Podcasts about sirolimus

Sirolimus-coated Balloon Vs. Drug-eluting Stent in Elderly Patients with Coronary Artery Disease: A Propensity-score Matched Comparison

In this episode of Audible Bleeding, Jamila, Anh, and Naveed discuss the LifeBTK Trial with Principal Investigator Dr. Brian DeRubertis, where we discuss the new Abbott Esprit everolimus-eluting resorbable scaffold for the below-knee popliteal space. Guest: Dr. DeRubertis, is the Principal Investigator of the LIFE-BTK trial. He is the Chief of the Division of Vascular & Endovascular Surgery at New York-Presbyterian and Weill Cornell Medicine in New York City. Audible Bleeding Team Dr. Jamila Hedhliis a general surgery resident at the University of Illinois. Anh Dang, (@QuynhAnh_Dang), is a fourth year medical student at the University of Pennsylvania.  Dr. Naveed A. Rahman, (@naveedrahmanmd), is a Vascular Surgery Fellow at the University of Maryland.    References: Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease (LIFE-BTK). Advances in Endovascular Treatment of CLTI: Insights From the LIFE-BTK Trial. Diversity, Equity, and Inclusion in the LIFE-BTK Trial Evaluating the Esprit™ BTK Drug-Eluting Resorbable Scaffold for the Treatment of Infrapopliteal Lesions in Patients with Chronic Limb-Threatening Ischemia, VIVA 2024. Sirolimus-eluting stents vs. bare-metal stents for treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial (YUKON). Randomized comparison of everolimus-eluting versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial occlusive disease (DESTINY).  A prospective randomized multicenter comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-eluting stent in patients with ischemic peripheral arterial disease (ACHILLES). Sex Differences in Outcomes Following Endovascular Treatment for Symptomatic Peripheral Artery Disease: An Analysis From the K- VIS ELLA Registry. Drug-Coated vs Uncoated Percutaneous Transluminal Angioplasty in Infrapopliteal Arteries: Six-Month Results of the Lutonix BTK Trial.  Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries).  The IN.PACT DEEP Clinical Drug-Coated Balloon Trial: 5-Year Outcomes.     Follow us @audiblebleeding Learn more about us at  https://www.audiblebleeding.com/about-1/ and provide us with your feedback with our listener survey.

In this podcast, Dr. Valentin Fuster discusses the Target for NA trial, which compares biodegradable polymer stents to second-generation drug-eluting stents for coronary intervention. While the results showed the biodegradable stents were non-inferior in preventing target lesion failure, questions remain regarding their real-world performance and procedural handling in clinical practice.

Learn more about Rapamycin and book your first session with Allure Medical.https://www.alluremedical.com/promising-anti-aging-drugs-may-reverse-skin-aging/Can Rapamycin prolong human life?In this episode, Dr. Charles Mok talks about topical Sirolimus (Rapamycin) and its skincare benefits. He discusses why it is studied to expand the length of healthspan and lifespan in animals, including humans, and why a lot of doctors use Rapamycin as part of an anti-aging regimen.Discover scientific studies that prove how Sirolimus can improve the quality of the skin to look better and younger. He also walks us through the proper timing of medication when taking it as part of a skincare regimen for quick improvement of the skin. Tune in to the Inside The Cure Podcast — Sirolimus (Rapamycin): Skin Care Benefits.————————————————————————————————Subscribe to Inside the Cure on Apple Podcasts and leave a 5-star review! https://podcasts.apple.com/us/podcast/inside-the-cure-with-dr-charles-mok/id1495870043?uo=4Read the latest research and advice from the doctors at Allure Medical: https://www.alluremedical.com/books/ Dr. Charles Mok received his medical degree from Chicago College of Osteopathic Medicine, Chicago, Illinois in 1989. He completed his medical residency at Mount Clemens General Hospital, Mt. Clemens, Michigan. He has worked with laser manufacturing companies to improve their technologies; he has performed clinical research studies and has taught physicians from numerous other states. His professionalism and personal attention to detail have contributed to the success of one of the first medical spas in Michigan.LinkedIn: https://www.linkedin.com/in/charles-mok-4a0432114/Instagram: https://www.instagram.com/alluremedicals/Website: https://www.alluremedical.com/YouTube: https://www.youtube.com/@AllureMedical Amazon Store: https://www.amazon.com/stores/Dr.-Charles-Mok/author/B0791M9FZQ?ref=ap_rdr&store_ref=ap_rdr&isDramIntegrated=true&shoppingPortalEnabled=true #Skincare #Rapamycin #Sirolimus #AntiAging #GlowingSkin #Longevity #Healthspan #SkinQuality #SkinCareRegimen #SkinMedication #Wellness #AestheticMedicine #LongLife #HealthPodcast

