Podcasts about Tacrolimus

In this episode of ASTCT Talks, Dr. Shernan Holtan welcomes Andrew Lin, Manager of Clinical Pharmacy Services of Adult BMT and CTS at Memorial Sloan Kettering Cancer Center, to discuss the evolving role of tacrolimus levels in GVHD prophylaxis within the post-transplant cyclophosphamide (PTCy) era. They explore findings from a recent retrospective study examining whether higher tacrolimus levels offer added protection against GVHD, what this means for toxicity and patient outcomes and how these insights are shaping dosing strategies. The conversation also looks ahead to future research areas, including MMF optimization and the potential for simplified, patient-centered prophylaxis regimens.

A Fibroblast Renaissance A New ACR A useful urinary biomarker for lupus nephritis ANA+ and no Autoimmune Disease? Check the liver CAR-T Therapy and Lupus Cyclophosphomide vs Mycophenolate vs Tacrolimus in Lupus Nephritis Evaluating ANA Patterns and Titers with AI Neuropsychiatric Lupus: The Forgotten Symptoms The 2024 ACR Guidelines for Lupus Nephritis Vaccine Responses:The DMARD Counts What is MCTD? The Great Debate  

JAKi Studies at ACR:Dr. Peter Nash Palliative Care in Rheumatology:Dr. Jiha Lee talks with Dr. Shannon Herndon Estimating Inflammation, Damage and Patient Distress:Dr. Jack Cush talks with Dr. Ted Pincus Methotrexate and the Gut Microbiome:Dr. Jonathan Kay talks with Dr. Rebecca Blank Poly-treatment of Polymyalgia Rheumatica?:Dr. Janet Pope Predicting Flares in Rheumatoid Arthritis:Dr. Jonathan Kay interviews Dr. John Isaacs  "Changing Mindsets about Methotrexate Side Effects":Dr. Mrinalini Dey Biologic Monotherapy vs Combination with cDMARDs in PsA:Dr. Adela Castro Cyclophosphomide vs Mycophenolate vs Tacrolimus in Lupus Nephritis:Dr. Mike Putman ANA+ and no Autoimmune Disease? Check the liver:Dr. Janet Pope SELECTing the right patients: upadacitinib in GCA:Dr. Brian Jaros Neuropsychiatric Lupus: The Forgotten Symptoms:Dr. Mrinalini Dey talks with Dr. Chris Wincup

Explore strategies for optimizing transplant outcomes through tailoring of tacrolimus therapy.    Credit available for this activity expires: 11/18/2025 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1001813?ecd=bdc_podcast_libsyn_mscpedu

The Journal of Rheumatology's Editor-in-Chief Earl Silverman discusses this month's selection of articles that are most relevant to the clinical rheumatologist. Patient-Reported Impact of Symptoms in Fibromyalgia (PRISM-FM) - doi.org/10.3899/jrheum.2023-0721 Investigating the Influence of Patient Eligibility Characteristics on the Number of Deferrable Rheumatologist Visits: Planning for a Patient-Initiated Follow-Up Strategy - doi.org/10.3899/jrheum.2023-0891 Psychometric Properties of Patient Global Assessment in Psoriatic Arthritis: A Systematic Literature Review - doi.org/10.3899/jrheum.2023-0722 Long-Term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis in Japan: 10-Year Analysis of the Real-World TRUST Study - doi.org/10.3899/jrheum.191008 Understanding the Employment Landscape in People With Systemic Sclerosis - doi.org/10.3899/jrheum.2023-0975

InpharmD's EBM podcast focuses on commonly asked DI questions. Every day, our queue gets tons of new questions asked from providers all around the country. Today's podcast focuses on the use of phenytoin to treat tacrolimus toxicity. 

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities. Episodes originally aired from 2016 to 2021. Originally released: February 13, 2019 In the second half of our two-part series on complications of organ transplantation, Dr. Raj Dhar (Neurocritical Care, Washington University in St. Louis) discusses his experience managing the noninfectious complications of organ transplantation--from drug toxicities to multidisciplinary medical care. Produced by James E Siegler and Raj Dhar. Music by Steve Combs, Lee Rosevere, and Scott Holmes. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. Be sure to follow us on Twitter (now X) @brainwavesaudio for the latest updates to the podcast. REFERENCES Dhar R, Young GB, Marotta P. Perioperative neurological complications after liver transplantation are best predicted by pre-transplant hepatic encephalopathy. Neurocrit Care 2008;8(2):253-8. PMID 17928960Dhar R. Neurologic complications of transplantation. Handb Clin Neurol 2017;141:545-572. PMID 28190435Mateen FJ, Dierkhising RA, Rabinstein AA, Van De Beek D, Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transplant 2010;10(4):908-14. PMID 20121751Muñoz P, Valerio M, Palomo J, et al. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore) 2010;89(3):166-75. PMID 20453603Senzolo M, Ferronato C, Burra P. Neurologic complications after solid organ transplantation. Transpl Int 2009;22(3):269-78. PMID 19076332Wu Q, Marescaux C, Wolff V, et al. Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol 2010;64(3):169-77. PMID 20699617 We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Dr David Colen gives his perspective on the article "The Effect of Local Purified Exosome Product, Stem Cells, and Tacrolimus on Neurite Extension" by Rademakers et al, which appears in the March 2024 issue of The Journal of Hand Surgery.

Dr David Colen gives his perspective on the article "The Effect of Local Purified Exosome Product, Stem Cells, and Tacrolimus on Neurite Extension" by Rademakers et al, which appears in the March 2024 issue of The Journal of Hand Surgery.

