Podcasts about microvascular

In this Leveling Up episode of the PRS Global Open Deep Cuts podcast, Dr. Scott Hansen talks about his new role as Chair of Plastic Surgery at UCSF, his experience as a program director, and his leadership approach to resident training. He also shares insights on performing awake hand surgeries, his role as a team hand surgeon for the San Francisco Giants, and the unique considerations when treating hand injuries in professional athletes. Dr. Hansen explores the surprising differences between college women's basketball and Major League Baseball, how his practice of hand surgery has evolved, the field of spinoplastic surgery, and why he finds treating hidradenitis rewarding. He also reflects on the lessons he's learned from Drs. Steve Mathes, Neil Ford Jones, and Prosper Benhaim. Read a recent PRS Global Open article by Dr. Hansen and his colleagues, “A Pilot Randomized Clinical Trial of Early Ambulation after Groin Reconstruction with Sartorius Muscle Flaps“: https://bit.ly/WalkingAfterGroinRecon  Dr. Scott Hansen is a Professor, Chief of the Division of Plastic Surgery, and the Program Director for the Plastic Surgery Residency at the University of California San Francisco. He also serves as the Chief of Hand and Microvascular surgery and the Director of the Microsurgery fellowship. He graduated from Eastern Virginia Medical School, and then completed a Plastic Surgery residency and a post-doctoral research fellowship at UCSF followed by a Hand and Microvascular surgery fellowship at UCLA. He joined UCSF as full-time faculty, and recently became the Chief of the Division of plastic surgery there. He is the Hand and Microsurgery section editor for the Annals of Plastic Surgery. He is the team hand surgeon for the San Francisco Giants. He has remained involved in basic science research, with a focus in wound healing, hemangiomas, and limb development. Your host, Dr. Puru Nagarkar, is a board-certified plastic and hand surgeon, and Associate Professor of Plastic Surgery at the University of Texas Southwestern Medical Center in Dallas. #PRSGlobalOpen #DeepCutsPodcast #PlasticSurgery #LevelingUp

The FiltrateJoel TopfSwapnil HiremathAC GomezSopia AmbrusoNayan AroraSpecial Guests Michelle Rheault, Director, Division of Pediatric Nephrology, Professor of MedicineTiffany Caza, Nephropathologist, Scientist and self-described Freely Filtered fan girlEditing bySimon Topf and Sophia AmbrusoShow Notes10. Healthcare Cyberattacks9. ApoE in C3 glomerulonephropathy8. Workforce woes in Adult and Pediatric Nephrology7. Hyponatremia correction meta-analysis6. Microvascular inflammation increases risk of graft loss - in all of its forms5. Xenotransplantation4. KDIGO CKD Guidelines3. Hypertension control trials (ESPRIT, BPROAD)2. The Renaissance of IgAN: IgAN treatment trials1. FLOW: GLP-1 RAs in CKD

Prof Alisa Clyne and Dr Callie Weber from the University of Maryland speak to Dr Gita Thapaliya about an eBioMedicine article examining the impacts of APOE-ε4 and exercise training on brain function and metabolism.Read the full article:https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00523-1/fulltext?dgcid=buzzsprout_icw_podcast_generic_ebiomContinue this conversation on social!Follow us today at...https://twitter.com/thelancethttps://instagram.com/thelancetgrouphttps://facebook.com/thelancetmedicaljournalhttps://linkedIn.com/company/the-lancethttps://youtube.com/thelancettv

Mirza Umair Khalid, MD, social media editor of JACC: Cardiovascular Interventions, and Amir Lerman, MD, discuss the phase II study examining coronary sinus reducer for treatment of microvascular dysfunction.

Microvascular disease is a silent but deadly condition that could be damaging your heart, brain, kidneys, and liver—without you even knowing it. In this episode of Everyday Health Stories, Dr. Kota Reddy uncovers how this overlooked disease quietly affects millions, often going undetected until serious complications arise. Learn how coronary microvascular dysfunction (CMD) impacts the heart, leading to heart failure with preserved ejection fraction (HFpEF), and discover the everyday habits that may be fueling vascular damage. Most importantly, find out simple, science-backed steps to protect your vital organs and fight back against this hidden threat before it's too late!