N Engl J Med 2004;350:221-31Background: For the past year we have been posting reviews of seminal trials in cardiovascular medicine. It is our anticipation that these will ultimately be published in a textbook format that will be indexed by major subject headings and the reviews will be presented in chronological order. However, in curating postings for Substack we have had to jump around in order to maintain some consistency in the topics being presented. We started this year by reviewing medical therapies for patients with acute coronary syndrome. After that we moved to the management of patients with mostly stable coronary artery disease and have completed reviews on trials involving CABG and percutaneous coronary interventions compared to medical therapy and to each other, in the case of patients with left main and multivessel disease. In completing that stream of trials, we intentionally skipped trials that have been instrumental in developing those techniques, especially coronary stenting. While perhaps not that important to general readers, medical trainees, especially in the field of cardiovascular medicine need to be familiar with these trials. They are not intended to address questions involving stenting versus medical care but instead, to address the question of “If you're going to stent, is it better to use product A or B?”In that vein, we recently reviewed the RAVEL trial that compared sirolimus-eluting stents to bare metal stents. This is an issue of interest because a common problem following PCI is restenosis of the treated area due to the process of neointimal proliferation that involves the migration and proliferation of smooth muscle cells from the injured arterial wall. The idea behind drug coated stents was that the drug coatings would reduce this process locally (at the level of stented arterial wall) by blocking the process of neointimal proliferation and hyperplasia, which is not the same as atherosclerosis.RAVEL was a small trial showing that a sirolimus-eluting stent improved the surrogate endpoint of in-stent luminal loss at 6 months compared to a bare metal stent. The TAXUS-IV trial was undertaken for similar purposes but on a larger scale and sought to test a more clinically relevant endpoint. It sought to test the hypothesis that a paclitaxel-eluting stent would reduce ischemia-driven target-vessel revascularization compared to a bare metal stent.*Note to learners: A common parlance for describing stents in the clinical setting is to refer to them based on generation (e.g., first, second, or third generation). First generation stents are bare metal stents. Second and third generation stents are drug eluting stents with newer generations often featuring improved biocompatibility and drug delivery mechanisms. Sirolimus- and paclitaxel-eluting stents are considered second generation stents.Patients: Patients had to be 18 years of age or older, have stable or unstable angina or provokable ischemia, and were undergoing PCI for a single, previously untreated lesion in a native coronary artery. Angiographic inclusion required a single target lesion with a reference-vessel diameter on visual examination of 2.5 to 3.75 mm and a lesion length of 10 to 28 mm that could be covered by a single study stent. There were many exclusion criteria that can be summarized as follows: acute MI, complex coronary disease (including left main, ostial target lesion or bifurcating target lesion), complex patient and predisposition to bleeding.Baseline characteristics: The average age of patients was 62 years and 72% were men. Approximately 30% of patients had diabetes with nearly a quarter requiring insulin. Over 20% were smokers and 30% had a previous MI. The average LV EF was 55%. The target lesion was located in the LAD in 40%, the circumflex in close to 30% and the right coronary artery in 30%. The reference-vessel diameter was >/=3.0 mm in over 75% of patients. The average lesion length was 13 mm, average reference-vessel diameter was 2.75 mm, average minimal luminal diameter was 0.92 mm, and average % stenosis was 66%.Procedures: Patients were assigned in equal proportions in a double-blind fashion to treatment with either the paclitaxel-eluting stent or a visually indistinguishable bare-metal stent. Unfractionated heparin was administered according to standard practice, and the use of glycoprotein IIb/IIIa inhibitors was at the operator's discretion. After mandatory balloon dilation, patients received an appropriately-sized stent. A postprocedural electrocardiogram was obtained, and cardiac enzymes were measured every 8 hours for 24 hours. Patients took 325 mg of aspirin daily indefinitely and 75 mg of clopidogrel daily for 6 months. Clinical follow-up was scheduled at 1, 4 and 9 months and yearly thereafter for 5 years.Endpoints: The primary end point was the 9 month incidence of ischemia-driven target-vessel revascularization. It was considered to be “ischemia driven” if the stenosis of the target vessel was at least 50% of the luminal diameter on the basis of quantitative analysis with either: 1) ECG changes while the patient was at rest or 2) a functional study indicating ischemia in the distribution of the target vessel. It was also considered “ischemia driven” if there was a 70% stenosis in conjunction with recurrent symptoms alone.*It should be noted that in this case “ischemia driven” does not necessarily mean symptom driven.Major adverse cardiac events were defined as death from cardiac causes, MI, or ischemia-driven target-vessel revascularization. Target-vessel failure was defined as death, MI or ischemia-driven target vessel revascularization related to the target vessel. Analysis was based on the intention-to-treat principle. A total of 1172 patients were needed to detect a 40% relative reduction (6% absolute reduction) in the primary endpoint based on an anticipated event rate of 15% in the bare-metal stent group. This sample size would have 85% power with an alpha level of 0.05 to detect the difference described above while allowing for a drop out rate of 10%.Results: A total of 1,326 patients were enrolled over a 3 month period from 73 US centers and 1,314 were included in the final analysis with 662 in the paclitaxel-eluting stent group and 652 in the bare-metal stent group. The initial angiographic results were similar in the 2 groups.At 9 months, paclitaxel-eluting stents reduced the primary endpoint of ischemia-driven target vessel revascularization by 61% (4.7% vs 12.0%; RR 0.39; 95% CI 0.26-0.59). There were no differences in death from cardiac causes (1.4% vs 1.1%), MI (3.5% vs 3.7%), or stent thrombosis (0.6% vs 0.8%). In a prespecified subset of patients who underwent coronary angiography at 9 months, paclitaxel-eluting stents were associated with better angiographic features compared to bare-metal stents.Conclusions: In patients with stable and unstable angina (not acute MI), paclitaxel-eluting stents significantly reduced ischemia-driven target vessel revascularization at 9 months of follow-up with a number needed to treat of approximately 14 patients. There were no differences in any hard endpoints. While some would hail this as a remarkably positive trial we have reservations. Firstly, the primary endpoint is not symptom-driven and it should be regarded as a surrogate endpoint. At the time this trial was undertaken it was routine practice for patients to undergo surveillance testing with ECG's and functional tests following coronary revascularization and this is likely how the majority of patients came to undergo revascularization (not via a symptom-driven route). Had these elective revascularizations not occurred, it is unknown whether it would have resulted in any deleterious consequences.Second, patients enrolled in the trial were highly selected and no information is provided in the main manuscript on how many underwent screening. Commonly-occurring angiographic features of coronary lesions, for which patients undergo PCI, were excluded (i.e., ostial and bifurcating lesions, lesions in vessels with reference vessel diameters

N Engl J Med 2002;346:1773-1780Background: Percutaneous revascularization of the coronary arteries is frequently performed for patients with stable and unstable angina. By the late 1990s and early 2000s, most percutaneous coronary interventions (PCI) were performed with intracoronary stent placement rather than balloon angioplasty alone given lower rates of angiographic detected restenosis with stent placement. However, stent restenosis was a common cause of repeat revascularization. Unlike the process of atherosclerotic plaque development, stent restenosis is caused by a distinct process of neointimal proliferation. When a blood vessel is injured during a procedure like coronary stenting, the body's natural healing response triggers the migration and proliferation of smooth muscle cells from the vessel wall into the inner lining (intima), creating a new tissue layer called neointima. If the neointima grows excessively, it can narrow the blood vessel lumen, leading to restenosis, which can cause symptoms like angina.Early coronary stenting was performed using bare-metal stents that were prone to neointimal proliferation. Animal studies and a small clinical study at the time suggested that the systemic or local administration of the drug sirolimus could reduce neointimal proliferation. Sirolimus is a macrocyclic lactone that inhibits cytokine-mediated and growth-factor–mediated proliferation of lymphocytes and smooth-muscle cells.The RAVEL trial sought to assess the performance of stents coated with sirolimus (drug-eluting stents ”DES”) compared to uncoated stents (bare-metal stents “BMS”).Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: Eligible patients had stable angina, unstable angina, or silent ischemia. Only patients with single target lesions in a native coronary artery were included. The stenosis had to be 51-99% and could be covered by an 18 mm stent. The coronary artery had to be 2.5 – 3.5 mm in diameter.Patients were excluded if they had evolving myocardial infarction, left main disease unprotected by a graft, ostial lesions, calcified lesions that couldn't be completely dilated, angiographically visible coronary thrombus, ejection fraction

