart! Get your tickets to Wine & Crime LIVE on 10/1! https://www.momenthouse.com/wineandcrime?ref=m1 For a full list of show sponsors, visit https://wineandcrimepodcast.com/sponsors/

Steve Rosenberg is the Chief of Surgery at the National Cancer Institute, a position he has held continuously for the past 47 years. Steve is a pioneer in the field of immunotherapies for cancer and a recipient of nearly every major award in science. In this episode, Steve discusses his inspiration for devoting his career to cancer research and describes his keen observation of two cases of spontaneous cancer remission, driving him to learn how to harness the immune system to treat cancer. Steve's personal story essentially serves as a roadmap for the field of immunotherapy, from the very non-specific therapies such as interleukin-2, the discovery of tumor-infiltrating lymphocytes, checkpoint inhibitors, CAR T-cells, and adoptive cell therapy. Perhaps most importantly, Steve expresses his optimism for what lies ahead, especially in the face of some of the more recent discoveries with respect to tumor antigenicity. Finally, Steve discusses the human side of cancer which helps him to never lose sight of why he chose to become a physician. We discuss: Steve's childhood and inspiration to become a physician and medical researcher [3:15]; Patients that influenced Steve's thinking about cancer and altered the course of his career [13:15]; The discovery of antigen presentation, Steve's first job, and why he knew he wanted to study cancer [19:30]; Cancer treatment in the early 1970's and Steve's intuition to utilize lymphocytes [26:45]; Cancer cells versus non-cancer cells, and why metastatic cancer is so deadly [31:45]; The problem with chemotherapy and promise of immunotherapy [38:30]; How the immune system works and why it seems to allow cancer to proliferate [43:15]; Steve discovers how to use interleukin-2 to mediate cancer regression [52:00]; The immunogenic nature of certain cancers and the role of mutations in cancer [1:03:45]; The improbable story of how CAR T cell therapy was developed [1:16:30]; The discovery of tumor infiltrating lymphocytes (TIL) and engineering of T cells to recognize specific antigens [1:28:00]; Steve's experience treating President Ronald Reagan's colon cancer [1:36:00]; Why Steve has turned down many tempting job offers to focus on his research at the National Cancer Institute [1:41:00]; The role of checkpoint inhibitors in cancer therapy and the promise of adoptive cell therapy [1:43:00]; Optimism for using immunotherapy to cure all cancers [1:48:00]; The human side of cancer and the important lessons Peter learned from working with Steve [1:52:15]; and More Learn more: https://peterattiamd.com/ Show notes page for this episode: https://peterattiamd.com/StevenRosenberg  Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.