$5 Q-BANK: https://patreon.com/highyieldfamilymedicine Intro 0:30, Diagnostic criteria 2:02, Type 1 vs type 2 diabetes 5:43, Metformin 6:57, Sulfonylureas 8:36, TZDs 9:09, DPP-4 inhibitors 9:54, GLP-1 agonists 10:39, SGLT2 inhibitors 12:39, Insulin 14:08, Diabetic ketoacidosis (DKA) 16:32, Hyperglycemic hyperosmolar syndrome (HHS) 23:07, Microvascular complications 25:06, Macrovascular complications 33:07, Practice questions 34:46

Microvascular dysfunction is a heart disease affecting the walls and inner lining of tiny coronary artery blood vessels that branch off from the larger coronary arteries. Younger women are at a higher risk of developing this disease, and the Women's Heart Center at MemorialCare Long Beach Medical Center want to ensure women understand the signs and symptoms of the disease early.

Audio Commentary by Dr. Valentin Fuster, Emeritus Editor in Chief

Dr. Sara Vasconcelos is a Senior Scientist and the John Kitson McIvor Endowed Chair in Diabetes Research at University Health Network. She is also an Associate Professor at the Institute of Biomedical Engineering at the University of Toronto. Her lab studies microvascular regeneration in cardiovascular diseases and diabetes, and are working to develop personalized patient-derived organ-chip models for drug screening and other applications. In this episode, she talks about modeling cardiac fibrosis and studying pancreatic islet vasculature. She also discusses working with microchips and with large animal models.

Commentary by Dr. Valentin Fuster

Commentary by Dr. Abdullah Al-Abcha and Dr. John Blair

Commentary by Dr. Valentin Fuster

On this week's listener series episode, we welcome Valerie. Valerie shares her journey with pregnancy and birth as a Type 1 Diabetic. Everything went smoothly until 2 days after discharge, when Valerie started to feel unwell. She shares how her family navigated a hospital stay postpartum and her second homecoming. What you will hear on this episode:- Pregnancy with Type 1 Diabetes- Preeclampsia diagnosis at 32 weeks- Induction and vacuum birth- Postpartum readmission- Microvascular angina- Postpartum while recovering from complicationsIf you have a birth trauma story you would like to share with us, click this link and fill out the form. For more birth trauma content and a community full of love and support, head to my Instagram at @birthtrauma_mama.Learn more about the support and services I offer through The Birth Trauma Mama Therapy & Support Services.

Many women who have typical symptoms of coronary artery disease actually have coronary microvascular disease (MVD). Gretchen Wells, M.D., a cardiologist, explains why it is important for physicians to proceed with tests for MVD when cardiac catheterization does not indicate coronary artery disease. She explores the common symptoms, proven and potential interventions, and the serious risks posed by MVD. Dr. Wells recommends patients explore multidisciplinary cardiac rehabilitation programs if they are diagnosed with MVD.

Commentary by Dr. Valentin Fuster

Editor in Chief Cecelia E. Schmalbach, MD, MSc, is joined by Associate Editor Babak Givi, MD, and lead author Leila J. Mady MD, PhD, MPH, to discuss “Gender Differences Among Head and Neck Microvascular Reconstructive Surgeons,” which published in the November 2023 issue of Otolaryngology–Head and Neck Surgery.  The research used a survey that was sent to facial plastic and maxillofacial surgeons, in addition to microvascular surgeons, to gain a comprehensive understanding of what causes gender differences in the subspecialty. One takeaway of note was that there were no gender differences when it came to training and practice patterns. Another revealed gender differences when explaining changes in practice—for men, the reasons related to career advancement; for women, the reasons related to burnout, usually related to work-life balance and especially if they have children.

