Podcasts about tnk

The JournalFeed podcast for the week of August 5-9, 2024.Monday Spoon Feed: For acute ischemic stroke patients with recent DOAC ingestion who (1) had their DOAC level measured, (2) had DOAC reversal with idarucizumab, or (3) inadvertently received thrombolytics with DOAC subsequently discovered, there was not evidence of increased significant intracranial hemorrhage associated with off-label thrombolytic therapy.Friday Spoon Feed:In patients with large vessel occlusions(LVO) presenting 4.5-24 hours after onset, without access to endovascular thrombectomy (ET), tenecteplase(TNK) administration bested standard medical treatment(SMT) in 90-day disability-free recovery.

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, and episodes originally aired from 2016 to 2021. Originally released: May 20, 2018 It's the age of thrombectomy. The DAWN of a new era. But should we give up on intravenous thrombolysis for acute ischemic stroke? In this installment of the Quanta series (typically shorter episodes, this one happens to be 19 minutes), we review the latest data on fibrinolytic agents and anticipate the upcoming paradigm shift in the management of patients with cerebral infarction. Produced by James E Siegler. Music by Hyson and Jon Watts. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. REFERENCESAssessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators; Van De Werf F, Adgey J, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999;354(9180):716-22. PMID 10475182Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med 2018;378(17):1573-82. PMID 29694815Haley EC Jr, Lyden PD, Johnston KC, Hemmen TM; TNK in Stroke Investigators. A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke 2005;36(3):607-12. PMID 15692126Haley EC Jr, Thompson JL, Grotta JC, et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke 2010;41(4):707-11. PMID 20185783Huang X, Cheripelli BK, Lloyd SM, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol 2015;14(4):368-76. PMID 25726502Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol 2017;16(10):781-8. PMID 28780236Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med 2012;366(12):1099-107. PMID 22435369 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.

Contributor: Travis Barlock MD Educational Pearls: Thrombolytic therapy (tPA or TNK) is often used in the ED for strokes Use of anticoagulants with INR > 1.7 or  PT >15 Warfarin will reliably increase the INR Current use of Direct thrombin inhibitor or Factor Xa inhibitor  aPTT/PT/INR are insufficient to assess the degree of anticoagulant effect of Factor Xa inhibitors like apixaban (Eliquis) and rivaroxaban (Xarelto)  Intracranial or intraspinal surgery in the last 3 months Intracranial neoplasms or arteriovenous malformations also increase the risk of bleeding Current intracranial or subarachnoid hemorrhage History of intracranial hemorrhage from thrombolytic therapy also contraindicates tPA/TNK Recent (within 21 days) or active gastrointestinal bleed Hypertension BP >185 systolic or >110 diastolic Administer labetalol before thrombolytics to lower blood pressure Timing of symptoms Onset > 4.5 hours contraindicates tPA Platelet count < 100,000 BGL < 50 Potential alternative explanation for stroke-like symptoms obviating need for thrombolytics References 1. Fugate JE, Rabinstein AA. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke. The Neurohospitalist. 2015;5(3):110-121. doi:10.1177/1941874415578532 2. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke a Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Vol 50.; 2019. doi:10.1161/STR.0000000000000211 Summarized by Jorge Chalit, OMSII | Edited by Jorge Chalit

TNK. Über Fragen oder Anregungen zu unserem Podcast würden wir uns sehr freuen. Bitte schreibt uns an: podcast@emmanuel-lindern.de

The transition from alteplase (ALT) to tenecteplase (TNK) in the management of acute ischemic stroke (AIS) has been an exciting and thoroughly discussed topic within the neurocritical care community. Although debates on the clinical efficacy and safety of TNK for AIS have subsided somewhat in light of recently published data, what remains lacking is a clear “road map” for institutions on how to properly implement the transition in thrombolytics. Brian Gilbert, PharmD, and Katie Qualls, PharmD, join Dr Lauren Koffman to discuss the transition from ALT to TNK for AIS. You can read Brian and Katie's February 2023 article in Currents at https://currents.neurocriticalcare.org/Leading-Insights/Article/transitioning-alteplase-to-tenecteplase-for-acute. 

1. JayLokas Ft Dyy Zan SA - A32. Royal MusiQ - Let's Go3. Stozee - Omphile4. TNK x DJ Maphorisa Ft Ricky Lenyora - Watsalang5. Kyika DeSoul & F3 Dipapa - Good Vibes Only6. Sam Deep & De Mthuda Ft Mawhoo - Inkinga Abangan Bam 7. Nkosazana Daughter Ft Chronical Deep - Chronicles Of Love8. ThackzinDJ - Amazinyo Endoda9. Tman Xpress - Osomatekisi10. Mosebo - Yesterday Is Burning11. Fiddia - The Eyes12. Avo, Syon & QT-High - Only You13. Leonidas K - Kupiga14. Bernard IT - Seat Out15. Masaki Morii - MDUB0116. Monserrat - Echo17. King Captain - Number Se7en18. JayLokas Ft Dyy Zan SA - New Chapter19. Cassie - Me & You (Amapiano Remix)20. Bob Marley Ft Igan Di Gan - No Woman No Cry (Amapiano Remix)21. Toby Franco & Musa Keys - Uthando22. Mateo 10 - Vuka Ubatshele23. Kabza De Small Ft DJ Maphorisa - Ayoba Yoga24. Lee Vocalist - Ekhaya25. DJ TPZ & Queen Thee Vocalist - Iza Unjalo26. NxOmS - Ngema Marafiki27. Hallex M Ft Stevo Atambire - Brave28. El Mukuka Ft GaZ Mawete & HVMZA - Bosana 29. Hallex M - Can't Turn Time Back30. Tswek Malabolo - People Like Us31. DJ Qness Ft Lizwi - Imithwalo 32. Bun Xapa - Paris

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Clouds_of_Torah_Presents_Funerals_and_Burial_in_the_TNK_for_Bnei_Noach

We're back!This week we've got another guest interview for you herb addicts. The legends behind the pumping IG page THE.TNK.LOFT joined Sam for an interview. Drew and Nicole kindly explain how they transformed their unremarkable inner-city dwelling into a spectacular living forest of plants. We also go into the therapeutic benefits of being surrounded by plants in your living space, using beneficial insects to fight "pest" species and gardening for mental health. Enjoy herb squad!S & CGet tickets for the SUMMER Kalamunda garden festival on December 3rd here: https://kalamundagardenfestival.com.au/Support the show

In this video, we'll perform a TNK stock analysis and figure out what the company looks like based on the numbers. We'll also try to figure out what a reasonable fair value is for TNK.. And answer is Teekay Tankers Ltd. one of the best shipping stocks to buy at the current price? Find out in the video above! Global Value's Teekay Tankers Ltd. stock analysis. Check out Seeking Alpha Premium and score an annual plan for just $119 - that's 50% off! Plus all funds from affiliate referrals go directly towards supporting the channel! Affiliate link - https://www.sahg6dtr.com/H4BHRJ/R74QP/ If you'd like to try Sharesight, please use my referral link to support the channel! https://www.sharesight.com/globalvalue (remember you get 4 months free if you sign up for an annual subscription!) Teekay Tankers Ltd. ($TNK) | Teekay Tankers Ltd. Stock Value Analysis | Teekay Tankers Ltd. Stock Dividend Analysis | TNK Dividend Analysis | $TNK Dividend Analysis | Teekay Tankers Ltd. Intrinsic Value | TNK Intrinsic Value | $TNK Intrinsic Value | Teekay Tankers Intrinsic Value (Recorded August 12, 2022) ❖ MUSIC ❖ ♪ "Lift" Artist: Andy Hu License: Creative Commons Attribution 3.0. ➢ http://creativecommons.org/licenses/b... ➢ https://www.youtube.com/watch?v=sQCuf... 8 Pillar Analysis Props to Everything Money ➢ https://www.youtube.com/c/EverythingMoney

Các tin khác: Đức thúc giục đồng minh gửi xe tăng chiến đấu đến Ukraine; Nghi phạm xả súng hàng loạt người Trung Quốc ở California không nhận tội; Thủ tướng Thái Lan giải tán Quốc hội sớm; Nhân viên bảo vệ tòa đại sứ Anh làm gián điệp cho Nga bị bỏ tù; Số người chết ở TNK và Syria vượt quá 42.000

Acompaña a Ricardo Cartas en una emisión más de la revista cultural De eso se trata, espacio de ciencia, de cultura, de gastronomía, de libros y más, de lunes a viernes de 08:30 a 10:00 horas. En Sónico, TNK-12, banda de folk-jazz originaria de Veracruz, conversa sobre su trayectoria musical, la fusión de ritmos de Oaxaca y de Veracruz, su gira artística por México y Puebla, e interpreta algunas de sus canciones: “El feo", "Toro Zacamandú" y "Pinotepa".

Voici un podcast en hommage au formidable travail musical d'un homme non moins formidable : Benoît "Maf" Charcosset ! Pas de chichi, juste de la musique, pour le plaisir de nos cages à miel, dont vous trouverez la liste des différents morceaux ci-dessous.Vous pouvez également télécharger le podcast sans générique, annonces de piste et petite intro, afin de ne profiter que des musiques de Maf :https://archive.org/download/mix-maf/Mix-Maf.mp3 Merci Maf pour ta musique et ta gentilesse ! Tu nous manques déjà ! Vous pouvez aussi aller lire deux entretiens de Maf, un sur Obligement et un autre sur Amiga Music Preservation : http://obligement.free.fr/articles/itwcharcosset.php http://amp.dascene.net/detail.php?view=4491&detail=interview Enfin, vous pouvez retrouver une bonne partie de sa discographie sur son Google Drive, qu'il avait mis à disposition de tous :https://drive.google.com/drive/folders/15_xa4gqTxow4jEi1-Vo0vmy2iyeygImd -- Liste des morceaux :Track 1 : Antoine Land (mod)Track 2 : Artichoke (mod)Track 3 : Aspartame (mod)Track 4 : Mario Light + Super Mario Land a Super Mario Land b + Super Mario Land c (mod)Track 5 : Dune Dream (mod)Track 6 : Basket Island Menu (mod)Track 7 : Windows Illusion (Maf & TNK, mod)Track 8 : Marmelade de ma grand-mèreTrack 9 : Battle Squadron IngameTrack 10 : La Soupe Aux ChouxTrack 11 : Mafland 2012Track 12 : Monkey Island remake

Dr. James Braun, Neurosciences Pharmacy Clinical Specialist at SSM Health St. Louis, and Dr. Kyle Hoelting, Senior Manager of Drug Information at Vizient, continue to share their insights on the use of TNK vs Alteplase for treating acute ischemic stroke. They also discuss the nuances of this therapeutic area and share recent work from an expert panel led by Vizient.   Guest speakers: James Braun, PharmD, BCCCP Neurosciences Pharmacy Clinical Specialist  SSM Health   Kyle Hoelting, PharmD, BCPS Senior Manager of Drug Information  Vizient   Moderator: Gretchen Brummel, PharmD, BCPS Pharmacy Executive Director Vizient Center for Pharmacy Practice Excellence   Show Notes: [00:30-3:59] Medication safety risks associated with thrombolytics [04:00-4:42] Using one drug over another [04:43-6:48] How frontline pharmacy staff can utilize this information [06:49-11:44] What Vizient can add to the discussion [11:45-11:55] When report will be released   Links | Resources: Tenecteplase vs alteplase in acute ischemic stroke: Vizient expert panel Verified Rx: Evidenced based medicine Click here Verified Rx: Show me the data! Updates on the evidence of thrombolytic use in ischemic strokes Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 1 Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 2 Click here   Subscribe Today! Apple Podcasts Amazon Podcasts Google Podcasts Spotify Stitcher Android RSS Feed

Pertenece a la agrupación TNK que ya se ha clasificado en ocasiones anteriores para la competición internacional, y con la que viajará hasta Arizona el próximo mes de agosto de 2022.