Author Robert W. Yeh, MD, FACC, and JACC Associate Editor Celina M. Yong, MD, FACC, discuss the results of the TARGET-IV NA trial. In the trial, 1720 patients with stable or acute coronary syndromes were randomized to undergo PCI with a BP-SES or any commonly used 2nd generation DES. At 12 months, BP-SES was non-inferior to control DES for the primary endpoint of Target Lesion Failure (cardiac death, target vessel-related myocardial infarction (MI), or ischemia-driven target lesion revascularization) which occurred in 3.4% of the BP-SES arm versus 3.3% in the control arm; p-value for non-inferiority. Secondary endpoints were also similar between groups.

David Fajgenbaum was in his third year of medical school when he was diagnosed with a rare and life-threatening disease that began shutting down his organs, bringing him perilously close to death. Although he survived the initial episode, he faced four additional relapses, each pushing him to the brink of death. In this episode, we speak with David about his relentless journey to discover the treatment that ultimately put his disease into remission. We also explore how his personal battle inspired the creation of a groundbreaking approach to help others suffering from rare diseases.Follow us on LinkedIn, X, Facebook and Instagram. Visit us at https://www.bio.org/

Drs Bui and Kelly discuss key long-term findings from the AMPECT trial investigating nab-sirolimus in patients with advanced malignant PEComa.

Dr Ganjoo discusses unmet needs for patients with malignant PEComa, treatment plan considerations, and the use of nab-sirolimus in this disease.

Dr Wagner discusses current unmet needs for patients with PEComa, how ongoing research aims to address some of these gaps, and how findings from the AMPECT trial in particular support the use of nab-sirolimus in patients with advanced malignant disease.

Autoimmune progesterone dermatitis - Sirolimus for KP rubra - Spironolactone does not cause cancer - Dupi -> Th17/23 issues - Berdazimer for molluscum - Want to donate to the cause? Do so here! http://www.uofuhealth.org/dermasphere Check out our video content on YouTube: https://www.youtube.com/@dermaspherepodcast and VuMedi!: https://www.vumedi.com/channel/dermasphere/ The University of Utah's Dermatology ECHO: ⁠https://physicians.utah.edu/echo/dermatology-primarycare - ⁠ Connect with us! - Web: ⁠https://dermaspherepodcast.com/⁠ - Twitter: @DermaspherePC - Instagram: dermaspherepodcast - Facebook: https://www.facebook.com/DermaspherePodcast/ - Check out Luke and Michelle's other podcast, SkinCast! ⁠https://healthcare.utah.edu/dermatology/skincast/⁠ Luke and Michelle report no significant conflicts of interest… BUT check out our friends at: - ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge) - ⁠https://www.levelex.com/games/top-derm⁠ (A free dermatology game to learn more dermatology!)

  Since his discovery in the 1990s sirolimus, also known as Rapamune, has been intriguing scientists with its antiaging and life extension potential. The cumulative research in labs have pointed towards strong biological evidence of cellular antiaging. Studies testing various types of mammals have all had consistent results of life extension up to 30% while preserving youthful vitality. Evidence in animal studies includes dogs who are having the same beneficial outcomes. The evidence has become so compelling that hundreds of thousands of people have started to make it part of their antiaging regimen. The clinical results have been impressive.   Dosed once a week, relatively inexpensive, extraordinarily low side effect profile, and an accumulating catalog of positive outcomes all are starting to build momentum for this agent. This podcast will share with you the science, philosophy and some of the evidence behind its use.   The episode kicks off with headlines from medical news including a cancer treatment that actually increases cancer risk, and when is prostate cancer not really cancer? And other topics.

A new research perspective was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 14, entitled, “Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?” In his new research perspective, Dr. Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center discusses aging and rapamycin (Sirolimus) — the only drug that consistently extends life span in countless animal studies in all species tested. He writes that individuals taking rapamycin and those not taking it will ultimately succumb to age-related diseases. However, if administered in disease-oriented dosages for an extended period of time, individuals taking rapamycin may experience a delayed onset of such diseases, and live longer. “The goal is to delay a particular disease that is expected to be life-limiting in a particular person.” Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. Dr. Blagosklonny further discusses the hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself. “I emphasize that aging is not programmed but, in contrast, quasi-programmed. Quasi means pseudo; seemingly; apparently but not really. Some scientists deliberately represent hyperfunction theory as theory of programmed aging. It's the opposite. Quasi-program is a continuation of a real program. Quasi-program has no intent, no purpose and it is always harmful.” DOI - https://doi.org/10.18632/aging.204920 Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204920 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, mTOR, hyperfunction, lifespan, health span, cancer, Alzheimer's disease About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