In this episode, we talk about GVHD prophylaxis, including recent data on post-transplant cyclophosphamide and abatacept with Dr. Shernan Holtan from the University of Minnesota. Here are the key trials we discussed:1. BMT CTN 1203 trial: Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of GVHD in allogeneic transplantation. https://pubmed.ncbi.nlm.nih.gov/30824040/ 2. BMT CTN 1703 study: Post-Transplantation Cyclophosphamide-Based GVHD prophylaxis  https://pubmed.ncbi.nlm.nih.gov/37342922/ 3. Patient-Reported Outcomes of BMT CTN 1703 https://ash.confex.com/ash/2023/webprogram/Paper187859.html 4. Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil https://pubmed.ncbi.nlm.nih.gov/37311510/ 5. BMT CTN 1301 trial: Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies https://pubmed.ncbi.nlm.nih.gov/34855460/ 6. Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2) https://pubmed.ncbi.nlm.nih.gov/33449816/ 7. Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus https://ash.confex.com/ash/2023/webprogram/Paper181292.html

Kent talks to Jaime Imhof, a dual donor double transplant recipient. In June 2022 she was rushed to the hospital raging with multiple infections and organ failure. and was given a 10% chance of survival. Jamie needed a liver transplant first to survive, breaking the six-month sobriety rule in a groundbreaking program led by Johns Hopkins Hospital. After that, she also required a kidney transplant as well due to acute kidney injury and failure from Hepatorenal Syndrome and Tacrolimus. She is 14 months post liver transplant and 7 months post kidney transplant.  If you have questions regarding items discussed during this episode or would like more information about Kidney Solutions weekly Support Group, contact Kent at kent.bressler@kidneysolutions.org For more information about Kidney Solutions, visit us at www.kidneysolutions.org Host: Kent Bressler Producer: Jason Nunez

Omega-3s help isotretinoin - Covid and autoimmune disease - Transient abdominal telangiectasia of the newborn - Systemic tacrolimus in derm - MTX + prednisone for alopecia totalis/universalis - Tofacitinib for BP - 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!)

Bacterial pneumonia treatment now available; FDA deny proposed anaphylaxis treatment; Results on flu vaccine efficacy; More flexible dosing for Talicia; Change in the therapeutic equivalence for organ rejection drug generic. 

Mr. Pierre Giguère and Dr. Swapnil Hiremath provide an overview of their study, "Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients," on behalf of their colleagues.

Mr. Pierre Giguère and Dr. Swapnil Hiremath provide an overview of their study, "Management and Outcome of COVID-19 Infection Using Nirmatrelvir/Ritonavir in Kidney Transplant Patients," on behalf of their colleagues.

In this episode, we review clinical pearls and common pitfalls of immunosuppression regimens for organ transplantation with a particular focus on tacrolimus and mycophenolate. Key Concepts Most recipients of an organ transplantation will be on a two or three drug regimen. The most common regimen is tacrolimus and mycophenolate with/without a corticosteroid. Tacrolimus is hepatically eliminated and susceptible to CYP3A4 and PGP drug interactions. Particularly at higher drug concentrations, it is associated with nephrotoxicity and neurotoxicity (among several other adverse effects). Mycophenolate is unstable in the acidic environment of the stomach. The two formulations on the market are CellCept (which uses a prodrug, mycophenolate mofetil, that is converted in the liver to an active compound) and Myfortic (an enteric-coated formulation of mycophenolic acid, which releases after exiting the stomach). The intensity of an immunosuppression regimen is determined by numerous factors, including the type of organ, how long ago the organ was transplanted, if acute rejection has occurred in the past, patient-specific risk factors, and more. Additional Resources Register to be a donor at Donate Life America (https://donatelife.net) or at the HRSA OrganDonor.gov site (https://www.organdonor.gov) Learn more about stem cell donation and transplant at https://bethematch.org

En entrevista con Pamela Cerdeira, para MVS Noticias, Maribel Ramírez Coronel, periodista especializada en temas de salud pública, columnista en El economista habló de ‘Tacrolimus' de mala calidad y pacientes renales afectados.See omnystudio.com/listener for privacy information.

1 Facial erythema in patients with atopic dermatitis treated with Dupilumab- a descriptive study of morphology and aetiology2 The need for potassium monitoring in women on spironolactone for dermatologic conditions3 Tacrolimus “swish and spit” for complex aphthosis: outcomes in 21 patients4 Increasing prevalence of ANA in the US5 Cutaneous polyarteritis nodosa diagnosis and treatment: retrospective case series6 Cutaneous manifestations of monogenic auto-inflammatory diseases: an international cohort study from the juvenile inflammatory rheumatism cohort7 Measuring atopic eczema control and itch intensity in clinical practice a consensus statement from the harmonising outcome measures for eczema in clinical practice (HOME-CP) initiative8 Apremilast in recalcitrant cutaneous dermatomyositis: a non-randomised controlled trial9 Isla Galpin. Violin Sonata in G minor, 1st and 2nd movement by Eccles

It can be helpful to hear from others going through the same struggle or journey as you. My guest today shares her powerful story of determination and never giving up on finding the root cause for her rashes which started in childhood. Today's guest is Dominika O'Sullivan, a former city girl thriving in the beautiful West of Ireland and transitioning to countryside living. She is a lifelong eczema warrier and Protopic withdrawal sufferer who was failed by several medical, skin and alternative medicine professionals and is currently discovering and addressing her root causes of the original condition while happily witnessing symptoms reduction and disappearance. Professionally, Dominika is a Human Resources and employment law consultant working with businesses and assisting employers in identifying simple solutions to complex people challenges. For those who are not familiar with Protopic -- it's a non-steroidal immunosuppressant drug also called Tacrolimus. Whether it's Protopic Withdrawal or suffering from other rashes, what has helped you on your journey? Let me know in the comments what was a turning point for you! In this episode: Dominika's journey of childhood to adulthood eczema + Protopic Withdrawal The many treatments she tried (both natural + conventional) What was the turning point for her? Where Dominika applied Protopic What has changed since working with Jen's practice Dominika's advice to others struggling with Protopic Withdrawal Quotes “Throughout my childhood, I just remember the stories of having to wear gloves like many kids with eczema and atopic dermatitis would have to, because I was scratching so bad that my hands would be covered in blood in the morning." [01:17] "I was probably at the verge of a nervous breakdown because I kept my full-time job, which is relatively stressful and it requires high focus of attention. But I couldn't sleep and I was experiencing all those debilitating symptoms." [7:05] Links Follow Dominika on Instagram here (Please note she can pick up messages but doesn't post.) TSW Podcast with Jennifer Fugo, MS, CNS interview mentioned by Dominika Book an assessment session with Jen's clinical practice here