In this podcast, Dr. Ron Tarrel, a Stroke Neurologist with Allina Health, discusses everything stroke. Dr. Tarrel walks through recognition, evaluation, and management of stroke. He also discusses current guidelines, as well as the future of stroke medicine. Enjoy the podcast! Objectives:   Upon completion of this podcast, participants should be able to: Identify and describe warning signs of stroke and its initial presentation. Assess when initial urgent/emergent evaluation, imaging, coordination of care and decision making needs to occur in regards to stroke. Discuss treatment options and indications in regards to stroke care. CME credit is only offered to Ridgeview Providers & Allied Health Staff for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within approximately 2 weeks. You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. To receive continuing education credit for this activity - click the link below, to complete the activity's evaluation. CME Evaluation (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  DISCLOSURE ANNOUNCEMENT  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition; and are property/rights of Ridgeview Medical Center & Clinics.  Any re-reproduction of any of the materials presented would be infringement of copyright laws.  It is Ridgeview's intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker's outside interest may reflect a possible bias, either the exposition or the conclusions presented. Ridgeview's CME planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. Thank-you for listening to the podcast. ADDENDUM TO SHOW NOTES:Please note the Dr. Tarrel refers to TPA as a blood thinner at one point throughout the podcast. He would like the listerner to know that this medication (TPA) is a clot dissolving medication and not a blood thinner. Dr. Tarrel does not wish to confuse the listner on the nomenclature of TPA vs blood thinners (i.e. anticoagulants). SHOW NOTES: FAST The American Heart Association (AHA) put forth an initative for the lay person to recognize signs and symptoms of stroke and that was the FAST assessment which is (Facial asymmetry or weakness, Arm weakness, Speech difficulties, and Time), but now it has moved to the BE-FAST screening test. the BE portion of the FAST exam is assessment of Balance and Eyes to determine if there are posterior circulation findings. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.116.015169 HINTS ExamThe HINTS exam is a bit more specific and sensitve, looking for posterior circulation strokes in the correct patient population. Briefly, HINTS is a Head Impulse test direction-changing Nystagmus in eccentric gaze, or skew deviation. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.109.551234 Common DeficitsThe majority of strokes are going to occur in the anterior circulation which would be the carotid distribution, then into MCA (M1, M2, M3, M4, M5). Most of the deficits are going to be unilateral weakness, sensory or cognitive symptoms - example: aphasia/ neglect (cortical symptoms). Whereas, posterior circulation (vertebrobasilar) may have more devastating qualities. Symptoms for posterior stroke can include dizziness, nausea and vomiting, nystagmus, coordination, ataxia. However, see the article linked below where posterior cirulation vs anterior crculation infarcts can sometimes be difficult to determine on a clinical exam alone. Therefore, neuroimaging is recommended to accurately determine stroke distribution. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.112.652420 This study indicates that the symptoms/signs considered typical of posterior circulation infarcts occur far less often than was expected. Inaccurate localization would occur commonly if clinicians relied on the clinical neurological deficits alone to differentiate posterior circulation infarcts from anterior circulation infarcts. Neuroimaging is vital to ensure acurate localization of cerebral infarction. Hemorrhagic vs Ischemic StrokeWhich one is it? According to Dr. Tarrel, intracranial hemorrhage appears to exhibit more headache symptoms, such as this is the "worst headache of my life" , whereas ischemic stroke appears to be more painless, usually. Blood pressure and loss of consciousness can closely mimic hemorrhagic vs ischemic. Telestroke GuidelinesTelestroke guidelines are generally insitution specific. Refer to the linked article below, on the current guidelines in telestroke medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802246/pdf/tmj.2017.0006.pdf BP / 1st Line AgentFor hemorrhagic strokes, the neurosurgeons and neurologist like the systolic blood pressure to be in the 140-160 range. BP is usually controlled with Nicardipine as a 1st line agent. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.117.020058 Last Known Well (LKW)Last Known Well (LKW) is extremely important especially since we know that we are working against the closk for the use of lytic therapy (currently 4.5 hour window).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630074/pdf/nihms699406.pdf https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.116.023336 Imaging Imaging modalities for stroke workup can often include an initial non-contrast CT of the head to rule out ICH, but hen what happens? Generally, it is recommended to work in concert with the stroke neurologist to then determine the next line of imaging studies. If it is determined the patient looks to have a high NIHSS and concerns for LVOT (Large Vessel Occulusion) a CTA of the head and neck can be considered. Perfusion studies and advanced MR imaging should be discussed with consulting neurologists. Clinicians should also remember to follow their specific institutional guidelines for imaging studies if the stroke neurologist is unavailable or there is a delay in consultation. LKW along with CTA and CT perfusion of the head in ischemic stroke patients can sometimes give us a picture of the infarct core with surrounding penumbra (ratio). If circumstances are faborable, it may allow the pursuit of a thrombectomy. The current guidelines are for thrombectomy within 6 hours, but consideration upwards of 24 and beyond in the right patient population. Please see the DAWN and DIFFUSE 3 trials. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.119.027974 ThrombectomyGenerally the neurointerventionalist does not pursue thrombectomy beyond the MCA (M2 region), sometimes depending on anatomy. ASPECT ScoreThe ASPECT Score (Alberta Stroke Program Early CT Score) determines the volume of subcortical and cortical infarct involvement via perfusion study. Generally the score provided is 1-10. Anything less than a 6 portends a poor outcome. More early changes seen on CT suggest poorer outcomes from stroke. Patients with scores >8 have a better chance for an independent outcome. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.117.016745 IV TPAIV TPA with thrombectomy is safe. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.109.568451 TNK appears to have the same efficacy as TPA. Single dose IV push over 5 minute infusion. Easier and faster delivery of TNK. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.119.025080 Institutions may have different absolute and relative contraindications to TPA. Practice should be guided by institutional protocol and consultation with neurology. https://www.ahajournals.org/doi/epub/10.1161/STR.0000000000000086 Secondary PreventionSecondary prevention of stroke with the aid of DAPT (Dual Antiplatelet Therapy) - usually Plavix and Aspirin. Patients with cerebra ischemia are at high risk for early recurrent stroke, and use of DAPT for secondary prevention is reflected in current guidelines. Good BP and lipid management is paramount for 2nd stroke prevention. https://www.ahajournals.org/doi/epub/10.1161/STROKEAHA.119.028400 Scoring SystemsHAS-BLED score for major bleeding risk. CHA2DS2-VASc Score for artrial fibrillation stroke risk. Anti-thrombotic Therapy & Elderly PatientsChoosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls.https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/484991 Fall risk and anticoagulatoin for atrial fibrillation in the elderly: A delicate balance. https://www.ccjm.org/content/ccjom/84/1/35.full.pdf  

In this episode we chat with Dr. Louise McCullough, professor and Chair of Neurology at Memorial Hermann Hospital in the Texas Medical Center and Co-Director of UTHealth Neurosciences. She is also the Conference Chair for this year's International Stroke Conference and offers an inside look into this year's event and UTHealth Houston's involvement. We discuss COVID and stroke, Dr. James Grotta's presentation on MSU cost effectiveness, TNK vs TPA use, up and comers from UTHealth Houston to look out for and so much more. Ideas and opinions are our own and this podcast is not a substitute for expert medical advice. The Institute for Stroke and Cerebrovascular Disease (UTHealth Stroke Institute) http://www.utstrokeinstitute.com/ UTHealth Stroke Institute Vascular Neurology Fellowship https://www.uth.edu/stroke-institute/training/vascular-neurology-fellowship Dr. Louise McCullough https://med.uth.edu/neurology/faculty/louise-d-mccullough-md-phd/ Host: Amy Quinn Communications Director, The Institute for Stroke and Cerebrovascular Disease at UTHealth Houston Twitter: @UTHealthStroke Instagram: @UTHealthStroke Facebook: facebook.com/uthealthstroke