In this episode, host Dr. Christopher Beck interviews Dr. Peter Soukas about his algorithm for below the knee (BTK) critical limb ischemia (CLI) interventions as well as his implementation of new evidence-based guidance. --- CHECK OUT OUR SPONSOR Medtronic HawkOne Directional Atherectomy System https://www.medtronic.com/hawkone --- SHOW NOTES Dr. Soukas serves as the director of vascular medicine, the interventional peripheral vascular lab, and the endovascular medicine fellowship at Brown University in Providence, RI. In addition, he holds the position of associate professor of medicine at The Warren Alpert Medical School at Brown University. Dr. Soukas began his career as an interventional cardiologist. Over the course of his 13-year tenure in Providence, he has dedicated his career to the treatment of CLI and BTK disease. Prior to any interventional work, Dr. Soukas follows a comprehensive work-up including an ankle-brachial index (ABI), arterial duplex, and evaluating kidney function for safe administration of contrast. For a majority of cases, he uses the common femoral artery as the access point, but prefers to prep multiple access sites in the event of needing both anterograde and retrograde, or pedal, access. He discusses the use of the chronic total occlusion crossing approach based on plaque cap morphology (CTOP) classification on angiogram in determining the need for a retrograde approach. The type I morphology is characterized by the convexity of the plaque pointing away and is often treated successfully by an anterograde approach alone, as CTOP types II, III, and IV benefited from the addition of retrograde tibiopedal access. Once access is gained and the plaque morphology is evaluated using angiography, it becomes crucial to address any issues with the inflow to the affected vessel. This step ensures proper blood flow and provides a stable foundation for further interventions. Intravascular ultrasound is then used to assess the size and extent of the plaque, and then depending on the amount of calcification, either intravascular lithotripsy or calcium modifying technology can be used. Scoring balloons with low pressure may also be used for vessels that are moderately calcified and have been shown to have low rates of recoil and dissection. The main initiative of the procedure is to provide blood flow to the target angiosome which is dependent on the location of the wound. During his last remarks, Dr. Soukas comments on the future of BTK interventions, including Paclitaxel vs Sirolimus eluting stents, the use of self-expanding stents, and LimFlow, a minimally invasive technology that creates a channel between an artery and vein allowing the vein to provide blood flow to the foot. With the increasing prevalence of critical limb-threatening ischemia (CLTI) and high 12-month mortality rates in patients with amputations, Dr. Soukas ends the discussion by emphasizing how revascularization should be the preferred initial approach in treating CLTI due to the potential benefits it offers in terms of limb preservation and mortality reduction, urging practitioners to educate patients in being aggressive in their care. --- RESOURCES CTOP article: https://evtoday.com/articles/2018-may/using-plaque-cap-morphology-to-determine-cto-crossing-approach Disrupt PAD III Observational study: https://pubmed.ncbi.nlm.nih.gov/34380334/ PRELUDE BTK Study: https://pubmed.ncbi.nlm.nih.gov/34802313/ Intravascular Ultrasound study: https://www.jacc.org/doi/10.1016/j.jcin.2022.01.001 Intravascular US in Medicare Beneficiaries: https://pubmed.ncbi.nlm.nih.gov/35998803/ PROMISE II study: https://limflow.com/us/clinical-evidence/promise-ii-study-results/

In this episode of TSC Now, host Dan Klein dives deep on a new clinical trial in tuberous sclerosis complex (TSC) called TSC-STEPS. TSC-STEPS is a study to learn more about a drug known as Sirolimus and determine if it can prevent seizures and epilepsy in children diagnosed with TSC. The study is currently enrolling … Continue reading Episode 43: The TSC-STEPS Trial →

Taylor and Liz focus this week's episode on their past experiences with two different medications for vascular anomalies - sirolimus and alpelisib. Taylor and Liz have experienced treatment with both medications as part of their care journey. This week's episode focuses on side effects experienced and their opinions on the treatment options. The episode ends with a discussion on the role patients can play in advancing treatment options through clinical trials and research.Looking for updates or a way to connect with Taylor and Liz? Look for us on Instagram at the NotSoRarePodcast as well as on Facebook at the NotSoRarePodcast. Also, feel free to message us at notsorarepodcast@gmail.com. We love to hear from all of you!

Don't just live longer, live healthier! A natural medication that was discovered in the Eastern Islands centuries ago, is now being studied for its anti-aging properties. Rapamycin (also known as Sirolimus) was originally used as an antifungal medication and was known to suppress the immune system in high doses. More recent studies show its ability to enhance the immune system in lower doses, giving you energy, vitality, and enthusiasm for a longer, healthier life! Join Dr. Hotze and his guest Dr. Donald Ellsworth, as they discuss the anti-aging properties of Rapamycin and how it can improve your overall health as you age. The typical American lifestyle contributes to a host of health problems and disease. The book “Rapamycin” by Dr. Ross Pelton has been referenced in over 50,000 studies. Rapamycin is the most powerful drug today for people over 50! Listen today to learn how to increase your health span, not just your lifespan. Watch now and subscribe to our podcasts at www.HotzePodcast.com If you have any of the signs and symptoms mentioned on this podcast, take our free symptom checker test at https://www.hotzehwc.com/symptom-checker/

This week we play a session of the podcast from SCAI 2022 in Atlanta with Professor of Pediatrics, Columbia University - Dr. Christopher Petit reviewing a recent publication on the topic of systemic sirolimus in concert with catheter interventions for the treatment of pulmonary vein stenosis. Who is a candidate for this sort of therapy? Does systemic sirolimus confer a survival benefit over local stent delivery? Who should be caring for patients with pulmonary vein stenosis? Who is a candidate for transcatheter intervention vs. surgical intervention? Dr. Petit provides the answers in this live session from SCAI 2022. doi: 10.1016/j.jacc.2021.04.013

'This med student was given his last rites before he found a treatment that saved his life. His method could help millions more.' Today, Dr. David Fajgenbaum is my guest, but he should not be here. Known by his friends as 'the beast' - he went from being a fit young man, champion weightlifter and college quarterback – to fighting a rare disease that nearly killed him…five times.    David Fajgenbaum was a gifted medical student, a degree he was pursuing to honour the early death of his Mom to brain cancer. During his third year, David began to experience the symptoms of a rare idiopathic multicentric Castleman disease, from which there is no cure. Blood work confirmed the worst. His liver, kidneys, bone marrow, heart and lungs were shutting down. The only treatment to delay death is a carpet-bombing of chemotherapy.    Over the next few years, David found himself back in hospital on several occasions and fighting to stay alive. He knew chemotherapy wasn't the answer as you can only 'nuke' so much before it causes irreversible organ damage. So David took it upon himself to chase his cure. He knew that most rare diseases didn't have an FDA-approved drug, but he wondered if a drug approved for another disease could combat his.   After countless trials, and the collaboration of researchers worldwide, David Fajgenbaum tested a drug on himself called Sirolimus. A drug sitting in every pharmacy he had ever walked past during the first 3 1/2 years of his illness. The drug worked. Today, eight years later, David Fajgenbaum is a groundbreaking physician-scientist, disease hunter, speaker, and author of the national bestselling memoir, Chasing My Cure. He is married to his childhood sweetheart, Caitlyn, and they have two lovely children. His methodology of repurposing existing drugs to help others suffering from rare diseases might help millions more.   Flora Do, VP of RBC Healthcare, joins the show to talk about how RBC is supporting healthcare workers across Canada.    Dr. David Fajgenbaum -   Twitter: @DavidFajgenbaum Linked In: https://www.linkedin.com/in/davidfajgenbaum/ Chasing My Cure: https://chasingmycure.com     Web:    https://chatterthatmatters.ca Twitter – @TonyChapman – https://twitter.com/tonychapman Linkedin – https://www.linkedin.com/in/tonychapmanreactions/ Instagram – https://www.instagram.com/chatterthatmatters/ Youtube – https://www.youtube.com/channel/UCcGvzmw9MFkUcGylrFA2xC  RBC - https://www.rbc.com Flora Do   https://www.linkedin.com/in/flora-d-7b52062/   RBC Healthcare Advantage https://www.rbcroyalbank.com/healthcare/en/plans/advantage/index.html   RBC  - Helping Hands  http://www.rbc.com/newsroom/news/2020/20200601-helping-hands.html  

Listen to a soundcast of the November 22, 2021, FDA approval of Fyarro (sirolimus protein-bound particles for injectable suspension (albumin-bound) for locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor.