Nirmatrelvir-Ritonavir continues to be recommended for outpatient treatment of COVID-19 infections, especially as cases continue to rise. However, this therapy does present clinical challenges – from drug interactions to off-label dosing and rebound COVID-19 infections, therapy is not as easy as it sounds. Listen as host Geoff Wall describes the clinical challenges and guest Jake Galdo describes the public health considerations for nirmatrelvir-ritonavir use.The GameChanger Nirmatrelvir-ritonavir has significant clinical challenges including various drug interactions with DOACs, statins, amiodarone, and tacrolimus, for example. It's also important to note that COVID-19 rebound after nirmatrelvir-ritonavir is not due to resistance based on the latest data.Show Segments 00:00 – Introductions 01:25 – Nirmatrelvir-Ritonavir Updates 04:27 – Nirmatrelvir-Ritonavir Controversy  06:30 – Drug Interactions  08:05 – DOACs and Nirmatrelvir-Ritonavir  11:44 – Statin and Nirmatrelvir-Ritonavir 13:04 – Amiodarone and Nirmatrelvir-Ritonavir 15:02 – Tacrolimus and Nirmatrelvir-Ritonavir  19:33 – COVID-19 Rebound  23:38 – Equity and Access 31:44 – Closing Remarks Host Geoff Wall, PharmD, BCPS, FCCP, CGP Professor of Pharmacy Practice, Drake University Internal Medicine/Critical Care, UnityPoint Health GuestJohn A. Galdo, PharmD, MBA, BCPS, BCGP (Jake)Course Content and Developer, CEimpactPharmacist, Ross Bridge PharmacyCEO, Seguridad, IncDr. Galdo have no relevant financial relationships to disclose. References and ResourcesUniversity of Liverpool Drug Interactions CDC Health Advisory on COVID Rebound InfectionsPaxlovid Patient Eligibility Screening Checklist Tool for PrescriberRedeem your CPE or CME creditCPE (Pharmacist) CME (Physician) Get a membership & earn CE for GameChangers Podcast episodes (30 mins/episode) Pharmacists: Get a MembershipPrescribers: Get a Membership  Continuing Education InformationLearning Objectives:1. Explain common drug interactions associated with Nirmatrelvir-Ritonavir2. Discuss COVID ‘rebound' infections3. Describe public health and healthcare data considerations for Nirmatrelvir-Ritonavir use 0.05 CEU | 0.5 HrsACPE UAN: 0107-0000-22-247-H01-PInitial release date: 07/11/22Expiration date: 07/11/2023Additional CPE & CME details can be found here

TCA peels for acanthosis nigricans – Allergen alternatives: Rubbers and plants – Fibroblasts and AD – Tacrolimus swish-and-spit – Nicotinamide for NMSC prevention 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 financial 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!)

On this episode, I discuss tacrolimus pharmacology. This medication is an immunosuppressant used to reduce the risk of transplant rejection. Tacrolimus has a long list of potential adverse effects such as hyperglycemia, renal impairment, GI toxicity, and hypertriglyceridemia. Important monitoring parameters for tacrolimus include drug levels, electrolytes, renal function, and blood sugars. CYP3A4 interactions are critical with tacrolimus. Inhibitors can raise concentrations and inducers can lower concentrations.

U.S. stocks rallied in overnight trade, with each of Wall Street’s main indices closing at record levels after President Donald Trump signed a long-awaited $2.3 trillion pandemic aid bill, increasing optimism for an economic recovery. The Dow Jones Industrial Average rose 68%, the S&P 500 gained 0.87% and the Nasdaq Composite added 0.74%. The U.S. House of Representatives, meanwhile, voted to increase stimulus payments to qualified Americans to $2,000 from $600, sending the measure on to the Senate for a vote. This bolstered investor hopes that a long-awaited U.S. pandemic relief package would be expanded, cheering Asian equities. Japan’s Nikkei leapt 0.9% to its highest since March 1991, while Australian shares climbed 0.7% and futures for the S&P 500 added 0.3%. Mirroring the upbeat global mood, the SGX Nifty futures were trading 0.41% higher at 13,944, indicating a firm start for the benchmark indices. Any positive development on the vaccine front could further boost investor sentiment. The UK is likely to approve the Covid-19 vaccine produced by AstraZeneca and the University of Oxford in a few days and it could also secure the regulator’s nod simultaneously in India, said Adar Poonawalla, CEO, Serum Institute on Monday. This apart, India should maintain its medium-term inflation target at 4% when it carries out a five-year review of the goal in March, two senior RBI officials recommended in a paper released on the bank's website on Monday. Now, a look at the stock-specific developments that are likely to sway the market today: IT services major Wipro's share buyback programme will commence today and close on January 11, 2021. In November, shareholders had approved the buyback plan for the purchase of up to 23.75 crore equity shares at Rs 400 per share, aggregating to an amount of up to Rs 9,500 crore. Life Insurance Corporation (LIC) has sold 2 per cent stake in private sector lender ICICI Bank through open market transactions. The insurer sold 13.8 crore shares, representing 2.002 per cent stake of ICICI Bank, over a period of November 27 to December 24, 2020, the bank said in a regulatory filing. Biocon has expanded its generic formulations portfolio with the launch of Tacrolimus capsules in the US.

This episode covers tacrolimus!