On Episode 8 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the September 2021 issue of Stroke: “Risk of Fractures in Stroke Patients Treated With a Selective Serotonin Reuptake Inhibitor” and “Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression.” She also interviews Drs. Jukka Putaala and Markku Kaste about their article “Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?”. Dr. Negar Asdaghi:         1) Are we ready to say goodbye to our old friend alteplase and replace it with a new one, tenecteplase, for acute stroke thrombolysis? 2) Does treatment of depression with SSRIs increase the risk of fractures in stroke patients? 3) When it comes to carotid intervention, should we continue offering treatment based on the degree of luminal stenosis, or are there better biomarkers in the horizon? These are some of the questions that we'll tackle in today's podcast. We're covering the best in Stroke. Stay with us. Dr. Negar Asdaghi:         Welcome back to Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. For the September 2021 podcast, we have an exciting program where we discuss some of the controversies in stroke therapies. The September issue also contains a Focused Update with a set of articles and comprehensive reviews on the topic of genetics and stroke, organized by Professor Martin Dichgans, which I encourage you to review in addition to our podcast today. Later in today's podcast, I have the pleasure of interviewing Drs. Putaala and Kaste, from Helsinki Institute, to help us with a burning question of whether there's enough evidence now to use tenecteplase instead of alteplase for ischemic stroke thrombolysis. But first with these two articles. Dr. Negar Asdaghi:         Over a third of stroke survivors either have depressive symptoms or a formal diagnosis of depression. Selective serotonin reuptake inhibitors, or SSRIs, are the mainstay of depression treatment and the most common antidepressants prescribed in the U.S. In addition, in 2011, we had the results of the FLAME trial suggesting that early poststroke treatment with fluoxetine, a commonly prescribed SSRI, improves motor recovery and functional independence in stroke patients with motor deficit. Though these results were not replicated in the subsequent larger FOCUS trial, the use of SSRIs poststroke dramatically increased over the past decade. So what are the side effects of using SSRIs poststroke? It's a known fact that adult stroke survivors are more likely to experience bone fracture, and that there's some evidence that SSRIs may increase this risk. Dr. Negar Asdaghi:         So, in the current issue of the journal, Dr. Graeme Hankey and Joshua Jones, from Faculty of Health and Medical Sciences, University of Western Australia, in Perth, and colleagues aimed to answer this question with a systematic review and meta-analysis of randomized controlled trials that included an SSRI treatment for an adult patient with a previous hemorrhagic or ischemic stroke and included incident fractures, either as a primary or secondary study outcome, amongst other criteria. So they found four randomized controlled trials that fulfilled their research criteria. Three of them looked at the effects of fluoxetine, used at a dose of 20 mg per day for six months duration, on functional recovery and outcomes after stroke. And one trial, which has studied neuroregeneration in vascular protection by citalopram, either at a 10 mg or 20 mg daily dose also for six months duration, in patients with acute ischemic stroke. So three studies included with fluoxetine and one study included citalopram. Dr. Negar Asdaghi:         So, what they found was that although the risk of falls, seizures and recurrent stroke were not statistically increased with SSRI treatment, it was actually a significant increased risk of fractures with a risk ratio of 2.36 in patients treated with SSRI as compared to the placebo. Now, how the SSRIs will increase the risk of fractures is still unknown. There are multiple postulated mechanisms that are discussed in the paper, such as SSRIs potentially increasing spastic motor activity, causing orthostatic hypotension, dizziness, delayed reaction time or temporary imbalance or sleep disorders. But the most important mechanism to keep in mind is the possibility of SSRIs lowering bone mineral density. It's also important to note that the duration of exposure to SSRIs is an important predictor of factors. It's worth noting that the usual SSRI exposure in patients with the primary diagnosis of depression is a lot longer than the exposure time in these trials. Dr. Negar Asdaghi:         So, what are the top two takeaway points for stroke physicians? Number one: Fluoxetine and citalopram SSRIs, used for six months poststroke, double the risk of fracture as compared to placebo in this meta-analysis. Number two: While the mechanism of this association is still debated, fracture prevention should be an important discussion point when considering prescribing an SSRI to stroke patients. Dr. Negar Asdaghi:         We all know that carotid disease is a major cause of ischemic stroke. Now we have to keep in mind that the bulk of the literature in carotid disease are practically concentrated on the association between the degree of luminal stenosis and the risk of recurrent stroke. So, in practice, we constantly counsel and discuss risk of future ischemia in symptomatic and asymptomatic carotid disease based on the degree of stenosis that's less than 50%, or between 50% to 70%, or over 70%. Dr. Negar Asdaghi:         But what if we learn that some plaques can be active despite causing small or little stenosis? And conversely, some may be active despite being very large. There seems to be a growing literature that much of the recurrent strokes are occurring in destabilized plaques. And it turns out that there are actually biomarkers that could cause this destabilization, and we can actually measure them. Xanthine oxidase, or XO, is one of these biomarkers. XO is a key enzyme involved in degradation of purine into uric acid. Now I'm trying to simplify a complex subject here. Xanthine oxidase oxidizes the conversion of hypoxanthine into xanthine and xanthine into uric acid. Along the way, it also does create a whole bunch of reactive oxygen species such as superoxide and hydrogen peroxide, which can create tissue damage. Dr. Negar Asdaghi:         Now, how is XO and serum uric acid levels related to carotid disease? Well, it turns out that XO is enhanced in carotid arteries with evidence of atherosclerosis. Better yet, in animal models, inhibition of XO is associated with reduction in progression of atherosclerosis. So, in the current issue of the journal, Drs. Morsaleh Ganji and Valentina Nardi, from Departments of Cardiovascular Medicine and Anatomic Pathology of Mayo Clinic in Rochester, Minnesota, and colleagues set out to investigate whether carotid plaques from symptomatic patients had increased expression of xanthine oxidase than their asymptomatic counterparts. So, what they did was they looked at 88 patients undergoing carotid endarterectomy for symptomatic or asymptomatic carotid disease, part of the routine clinical practice, and then measured the XO expression by immunohistochemical staining in CA obtained specimens. Dr. Negar Asdaghi:         In addition, they collected a number of serum samples and other demographics and vascular risk factors from the participating patients. They found four major findings in their paper. Number one: XO expression was indeed higher in symptomatic carotid arteries. Number two: Symptomatic patients had a higher serum uric acid levels. Number three: Higher XO expression was inversely associated with the serum levels of HDL. Number four: The symptomatic plaques had higher amount of macrophages expressing XO. Dr. Negar Asdaghi:         Very interesting, but these findings were irrespective of the actual degree of luminal stenosis. In fact, the asymptomatic carotid plaques patients, as routine practice dictates, had a higher degree of luminal stenosis, but they had lower expression of XO and other associated findings. So what did we learn from this study? Well, there seems to be a strong association between certain biomarkers, in this case xanthine oxidase, and symptomatic state of carotid plaques, suggesting that perhaps in future we'll have other ways of measurements that may help us decide on carotid intervention rather than just the symptomatic state of the artery and the degree of stenosis. Dr. Negar Asdaghi:         It's been over 25 years since alteplase was approved as the thrombolytic agent of choice for treatment of patients with acute ischemic stroke. But in the past decade, tenecteplase, a genetically modified variant of alteplase with regulatory approval for treatment of ST-segment–elevation, myocardial infarction, has gained interest as an alternative reperfusion therapy for treatment of patients with acute ischemic stroke. Whether tenecteplase is ready to completely replace alteplase in clinical practice is certainly a burning question faced by the stroke community today. This was the subject of a lively debate at the most recent and entirely virtual 2021 International Stroke Conference, where a panel of experts reviewed the current evidence regarding the use of tenecteplase in acute ischemic stroke, examining data from animal models, preclinical studies to dose escalation studies and randomized trials, directly comparing tenecteplase with alteplase, as well as the collective clinical experience to date with this thrombolytic agent. Dr. Negar Asdaghi:         The proponents of change point out the many advantages of tenecteplase over alteplase, including its ease of use, increased fibrin specificity, longer half-time and its non-inferiority to alteplase in the head-to-head trials. On the other hand, the opponents caution stroke physicians, drawing attention to the inherent issues with the already completed clinical trials of tenecteplase, and argue that more data is needed before tenecteplase is considered as a thrombolytic agent of choice in routine clinical practice. Continuing on this debate in the September issue of the journal as part of the Controversies in Stroke series, Drs. Jeffrey Saver and May Nour provide opposing views to Drs. Dawn Kleindorfer and Mollie McDermott on the present evidence and current guidelines around tenecteplase use in acute ischemic stroke. Dr. Negar Asdaghi:         Acting as moderators, the senior authors of paper, Dr. Jukka Putaala, Head of Stroke Unit at Neurocenter, Helsinki University Hospital, and Dr. Markku Kaste, Emeritus Professor of Neurology at the University of Helsinki and past chairman of Neurocenter, Helsinki University Hospital, in Finland, provide us with the balancing remarks on the issue. I'm joined today by Professors Putaala and Kaste to give us an overview on the debate of tenecteplase versus alteplase. Is it time to make the switch? Good morning from sunny Florida and good afternoon to you both in Finland. Thank you for joining us on the podcast. I hope the weather is as beautiful in Helsinki today as it is here in Miami. Dr. Jukka Putaala:           Here it is not as warm as you have, but we have had a really beautiful summer, and at the moment, although it is also autumn, temperature is around 20 Celsius, so it's just great. Dr. Negar Asdaghi:         It's great to have you both. The paper outlines a generally recognized criteria to support the use of any new pharmacotherapy. Can you please start us off by reviewing the components of this criteria and tell us, please, how many checkmarks does TNK get on this checklist when considered as a reperfusion therapy in acute ischemic stroke? Dr. Jukka Putaala:           These eight criteria include a well-characterized mechanism of action; strong preclinical data; evidence of benefits and safety in a closely related clinical condition, which here is myocardial infarction; important practical advantages over existing agents; the clinical efficacy in how the patient has demonstrated in randomized trials; and endorsement by national practice guidelines. Also, support from regulatory authorities. And finally, clinical effectiveness, which has demonstrated in routine care. We think that tenecteplase for acute ischemic stroke meets actually all of these eight criteria. But we could also think that a smaller number of criteria will be enough to satisfy or meet, would be sufficient. Dr. Negar Asdaghi:         Perfect. So definitely many important steps, starting with the basics all the way to post-marketing clinical experience. Markku, now over to you. Can you remind us about the mechanism of action of tenecteplase? And what are some of the similarities and differences in terms of pharmacodynamic and pharmacokinetics with alteplase? Dr. Markku Kaste:           So alteplase catalyze plasminogen cleavage to plasmin and, in turn, degrades fibrin in thrombi, yielding clot lysis. TNK, compared to alteplase, is 14-fold greater fibrin activity and 80 times higher resistance to plasminogen activator inhibitor-1, which means it has a longer half-life, which is a major advantage. Patients need only one injection. In case you're compared to alteplase, when you had to have third dose injection and then one-hour infusion, which delay the care of patient, if the patient need thrombectomy. So it takes an hour for the infusion before patient can be transferred to thrombectomy, and time matters in brain infarction. So the faster you are, the better it is for patients. Dr. Negar Asdaghi:         Perfect. So more fibrin specificity, as you mentioned, and longer half-time for TNK. And in addition, TNK is not a new drug. In fact, there is over two decades' worth of experience with this in cardiology. Can you also tell us about this? And also some of the preclinical and animal studies that make TNK a potential candidate as a thrombolytic therapy in stroke? Dr. Markku Kaste:           In animal studies, both in vitro model of mural platelet deposits under arterial flow and a rabbit model using extracorporeal arterial-venous shunts, TNK was more potent, showing benefits up to three hours versus one hour when alteplase was used. So, it's a major benefit already in animal experiments and in the code team, of course, it will be transferred in clinical practice. So, in myocardial infarctions, in three randomized trials, including our 17,000 patients, TNK showed significant reduction for bleeding rates and similar intracerebral hemorrhage rates and 30-day mortality. Dr. Markku Kaste:           So, these facts support the use of TNK, also in ischemic stroke, the results from myocardial infarction, some steady encouraging. Although we have to keep in mind that myocardial infarction is very homogeneous disease, it's arterial occlusion, while ischemic stroke can be caused by the local occlusion just like myocardial infarction, but also from artery-to-artery thrombi or from a cardiac emboli. And these three [inaudible 00:17:43] mechanisms generate different kind of thrombi, so we need a better drug than alteplase, which really is effective, whatever is the etiology of the occlusion of brain artery. Dr. Negar Asdaghi:         Right. Thank you. Jukka, now over to you. Before we review the data from randomized trials of tenecteplase, can you please tell us about some of the practical advantages of tenecteplase over alteplase? We're comfortable with alteplase. Why should we make the switch? Dr. Jukka Putaala:           The key practical advantages arise from the fact that tenecteplase can be given as one single dose; it takes only one minute. And if you compare that to alteplase, you'll have to give the bolus first, and then following the bolus is 60 minutes infusion. And that also has many advantages in clinical practice, for example, if you have a patient with large vessel occlusion in a remote hospital, which is not thrombectomy-capable, you can give tenecteplase and then put the patient in the ambulance and transfer swiftly the patient to the thrombectomy center. While, when using alteplase, you have to start infusion, which you have to have the nursing staff that is capable of monitoring the infusion and taking care of any complications arising during the infusion and so forth. Dr. Jukka Putaala:           With tenecteplase, you can immediately transport the patient to a thrombectomy site after the bolus without any infusion-capable paramedics staff. Another practical advantage is that by using tenecteplase, you avoid the potential gap between the bolus and the infusion, which means that there is at least several minutes or longer gap in four out of five patients treated with alteplase. You can also think the other scenarios during this coronavirus era, and you have 15 patients with suspected or very fast coronavirus infection. By using bolus, you don't need to put nurses in the same room with the patients many times with the infusion if you use alteplase. Instead, you can use tenecteplase, it's only one single bolus, and you can go away and you don't have to be exposed to potential coronavirus infection. Dr. Negar Asdaghi:         So, many important advantages, as you mentioned. It seems very reasonable, then, to use tenecteplase in routine practice if it is indeed non-inferior to alteplase. Jukka, what dose of tenecteplase should be used for treatment of acute ischemic stroke patients? And we're definitely excited to hear about the head-to-head trials with tenecteplase versus alteplase. Dr. Jukka Putaala:           Well, the trial, the dose is 0.25 mg/kg or 0.4 mg/kg. It depends if you have LVO, if you review the evidence what we have now available, you have to use the lower dose in LVO patients. But you can use the higher dose in non-LVO patients. All of this arises from the evidence we have available right now. So, basically, five randomized trials have been completed, to date, comparing tenecteplase with alteplase in acute ischemic stroke. And shortly, if they pull out these five trials and compare primary outcome, which is modified Rankin Scale 0 to 1 versus prior, which means excellent outcome. Dr. Jukka Putaala:           So, when pulling out these five trials, 58% percent of patients rates excellent outcome versus 55% of alteplase, and this satisfied the criteria for non-inferiority. Regarding safety and secondary outcomes, major intracranial bleeding, mortality, this meta-analysis according to five trials shows similar results for tenecteplase and alteplase. You have to consider some details of this trial. I think Markku was going to quickly review some of the details of the science and doses used in these trials later on. Dr. Negar Asdaghi:         So, yes, this sounds great for tenecteplase, but so now over to you, Markku. As Jukka mentioned, do we hear a "not so fast for tenecteplase"? Is the current data enough to say goodbye to alteplase entirely and completely turn over to tenecteplase? What are some of the issues with the already completed trials? Dr. Markku Kaste:           It's not today, we cannot say goodbye to alteplase. As Jukka referred to those trials, there's no reason to go into these really deep details because the trials are quite small compared to ordinary clinical randomized trials studying stroke care. Like I don't want to give neuroprotection agents, for example. One larger trial was, let's say, reasonably well designed. But as to say that most of these trials are not really double-blind randomized clinical trials. And so the results which can be generated is not as reliable as double-blind trials because, of course, there are reasons, I mean, colleagues randomizing cases may think that, OK, a randomizing case and I'm not totally convinced about TNK. And I think this gentleman or this lady really needs effective thrombolytic agents, so I give alteplase, while if another patient with a mild symptom, same physician may think, OK, this stroke patient will recover no matter what, so let us randomize the patient. Dr. Markku Kaste:           So, it means these kind of unbalanced randomization provides data which is not really reliable. We had to have lots double-blinded randomized trials before it's time to say goodbye, if this double-blinded randomized trial verified that TNK beats alteplase. And, of course, we need also meta-analysis of those advanced trials, and these things can take time, although many guidelines, like AHA guidelines, European Stroke Organization guidelines, Chinese guidelines, Indian guidelines, they, in a way, how do you say, might recommend use of TNK, but I think we need more reliable scientific evidence before it's time to say goodbye to alteplase. Dr. Negar Asdaghi:         So, Jukka, Markku already alluded to this. I wanted you to review this for our listeners, the national practice guidelines and drug regulatory authority guidelines around the globe with regards to the issue of tenecteplase versus alteplase. Dr. Jukka Putaala:           Yeah, actually, already American, European, Chinese, Australian and Indian guidelines are recommending tenecteplase into the guidelines, which were recently published in 2019, between 2019 and 2021. What we can read from the guidelines is that tenecteplase can be considered over alteplase. But we have to remember that the strength of the recommendation will remain weak at present and quality of evidence is by the facts that we discussed of these five completely randomized trials and meta-analysis pulling out the data. Qualitative evidence remains slow, and, therefore, the wording in the guidelines is that it may be reasonable to choose or consider alteplase. Tenecteplase might be considered as an alternative to alteplase in certain conditions. Dr. Jukka Putaala:           The recommendations are a little bit mixed in the guidelines, but generally, in large vessel occlusions, the guidelines say that you could consider TNK over alteplase or even that you should consider TNK over alteplase in large vessel occlusion before proceeding to thrombectomy. However, in cases without large vessel occlusion, the statements are more mixed and they say tenecteplase might be considered or even that alteplase is preferred over tenecteplase until we have more evidence. Dr. Negar Asdaghi:         Thank you, Jukka. Markku, what should be our final takeaway message for the practicing stroke physicians at this point considering the use of tenecteplase in routine practice?   Dr. Markku Kaste:           Before your paper has been accepted and published in high-quality journal, it takes weeks, mostly it takes months, even a half a year. While in Stroke Conference, you get the most recent data, which is, let's say, generated last week or even the same day. So, when you want to really provide high-quality care of your patient, keep you updated. And then it's best for you and her, and it's better, of course, for your patient. International Stroke Conference and also European Stroke Conference, they are excellent places to get the most recent, yet unpublished, reliable information. Dr. Negar Asdaghi:         Professors Jukka Putaala and Markku Kaste, thank you for summarizing a large body of evidence for our listeners. We're definitely excited to learn how tenecteplase will ultimately stand against the old competitor and perhaps learn that both may be reasonable thrombolytic options, depending on the specifics of the clinical setting. Dr. Negar Asdaghi:         And this concludes our podcast for the September 2021 issue of Stroke. Please be sure to check the September table of contents for the full list of publications, including two special reports on consensus recommendations from the 11th STAIR Consortium, that is, Stroke Treatment Academic Industry Roundtable. Dr. Negar Asdaghi:         The first report is intended to enhance patient, clinician and policymaker comprehension at modified Rankin Scale findings in clinical trials and quality improvement initiatives. The second report from the STAIR Consortium is on top priorities for cerebroprotective studies, an important manuscript where the roundtable considered and presented a new paradigm for evaluation of putative therapies that may work together with recanalization treatments to improve outcome after ischemic stroke, with special attention to using the correct nomenclature, such as replacing the term "neuroprotection" with "cerebroprotection" when the intention of an investigation is to demonstrate that a new treatment benefits the entire brain, rather than neurons alone. Or replacing the term "time window" with "tissue window" or "target window" when selecting patients for recanalization therapies to enhance the notion that various elements of the neurovascular unit show vulnerability to ischemia evolving over different time scales in different brain regions. An important paradigm shift in ways we think of the brain under ischemic attack. With that, we invite you to continue to stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.