Jose M. de la Torre Hernandez, MD, PhD; Imanol Otaegui, MD; Asier Subinas, MD, PhD; Antonio Gomez-Menchero, MD, PhD; Raul Moreno, MD, PhD; Juan Rondan, MD, PhD; Erika Munoz-Garcia, MD; Fermin Sainz-La

Commentary by Dr. Julia Grapsa

Dr. Jon Ho on the Future of Dermpath and Education - Marijuana for Chronic Pruritus - Minoxidil for Loose Anagen Syndrome - Wildfire Smoke Worsens AD and Pruritus - Topical Sirolimus for Nevus Sebaceous and Epidermal Nevus - Dr. Ho's Knowledge In, Knowledge Out project: http://www.kikoxp.com/ - http://www.dermaspherepodcast.com/- Luke and Michelle report no conflicts of interest.

Commentary by Dr. Valentin Fuster

Why is the Asian population so different and difficult to treat for BTK complications compared to their European counterparts? This month's vascularPODCAST episode features guest host, Associate Professor Andrew Choong and panellists Associate Profs Tjung Tang and Edward Choke (Sengkang General Hospital, Singapore) to discuss chronic limb-threatening ischaemia (CLTI) with a focus on why ‘endovascular-first' is the go-to treatment option in Singapore. They examine the latest trial data available to support treatment options and consider what the future holds for CLTI treatment and BTK vasculature. Hear them discuss: - The differences between treating patients for BTK: Asia vs Europe - Examination of available data: FUTURE-BTK and MERLION - The Paclitaxel safety controversy, including an examination of the Katsanos meta-analysis - Sirolimus as a future technology for SFA, popliteal disease and BTK - DBCs to treat BTK: which are appropriate? - The future for CLTI treatment options and BTK vasculature

Environmental causes of skin aging - Sirolimus cream for CARP and AN - Lichen Sclerosus with Dr. Beth Morrel - Nutraceutical-drug interactions (part 2) (featuring Flava Flavinoid) Lichen Sclerosus Go Fish illustrator: swanbornillustrating.com/wp/ Dr. Morrell’s institution: www.eur.nl/en Dr. Morrel’s publications: pubmed.ncbi.nlm.nih.gov/?term=beth+mo…rel&sort=date www.dermaspherepodcast.com Luke and Michelle report no conflicts of interest.

This episode covers sirolimus!

The cover for issue 31 of Oncotarget features Figure 4, "Concentration dose-response curves of sirolimus effect [55 nM–1 nM] on the number of cells per surviving colony in U2OS cell line after 2 weeks exposure," by Vasuri, et al. which reported that the authors evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival. Three cell lines were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus. The number of colonies and the number of cells per colony were counted. As a result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus, while the number of U2OS colonies progressively decreased. In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types. Dr. Gianandrea Pasquinelli from The Bologna University said, "Rapamycin (sirolimus) is a widely used cytostatic drug blocking the cell cycle in the phase G1/S through the inhibition of the mammalian target of Rapamycin (mTOR) pathway, that has found several clinical applications, from immunosuppression in diabetes and organ transplantation to cancer therapy and drug-eluting stents (DES)" Beside to its cytostatic activity, sirolimus was also discovered to protect normal human oral keratinocytes from apoptosis by activating autophagy, and to act as a basal stem cell keratinocyte-protecting drug in irradiated mice. The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis. Sirolimus seems to block the proliferation and the migration of vascular smooth muscle cells, but we lack information concerning the effects on other cells composing atherosclerotic plaques. The aim of the present paper is to evaluate the long-term effects of sirolimus, rather than short-term cell survival, on three different cell in vitro models, cultured in Minimum Essential Medium, which simulates physiological conditions (w/o CO2 and glucose, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival. The Pasquinelli Research Team concluded in their Oncotarget Research Paper that the plaque typology and the different cell composition of the plaque, e. g., the presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus. Moreover, it is known that the clonal capacity varies between cells and we should consider this matter when evaluating the effectiveness of eluted stent. Finally, additional mechanisms can have a role, such as amitotic cell division. These mechanisms were also observed in human atherogenesis and could be fundamental to evaluate the in vivo effect of sirolimus too. Full text - https://www.oncotarget.com/article/27554/text/ Correspondence to - Gianandrea Pasquinelli - gianandr.pasquinelli@unibo.it Keywords - atherosclerosis, cell proliferation, sirolimus, stents About Oncotarget Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