Cast:Joel TopfSwapnil HiremathSamira FaroukJennie LinMatt SparksAnd special guest Joshua WaitzMartin Pollak: http://www.nasonline.org/member-directory/members/20033579.htmlJosh Waitz @jwaitz100 Days of COVID-19: https://www.voanews.com/episode/100-days-covid-19-4236811MinTac: http://www.nephjc.com/news/mintacMy magical experience with minimal change disease. This is not the actual tweet, but a dramatization: http://pbfluids.com/2020/04/the-magic-of-treating-minimal-change-disease/Non-inferiority, NephJC: http://www.nephjc.com/news/2019/7/8/understanding-the-vortex-of-non-inferiority-trialsNon-inferiority, through the looking glass: https://pubmed.ncbi.nlm.nih.gov/21539749/Kevin Fowler on Tacrolimus side effects: https://twitter.com/gratefull080504/status/1247697780736512000?s=20Mt Sinai is converting some transplant patients from tacrolimus to belatecept: https://www.nejm.org/doi/full/10.1056/nejmoa1506027CAPSULOLOGY: Open the “Images” tab https://www.webmd.com/drugs/2/drug-10097-6108/tacrolimus-oral/tacrolimus-oral/detailsTacrolimus for your cat and dog dry eye needs: https://vcahospitals.com/know-your-pet/tacrolimus-ophthalmic-in-dogsWHO, NSAIDs, and double negatives: https://twitter.com/kidney_boy/status/1240452941187821570?s=20CJASN stands for the Clinical Journal of the American Society of Nephrology. The C does not stand for Canada. Sorry Swap.Conversion calculator from old world (SI) units, mg/mole Cr, to freedom units (gram protein / gram creatinine): http://www.scymed.com/en/smnxps/psdjf223.htmMichelle Rheault about starting the clock to relapse tweet: https://twitter.com/rheault_m/status/1247703322200596483?s=20Marvin Gonzalez calls for larger studies: https://twitter.com/MarvinGonzlez16/status/1247701186972733442?s=20Acute PD for COVID-19 is discussed in this article from CJASN: https://cjasn.asnjournals.org/content/early/2020/04/03/CJN.03750320PD for AKI, the experience from Brazil https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525422/The lead author, Daniela Ponce is really the world authority on PD and AKI: https://www.ncbi.nlm.nih.gov/pubmed/?term=Ponce%20D%5BAuthor%5D&cauthor=true&cauthor_uid=22641732Nursing home outbreaks in Durham: https://www.newsobserver.com/news/coronavirus/article241975401.htmlPrison outbreak: https://www.npr.org/2020/04/06/827922287/inmates-staff-on-edge-as-covid-19-spreads-through-federal-prisonsOttawa COVID-19: https://ottawacitizen.com/news/local-news/covid-19-long-term-care-outbreaks-continue-devastating-spread-across-ontario/West Coast herd immunity: https://www.ksbw.com/article/new-study-investigates-californias-possible-herd-immunity-to-covid-19/32073873#The History of HIV associated Nephropathy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494840/Racial breakdown of NYC coronavirus deaths reveals ‘disparities,’ de Blasio says https://nypost.com/2020/04/08/de-blasio-releases-racial-breakdown-data-of-coronavirus-deaths/Michelle Rheault is tired: https://twitter.com/rheault_m/status/1248371721356402689?s=20KidneyCon Lite! Saturday April 18 from 9-11. Kidney Pathology workshop.Lunch Doodles with Mo Willems: https://youtu.be/7KBkUyE6MOwDr Glaucomflecken and Telehealth: https://twitter.com/DGlaucomflecken/status/1247709538322657282?s=20NephSim for kindergartner’s https://nephsim.comNephSim live: https://twitter.com/Neph_SIM/status/1247637727048327170?s=20

This is a podcast article summary of "Randomized Controlled Trial of Tacrolimus and Prednisolone Monotherapy for Adults with De Novo Minimal Change Disease" by Megan Griffith on behalf of herself and her coauthors.

This is a podcast article summary of "Randomized Controlled Trial of Tacrolimus and Prednisolone Monotherapy for Adults with De Novo Minimal Change Disease" by Megan Griffith on behalf of herself and her coauthors.

2019 was a big year. The year of the Mueller report. The American college admissions scandals. Brexit. But it was also the year the US Women's team won the World Cup, and lobbied for the equal pay of women and men in sports. It was the year of NMO, in which several pivotal trials showed benefit of disease modulating therapy in this condition. The year Will Smith played Genie in Aladdin. 2019 was a great year. And as we wrap up 2019, this week's episode includes some of the highlights. Enjoy! Produced by James E. Siegler with support from Erika Mejia, Rajat Dhar, and the entire Siegler family. Music courtesy of Axletree, Chris Zabriskie, John Paston, Kevin Mcleod, Josh Woodward, Steve Combs, Lee Rosevere, Scott Holmes, Advent Chamber Orchestra, Coldnoise, and Pachyderm. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast. REFERENCES [BRAIN FOOD] Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A and Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91:1590-7. Devore EE, Kang JH, Breteler MM and Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Annals of neurology. 2012;72:135-43. Norton S, Matthews FE, Barnes DE, Yaffe K and Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. The Lancet Neurology. 2014;13:788-94. Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA and Aggarwal NT. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015;11:1015-22. Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez MA, Martinez-Lapiscina EH, Fito M, Perez-Heras A, Salas-Salvado J, Estruch R and Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA internal medicine. 2015;175:1094-1103. Newman JC, Covarrubias AJ, Zhao M, Yu X, Gut P, Ng CP, Huang Y, Haldar S and Verdin E. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice. Cell Metab. 2017;26:547-557 e8. Miller MG, Hamilton DA, Joseph JA and Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018;57:1169-1180. Okkersen K, Jimenez-Moreno C, Wenninger S, Daidj F, Glennon J, Cumming S, Littleford R, Monckton DG, Lochmuller H, Catt M, Faber CG, Hapca A, Donnan PT, Gorman G, Bassez G, Schoser B, Knoop H, Treweek S, van Engelen BGM and consortium O. Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial. The Lancet Neurology. 2018;17:671-680. Radd-Vagenas S, Duffy SL, Naismith SL, Brew BJ, Flood VM and Fiatarone Singh MA. Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials. Am J Clin Nutr. 2018;107:389-404. Xu W, Wang H, Wan Y, Tan C, Li J, Tan L and Yu JT. Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies. Eur J Epidemiol. 2017;32:31-42. Lefevre-Arbogast S, Gaudout D, Bensalem J, Letenneur L, Dartigues JF, Hejblum BP, Feart C, Delcourt C and Samieri C. Pattern of polyphenol intake and the long-term risk of dementia in older persons. Neurology. 2018;90:e1979-e1988. Liu QP, Wu YF, Cheng HY, Xia T, Ding H, Wang H, Wang ZM and Xu Y. Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies. Nutrition. 2016;32:628-36. [OF MEASLES AND MEN] Murch SH, Anthony A, Casson DH, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Valentine A, Davies SE and Walker-Smith JA. Retraction of an interpretation. Lancet. 2004;363:750. Perry RT and Halsey NA. The clinical significance of measles: a review. The Journal of infectious diseases. 2004;189 Suppl 1:S4-16. Campbell H, Andrews N, Brown KE and Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol. 2007;36:1334-48. Poland GA and Jacobson RM. The age-old struggle against the antivaccinationists. The New England journal of medicine. 2011;364:97-9. Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, Shanman R, Perry T, Goetz MB and Gidengil C. Safety of vaccines used for routine immunization of U.S. children: a systematic review. Pediatrics. 2014;134:325-37. Bester JC. Measles and Measles Vaccination: A Review. JAMA Pediatr. 2016;170:1209-1215. Bester JC. Not a matter of parental choice but of social justice obligation: Children are owed measles vaccination. Bioethics. 2018;32:611-619. Fournet N, Mollema L, Ruijs WL, Harmsen IA, Keck F, Durand JY, Cunha MP, Wamsiedel M, Reis R, French J, Smit EG, Kitching A and van Steenbergen JE. Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews. BMC Public Health. 2018;18:196.  Trump’s tweet: https://twitter.com/realdonaldtrump/status/449525268529815552?lang=en [NON-INFECTIOUS NEUROLOGIC COMPLICATIONS OF ORGAN TRANSPLANT] Senzolo M, Ferronato C and Burra P. Neurologic complications after solid organ transplantation. Transpl Int. 2009;22:269-78. Dhar R. Neurologic complications of transplantation. Handbook of clinical neurology. 2017;141:545-572. Mateen FJ, Dierkhising RA, Rabinstein AA, van de Beek D and Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transplant. 2010;10:908-14. Munoz P, Valerio M, Palomo J, Fernandez-Yanez J, Fernandez-Cruz A, Guinea J and Bouza E. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore). 2010;89:166-75. Wu Q, Marescaux C, Wolff V, Jeung MY, Kessler R, Lauer V and Chen Y. Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol. 2010;64:169-77. Dhar R, Young GB and Marotta P. Perioperative neurological complications after liver transplantation are best predicted by pre-transplant hepatic encephalopathy. Neurocritical care. 2008;8:253-8.