I could NOT wait! It is time to get ready for the Old Testament.Let's begin our preparation for the Old TestamentKeep studying Doctrine and Covenants, of course. But if you are starting to prepare and need a little more preparation and background for this MASSIVE amount of scripture, join me.In this lesson we'll talk aboutStructureFlash BackTNK, Torah, Nevi'im, Ketuvim,Styles, like Narrative, Poetry, and moreI am SO EXCITED to start our preparation for the Hebrew Bible.

КРАСИВЕЙШАЯ ПОДБОРКА. третья часть ) ТЕПЕРЬ МИКСОМ И В ФОРМАТЕ РАДИОШОУ. Собраны Золотые Треки. КАЧАЕМ, СЛУШАЕМ ВМЕСТЕ С ЛЮБИМЫМ ЧЕЛОВЕКОМ ) ЕСЛИ ПОНРАВИЛОСЬ, ДАЙТЕ ЗНАТЬ --- BEAUTIFUL COMPILATION. the third part ) NOW mix and in the format radio show. Collected Golden Tracks. Download, listen together with a loved one) If you like it, let me know, and you can comment on the impressions) Good luck in the audition! P.P.S. Below - CLIP AT LAST TREK. Tnk to MOONBEAM! https://www.youtube.com/watch?v=HdZw54kJR4M Join now! I - Van der Jacques) --- TRACKLIST: 01. Delerium Feat. Sarah McLachlan - Silence (Acoustic) 02. Dipper - Sacrifice 03. Arno Elias - El Corazon 04. Paco Fernandez and Neve - Indescribable Feeling 05. Reunited - Sun is Shining 06. Sunlounger - Balearic Breakfast (Chill) 07. Sunlounger - Catwalk (Chill) 08. Accadia - Blind Visions 09. Humate - Love Stimulation ( Michael Woods mix) 10. Leama - Requiem For A Dream (Leama Ambient Mix) 11. Lost Tribe - Angel (Reuben Halsey Remix) 12. Moonbeam feat. Aelin - You Win Me --- site http://keksfm.kiev.ua/ Subscribe to our podcast RSS (Подписывайтесь на наш подкаст): http://feeds.feedburner.com/KEXXX-FM or Apple podcast: https://itunes.apple.com/ua/podcast/kexxx-fm-kiev/id1455141824 Весь архив подкаста/скачать тут (Podcast Archive / Download here) https://hearthis.at/kexxx-fm-2/ https://hearthis.at/kexxx-fm/ Podcast by Van der Jacques https://hearthis.at/a1dj/

Marat Atnashev is a Professor of business practice, co-founder of the Center for Negotiation and Network Studies at SKOLKOVO business school. He is Director of Asset Management at CTF Consultancy Limited and a member of the Supervisory Board of Alfa Group. From 2016 to 2019, he was Dean of the Moscow School of Management SKOLKOVO. From 2011 to 2015, he worked at EVRAZ plc. as Vice President, Major Projects, Head of the Iron Ore Division. From 2010 to 2011, Marat held a position of a Director of the Directorate of Major Projects at JSC Garzpromneft. From 2000 to 2010, he worked at TNK (from 2003 – TNK-BP) at various positions in supply chain management, finance and major project management. Marat graduated with honors from the Energy Department of the State University of Management (SUM), Moscow, in 1999; in 2003, he became a PhD (Candidate) in Economics. Marat also holds an MBA from INSEAD, France (2002). In 2008, he graduated from the BP Major Projects and Engineering academy, MIT (USA) and in 2016 received an MPA from Harvard Kennedy School (USA). Marat is a member of the Board of Directors of Management Company “Rosvodokanal”, a member of the Board of Directors of AO “ALFA-BANK”, a member of the Supervisory Board of A1 Investment Holding S.A., a member of the Board of Directors of ABH Holdings S.A., a member of the Supervisory Board at X5 Retail Group and a member of «AlfaStrakhovanie» PLC. Marat's academic interests at the SKOLKOVO business school include project management, organizational development, Dutch disease problem, institutional model of economics and macroeconomic issues in countries with a dominance of the commodity sector. Marat has a numerous publications on macroeconomics and energy topics. He is actively developing these areas at academic conferences and has published articles in most prestigious Russian media – Vedomosti, Republic, TV Rain and others. Marat was born in Moscow, Russia in 1977. FIND MARAT ON SOCIAL MEDIA LinkedIn | Facebook ================================ SUPPORT & CONNECT: Support on Patreon: https://www.patreon.com/denofrich Twitter: https://twitter.com/denofrich Facebook: https://www.facebook.com/denofrich YouTube: https://www.youtube.com/denofrich Instagram: https://www.instagram.com/den_of_rich/ Hashtag: #denofrich © Copyright 2022 Den of Rich. All rights reserved.

Marat Atnashev is a Professor of business practice, co-founder of the Center for Negotiation and Network Studies at SKOLKOVO business school. He is Director of Asset Management at CTF Consultancy Limited and a member of the Supervisory Board of Alfa Group. From 2016 to 2019, he was Dean of the Moscow School of Management SKOLKOVO. From 2011 to 2015, he worked at EVRAZ plc. as Vice President, Major Projects, Head of the Iron Ore Division. From 2010 to 2011, Marat held a position of a Director of the Directorate of Major Projects at JSC Garzpromneft. From 2000 to 2010, he worked at TNK (from 2003 – TNK-BP) at various positions in supply chain management, finance and major project management.Marat graduated with honors from the Energy Department of the State University of Management (SUM), Moscow, in 1999; in 2003, he became a PhD (Candidate) in Economics. Marat also holds an MBA from INSEAD, France (2002). In 2008, he graduated from the BP Major Projects and Engineering academy, MIT (USA) and in 2016 received an MPA from Harvard Kennedy School (USA).Marat is a member of the Board of Directors of Management Company “Rosvodokanal”, a member of the Board of Directors of AO “ALFA-BANK”, a member of the Supervisory Board of A1 Investment Holding S.A., a member of the Board of Directors of ABH Holdings S.A., a member of the Supervisory Board at X5 Retail Group and a member of «AlfaStrakhovanie» PLC. Marat's academic interests at the SKOLKOVO business school include project management, organizational development, Dutch disease problem, institutional model of economics and macroeconomic issues in countries with a dominance of the commodity sector. Marat has a numerous publications on macroeconomics and energy topics. He is actively developing these areas at academic conferences and has published articles in most prestigious Russian media – Vedomosti, Republic, TV Rain and others. Marat was born in Moscow, Russia in 1977.FIND MARAT ON SOCIAL MEDIALinkedIn | Facebook