In this weeks episode, we'll learn more about the role of IL-7 receptor signaling in the differentiation and expansion of human B-cell progenitors, discuss the use of fixed-duration venetoclax plus obinutuzumab in older patients with chronic lymphocytic leukemia, and learn how low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand Factor self-association 

Tigist Wodaje, Kardiolog, Doktorand, KS, KI berättar om att asymptomatiska patienter inte är evaluerade med bilddiagnostik ganska ofta pga. risker associerade med bilddiagnostiken. PP-ELI-SWE-2812

A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 16, entitled, “Microvascular contributions to white matter injury in Alzheimer's disease.” In their new editorial, researchers Zsolt Bagi, Larry S. Sherman and Stephen A. Back from Augusta University discuss mechanisms of cognitive impairment and dementia. Impairments in cognitive and executive function of presumed cerebral microvascular origin are important and recently recognized neuropathological manifestations of vascular contributions to cognitive impairment and dementia (VCID). It has been long known that hypertensive cerebrovascular disease also involves a spectrum of subcortical small vessel diseases, such as arteriolosclerosis and lipohyalinosis of small penetrating arterioles, which contribute to progressive injury of periventricular, frontal and parietal white matter (WM). “However, until recently, recognition of the role of WM injury during aging and the progression of Alzheimer disease and related dementias (AD/ADRD) was very limited.” Despite growing interest in VCID and AD/ADRD, there have been few studies of mechanistic links between subcortical small vessel disease, WM injury and cognitive decline. Even though WM constitutes >80% of the human cerebral hemispheres, a PubMed search of AD and WM injury yielded only 381 articles (including reviews) vs. 193,303 articles for AD alone. Notably, 50% of diagnosed AD patients have mixed vascular and AD pathology. Hence, there is a critical need to explore connections between AD, WM injury and cerebral small vessel disease to define mechanisms and diagnostic features of mixed vascular and AD neuropathological change (ADNC). “To provide rigorous access to human WM lesions, we recently developed a unique rapid autopsy brain procurement protocol using specimens donated by participants in the Adult Changes in Thought (ACT) study, a prospective, population-based study of aging and incident dementia among men and women in Seattle, Washington [5].” DOI - https://doi.org/10.18632/aging.204997 Corresponding author - Zsolt Bagi - zbagi@augusta.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204997 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cerebrovascular, neuropathology, vasodilation, parenchymal, arteriole About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Dr Alessandro Cicchetti and Luca Possenti present the results of the AIRC project “Mechanistic computational modelling of radiation damage to microvasculature and of its effect on tumour microenvironment”. This research comprises pre-clinical microfluidic chips, in-silico models, and patient data. The interview by Dr Orazio Fortunato gives an overview of the methodology and the possible impact on clinical practice.

Nanoparticles are manmade fibers, particulates, and other objects that are so small that when inhaled, they can escape the lungs and enter other body systems. Timothy Nurkiewicz, West Virginia University, studies the effects of these and other particulars. He discusses his inhalation and nanotoxicology research, as well as work with the National Guard on developing facemasks to protect against airborne diseases, with co-hosts Anne Chappelle and David Faulkner.About the GuestTimothy R. Nurkiewicz, PhD, is the E.J. Van Liere Medicine Professor and Chair of the Department of Physiology and Pharmacology at the West Virginia University (WVU) School of Medicine. He is also the Director of the WVU Inhalation Facilities and Center for Inhalation Toxicology (iTOX) and has been a guest researcher with the National Institute for Occupational Safety and Health since 2008.Dr. Nurkiewicz's research is in the fields of microvascular physiology and toxicology, with specific focus on pulmonary exposure to particulate matter and engineered nanomaterials. His research program pioneered novel investigations in the field of maternal nanomaterial exposures and fetal microvascular ramifications. Through iTOX, his lab and team are able to replicate the atmospheres that humans are exposed to in order to advance understanding of their acute and chronic toxicities.Dr. Nurkiewicz earned a BS in exercise and sport science from Pennsylvania State University, a MS in exercise physiology from WVU, and a PhD in physiology from WVU. He completed postdocs at Texas A&M University and WVU. Currently, Dr. Nurkiewicz serves as an Associate Editor for Frontiers—Vascular Physiology and Particle and Fibre Toxicology and is a founding member and Past President of the SOT Cardiovascular Toxicology Specialty Section.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547081v1?rss=1 Authors: Mihelic, S. A., Engelmann, S. A., Sadr, M. S., Jafari, C. Z., Zhou, A., Williamson, M. R., Dunn, A. K. Abstract: This research article quantitatively investigates neuro-microvascular network remodeling dynamics following stroke using a novel in vivo two-photon angiography (cubic millimeter volume, weekly snapshots) and high throughput (thousands of connected capillaries) vascular vectorization method. The results suggest distinct temporal patterns of cerebrovascular plasticity, with acute remodeling peaking at one week post-stroke. The network architecture then gradually stabilizes, returning to a new steady state after four weeks. These findings align with previous literature on neuronal plasticity, highlighting the correlation between neuronal and neurovascular remodeling. Quantitative analysis of neurovascular networks using length- and strand-based statistical measures reveals intricate changes in network anatomy and topology. The distance and strand-length statistics show significant alterations, with a peak of plasticity observed at one week post-stroke, followed by a gradual return to baseline. The orientation statistic plasticity peaks at two weeks, gradually approaching the (conserved across subjects) stroke signature. The underlying mechanism of the vascular response (angiogenesis vs. tissue deformation), however, is yet unelucidated, requiring network registration advancements. Overall, the combination of two-photon angiography, vectorization, reconstruction/visualization, and statistical analysis enables both qualitative and quantitative assessments of neurovascular remodeling dynamics, demonstrating an impactful method for investigating neuro-microvascular network disorders and the therapeutic modes of action thereof. Understanding the timing and nature of neurovascular remodeling allows for optimized interventions, including personalized medicine for stroke rehabilitation. Additionally, the evaluation of pharmaceutical interventions using these tools may facilitate targeted drug development. Furthermore, neurovascular coupling dynamics have implications for neurodegenerative diseases, brain aging, and the field of brain-computer interfaces. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