How can you integrate decision-making resources into your clinical practice? In this resident takeover of the podcast, three dermatology residents — Dr. Daniel Mazori, Dr. Elisabeth Tracey, and Dr. Julie Croley — discuss clinical decision support tools such as scoring systems and other resources available for dermatologists. These tools should be used as a supplement, not as a substitute for one’s clinical judgment. “The optimal treatment for patients in a complex medical system requires not just coming to the correct diagnosis and using your clinical judgment to make a decision but effectively communicating that decision to the insurance companies [and] to the primary team that’s taking care of them on the inpatient service. ... Some objective data can really be useful in those situations,” advises Dr. Tracey. *   *   * Help us make this podcast better! Please take our short listener survey: https://www.surveymonkey.com/r/podcastsurveyOct2019 *   *   * We bring you the latest in dermatology news and research: 1. No tacrolimus/cancer link in atopic dermatitis in 10-year study 2. PASI-75 with ixekizumab approaches 90% in pediatric psoriasis study 3. NAM offers recommendations to fight clinician burnout *  *  *   Things you will learn in this episode: Evaluate for psoriatic arthritis with the Psoriasis Epidemiology Screening Tool (PEST). “It’s the kind of thing that I’ll use in addition to asking a patient with psoriasis questions about symptoms like joint pain and morning stiffness,” Dr. Mazori says. Consider UpToDate.com and VisualDx.com for clinical decision support, to formulate differential diagnoses, and as a resource for patient education. “The other day, I had a patient who was diagnosed with scabies,” Dr. Tracey explains. “We were counseling the patient on how to decontaminate their environment. I wanted to get the exact number of hours their belongings needed to be in a plastic bag or how to wash their clothes. So, we went on UpToDate and read it together in the clinic.” The SCORTEN system predicts hospital mortality from Stevens-Johnson syndrome/toxic epidermal necrolysis and is useful for the primary team. “I’ve found it useful ... as a measure of risk to communicate to the primary team, even the patient’s family,” Dr. Mazori says. But the SCORTEN isn’t perfect. “There are studies that have found it can overestimate or underestimate mortality,” he warns. To differentiate cellulitis from pseudocellulitis in adult patients, consider the ALT-70 score. “It gives me an objective measure of risk to communicate to the primary team in support of one diagnosis or another in addition to my clinical judgment,” advises Dr. Mazori. The Mohs Appropriate Use Criteria (AUC) helps guide decision making for Mohs micrographic surgery, but it has been scrutinized for classifying most primary superficial basal cell carcinomas as appropriate for treatment, omitting important European trials, and for having ratings that are based on expert opinion rather than evidence. The MyDermPath+ app can assist clinicians in forming differentials based on histopathologic patterns. Hosts: Elizabeth Mechcatie, Terry Rudd Guests: Daniel R. Mazori, MD (State University of New York Downstate Medical Center); Elisabeth (Libby) Tracey, MD (Cleveland Clinic Foundation); Julie Ann Amthor Croley, MD (University of Texas Medical Branch at Galveston) Show notes by: Jason Orszt, Melissa Sears, Elizabeth Mechcatie   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgeDerm

In this episode I cover liver transplants.If you want to follow along with written notes on liver transplants go to zerotofinals.com/livertransplant or find the gastroenterology section in the Zero to Finals medicine book.This episode covers the types of liver transplant, indications, contraindications, liver transplant surgery and the post transplantation care.The audio in the episode was expertly edited by Harry Watchman.

In the second half of our two-part series on complications of organ transplantation, Dr. Raj Dhar (Neurocritical Care, Washington University in St. Louis) discusses his experience managing the non-infectious complications of organ transplantation--from drug toxicities to multi-disciplinary medical care. Produced by James E. Siegler and Raj Dhar. Music by Steve Combs, Lee Rosevere, and Scott Holmes. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast. REFERENCES Senzolo M, Ferronato C and Burra P. Neurologic complications after solid organ transplantation. Transpl Int. 2009;22:269-78. Dhar R. Neurologic complications of transplantation. Handbook of clinical neurology. 2017;141:545-572. Mateen FJ, Dierkhising RA, Rabinstein AA, van de Beek D and Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transplant. 2010;10:908-14. Munoz P, Valerio M, Palomo J, Fernandez-Yanez J, Fernandez-Cruz A, Guinea J and Bouza E. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore). 2010;89:166-75. Wu Q, Marescaux C, Wolff V, Jeung MY, Kessler R, Lauer V and Chen Y. Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol. 2010;64:169-77. Dhar R, Young GB and Marotta P. Perioperative neurological complications after liver transplantation are best predicted by pre-transplant hepatic encephalopathy. Neurocritical care. 2008;8:253-8.