On Episode 2 of the Stroke Alert podcast, host Dr. Negar Asdaghi highlights two featured articles from the March 2021 issue of Stroke. This episode also features a conversation with Dr. Joan Montaner from Neurovascular Research Laboratory at the Universitat Autònoma in Barcelona, Spain, to discuss his article “D-Dimer as Predictor of Large Vessel Occlusion in Acute Ischemic Stroke.” Dr. Negar Asdaghi:           Can your microRNA profile predict your future risk of stroke? Is stroke that wake-up call to finally live a healthier lifestyle, better diet, exercise more, and stop smoking? Can a simple blood test improve our clinical predictive models for presence of a large vessel occlusion in patients with suspected ischemic stroke? We have the answers and much more in today's podcast. You're listening to Stroke Alert. Stay with us. Dr. Negar Asdaghi:           From the Editorial Board of Stroke, welcome to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami, Miller School of Medicine, and the host of the monthly Stroke Alert Podcast. In today's podcast, I'm going to interview the senior author of the study on the values of D-dimer and predicting the presence of large vessel occlusion in stroke. But first with these two articles. Dr. Negar Asdaghi:           DNA noncoding sequences and introns, once thought to represent the, quote, junk DNA, quote, have been found to play an important role in the modulation of gene expression at the post transcriptional level through coding for regulatory molecules, such as microRNAs, or miRNA. Whether the presence of certain miRNAs can signal a future risk of development of stroke is unknown. In their paper titled “Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk: The Rotterdam Study,” Dr. Michelle Mens and colleagues from the Department of Neurology, University Medical Center, in Rotterdam, Netherlands, discuss their findings related to microRNA samples collected between 2002 and 2005 from over 1900 stroke-free participants of the Rotterdam Study. Participants were assessed for incident stroke through continuous monitoring of medical records until January 1, 2016. Dr. Negar Asdaghi:           At baseline, using next-generation sequencing, they measured expression levels of over 2083 miRNAs in plasma samples. During a mean follow-up of close to 10 years, the incidence of stroke was 7% in their study population, and they found, in total, 39 miRNAs were at least nominally related with that incidence of stroke. In their fully adjusted model, they found significant association between expression level of three particular microRNAs and risk of stroke, with the hazard ratio ranging between 1.1 to 2.6. Interestingly, the area under the curve for the longitudinal predictive models improved when the miRNA data was added to the vascular risk factor model. And in conclusion, they found miRNA 6124, 5196-5p and 4292 were associated with future risk of stroke in their population. The elevated levels of these miRNAs may serve as plasma biomarkers for predicting future risk of stroke in combination with other known vascular risk factors for stroke. Dr. Negar Asdaghi:           So, speaking of vascular risk factors, let's move on to our second paper for today's podcast. There's a growing emphasis on adherence with pharmaceutical interventions, such as diabetic and blood pressure treatments, statin therapy, to control the risk factors for stroke and prevent recurrent vascular events. All the while, the non-pharmaceutical interventions, such as smoking cessation, diet control, and increased physical activity, seem to represent the somewhat easy or implied aspect of our secondary preventive efforts. But how well are stroke survivors doing with regards to making these healthy lifestyle modifications? In the March issue of Stroke, Dr. Chelsea Liu and colleagues from Johns Hopkins School of Public Health presented their findings on lifestyle and behavioral changes pertaining to cardiovascular health in the study titled, “Change in Life's Simple 7 Measure of Cardiovascular Health After Incident Stroke: The REGARDS Study.” Dr. Negar Asdaghi:           So, this was a population-based, epidemiological study of over 7,000 stroke-free participants between 2003 and 2007, who had data on Life's Simple 7, what the author called “LS7 measures,” which studied seven different domains. Four of them behavioral, including smoking, diet, physical activity, body mass index, and three medication-controlled, including blood pressure, total cholesterol, and fasting glucose, both at study entry and their follow-up visit. At which point, either they did not have a stroke or had an ischemic stroke and were included if that stroke had happened more than one year before the follow-up visit. And so the study authors hypothesized that those with a stroke would have had a significant improvement in their Life's Simple 7 data poststroke as compared to the stroke-free participants. Dr. Negar Asdaghi:           But what they found was completely the opposite. At 10 years follow-up, a total of 149 patients had suffered a stroke in their study. On a scale of zero to 14 at study entry, all participants scored low or relatively low in these seven simple measures, but those participants who would ultimately suffer a stroke scored significantly lower at baseline. What was alarming, though, was that after adjusting for all confounders, at follow-up, participants who had experienced an ischemic stroke showed a significantly further decline in their total LS7 score at 10-year follow-up. And the greatest declines were noted in behavioral domains, most notably physical activity and diet scores. The authors noted a non-significant improvement, in other words, improvement in weight in the BMI score among stroke survivors, but they caution that that may indeed be actually related to muscle loss, a downstream effect of decreased physical activity poststroke, rather than representing active dietary interventions with weight loss. So, in summary, this important paper highlights, on a population level, the urgent need for behavioral interventions to improve secondary prevention after a stroke event up and beyond our efforts to improve medication adherence. Dr. Negar Asdaghi:           So now moving on from secondary preventative measures to the acute phase, our next paper discusses ways in which we can improve our diagnostic accuracy in the acute setting. Identification of large vessel occlusions is the first step in determining patients' eligibility for endovascular thrombectomy, a highly effective treatment to improve outcomes in acute ischemic stroke. But without vascular imaging, which may not be readily available in the small or community hospitals, the decision to transfer patients to thrombectomy-capable centers is entirely dependent on clinical scales, which, as we all know, may have suboptimal sensitivity and specificity. So the question is, could a simple blood test improve the predictive capabilities of our current clinical scales for presence of a target LVO, or large vessel occlusion? Joining me now is Dr. Joan Montaner from Neurovascular Research Laboratory at the Universitat Autònoma in Barcelona, who is the senior author of the study titled “D-Dimer as Predictor of Large Vessel Occlusion in Acute Ischemic Stroke.” Good morning, Joan, all the way from the sunny Florida to the beautiful Barcelona. Good to have you with us, and thank you for joining us. Dr. Joan Montaner:         Hello. Nice to talk with you on blood biomarkers for stroke management. Dr. Negar Asdaghi:           Thank you, Joan. Your study touches on the importance of improving the ways in which the systems of care are set up in triage and transfer of patients with thrombectomy-capable centers. Can you please tell us briefly about the stroke systems of care in Catalonia where you practice and where your study is based out of? And what clinical scales are currently used for transfer of patients with suspected acute stroke to a comprehensive stroke center? Dr. Joan Montaner:         Yes, Catalonia, it's a region of about 7.5 million inhabitants. And when we did this study, most of the comprehensive stroke centers were located in Barcelona itself, in the capital. So it's true that there are several areas of the region that are far away from Barcelona. It took more than two hours to bring some patients from those distant regions to Barcelona. That's why we began to use these clinical scales that you are talking about. Mainly they are RACE, it's like a simplification of the NIHSS subscale. And, in fact, a large study RACE card that was presented last year in the European Stroke Conference was done to try to see if we could, by using these scales, RACE, select the right patients to come directly to the thrombectomy centers instead of going to the closest hospital. But, unfortunately, the results were neutral. So, we were a little bit disappointed, and we think, as you were saying, that these neurological scales are suboptimal, probably not enough sensitivity and specificity for identifying LVO. That's why we think that these biomarkers could improve the accuracy of those scales. Dr. Negar Asdaghi:           Perfect. I totally agree with you. And now, before you tell us about the biomarkers, can you just briefly tell us about the Stroke-Chip study, your study population, and what prompted you to look at these various biomarkers that you addressed in the paper? Dr. Joan Montaner:         Stroke-Chip was a lot, it was really a massive collaborative effort among all the public hospitals in this network here in Catalonia. We were able to collect more than 1,300 patients in this particular study that we are talking about. Dr. Anna Ramos-Pachón and Elena Cancio were leading the analysis on the relation of these biomarkers with LVO. But I have to say that this was not the original intention of our study. Really, and perhaps we were naive at that time, we were looking for biomarkers to differentiate ischemia from hemorrhagic strokes or from stroke mimicking conditions to try to give TPA or TNK in the ambulance. But, as I was saying, perhaps that was a little bit naive, and we know how difficult that would be and perhaps with some liabilities. That's why it came this idea of, "Well, if we use those markers, not for giving a drug in the ambulance, but for doing triage and sending the patient to the right hospital, that could be more simple and more useful even." Dr. Negar Asdaghi:           Thank you very much. Can you briefly tell us about the study? What were your inclusion criteria? Dr. Joan Montaner:         Well, in this study, we selected all consecutive acute stroke patients attending the stroke unit of all these hospitals. We were including all stroke suspicions, if their symptoms onset happened within six hours. So, it's really hyperacute patients. And we were able to collect, like this, more than 1,300 patients. And then at the hospital, with the angio CT or duplex, we were able to categorize those with LVO, and we measured a panel of different biomarkers in the blood stream of those patients and trying to associate which of these markers were related with having or not having an LVO. Dr. Negar Asdaghi:           Very interesting. So tell us, please, your study's main finding? Dr. Joan Montaner:         The main finding, what we liked more, let's say, of our results was that some of those markers, specifically NT-proBNP and D-dimer, were really high among patients with a large vessel occlusion. When we combined these results, for example, having high levels of D-dimer, those patients above fourth quartile of D-dimer with more stroke severity, patients with NIH of more than 10, the accuracy was really good. It was very specific, 93% specificity, 34% sensitivity, to predict an LVO. So this means that without almost any mistake, you select more than one third of the patients that have an LVO, that could be very useful. To bring those patients, we were talking from far away of these thrombectomy centers, to the right place. And perhaps we could be doing a thrombectomy one or two hours before with these technologies. Dr. Negar Asdaghi:           Perfect. So basically, just to reiterate what you're saying, is that D-dimer, as non-specific as it is and as important as it is to note that it can be elevated in the setting of aging or increase NIH Stroke Scale severity, this increase in D-dimer noted in patients with LVO was just not a factor of just age simply or increased severity of the stroke scale. Can you tell us about your multivariate analysis and what other factors you adjusted for in your final model? Dr. Joan Montaner:         You are right that D-dimer can be modified by many things, as you were saying. That's why we took a lot of care about the multivariate analysis and all factors, all clinical factors that were related with LVO were included in the model. And finally, only eight NIH Stroke Scale scores D-dimer and the vast history of atrial fibrillation were included in the model. Odds ratio for D-dimer was 1.59 that I think it's quite acceptable. And it's true that in that model, NT-proBNP was not included anymore, probably because it's related with a fee. So, that's something interesting if perhaps in the ambulance, you don't know about the story, the history of a patient, of a fee, we could use NT-proBNP, so I think this opens the possibility of using different clinical neurological scales biomarkers in combination to make the prediction of LVO. Dr. Negar Asdaghi:           Yes. Very, very exciting results for sure. So what is our main takeaway from your study? Are we thinking that D-dimer or a particular level of elevations of D-dimer will one day become the, quote, Troponin equivalent of LVO for stroke? Dr. Joan Montaner:         Well, it sounds nice, but I know it's several technical issues here. You are right that there is variability among labs in the measurement of D-dimer so now what we are doing is really, in a prospective study called BIO-FAST in the south of Spain, in Seville, in a large network of ambulances, we are measuring D-dimer, but in a rapid fashion with a rapid point of care test in the ambulance itself. We think that we are not going to have a magic biomarker. Not that Troponin you are talking about. Probably we need to combine it with others. We think that the marker of brain damage would add a lot on top of D-dimer, probably D-dimer is very good for the clot burden, but we think other markers could improve the accuracy of the test. And we are measuring them together with these. Our dream would be really to have cost utility study in the future and to see if really we are able to randomize patients based on these biomarkers in the ambulance, will have an impact on outcome if we are able really to do thrombectomies much faster. Dr. Negar Asdaghi:           Well, we certainly look forward to covering your future studies on this topic of biomarkers. Dr. Joan Montaner, thank you for joining us and congratulations on your work. Dr. Joan Montaner:         Thanks a lot. Dr. Negar Asdaghi:           And this concludes our podcast. Don't forget to check online for the full list of publications, including two papers on the state of pediatric thrombectomy and a study on the association between stroke and subsequent risk of suicide that are published online ahead of their presentations at the International Stroke Conference. Until our next podcast, stay alert with Stroke Alert.