JACC: Case Reports - Audio Summary by Dr. Julia Grapsa

Commentary by Dr. Valentin Fuster

C. Michael Gibson and Hiroki Shiomi look at long-term outcomes from RESET.

http://RunningAFEVER.com Caloric restriction (CR) is a reduction in caloric intake of 20-50% without malnutrition. NOT STARVING! There are no long-term benefits to starving :-). There's not even a long term. The process we are concerned with is called hormesis, which is when the body goes into defense mode, abating some aging processes. There is no definitive answer on how CR works. But quite a bit of research has been conducted. A 2017 report on primate study found fewer age-related disorders in CR primates. Since the 1930's CR in rats has shown increased lifespan. Suprisingly, CR has been found to preserves muscle tissue in primates. The longevity is not just due to fat reduction, which is insignificant factor. 1200 calories, she says Dr. Anne Brunet, PhD on the Standord University YouTube channel, is hard to achieve, but is in the optimal range for CR. CR has also been found in many of the Blue Zones (see episode 128). Since true CR is difficult to achieve while getting all the energy and nutrients you need, there is research on how to mimic the benefits of CR. One way is through intermittent fasting. An National Institute on Aging study found that fasting increases lifespan regardless of diet. One popular IF diet is the 5:2 diet, 5 days of normal caloric intake, followed by 2 days of 500-600 calories per day. There are also compounds called Caloric Restriction Mimetics (CRM's) that may provide the benefits of CR in supplementation. Here are some of them: Rapamycin, a compound found in soil on easter island (named after local name of that place) increases longevity in mice and other organisms. Aspirin: an NIH report says aspirin improves autphagy in mice. Autophagy is a detox process to clean out dead cells and make new ones. This is just another reason to take aspirin, recommended to prevent cardiovascular disease. Metformin is an anti-diabetic drug that comes from french lilac plants. It increases insulin sensitivity, making the liver produce less glucose. This reduces glycation, which is a kind of body fueling-gone-wild, and is associated with aging. Resveratrol is found in skin of grapes, and is also what people take to get the "red wine benefit" without drinking. It is also an anti-inflamatory. Wikipedia is critical of longevity claims, and says resveratrol has not increased longevity in rats in any study. NAD+ is another one, and for an in-depth look at this, go back and listen to episode #125. Gynostemma pentaphyllum (G. pentaphyllum) supplementation in humans has been shown to exert effects seen in CR, such as improved glucose metabolism and reduced body weight. There are detriments. The big one is risk of malnutrition. There was a very dangerous Minnesota Starvation Experiment 1944 conducted on WWII concientious objectors. The results included anemia, edema, muscle wasting, weakness, neurological deficits, dizziness, irritability, lethargy, and depression. CR can interfere with growth processes, and should not be tried by anyone who is under the age of 21 or pregnant. Also, CR in people with a lower than normal BMI has an increased mortality rate. The bottom line is that like blue zone observations, CR seems to be a factor in longevity, but it can be harmful if not done correctly. Beware of the dangers, especially malnutritious. Trying to figure out how to be adequately (or better OPTIMALLY) nourished is not something I've found easy to do. Sources: Dr. Anne Brunet lecture https://www.youtube.com/watch?v=sppJywBkKB8 CR and supplements to mimic https://www.lifeextension.com/Protocols/Lifestyle-Longevity/Caloric-Restriction/Page-01 Rapamycin https://en.wikipedia.org/wiki/Sirolimus https://en.wikipedia.org/wiki/MTOR CR qualities of Aspirin https://www.ncbi.nlm.nih.gov/pubmed/29490275 https://blog.bulletproof.com/autophagy-for-longevity-detoxification/ Wikipedia article on CRMs https://en.wikipedia.org/wiki/Caloric_restriction_mimetic Wikipedia article on CR https://en.wikipedia.org/wiki/Calorie_restriction https://www.nia.nih.gov/news/longer-daily-fasting-times-improve-health-and-longevity-mice https://www.nia.nih.gov/health/calorie-restriction-and-fasting-diets-what-do-we-know Weight (change since Jan 2018): 205 (-69) Workout time: 187 Minutes Total Distance (total since Nov 2017): 8.63 Miles (419.21) Steps: 19,032 Muscle Mass (change since Aug 2018): 153.64 (+10) Body Fat: 25.20% Daily Sleep Duration 7-day Avg: 8 hours 2019 Goal: 15% Body Fat

This week we explore the world of cardiac transplantation with particular emphasis on the Fontan patient and transplantation. Outcomes are improving rapidly. Why is this? What about the liver and how are decisions made regarding cardiac versus cardiac+hepatic transplantation in this patient population? We review all of these questions with world authority on cardiac transplantation Dr. Daphne Hsu, Professor of Pediatrics, Chief of Pediatric Cardiology and Interim Chair of Pediatrics at Montefiore - Albert Einstein College of Medicine. Her insights into this complex patient group are valuable and novel. Article reviewed: DOI: 10.1016/j.athoracsur.2016.08.110

This week we explore the world of cardiac transplantation with particular emphasis on the Fontan patient and transplantation. Outcomes are improving rapidly. Why is this? What about the liver and how are decisions made regarding cardiac versus cardiac+hepatic transplantation in this patient population? We review all of these questions with world authority on cardiac transplantation Dr. Daphne Hsu, Professor of Pediatrics, Chief of Pediatric Cardiology and Interim Chair of Pediatrics at Montefiore - Albert Einstein College of Medicine. Her insights into this complex patient group are valuable and novel. Article reviewed: DOI: 10.1016/j.athoracsur.2016.08.110

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Thu, 20 Nov 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18190/ https://edoc.ub.uni-muenchen.de/18190/1/Hoffmann_Anna_Lena.pdf Hoffmann, Anna Lena