ESC TV Today brings you concise analysis from the world's leading experts, so you can stay on top of what's happening in your field quickly. This episode covers: Cardiology This Week: A concise summary of recent studies Microvascular angina Minimally invasive tricuspid valve surgery Mythbusters: An apple a day keeps the doctor away Host: Rick Grobbee Guests: Volkmar Falk and Eva Prescott Want to watch that episode? Go to: https://esc365.escardio.org/event/1095   Disclaimer This programme is supported by Siemens Healthineers in the form of an educational grant. The scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is supported by Siemens Healthineers in the form of an educational grant. The scientific content and opinions expressed in the programme have not been influenced in any way by its sponsor. This programme is intended for health care professionals only and is to be used for educational purposes. The European Society of Cardiology (ESC) does not aim to promote medicinal products nor devices. Any views or opinions expressed are the presenters' own and do not reflect the views of the ESC.   Declarations of interests Stephan Achenbach, Rick Grobbee, Nicolle Kraenkel and Eva Prescott have declared to have no potential conflicts of interest to report. Carlos Aguiar has declared to have potential conflicts of interest to report: personal fees for consultancy and/or speaker fees from Abbott, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Ferrer, Gilead, Lilly, Novartis, Pfizer, Sanofi, Servier, Tecnimede. Davide Capodanno has declared to have potential conflicts of interest to report: Sanofi, Daiichi Sankyo, Terumo, Medtronic, Chiesi. Volkmar Falk has declared to have potential conflicts of interest to report: Medtronic GmbH, Biotronik SE & Co., Abbott GmbH & Co. KG, Boston Scientific, Edwards Lifesciences, LivaNova, Berlin Heart, Novartis Pharma GmbH, JOTEC GmbH, Zurich Heart.  Emma Svennberg has declared to have potential conflicts of interest to report: institutional research grants from Bayer, Bristol-Myers, Squibb-Pfizer, Boehringer- Ingelheim, Johnson & Johnson, Merck Sharp & Dohme.