This episode's guest: Jon and Peggy Premo of Tri County Painting and TNK Manufacturing Mike and Brian are joined by Jon and Peggy Premo, CEO and COO, respectively, of Tri County Painting and TNK Manufacturing. Starting at 15 years old working for his grandfather's wallpaper hanging company in New York, Jon took care of all things painting. Eventually starting Tri County Painting with his wife, Peggy, they made the move to California and brought the company with them. Fast forward a decade or so, while on a large job in California, Jon thought of an innovative new product idea and they founded TNK Manufacturing. TNK now manufactures the newly patented Boom Shade product - a unique product that attaches to a boom lift to provide shade and protection for contractors on the jobsite while working! Ingenious! Shoutout to Jon and Peggy for joining us on the show today!

Pulmonary Embolus and COVID.   Is there any connection?  Join us as we circle back on Pulmonary Embolus from our podcast from a couple of years ago. Pulmonary Embolus cases are on the rise in central Ohio and has treatment changed along with it?       Listen to our expertise’s from OhioHealth Riverside Hospital  as we dive into Covid and the link that can lead to Pulmonary Embolus.  The conversation progresses to the algorithm for PE treatment and  if thrombolytic Medication is indicated, which one is better TPA or TNK? We finish up with trends in future treatments.     Come join us…

Mathan Somasundaram from Deep Data Analytics and Gaurav Sodhi from Intelligent Investor go in-depth and stock-specific. Stocks: TPG, IAG, AZj, RDF, LEP, TNK, MOZ, UWL, AL3, SHM. Stock of the day is GPT Group (GPT). See acast.com/privacy for privacy and opt-out information.

FDA 批准卡那单抗用于治疗成人Still病Lancet 苏金单抗与阿达木单抗治疗银屑病关节炎的头对头比较Arthri & Rheumatol重组腺苷脱氨酶可改善系统性硬化症模型的纤维化卡那单抗（canakinumab）上周一的心脏科专题中，我们聊到了冠心病的抗炎治疗最新进展，目前研究热点集中在IL-1β单克隆抗体卡那单抗和秋水仙碱。今天我们来聊一聊卡那单抗在免疫科中的应用。卡那单抗（canakinumab）最初于2009年被FDA批准用于治疗Cryopyrin相关周期性综合征（CAPS）、全身型幼年特发性关节炎以及三种少见的周期性发热综合征；2020年6月，卡那单抗被FDA批准用于治疗成人Still病。《卡那单抗用于治疗成人Still病以减少关节炎的表现：2期临床试验》Annals of Rheumatic Diseases，2020年8月 (1)这项多中心、双盲、随机、安慰剂对照试验，旨在评价其治疗成人Still病的有效性和安全性。研究纳入19名多关节受累的成人Still病患者，随机给予卡那单抗和安慰剂治疗。基线时，卡那单抗组和安慰剂组的平均疾病活动评分为5.4和5.3。在卡那单抗组中，61%的患者达到30%应答率，50%的患者达到50%应答率，28%的患者达到70%应答率；而对照组仅为20%、6.7%和0%（p=0.033，0.009和0.049)。卡那单抗组的两名患者经历了严重的不良事件。结论：卡那单抗治疗可改善多项成人Still病的疗效指标。银屑病性关节炎银屑病关节炎（psoriatic arthritis，PsA）是一种与银屑病有关的炎症性肌肉骨骼疾病。主要表现为受累关节疼痛和僵硬，可同时累及周围关节和中轴关节，常呈非对称性分布。70%的关节炎就诊时有银屑病病史，80-90%伴有甲病变。实验室检查没有特征性的变化，类风湿因子（RF）、抗核抗体（ANA）和抗瓜氨酸肽抗体（ACPA）大多呈阴性。《荟萃分析：银屑病关节炎关节外表现的患病率》Rheumatology，2020年9月 (2)研究的目的是评价银屑病关节炎关节外症状的流行情况（肌腱炎、指炎、指甲疾病、葡萄膜炎和炎症性肠病），及其对纵向疾病结局的影响。研究纳入65项研究，共计163 299例银屑病关节炎患者。在进行报道的文献中，肌腱炎平均发病率为30%，指炎平均发病率为25%，甲疾病发病率为60%，葡萄膜炎为3.2%，炎症性肠病3.3%。其中，合并指炎的患者影像学进展的可能性增加。结论：银屑病关节炎患者中，常合并肌腱炎、指炎和甲病；而葡萄膜炎和炎症性肠病不常见。《真实世界：银屑病或银屑病关节炎患者严重感染的风险》Annals of Rheumatic Diseases，2020年2月 (3)研究的目的是使用IL-17、IL-12/23或肿瘤坏死因子（TNF）抑制剂，是否与银屑病或银屑病关节炎患者严重感染风险的增加有关。研究共包括11560个新的治疗事件，9264人年的随访。研究共发现190例严重感染（占治疗期的2%），IL-17和TNF抑制剂的感染发生率相似，而IL-12/23抑制剂则明显降低（风险比0.59）。在曾经使用过生物制剂的患者中，各组感染风险无差异。结论：相对于TNF和IL-17抑制剂，IL-12/23抑制剂可以降低银屑病或银屑病关节炎患者的严重感染的风险。《纵向队列研究：银屑病性关节炎的DAPSA、颈动脉斑块和心血管事件》Annals of Rheumatic Diseases，2020年11月 (4)研究的目的是评价反映银屑病关节炎炎症成分的银屑病关节炎的疾病活动评分（DAPSA）是否能够预测心血管事件，而不依赖于传统的心血管危险因素和亚临床颈动脉粥样硬化。研究纳入189例银屑病关节炎患者，平均年龄48.9岁。平均9.9年的随访后，较高的银屑病关节炎的疾病活动评分与心血管事件的风险增加显著相关（风险比 1.04， p=0.009），在多变量模型中调整所有心血管风险后，这种关联仍然有统计学意义。亚组分析中，调整其他心血管风险后，颈动脉斑块与发生CV事件的风险增加显著相关（风险比 3.42）。结论：较高的DAPSA和CP的存在可以独立预测银屑病关节炎患者的心血管事件事件，这种风险不依赖于传统的心血管疾病风险。小羽点评：银屑病性关节炎不仅累及皮肤、关节，还可能增加感染和心血管疾病的发生风险，在临床实践中，需要对银屑病关节炎的患者进行多个系统的功能进行跟踪和随访。银屑病关节炎的治疗银屑病关节炎中，外周关节炎常使用NSAID治疗；若效果不佳，常采用传统改变病情的抗风湿药物（DMARD），如甲氨蝶呤（MTX）、来氟米特（LEF）；若多个关节侵蚀及功能受限，建议使用生物性DMARD，如TNF抑制剂为一线治疗（依那西普、阿达木单抗、英夫利西单抗、塞妥珠单抗和戈利木单抗）。一种TNF抑制剂无效时，可换用另一种TNF抑制剂；两种TNF抑制剂无效时，可使用IL-17抑制剂（苏金单抗、依奇珠单抗）、IL-12/23抑制剂（优特克单抗）、T细胞共刺激调节因子（阿巴西普）、JAK抑制剂（托法替尼）。累及骶髂关节和脊柱关节、附着点炎时，通常不推荐使用传统DMARD。银屑病关节炎患者一般应避免使用糖皮质激素，因为可能增加红皮病或脓疱型银屑病的几率。《回顾性队列研究：传统合成抗风湿药治疗银屑病性关节炎中，单药保留甲氨蝶呤优于柳氮磺胺吡啶》Rheumatology，2020年8月 (5)比较传统合成抗风湿药物的疗效和使用时间的研究有限，此研究的目的是比较一线传统合成抗风湿药物单药治疗的银屑病关节炎的药物保留和药物保留的预测因子。文章回顾性的研究了首次使用传统抗风湿药物作为单一药物治疗银屑病关节炎的187例患者，主要终点是治疗失败、停止用药或添加另一个抗风湿药物的时间。患者中单药使用甲氨蝶呤共163人，单药使用柳氮磺胺吡啶共21人，平均药物保留事件为31.8个月。其中甲氨蝶呤平均使用34.5个月，柳氮磺胺吡啶平均使用12.0个月（P =0.016）。使用甲氨蝶呤的患者中，随着年龄增长药物保留率逐渐增加。治疗失败的主要原因是无效(52%)和副作用(28%)。结论：在临床实践中，甲氨蝶呤单药治疗银屑病关节炎优于柳氮磺胺吡啶。《GO-DACT研究：治疗银屑病关节炎患者的指炎方面，戈利木单抗联合甲氨蝶呤优于单用甲氨蝶呤》Annals of Rheumatic Diseases，2020年4月 (6)戈利木单抗是一种抗肿瘤坏死因子α单抗，研究的目的是评价戈利木单抗联合甲氨碘呤和单用甲氨蝶呤治疗银屑病性关节炎指炎的疗效。这个多中心、随机、双盲、安慰剂对照、平行设计的3b期试验中，银屑病关节炎伴有活动性指炎的患者被分配到戈利木单抗或安慰剂组，两者均与甲氨蝶呤联合使用。24周后，与甲氨蝶呤单药治疗相比，戈利木单抗联合甲氨蝶呤显著改善指炎的临床症状（指炎严重程度评分变化分别为5和2，p = 0.026）。联合治疗组的指炎严重程度评分改善50%或70%的患者和Leeds指炎指数改善20%、50%或70%的患者比例显著高于单用甲氨蝶呤的患者。结论：戈利木单抗联合甲氨蝶呤作为一线生物抗风湿治疗银屑病指炎优于甲氨蝶呤单药治疗。《荟萃分析：生物制剂对银屑病关节炎患者外周关节影像学进展的影响》Rheumatology，2020年11月 (7)研究的目的是确定生物制剂在预防银屑病关节炎患者、外周关节影像学进展中的有效性。研究包括11项临床试验，涉及5382名患者，9种药物和18种治疗方法。与安慰剂相比，接受生物制剂的患者更有可能实现影像学无进展（优势比2.40，其中TNF抑制剂的优势比 2.94，IL抑制剂的优势比 2.15，阿巴西普的优势比 1.54）。生物制剂显著降低了外周关节影像学进展的风险（影像学进展评分平均下降-2.16，其中TNF抑制剂下降 -2.82，IL抑制剂下降 -1.60，阿巴西普下降 -0.40。生物制剂联合甲氨蝶呤的方案，并不优于单一生物制剂治疗的效果；尤特克单抗和苏金单抗的疗效，不受先前抗TNK治疗的影响。结论：与安慰剂相比，生物制剂可能在骨侵蚀和关节间隙狭窄方面延缓银屑病关节炎患者的影像学进展。甲氨蝶呤似乎没有额外的获益；先前的抗肿瘤坏死因子治疗似乎不会影响IL抑制剂的治疗效果。上一次的节目介绍了IL-17抑制剂（苏金单抗、依奇珠单抗）最近刚刚被FDA批准用于治疗中轴型脊柱关节炎，今天来和大家聊一聊IL-17A单抗在银屑病关节炎中的应用，以及比较这两个药物和肿瘤坏死因子抑制剂阿达木单抗的头对头研究。《Future 5研究：苏金单抗治疗银屑病性关节炎的3期研究结果》Rheumatology，2020年6月 (8)研究目的是评估苏金单抗治疗银屑病性关节炎52周后患者的影像学进展。纳入的银屑病性关节炎参与者，既往没有治疗过、或者TNF-α抑制剂无效，被随机分入苏金单抗 300mg组、150mg组、150mg无负荷给药组或安慰剂组，前4周q1w负荷给药，4周后q4w给药。其中300mg组有91.8%的患者52周后，没有出现影像学进展；在150mg组和150mg无负荷给药组中，这里比例分别是85.2%和87.2%。苏金单抗 300mg组、150mg组和150mg无负荷给药组中，影像学vdH-mTSS评分的随机斜率为-0.18、0.11和-0.20。临床疗效持续稳定，52周内没有报告新的或意料之外的安全事件。结论：苏金单抗 300mg、150mg和150mg无负荷剂量组，治疗银屑病性关节炎显示出持续稳定的低进展率。《SPIRIT-P1研究：依奇珠单抗治疗活动性银屑病关节炎患者的III期临床试验3年结果》Rheumatology，2020年2月 (9)研究的目的是评估长达156周的依奇珠单抗（IL-17A单抗）治疗银屑病关节炎的安全性和有效性。银屑病关节炎患者被随机分配到安慰剂组、阿达木单抗或依奇珠单抗q2w或q4w组。在第24周时，阿达木单抗和安慰剂组的患者被重新随机分配到依奇珠单抗q2w或q4w组，并继续延长治疗至第156周，共243例患者完成了为期3年的研究。依奇珠单抗q2w组患者治疗紧急和严重不良事件的发生率分别为38.0%和5.2%，依奇珠单抗q4w组患者为38.1%和8.0%。156周时，两组患者ACR响应≥20%的比例占69.8%和62.5%；响应≥50%的比例为51.8%和56.1%，响应≥70%的比例为33.4%和43.8%。银屑病面积和严重程度指数（PASI）缓解75%的占（63.5%和69.1）；缓解90%的展51.2%和64.5；缓解100%的占43.6%和60.5%。直至156周，在q2w组中的61%和q4w组中的71%的患者，影像学进展得到抑制。结论：依奇珠单抗治疗156周后，其安全性与之前的报道保持一致，并且观察到银屑病关节炎患者症状和体征的持续改善，包括影像学进展率持续较低。《EXCEED研究：头对头比较苏金单抗与阿达木单抗治疗银屑病关节炎疗效的3b期试验》Lancet，2020年5月 (10)EXCEED研究评估了苏金单抗与阿达木单抗作为一线生物单药治疗活动性银屑病关节炎患者的安全性和有效性。这个平行、双盲、多中心、主动对照的3b阶段的研究，招募18岁以上的、活动性银屑病关节炎患者，主要终点是52周时ACR反应标准至少改善20%（ACR20）。研究过程中853例患者完成了52周的研究，研究结束后，苏金单抗组14%和阿达木单抗组24%的患者选择停止使用研究中的治疗方案。第52周时，67%的苏金单抗组患者和62%的阿达木单抗组患者达到治疗的主要终点，两组间无统计学差异。苏金单抗组2%和阿达木单抗组1%的患者出现严重感染，苏金单抗出现一例与研究药物无关的死亡，其他的安全性与之前报道一致。结论：苏金单抗与阿达木单抗的疗效没有统计学差异，但是苏金单抗的治疗保留率更高。《SPIRIT研究：头对头比较依奇珠单抗和阿达单抗治疗银屑病关节炎的疗效和安全性》Annals of Rheumatic Diseases，2020年7月 (11)SPIRIT研究头对头的比较了依奇珠单抗（IL-17A单抗）和阿达单抗治疗银屑病关节炎的有效性和安全性。 研究纳入566例银屑病关节炎的患者，将患者随机分为依奇珠单抗和阿达单抗治疗组，评价标准是24周和52周时，患者ACR反应标准改善50%（ACR50）和银屑病面积和严重度评分改善100%（PASI100）。52周时，依奇珠单抗治疗组中同时达到ACR50和PASI100的患者的比例显著高于阿达木单抗 (39% vs 26%， p