Thu, 11 Jun 2015 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18344/ https://edoc.ub.uni-muenchen.de/18344/1/Mohamad-Ali_Niazi.pdf

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

Tacrolimus or FK506 is a macrocyclic lactone that is commonly used along with other immunosuppressant drugs to reduce graft rejection in organ transplantation by suppressing the immune system. Because of its narrow therapeutic window, it is critical to accurately monitor blood concentrations of this drug for optimal efficacy.

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

Clinical Outcomes Associated with Conversion from Brand-name to Generic Tacrolimus in Hospitalized Kidney Transplant Recipients Author Eric Tichy discusses with Guy Hasegawa, Senior Editor of AJHP, the concerns, including the need for pharmacokinetic monitoring, associated with converting between brand-name and generic tacrolimus in hospitalized kidney transplant patients. The article under discussion appears in the September 1, 2013, issue of AJHP. For more information visit www.ajhp.org.

Background. Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization. Methods. Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification. Results. Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT >= CAV(1) after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected. Conclusion. Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival.

Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts.

Thu, 22 Nov 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15747/ https://edoc.ub.uni-muench

In der Behandlung der Psoriasis bei Kindern wird von Experten immer wieder auf die unterschiedliche Verschreibungspraxis von Dermatologen, Pädiatern und Allgemeinmedizinern hingewiesen. Eine aktuelle US-Studie in den Archives of Dermatology konnte zeigen, dass Dermatologen dazu neigen, in allen Altersgruppen höher potente Corticosterioide für die Lokaltherapie zu verwenden während Kinderärzte z.B. sehr häufig zu Calcineurin-Inhibitoren greifen wie zum Beispiel dem Tacrolimus. Billrothhaus-News Expertin Univ.-Prof. Dr. Beatrix Volc-Platzer geht davon aus, dass in Österreich eine ähnliche Situtation besteht. Entscheidend für eine optimale Behandlung der Psoriasis bei Kindern sind damit neben aktuellen Guidelines vorallem hochwertige Fortbildungsveranstaltungen für Dermatologen und Pädiater. Weiterführende Imformation: Trends in Pediatric Psoriasis Outpatient Health Care Delivery in the United States Sinae A. Vogel, BS; Brad Yentzer, MD; Scott A. Davis, MA; Steven R. Feldman, MD, PhD; Kelly M. Cordoro, MD

Diese prospektiv randomisierte Studie untersucht, ob eine spiegeladaptierte MMF-Dosierung in Kombination mit Tacrolimus (Tac) bzw. Ciclosporin (CsA) in der immunsuppressiven Therapie nach Herztransplantationen effektiver sein würde. 60 Patienten (Tac n=30; CsA n=30) wurden nach Herztransplantation randomisiert auf beide Untersuchungsgruppen verteilt. Die immunsupressive Therapie bestand entweder aus Tac oder CsA jeweils in Kombination mit MMF und Steroiden. Die Zielspiegel für Tac, CsA und MMF sollten bei 10-15 ng/ml, 100-300 ng/ml bzw. 1,4-4 µg/ml liegen. Untersucht wurden die Auswirkungen auf die Abstoßungsrate, das Überleben, die unterschiedlichen Ausprägungen der Nebenwirkungen wie Infektionen, Diabetes mellitus, arterielle Hypertonie, Hypercholesterinämie und die Transplantatvaskulolpathie. In der Tac-Gruppe war die Freiheit von akuten Abstoßungen signifikant höher, die Inzidenz akuter Abstoßungen bezogen auf 100 Patiententage signifikant niedriger als in der CsA-Gruppe (0.03 vs. 0.15; P = 0.00007). Das Gesamtüberleben war in beiden Gruppen ähnlich (93% vs. 90%). In der Tac-Gruppe wurde zum Erreichen der MMF-Zielspiegel signifikant weniger MMF gegeben als in der CsA-Gruppe. Am Ende der Nachbeobachtungszeit war der durchschnittliche GVD-Score der Tac-Gruppe 1.85 +/- 3.18, der der CsA-Gruppe 3.95 +/- 4.8 (p=0,08). Zusammenfassend zeigt diese Untersuchung, dass bei den gewählten CsA- und Tac- Spiegeln die spiegeladaptierte Dosierung von MMF in Kombination mit Tac effektiver Abstoßungsreaktionen vorbeugt. Darüber hinaus benötigen CsA Patienten signifikant mehr MMF, um ähnliche MPA-Spiegel zu erreichen.