Dr Sanjeev Goel interviews world renowned expert Dr Hans Vink on the science of the Glycocalyx and Robert Long from Microvascular Health Solutions.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.16.537063v1?rss=1 Authors: Caratis, F., Karaszewski, B., Klejbor, I., Furihata, T., Rutkowska, A. Abstract: The EBI2 receptor is a major modulator of innate immunity and, together with its ligand, oxysterol 7,25OHC, has been implicated in several neuroinflammatory and autoimmune diseases. 7alpha,25OHC is synthesised from cholesterol with CH25H and CYP7B1 enzymes and degraded with HSD3B7. The concentration of 7alpha,25OHC in the brain increases in the early phases of the murine model of multiple sclerosis, leading to an enhanced central nervous system (CNS) infiltration with EBI2-expressing lymphocytes. Here, we aimed to investigate whether the enzymes involved in the synthesis and degradation of 7alpha,25OHC are expressed directly in the mouse brain microvascular cells and whether systemic inflammation modulates their levels in these cells. Normal mouse brain capillaries were isolated and immunostained for EBI2, CH25H, CYP7B1 and HSD3B7. Subsequently, mice were challenged with lipopolysaccharide and the mRNA expression in whole brain homogenates was measured. Changes in the receptor and enzyme levels were quantified directly in endothelial cells (ECs), pericytes and astrocytes. The data indicated high levels of EBI2 in the brain microvascular ECs, pericytes and astrocytes with the highest co-localisation in pericytes. CH25H was detected in ECs and astrocytes with low levels in pericytes. CYP7B1 was moderately expressed in ECs, astrocytes and pericytes. The 7alpha,25OHC degrading enzyme HSD3B7 was the least detected in astrocytes. Moreover, the data indicated that systemic inflammation downregulated the mRNA levels of Ebi2 and upregulated Ch25h expression in the whole brain. Specifically in each cell type, EBI2 was not induced in ECs but increased in astrocytes and pericytes. CH25H levels increased in astrocytes and pericytes and CYP7B1 in ECs and astrocytes. The degrading enzyme, HSD3B7, was least affected by systemic inflammation. Taken together, we here demonstrate that EBI2 and the enzymes regulating its ligand levels are differentially expressed in mouse brain microvessels and are highly modulated by systemic inflammation. Upregulated concentration of 7alpha,25OHC in the brain during inflammation may lead to an increased migration of EBI2-expressing immune cells into the CNS during infection or neuroinflammatory disease. Modulation of the EBI2/oxysterol system in the brain or directly in the brain blood vessels may thus provide a new approach to treating neuroinflammatory diseases including multiple sclerosis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Commentary by Dr. Candice Silversides

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.03.535441v1?rss=1 Authors: Bei, J., Miranda-Morales, E. G., Gan, Q., Qiu, Y., Husseinzadeh, S., Liew, J. Y., Chang, Q., Krishnan, B., Gaitas, A., Yuan, S., Felicella, M., Qiu, W., Fang, X., Gong, B. Abstract: Background: Blood-brain barrier (BBB) breakdown is a component of the progression and pathology of Alzheimer's disease (AD). BBB dysfunction is primarily caused by reduced or disorganized tight junction or adherens junction proteins of brain microvascular endothelial cell (BMEC). While there is growing evidence of tight junction disruption in BMECs in AD, the functional role of adherens junctions during BBB dysfunction in AD remains unknown. Exosomes secreted from senescent cells have unique characteristics and contribute to modulating the phenotype of recipient cells. However, it remains unknown if and how these exosomes cause BMEC dysfunction in AD. Objectives: This study aimed to investigate the potential roles of AD circulating exosomes and their RNA cargos in brain endothelial dysfunction in AD. Methods: We isolated exosomes from sera of five cases of AD compared with age- and sex-matched cognitively normal controls using size-exclusion chromatography technology. We validated the qualities and particle sizes of isolated exosomes with nanoparticle tracking analysis and atomic force microscopy. We measured the biomechanical natures of the endothelial barrier of BMECs, the lateral binding forces between live BMECs, using fluidic force miscopy. We visualized the paracellular expressions of the key adherens junction protein VE-cadherin in BMEC cultures and a 3D BBB model that employs primary human BMECs and pericytes with immunostaining and evaluated them using confocal microscopy. We also examined the VE-cadherin signal in brain tissues from five cases of AD and five age- and sex-matched cognitively normal controls. Results: We found that circulating exosomes from AD patients suppress the paracellular expression levels of VE-cadherin and impair the barrier function of recipient BMECs. Immunostaining analysis showed that AD circulating exosomes damage VE-cadherin integrity in a 3D model of microvascular tubule formation. We found that circulating exosomes in AD weaken the BBB depending on the RNA cargos. In parallel, we observed that microvascular VE-cadherin expression is diminished in AD brains compared to normal controls. Conclusion: Using in vitro and ex vivo models, our study illustrates that circulating exosomes from AD patients play a significant role in mediating the damage effect on adhesions junction of recipient BMEC of the BBB in an exosomal RNA-dependent manner. This suggests a novel mechanism of peripheral senescent exosomes for AD risk. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

https://psychiatry.dev/wp-content/uploads/speaker/post-12259.mp3?cb=1678922888.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model – Faye McKenna et al.Full EntryMicrostructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model –