Kali ini kita ke salah satu destinasi wisata yang paling unik di Indonesia, Taman Nasional Komodo! Di episode TNK pertama ini Dohets akan menceritakan pengalamannya di Pulau Kelor, Pulau Rinca, dan Pulau Padar. Enjoy!

C'est dans les rues de Manille, que le Père Matthieu Dauchez exerce son ministère de prêtre. Il s'occupe de l'association ANAK-Tnk, qui vient en aide aux enfants pauvres de la capitale des Philippines, association qui fête cette année ses 20 ans. Le Père Dauchez a raconté son aventure humaine et spirituelle dans plusieurs livres. En 2015, il était sur RCF pour témoigner de son parcours à l'occasion de la sortie de son ouvrage, "Plus fort que les Ténèbres" (éd. Artège, 2015).   "Qu'un enfant puisse ne pas être aimé ça me paraît être le plus grand scandale"   De Versailles aux rues de Manille Un jour, des amis séminaristes, souhaitant le provoquer, lui ont dit qu'avec ses origines versaillaises il serait bien incapable de partir en mission. Les prenant au mot, Matthieu Dauchez décide de les suivre jusqu'à Manille et d'accompagner le jésuite Jean-François Thomas dans la fondation de ce qui s'appellera ANAK-Tnk. "Anak" qui signifie "enfant" en tagalog et les trois lettres "TNK" sont les initiales de la fondation connue à Manille sous le nom de "Tulay Ng Kabataan", qui signifie "Un pont pour les enfants". En 1998, le jeune séminariste entame donc un séjour de deux ans aux Philippines, deux ans qui vont changer sa vie. Et révéler ce qu'il appelle à la suite de mère Teresa, "un appel dans l'appel". Lui qui sait qu'il veut devenir prêtre ne se doutait pas que ce serait pour être au service des enfants des rues, des bidonvilles et de la décharge. "J'ai compris que je voulais donner ma vie pour ça." Donner sa vie pour l'amour qui manque aux plus pauvres. "J'ai compris que la plus grande misère n'était pas d'abord une misère matérielle mais cet amour qui n'était pas donné à ces enfants, dont ils manquaient tant."     "Une misère qui vous donne des claques" La première fois qu'il a mis les pieds à Manille, il a été "extrêmement surpris, déstabilisé" par cette grande pauvreté dans laquelle vit 70% de la population. "Vous arrivez dans un pays qui a une misère qui nous donne des claques." La peur ? Elle lui vient quand il regarde en arrière et constate tout le chemin parcouru. Et en se disant que "si Dieu n'était pas à ses côtés", il ne serait "pas là aujourd'hui". Il se souvient de la première nuit qu'il a passée dans la rue avec les éducateurs, pour aller à la rencontre d'enfants âgés de 7 à 8 ans drogués ou dormant dans les ordures. Très loin du Versailles où il a grandi ! "J'ai toujours été d'une certaine façon très marqué par l'amour que doivent donner des parents, ayant eu la chance d'avoir des parents très aimants, et qu'un enfant puisse ne pas être aimé ça me paraît être le plus grand scandale."   Où se situe la vraie richesse Après son premier séjour à Manille, il lui a fallu rentrer en France, pour poursuivre ses études au séminaire. Et surtout discerner. "Il a fallu trois ans pour discerner, être accompagné, comprendre comment se donner totalement à cette vie-là." Le Père Dauchez a été ordonné diacre en 2003 puis prêtre en 2004 pour le diocèse de Manille. Lui qui se voyait très bien en curé de paroisse dans les Yvelines s'est découvert "pris aux tripes" et appelé bien loin de là, aux périphéries, comme le dit le pape François. Cette formidable et terrible aventure humaine et spirituelle auprès des pauvres de Manielle, il l'aborde en "témoin privilégié". "Les plus belles leçons je les reçoit des familles des bidonvilles, des familles de la décharge." Témoignage qu'il s'efforce de transmettre dans ses livres. "Le pape François nous incite à être sans cesse à l'écoute de ces plus pauvres et je m'aperçois qu'effectivement la vraie richesse elle se situe dans les ordures de Manille."     Émission enregistrée en décembre 2015  

C'est dans les rues de Manille, que le Père Matthieu Dauchez exerce son ministère de prêtre. Il s'occupe de l'association ANAK-Tnk, qui vient en aide aux enfants pauvres de la capitale des Philippines, association qui fête cette année ses 20 ans. Le Père Dauchez a raconté son aventure humaine et spirituelle dans plusieurs livres. En 2015, il était sur RCF pour témoigner de son parcours à l'occasion de la sortie de son ouvrage, "Plus fort que les Ténèbres" (éd. Artège, 2015). "Qu'un enfant puisse ne pas être aimé ça me paraît être le plus grand scandale"   De Versailles aux rues de Manille Un jour, des amis séminaristes, souhaitant le provoquer, lui ont dit qu'avec ses origines versaillaises il serait bien incapable de partir en mission. Les prenant au mot, Matthieu Dauchez décide de les suivre jusqu'à Manille et d'accompagner le jésuite Jean-François Thomas dans la fondation de ce qui s'appellera ANAK-Tnk. "Anak" qui signifie "enfant" en tagalog et les trois lettres "TNK" sont les initiales de la fondation connue à Manille sous le nom de "Tulay Ng Kabataan", qui signifie "Un pont pour les enfants". En 1998, le jeune séminariste entame donc un séjour de deux ans aux Philippines, deux ans qui vont changer sa vie. Et révéler ce qu'il appelle à la suite de mère Teresa, "un appel dans l'appel". Lui qui sait qu'il veut devenir prêtre ne se doutait pas que ce serait pour être au service des enfants des rues, des bidonvilles et de la décharge. "J'ai compris que je voulais donner ma vie pour ça." Donner sa vie pour l'amour qui manque aux plus pauvres. "J'ai compris que la plus grande misère n'était pas d'abord une misère matérielle mais cet amour qui n'était pas donné à ces enfants, dont ils manquaient tant."     "Une misère qui vous donne des claques" La première fois qu'il a mis les pieds à Manille, il a été "extrêmement surpris, déstabilisé" par cette grande pauvreté dans laquelle vit 70% de la population. "Vous arrivez dans un pays qui a une misère qui nous donne des claques." La peur ? Elle lui vient quand il regarde en arrière et constate tout le chemin parcouru. Et en se disant que "si Dieu n'était pas à ses côtés", il ne serait "pas là aujourd'hui". Il se souvient de la première nuit qu'il a passée dans la rue avec les éducateurs, pour aller à la rencontre d'enfants âgés de 7 à 8 ans drogués ou dormant dans les ordures. Très loin du Versailles où il a grandi ! "J'ai toujours été d'une certaine façon très marqué par l'amour que doivent donner des parents, ayant eu la chance d'avoir des parents très aimants, et qu'un enfant puisse ne pas être aimé ça me paraît être le plus grand scandale."   ÉCOUTER ► "Aller vers les périphéries", comprendre la spiritualité du pape François   Où se situe la vraie richesse Après son premier séjour à Manille, il lui a fallu rentrer en France, pour poursuivre ses études au séminaire. Et surtout discerner. "Il a fallu trois ans pour discerner, être accompagné, comprendre comment se donner totalement à cette vie-là." Le Père Dauchez a été ordonné diacre en 2003 puis prêtre en 2004 pour le diocèse de Manille. Lui qui se voyait très bien en curé de paroisse dans les Yvelines s'est découvert "pris aux tripes" et appelé bien loin de là, aux périphéries, comme le dit le pape François. Cette formidable et terrible aventure humaine et spirituelle auprès des pauvres de Manielle, il l'aborde en "témoin privilégié". "Les plus belles leçons je les reçoit des familles des bidonvilles, des familles de la décharge." Témoignage qu'il s'efforce de transmettre dans ses livres. "Le pape François nous incite à être sans cesse à l'écoute de ces plus pauvres et je m'aperçois qu'effectivement la vraie richesse elle se situe dans les ordures de Manille."     Émission enregistrée en décembre 2015  

In this week’s episode I talk to two nonbelivers in India.First I talk to Jahnavi. We talk about her growing up in a religious family. We talk about the importance of education. And how she decided to make small changes influencing kids by becoming a teacher.Then I talk to TNK from Indian Humanists. We talk about his road to humanism. We talk about the cast system. And we talk about his involvement in activities debunking the widespread superstition in India.Federation of Indian Rationalist Associations: https://www.facebook.com/FIRAsocial/Indian Humanists: https://www.facebook.com/IndianHumanistsOfficial/Support Babelfish on: https://babelfish.10er.dk/ or https://www.patreon.com/babelfish Find Babelfish on:Facebook: www.facebook.com/babelfishthepodcast/Instagram: https://www.instagram.com/babelfishthepodcast/ Support the show (https://www.patreon.com/babelfish)

In this portion God is revealing Himself to the Israelites with a name they did not yet know Him by. It is a beautiful and revolutionary name. It will engage them, free them, and transform them. It is found in nearly 7000 places in the TNK, but in almost every translation the Name is hidden, obscured, and replaced with fundamentally different names and titles. God's name is not Adonai nor the LORD! That is simply a lie! Join me as we look more closely at God's name as found in the sacred text of the TNK.