Seit Beginn der 1990er Jahre sind protektive Wirkungen von Tacrolimus auf Ischämie-Reperfusionsschäden der Leber bekannt. Die in bisherigen experimentellen Arbeiten beschriebene Spenderpräkonditionierung erscheint jedoch wegen potenzieller Nebenwirkungen klinisch nicht umsetzbar. Eine amerikanische Arbeitsgruppe konnte dabei in einer klinischen Pilot-Studie zeigen, dass die Spülung humaner Lebern mit Tacrolimus (20ng/ml) vor Implantation zu einer signifikanten Reduktion von Ischämie-Reperfusionsschäden nach Lebertransplantation führte. Unsere Arbeitsgruppe hat umfangreiche Untersuchungen mit Glutathion als Therapeutikum von Ischämie-Reperfusionsschäden nach warmer und kalter Ischämie durchgeführt. Gleichzeitig scheint, dass intrazelluläres Glutathion bei Anwesenheit hoher Konzentrationen von ROS über die Induktion von Radikalkettenreaktionen beziehungsweise die Thiolierung anderer Proteine selbst als Mediator von Ischämie-Reperfusionsschäden fungieren kann. In Vorarbeiten untersuchten wir die Wirkung von Tacrolimus im isoliert-perfundierten Modell der Rattenleber. Die Vorbehandlung mit Tacrolimus bewirkte bei Zufuhr von H2O2 eine Verringerung des ROS-induzierten zellulären Schadens, ausgedrückt in einer dosisabhängigen, signifikanten Verringerung des LDH-Efflux. Als Ursache hierfür wird eine verminderte intrazelluläre Akkumulation von zytotoxischem GSSG diskutiert, das nach Tacrolimus-Gabe vermehrt in Galle und Blut freigesetzt wurde, während die Aktivität der an Bildung und Abbau von GSH/GSSG beteiligten Enzyme Katalase, GSH-Peroxidase und GSSG-Reduktase unverändert war. Dieser Effekt konnte durch Gabe des p38 MAPK Inhibitors SB203580 imitiert werden. Wir übertrugen daraufhin das Konzept der Tacrolimus-Rinse in das Modell der arterialisierten, orthotopen Lebertransplantation an der Ratte. Die Spülung der Leber (20ml) mit Tacrolimus unmittelbar vor Implantation in den Empfängerorganismus führte zu einer signifikanten Reduktion des Ischämie-Reperfusionsschadens, gemessen in Transaminasen, LDH sowie Gallefluss. Das höchste Ausmass an Zytoprotektion wurde durch eine Tacrolimus-Konzentration von 10 ng/ml erreicht, wobei die protektive Wirkung der Tacrolimus-Rinse in der 10 ng-Gruppe stärker ausgeprägt war als in der 50 ng-Gruppe. Die Ursachen für diese inverse Dosis-Wirkungsbeziehung sind unklar, zumal keine statistische Signifikanz zwischen den beiden Gruppen besteht. Außerdem fehlen bislang systematische Untersuchungen zur optimalen Tacrolimus-Dosis in dieser Versuchsanordnung. Als Wirkmechanismus der Tacrolimus-Rinse postulieren wir - aufbauend auf Voruntersuchungen im isoliert perfundierten Modell und den erhobenen in-vivo-Daten - Veränderungen der zellulären Glutathionhomöostase: Hepatozyten setzten im Modell der Lebertransplantation nach Tacrolimus-Rinse vermehrt zytotoxisches GSSG in Blut und Galle frei, wodurch ROS-vermittelte Zellschäden während der Reperfusion minimiert werden. Zusammenfassend kann aufgrund der bisherigen Untersuchungen gezeigt werden, dass die Tacrolimus-Rinse eine neue und klinisch praktikable Therapieoption von Ischämie-Reperfusionsschäden der Leber darstellen könnte.

Bei Herztransplantationen steht heute die Behandlung von Langzeiterscheinungen wie z.B. die Transplantatvaskulopathie im Vordergrund. Die TVP ist die Haupttodesursache bei den Langzeitüberlebenden nach Herztransplantationen und ihre multifaktorielle Pathogenese ist noch nicht völlig geklärt. In dieser Studie wurde der Zusammenhang zwischen immunsuppressiven Therapieregimen und der Transplantatvaskulopathie untersucht. Dafür wurden 289 Patienten die im Klinikum Großhadern im Zeitraum von April 1994 bis Oktober 2001 Herztransplantiert wurden jährlich koronarangiographiert und die Katheterergebnisse mit einem CAV-Score bewertet. Die Patienten wurden in vier Gruppen eingeteilt mit den Immunsuppressivakombinationen 1 Cyclosporin/Azathioprin, 2 Cyclosporin/Mycophenolat mofetil, 3 Tacrolimus/Azathioprin sowie 4 Tacrolimus/Mycophenolat mofetil. Außerdem wurden Gruppen gebildet um die primären Immunsuppressiva Cyclosporin und Tacrolimus sowie die sekundären Immunsuppressiva Azathioprin und Mycophenolat mofetil zu vergleichen. Somit war es möglich für jede Medikamentenkombination die Dauer der Freiheit von TVP sowie die Ausprägung und Progression der Gefäßschädigungen zu ermitteln und statistisch auszuwerten. Dabei zeigte sich, dass die Gruppe 1 Cyclosporin/Azathioprin ein hoch signifikant schlechteres Langzeitergebnis hat, als die Gruppe 4 Tacrolimus/Mycophenolat mofetil. Im direkten Vergleich hat Tacrolimus bessere Ergebnisse als Cyclosporin und Mycophenolat mofetil bessere Ergebnisse als Azathioprin. Bei der Analyse der bewerteten Katheteruntersuchungen zeigte sich in der Gruppe 1 Cyclosporin/Azathioprin die stärkste Ausprägung der TVP sowie die stärkste Progredienz. Die geringste Ausprägung und Progredienz fand sich in Gruppe 4 Tacrolimus/Mycophenolat mofetil. Diese Ergebnisse zeigen sehr deutlich, dass die immunsuppressive Therapie einen erheblichen Einfluss auf die Entwicklung einer Transplantatvaskulopathie hat. Es stellten sich so klare Unterschiede zwischen den einzelnen Medikamentenkombinationen heraus, dass für die postoperative Therapie die Kombination Tacrolimus/Mycophenolat mofetil als deutlich überlegen angesehen werden muss. Vergleicht man Azathioprin mit Mycophenolat mofetil, so ist MMF in allen Bereichen dem Azathioprin deutlich überlegen. Es reduziert das TVP-Auftreten, senkt die Abstoßungsreaktionen und beschleunigt das Absetzen von Kortison. Somit gibt es kaum noch triftige Gründe, in Zukunft Azathioprin bei Herztransplantationen zu verwenden.