Systemische Immunsuppression nach Herztransplantation wurde in den letzten zwanzig Jahren fast ausschließlich unter Zuhilfenahme von Calcineurininhibitoren (CNI) wie Tacrolimus oder Ciclosporin A durchgeführt. Diese Medikamente besitzen jedoch ein erhebliches Nebenwirkungsprofil, und reduzieren insbesondere aufgrund ihrer Nephrotoxizität die Lebensqualität und Lebenserwartung der Patienten. Mit Proliferations-Signal-Inhibitoren wie Sirolimus und Mycophenolat Mofetil (MMF) stehen jedoch auch Immunsuppressiva zu Verfügung die ein anderes Nebenwirkungsprofil besitzen. Frühere Studien, mit dem Versuch Therapieregime zu ändern, auf Calcineurininhibitoren zu verzichten und ausschließlich auf Sirolimus und MMF zu wechseln, brachten vielversprechende Ergebnisse in Bezug auf Abstoßungsfreiheit und Transplantatvaskulopathie. Die Nierenfunktion konnte durch den Therapiewechsel erhalten werden und eine fortschreitende Nierenschädigung sogar verhindert werden (Fenandez-Valls M.2005). Alle diese bisherigen Untersuchungen basierten jedoch auf Studienprotokollen, die ein spätes Absetzen der Calcineurininhibitoren vorsahen. In dieser Studie wurden fünfzehn Patienten unmittelbar ab dem Zeitpunkt der orthotopen Herztransplanatation mit einer Calcineurininhibitor freie Immunsuppression behandelt. Als Basis- immunsuppression erhielten die Patienten Sirolimus (Rapamune®, Wyeth Pharma, Münster) mit angestrebtem Plasmaspiegel zwischen 10 und 15ng/ml, MMF (Cellcept®, Roche Pharmaceuticals AG, Basel, Schweiz) mit angestrebtem Talspiegel zwischen 1,5 und 4 µg/ml, sowie Corticosteroide (Prednisolut®, Mibe GmbH, Sandersdorf-Brehna) mit einer Dosis von initial 1mg/kg/Tag auf 0,1mg/kg/Tag ausgeschlichen. Die Patienten wurden über einen Zeitraum von fünf Jahren nachuntersucht. Dabei wurde neben dem Überleben der Patienten unter anderem die Häufigkeit von Abstoßungsreaktionen, Transplantatvaskulopathie, Pumpfunktion des Grafts, Nierenfunktion sowie Lipid und Glucosestoffwechsel beobachtet. Unsere Studie zeigte, dass de novo Calcineurininhibitor-freie Immunsuppression nach Herztransplantation mit guten klinischen Ergebnissen möglich ist, 14 der 15 in die Studie eingeschlossenen Patienten waren nach fünf Jahren am Leben. Die Anzahl der Abstoßungsreaktionen war jedoch höher als unter konventioneller Immunsupression. In unserer Studie, mit komplett CNI freiem Therapieprotokoll, war nach fünf Jahren lediglich bei 40% der Patienten keine Abstoßungsreaktion aufgetreten. Im Rahmen der Transplantatvaskulopathie kommt es nach Herztransplantation häufig zu einer Intimaproliferation und so zu einer Einengung der Gefäßdurchmesser. Die TVP stellt langfristig die primäre Ursache für ein Transplantatversagen dar und führt so entweder zum Tode oder zu einer erneuten Transplantation. In unserer Kohorte wurde über einen Beobachtungszeitraum von 5 Jahren keine Transplantatvaskulopathie beobachtet. Die Serumtriglyceridspiegel waren trotz Therapie mittels Statinen erhöht. Die chronische Nierenschädigung durch Calcineurininhibitoren ist irreversibel und die Nierenfunktion kann sich nur in geringem Maße erholen, wenn diese abgesetzt werden (Ojo AO, 2003). Sowohl MMF als auch Sirolimus haben keine nephrotoxischen Effekte und die Kombination beider verspricht einen Erhalt der Nierenfunktion über lange Zeit. Die Nierenfunktion in unserer Kohorte blieb nicht nur stabil, sondern verbesserte sich sogar leicht in dem Zeitraum der 5-Jahres Untersuchung. In keinem Fall wurde eine Nierenersatztherapie erforderlich. Die Kombination von MMF und Sirolimus mit kompletter Vermeidung von Calcineurininhibitoren scheint die Nierenfunktion zu erhalten und verbessert daher auch das Langzeit - Überleben. Während die Nephrotoxizität vermieden werden konnte, traten aber häufig andere nachteilige Ereignisse auf. Chirurgische Interventionen aufgrund von Perikardergüssen wurden in 5 Fällen erforderlich. Auch Pleuraergüsse, periphere Ödeme und venöse Thrombosen wurden beobachtet. Zwei Patienten mussten zwischenzeitlich aus der Studie genommen werden, da schwere gastrointestinale Nebenwirkungen auftraten. In drei Fällen wurde eine Konversion zu Calcineurininhibitoren nötig, da verzögerte Wundheilung auftrat, die eventuell auf den antiproliferativen Effekten von Sirolimus auf Fibroblasten beruht. Beim Vergleich mit Calcineurininhibitor basierter Immunsuppression, sollten uns mehrere Ergebnisse davor warnen, diese Therapie als Standard nach Herztransplantation zu verwenden. Allen voran die Anzahl der Abstoßungsreaktionen. Diese können schwerwiegende Folgen haben und schlimmstenfalls zu irreversiblem Transplantatversagen führen. Für Patienten, die beispielsweise ein beginnendes Nierenversagen haben, ist diese Immunsuppression jedoch ins Auge zu fassen. Unsere Daten zeigen einen außergewöhnlichen Effekt in Bezug auf das Auftreten der Transplantatvaskulopathie, dem Verlauf der Nierenfunktion und dem Auftreten von Transplantatvaskulopathie, verglichen mit Patienten, die mit Calcineurininhibitoren behandelt wurden. Die Verbesserung der Nierenfunktion für Patienten, mit beginnendem Nierenversagen ist ermutigend, hinsichtlich Erhaltung von Nierenfunktion und damit Lebensqualität nach Herztransplantation

Thu, 3 Apr 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17673/ https://edoc.ub.uni-muenchen.de/17673/1/Stroeh_Katja.pdf Ströh, Katja