In this portion God is revealing Himself to the Israelites with a name they did not yet know Him by. It is a beautiful and revolutionary name. It will engage them, free them, and transform them. It is found in nearly 7000 places in the TNK, but in almost every translation the Name is hidden, obscured, and replaced with fundamentally different names and titles. God’s name is not Adonai nor the LORD! That is simply a lie! Join me as we look more closely at God’s name as found in the sacred text of the TNK.

Today I will be interviewing Trevor Swim, the co-author of the children’s book series Adventures with Bodie the English Bulldog. Trevor Swim co-authors this book series with his girlfriend, Katie Thoe. They are known as TnK. Adventures with Bodie the English Bulldog is a children’s storybook series that is aimed to teach children about each state in the United States of America. As Trevor and Katie travel full time in their RV across the country they are transforming their adventures in each state into a fun engaging educational children’s book written through the eyes of Bodie the English Bulldog. They have been traveling since February 2019, which is almost 1 year! Bodie is a 5 year-old English Bulldog with a hilarious personality. The books stem from their desire to cherish life adventures and to share them with others. They share their travels through various social media accounts: Facebook: @adventureswithbodie Instagram: @bodietheenglishbulldog Website: www.bodietheenglishbulldog.com To learn more about this series of books with language and learning tips click here.

Aspirin, Aspirin, give the patient Aspirin!  On this episode Dave highlights the value and importance of giving your patient Aspirin. Unless there is a major contraindication,  if you think your patient is suffering from cardiac ischemia or acute coronary syndrome, give them the Aspirin!  Also in this Episode: Evidence based research supporting the importance of ASA ASA vs TNK in the treatment of ACS and mortality reduction ASA use case story - sort of ;)   Subscribe to the video version of this podcast to have access to the visuals that accompany the audio as well as additional tools and resources to help improve your understanding.    Subscribe now at CurrentECG.com  And Stay Current!    

Dramaturg, actor, and writer, Linnea Barklund, joins us this week to help us distinguish one Noble Kinsman from the other, among other things. The Rhetorical Device of the Week is polysyndeton (aka the dinosaur that poops conjunctions); Linnea's Burbage Break is all about the interchangeability of men in TNK; Linnea teases out some of the more complicated themes that run through the play and gives us a sneak peak into the Bards Ablaze Theatre Collective's upcoming production of it; we play a little Line Roulette, issue a *very important* budgie-smuggler-related correction; spill some hot ShakesBubble Gossip and reveal the next #DickBracket match up. Thanks again, Linnea, for joining us to talk about Two Noble Kinsmen!

Emma and Charlotte get festive by watching The Crown before discussing the problematic humanisation of the royal family, racism and modernisation, dramatic licence and what honour and obedience is really about. Plus: our favourite Reese Witherspoon films. Episode footnotes - including what Clarie Foy thinks of corsets, all you need to know about the Profumo Affair, Prince Philip's racism, the plans already in place for the Queen's funeral and much more - are available at www.tomorrowneverknowspod.com Get in touch: we'd love to hear your thoughts on our episodes, and are very keen to answer any questions you might have. We're on Twitter as @TNKpod (also @lottelydia and @emmaelinor) and Facebook (@TNKpod). Send us an email at tomorrowneverknowspod@gmail.com or subscribe to our newsletter! You can also support us by donating to our hosting fund (if you do so, we'll send you TNK merch as a thank-you) - read more here.

NTV Radyo'nun Bizim Rock'çılar programında TNK grubunun kurucusu ve solisti Caner Karamukluoğlu vardı. Caner Karamukluoğlu müzik hikayesini Bizim Rock'çılar'da anlattı. Caner Karamukluoğlu müziğe küçük yaşlarda rock müzik dinleyerek ve gitar çalarak başladı. Lisede kurdukları TNK grubuna uzun süre vokal aradılar ancak bir türlü bulamadılar. Caner'in heavy metal şarkıcılarını taklit etmesi ve onlar gibi şarkı söylemesi grubun dikkatini çekti. Böylece grubun hem kurucusu hem gitaristi hem de solisti oldu.  Programda, Melankoli albümünden “Olsun” adlı parçayı çaldık. “Olsun” parçasının Caner için özel bir yönü de var. Parçayla ilgili şunları söyledi; “Çok karanlık bir sabaha uyanmıştım. Kendimi hiç iyi hissetmiyordum.

Consent, power relationships and career-ending moments: Charlotte and Emma discuss the #MeToo movement, testifying as punishment, and how to keep the anger alive. Episode footnotes - including Tarana Burke's founding of the 'me too' movement, the original Harvey Weinstein investigations by Jodi Kantor, Megan Twohey and Ronan Farrow, the idea of perfect victimhood and much more - are available at www.tomorrowneverknowspod.com Get in touch: we'd love to hear your thoughts on our episodes, and are very keen to answer any questions you might have. We're on Twitter as @TNKpod (also @lottelydia and @emmaelinor) and Facebook (@TNKpod). Send us an email at tomorrowneverknowspod@gmail.com or subscribe to our newsletter! You can also support us by donating to our hosting fund (if you do so, we'll send you TNK merch as a thank-you) - read more here.

Emma and Charlotte discuss populism and polarisation, how economic precarity and racism aren’t mutually exclusive, and what is happening in Sweden right now. Plus: Charlotte’s guide to the ‘no-go zone’ of Tower Hamlets… Episode footnotes - including updates on the Swedish election, Charlotte's review of Douglas Carswell's book, links to the works of Lynsey Hanley and Dominic Hinde and much more - are available at www.tomorrowneverknowspod.com Get in touch: we'd love to hear your thoughts on our episodes, and are very keen to answer any questions you might have. We're on Twitter as @TNKpod (also @lottelydia and @emmaelinor) and Facebook (@TNKpod). Send us an email at tomorrowneverknowspod@gmail.com or subscribe to our newsletter! You can also support us by donating to our hosting fund (if you do so, we'll send you TNK merch as a thank-you) - read more here.

Charlotte and Emma discuss glass cliffs, ticking the wrong box and how proportional representation is a lot like a bag of pick and mix. Plus: why losing an election could be a good thing. Episode footnotes - including all you might want to know about the Great Offices of State, the most gender-equal government in the world, what Tony Blair might smell like, and Paddy Pantsdown - are available at www.tomorrowneverknowspod.com Get in touch: we'd love to hear your thoughts on our episodes, and are very keen to answer any questions you might have. We're on Twitter as @TNKpod (also @lottelydia and @emmaelinor) and Facebook (@TNKpod). Send us an email at tomorrowneverknowspod@gmail.com or subscribe to our newsletter! You can also support us by donating to our hosting fund (if you do so, we'll send you TNK merch as a thank-you) - read more here.

Charlotte and Emma discuss fiction as a source for political history, comfort reads, classics bound up in class and the problem with Elena Ferrante’s book covers. Plus: join the TNK book club. Episode footnotes - including things about the Mitfords, Charlotte's least favourite book, Swedish proletariat literature and links to every single work of fiction that we mention - are available at www.tomorrowneverknowspod.com Get in touch: we'd love to hear your thoughts on our episodes, and are very keen to answer any questions you might have. We're on Twitter as @TNKpod (also @lottelydia and @emmaelinor) and Facebook (@TNKpod). Send us an email at tomorrowneverknowspod@gmail.com or subscribe to our newsletter! You can also support us by donating to our hosting fund - read more here.

The hosts of the Otaku Spirit Animecast are back to break down the biggest anime news of the last two weeks. Listen in and find out their thoughts on anime growth, Miyazaki’s movie title, crowdfunding initiatives, and other bits of news. Topics this episode: Evangelion Anima, Grandblue Fantasy Anime Season 2, Kokkoku Moment by Moment Anime, Netflix Rankings and initiatives, Yasuhiro Irie Kickstarter, Ore ga Suki nano wa imouto Anime, School-Live Manga, Scum’s Wish Manga, Kud Wafter International Crowdfunding, High School DxD Season 4, Takunomi Anime, AJA Anime Heath, Broccoli drop, Re:Creators Magane Manga, KyoAni’s Tsurune Adaptation, Miyazaki’s New Film, Testament of Sister New Devil OVA, Umaru-chan new Character, LiSA illness, Kemono Friends’ Director new Short, and much more! Thanks to Star-K, fragoff, Yumemi Star, and MyBalls for the great questions featured in this episode! The intro music for this episode is called “Kizukeyo Baby” by THE ORAL CIGARETTES and is available on iTunes. The outro music for this episode is from the anime Fuuka called “For You” by Lynn and is available on iTunes.

V této dokumentární rekonstrukci nahlédneme do zákulisí studia TNK a zjistíme, co všechno vedlo ke vzniku tohoto velmi úspěšného anime.

The Book of Jeremiah begins (1:1-4), “The words of Jeremiah the son of Hilkiah, of the priests who were in Anathoth in the land of Benjamin, to whom the word of the Lord came in the days of Josiah the son of Amon, king of Judah, in the thirteenth year of his reign. It came also in the days of Jehoiakim the son of Josiah, king of Judah, until the end of the eleventh year of Zedekiah the son of Josiah, king of Judah, until the exile of Jerusalem in the fifth month. Now the word of the Lord came to me, saying . . . “ Consider doing theology from the Old Testament. Are we reading a Hebrew Bible or an Old Testament? Consider Marcion and that in erasing the Old Testament Marcion effectively attacked the Jesus of the church's memory. Explore the various Jewish names for Scripture. Ha-sefarim is Hebrew for 'the books' and the Greek, τα βιβλια means 'The book'. Torah or Tanakh is also used. Tanakh is the Torah (law) and Nebi’im (prophets) plus the Ketubim (writings) or TNK. What is a testament? Testamentum in Latin means ʻcovenantʼ or ʻcontractʼ. The Hebrew is berit. For Calvin, "The covenant made with all the patriarchs is so much like ours in substance and reality that the two are actually one and the same. Yet they differ in the mode of dispensation." The Bible itself gives us internal testimony. In the Old Testament we have Jeremiah 31,31-34 and Ezekiel 34,25-31. In the New Testament we have Hebrews 9,15-22 and 1 Corinthians 11,25. Luther stated, "For the New Testament is nothing more than a revelation of the Old, just as if somebody at first had a sealed letter and then opened it. So the Old Testament is the testamental letter of Christ, which he caused to be opened after his death and read and proclaimed everywhere through the Gospel." View a picture of a cathedral’s stained glass windows. How do stained glass windows work? Consider biblical theology and Jerome's statement. What makes theology biblical? Consider Childs on biblical theology, "It can either denote a theology contained within the Bible, or a theology which accords with the Bible."

Visvambhar 4.24.17 TNK at The Bhakti Center by Concrete Jungle Kirtan