Harrison's Online

Thu, 9 Nov 2006 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/6018/ https://edoc.ub.uni-muenchen.de/6018/1/Sedighiani_Fazilat.pdf Sedighiani, Fazilat

Einleitung: Im Klinikum Innenstadt der Ludwig-Maximilians-Universität München werden herztransplantierte Patienten im Rahmen der nachsorglichen Betreuung in regelmäßigen Abständen sonographisch untersucht. Ziel dieser Arbeit ist es, bei einem dort regelmäßig betreuten Patientengut Infektionen, Neoplasien und andere unerwünschte Wirkungen der Immunsuppression wie vor allem die anhand der routinemäßigen Abdominalsonographien erhobenen pathologischen Befunde und morphologischen Organveränderungen deskriptiv zu dokumentieren. Dadurch soll ein Eindruck von der klinischen Relevanz der routinemäßigen Abdominalsonographie als Screening-Methode in der Nachsorge bei herztransplantierten Patienten zur frühzeitigen Erfassung pathologischer Befunde infolge immunsuppressiver Medikation geschaffen werden. Methode: Das Patientengut der vorliegenden Studie bestand ausschließlich aus herztransplantierten Patienten, die zur Vermeidung einer Transplantatabstoßung eine immunsuppressive Medikation erhielten und zwar als Kombination aus den immunsuppressiven Substanzen Cyclosporin A oder Tacrolimus, Azathioprin, Mycophenolat mofetil und Prednisolon. Insgesamt handelte es sich um 122 Patienten, die im Zeitraum von 1983 bis 1999 ein Spenderherz erhalten haben und von denen 85 Cyclosporin und 37 Tacrolimus als Basisimmunsuppressivum bekamen. Dazu wurden die pathologischen Befunde des Gesamtkollektivs ein Jahr, drei Jahre und fünf Jahre nach Herztransplantation des jeweiligen Patienten graphisch dargestellt. Zusätzlich zu den pathologisch-morphologischen sonographischen Befunden sollten auch die Häufigkeitsverteilungen der Neoplasien, opportunistischen Infektionen, das Neuauftreten von Diabetes mellitus, arterieller Hypertonie, Hyperlipidämie, Hyperurikämie, koronarer Herzkrankheit, peripherer arterieller Verschlusskrankheit sowie das Auftreten einer transitorischen ischämischen Attacke nach Herztransplantation dokumentiert werden. Abgesehen von den Häufigkeitsverteilungen im Gesamtkollektiv sollten auch die Häufigkeitsverteilungen in der Cyclosporin-Gruppe und der Tacrolimus-Gruppe angegeben werden. Von einem Vergleich dieser beiden Gruppen mit Signifikanzberechnungen sollte jedoch aufgrund mannigfaltiger Einflussgrößen abgesehen werden. Ergebnisse: Fünf Jahre nach Transplantation ergaben sich im Gesamtkollektiv unter anderem folgende Befunde: • 38,5 % Cholelithiasis • 9,0 % Cholezystitis • 21,3 % Hepatomegalie • 51,6 % Echogenitätserhöhung der Leber (Fettleber) • 36,1 % Größenabnahmen der Nieren • 86,9 % Echogenitätserhöhung der Nieren • 76,2 % Verminderung der Parenchymbreite der Nieren • 77,0 % Niereninsuffizienz im Stadium der kompensierten Retention • 9,8 % Niereninsuffizienz im präterminalen bzw. terminalen Stadium • 17,2 % sekundärer Hyperparathyreoidismus • 27,0 % Osteoporose • 19,7 % Pankreaslipomatose • 23,8 % Splenomegalie • 38,5 % Aortensklerose • 27,0 % maligne Entartungen • 52,5 % opportunistische Infektionen • 70,5 % Neuauftreten von arterieller Hypertonie • 65,6 % Neuauftreten von Hyperlipidämie • 16,4 % Neuauftreten der koronaren Herzkrankheit (KHK) • 18,0 % Neuauftreten der peripheren arteriellen Verschlusskrankheit (pAVK) • 5,7 % Erstmanifestation einer transitorischen ischämischen Attacke (TIA) Schlussfolgerung: In Anbetracht der Häufigkeit der anhand serieller Sonographien frühzeitig erfassbaren pathologisch-morphologischen Veränderungen der Abdominalorgane ist zu schließen, dass die in regelmäßigen zeitlichen Intervallen durchgeführte Sonographie, eine kostengünstige und nicht-invasive Untersuchung, fester Bestandteil der nachsorglichen Betreuung (herz-) transplantierter Patienten sein sollte. Die möglichst frühzeitige Detektion pathologisch-morphologischer Veränderungen der Abdominalorgane ermöglicht dem behandelnden Arzt, rasch entsprechende Maßnahmen zu ergreifen, um eine weitere Verschlechterung der krankhaften Befunde zu verhindern bzw. wenigstens zu verzögern. So kann beispielsweise nach sonographischer Erfassung einer pathologisch verringerten Parenchymbreite der Nieren, die mit der Nephrotoxizität des verabreichten Calcineurin-Inhibitors Cyclosporin oder Tacrolimus im Zusammenhang stehen kann, das nicht nephrotoxische Mycophenolat mofetil (eventuell im Austausch gegen Azathioprin) in die immunsuppressive Kombinationstherapie integriert werden, was eine schrittweise Reduzierung der Erhaltungsdosis des nephrotoxischen Calcineurin-Inhibitors ermöglicht.

Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which antigen-presenting epidermal dendritic cells (DCs), ie, Langerhans cells and the so-called inflammatory dendritic epidermal cells (IDECs) expressing the high-affinity receptor for IgE (FcepsilonRI) may play a significant pathophysiologic role. Therapeutic efficacy of the immunosuppressive macrolide tacrolimus (FK506) in AD has been demonstrated in clinical trials, but little is known of its mode of action. OBJECTIVE: The present study focused on the effects of topical tacrolimus treatment on epidermal CD1a+/FcepsilonRI+ DC populations in lesional AD. METHODS: Immunohistological analysis, epidermal DC phenotyping, and functional studies were performed on skin biopsy specimens from treated and untreated lesional skin of 10 patients with AD participating in a clinical trial with tacrolimus. RESULTS: Untreated lesional skin was characterized by a high proportion of CD1a+ cells, which was largely due to a high proportion of IDECs strongly expressing FcepsilonRI. Epidermal DCs isolated from untreated lesional skin exhibited high stimulatory activity toward autologous T cells, which was strongly reduced while clinical improvement was seen during application of tacrolimus. Concomitantly, a decreased FcepsilonRI expression was observed in both Langerhans cells and IDECs. Finally, topical tacrolimus led to a progressive decrease in the IDEC population within the pool of CD1a+ epidermal DCs and also to a decrease in their CD36 expression, which is indicative of lower local inflammation. CONCLUSION: Epidermal CD1a+ DCs may represent a target for topical tacrolimus in the treatment of AD.

Fri, 18 Jul 2003 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/1515/ https://edoc.ub.uni-muenchen.de/1515/1/Wolf_Tanja-Martina.pdf Wolf, Tanja-Martina