Background: Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. Methods: Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 +/- 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. Results: The mean loss of FEV(1) was - 2.30 +/- 0.52 ml/day before therapy and a significant mean gain of FEV(1) of 1.19 +/- 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV(1) and FVC at baseline were 1.12 +/- 0.15 l (36.1 +/- 4.5%pred.) and 2.47 +/- 0.25 l (69.2 +/- 6.5% pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months Delta FEV(1): 220 +/- 82 ml, p = 0.024; 6 months Delta FEV(1): 345 +/- 58 ml, p = 0.001); (3 months Delta FVC: 360 +/- 141 ml, p = 0.031; 6 months Delta FVC: 488 +/- 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. Conclusions: Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Die akute GvHD stellt eine der Hauptkomplikationen nach allogener hämatopoetischer Stammzelltransplantation dar. Gerade bei Refraktärität auf die primäre Standardtherapie mit Kortikosteroiden liegt ein sehr hohes Risiko vor, an den Folgen der unbeherrschten GvHD oder an Infektionen im Rahmen der ausgeprägten Immunsuppression zu versterben. Bisher konnte keine Zweitlinientherapie bei Steroidrefraktärität als erfolgsversprechend etabliert werden. Die extrakorporale Photopherese ist eine extrakorporale Photochemotherapie, bei der mittels UVA-Licht und 8-Methoxypsoralen die behandelten Leukozyten in Apoptose gehen und anschließend zu einer Immunmodulation mit Entstehung einer Toleranz führen. Der genaue Mechanismus dieses gut tolerablen Verfahrens ist nicht abschließend geklärt. Nachdem die Anwendung im Rahmen der chronischen GvHD gute Ergebnisse erzielen konnte, werden zunehmend auch Patienten mit akuter GvHD mittels ECP behandelt. Bisher existieren jedoch nur wenige Vorberichte, die größte Studie umfasst 59 Patienten. In der hier vorliegenden retrospektiven Analyse von 30 Patienten mit steroidrefraktärer akuter GvHD wiesen 7 Patienten (23,3%) eine GvHD Grad II, 13 Patienten (43,4%) eine GvHD Grad III und 10 Patienten (33,3%) eine GvHD Grad IV auf. Die akute GvHD trat im Median an Tag 20 nach Stammzelltransplantation auf und im Median wurde 18 Tage nach Beginn der GvHD mit ECP gestartet. Die Kriterien des Ansprechens wurden abhängig von der benötigten Menge an Kortikosteroiden folgendermaßen definiert: CR bedeutet ein komplettes Absetzen der Kortikosteroide, PR eine maximale Dosis von 10 mg täglich, MR eine Reduktion der Dosis auf weniger als 50% der Ausgangsdosis vor ECP aber mehr als 10mg und NR eine Reduktion um weniger als 50% oder keinerlei Ansprechen. Nach einer medianen Anzahl von 15 ECP-Sitzungen über einen Zeitraum von 54 Tagen (Median) ergaben sich folgende Ansprechraten: 11 Patienten (36,7%) erreichten eine CR, 9 (30,0%) eine PR, 4 (13,3%) eine MR und 6 (20,0%) eine NR. Im Median konnten die Steroide von 150mg vor ECP auf 5 mg nach ECP reduziert werden. Während des Nachbeobachtungszeitraums von maximal 1073 Tagen und einer medianen Follow-Up-Zeit von 777 Tagen überlebten insgesamt 12 der 30 Patienten, entsprechend 40,0%. Das mediane Gesamtüberleben lag bei 394 Tagen. Ein signifikanter Unterschied (p=0,015) im Gesamtüberleben ergab sich zwischen Patienten mit GvHD Grad II (57,1) / Grad III (53,8%) und Grad IV (10,0%). Ebenso signifikant besser überlebten die Patienten, die sehr gut oder gut (CR und PR) auf die ECP angesprochen haben (OS 54,5% und 55,5%) im Gegensatz zu denen, die kaum (MR, OS 25,0%) oder nicht (NR, OS 0,0%) von der ECP profitierten. Patienten mit GvHD-Befall von maximal 2 Organen (OS 68,8%) zeigten einen signifikanten Überlebensvorteil (p=0,01) gegenüber den Patienten mit Befall von 3 oder mehr Organen (OS 7,1%). Weitere Parameter, die Einfluss auf das OS nehmen, aber aufgrund der kleinen Patientengruppe nicht statistisch signifikant waren, sind das Auftreten einer Mikroangiopathie (OS 41,2% ohne Mikroangiopathie versus 20,0% mit Mikroangiopathie), der Zeitpunkt der GvHD (OS 31,0% bei GvHD vor Tag 20 versus 50,0% bei GvHD ab Tag 20) und die Spender-Empfänger-Geschlechts-Konstellation (OS 60,0% bei weiblichem Spender/männlichem Empfänger versus 30,0% bei den anderen Konstellationen). Patienten, die zusätzlich zur ECP Sirolimus erhielten, erreichten bessere Überlebensraten als Patienten ohne Sirolimus (46,2% versus 35,3%).Die TRM ein Jahr nach SCT betrug 40%, wobei auch hier für GvHD Grad II und III im Gegensatz zu GvHD Grad IV ein deutlicher Vorteil vorhanden war. Die TRM an Tag 365 in den einzelnen Response-Gruppen teilt sich folgendermaßen auf: 18,2% in der CR-Gruppe, 22,2% in der PR-Gruppe, 50,0% in der MR-Gruppe und 100,0% in der NR-Gruppe. An Todesursachen führend waren infektiöse Komplkationen, teiweise in Kombination mit Folgen der GvHD. 83,3% der am Leben verbliebenen Patienten litten im weiteren Verlauf an einer chronischen GvHD, davon aber nur 33,3% an einer schweren chronischen GvHD. Als signifikanter Faktor für das Erreichen einer CR oder PR erwies sich in einer univariaten Analyse lediglich der Grad der GvHD. Zusammenfassend konnte durch Einsatz der ECP bei steroidrefraktären Patienten mit akuter GvHD im Vergleich zu anderen Therapieoptionen ein für die Situation der Steroidrefraktärität gutes Gesamtüberleben erreicht werden, wobei kein Überlebensunterschied zwischen Patienten mit CR und PR festzustellen war. Insgesamt profitieren jedoch nicht alle Patienten und die Effektivität sollte in Zukunft anhand prospektiver Studien genauer evaluiert werden.

Thu, 14 Oct 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12472/ https://edoc.ub.uni-muenchen.de/12472/1/Adnan_Yerli.pdf Yerli, Adnan

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate antineoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor- free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor- free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor- free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2(1/2)-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.

Wed, 18 Oct 2006 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/7928/ https://edoc.ub.uni-muenchen.de/7928/1/Gerstorfer_Michael.pdf Gerstorfer, Michael Johann

Quantification of the new immunosuppressant sirolimus (syn. rapamycin; Rapamune((R))) in whole blood by chromatography is essential for its clinical use since no immunoassay is available although monitoring is mandatory. Here we report on a rapid and convenient liquid chromatography (LC)-tandem mass spectrometry method and describe our practical experience with its routine use. Whole blood samples were hemolyzed and deproteinized using an equal volume (150 mul) of a mixture of methanol/zinc sulfate solution containing the internal standard desmethoxy-rapamycin. After centrifugation, the clear supernatants were submitted to an on-line solid-phase extraction procedure using the polymeric Waters Oasis HLB(R) material, with elution of the extracts onto the analytical column in the back-flush mode by column switching. For analytical chromatography a RP-C18 column was used with 90/10 methanol/2 mM ammonium acetate as the mobile phase. A 1:10 split was used for the transfer to the mass spectrometer, a Micromass Quattro LC-tandem mass spectrometry system equipped with a Z-spray((R)) source and used in the positive electrospray ionization mode. The following transitions were recorded: sirolimus, 931>864 m/z, and desmethoxy-rapamycin (I.S.), 901>834 m/z. The analytical running time was 5 min, including on-line extraction. The method has a linear calibration curve (r>0.99; range 1.6-50 mug/l) and is rugged and precise with monthly CVs