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.12.532316v1?rss=1 Authors: Ullah, K., Ai, L., Li, Y., Liu, L., Zhang, Q., Pan, K., Humayun, Z., Sitikov, A., Su, Q., Zhao, Q., Sharp, W. W., Fang, Y., Wu, D., Liao, J. K., Wu, R. Abstract: Rationale: Cardiac microvascular leakage and inflammation are triggered during myocardial infarction (MI) and contribute to heart failure. Hypoxia-inducible factor 2 (Hif2) is highly expressed in endothelial cells (ECs) and rapidly activated by myocardial ischemia, but whether it has a role in endothelial barrier function during MI is unclear. Objective: To test our hypothesis that the expression of Hif2 and its binding partner aryl hydrocarbon nuclear translocator (ARNT) in ECs regulate cardiac microvascular permeability in infarcted hearts. Methods and Results: Experiments were conducted with mice carrying an inducible EC-specific Hif2-knockout (ecHif2-/-) mutation, with mouse cardiac microvascular endothelial cells (CMVECs) isolated from the hearts of ecHif2-/- mice after the mutation was induced, and with human CMVECs and umbilical-vein endothelial cells transfected with ecHif2 siRNA. After MI induction, echocardiographic assessments of cardiac function were significantly lower, while measures of cardiac microvascular leakage (Evans blue assay), plasma IL6 levels, and cardiac neutrophil accumulation and fibrosis (histology) were significantly greater, in ecHif2-/- mice than in control mice, and RNA-sequencing analysis of heart tissues from both groups indicated that the expression of genes involved in vascular permeability and collagen synthesis was enriched in ecHif2-/- hearts. In cultured ECs, ecHif2 deficiency was associated with declines in endothelial barrier function (electrical cell impedance assay) and the reduced abundance of tight-junction proteins, as well as an increase in the expression of inflammatory markers, all of which were largely reversed by the overexpression of ARNT. We also found that ARNT, but not Hif2, binds directly to the IL6 promoter and suppresses IL6 expression. Conclusions: EC-specific deficiencies in Hif2 expression significantly increase cardiac microvascular permeability, promote inflammation, and reduce cardiac function in infarcted mouse hearts, and ARNT overexpression can reverse the upregulation of inflammatory genes and restore endothelial-barrier function in Hif2-deficient ECs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.09.527854v1?rss=1 Authors: Kaur, G., Pant, P., Bhagat, R., Seth, P. Abstract: Neurotropic viruses can cross the otherwise dynamically regulated blood-brain barrier (BBB) and affect the brain cells. Zika virus (ZIKV) is an enveloped neurotropic Flavivirus known to cause severe neurological complications, such as encephalitis and foetal microcephaly. In the present study, we used human brain microvascular endothelial cells (hBMECs) and human progenitor derived astrocytes to form a physiologically relevant BBB model. We used this model to investigate the effects of ZIKV envelope (E) protein on properties of cells comprising the BBB. E protein is the principal viral protein involved in interaction with host cell surface receptors, facilitating the viral entry. Our findings show that ZIKV E protein results in activation of both hBMECs and astrocytes. hBMECs showed reduced expression of endothelial junction proteins - ZO-1, Occludin and VE-Cadherin, which are crucial in establishing and maintaining the BBB. As a result, ZIKV E protein triggered alteration in BBB integrity and permeability. We also found upregulation of genes involved in leukocyte recruitment along with increased proinflammatory chemokines and cytokines upon exposure to E protein. Furthermore, E protein resulted in astrogliosis as seen by increased expression of GFAP and Vimentin. Both BBB cell types exhibited inflammatory response following exposure to E protein which may influence viral access into the central nervous system (CNS), resulting in infection of other CNS cells. Overall, our study provides valuable insights into the transient changes that occur at the site of BBB upon ZIKV infection. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.23.525218v1?rss=1 Authors: Chen, C., Qin, Y., Xu, Y., Chen, L., Wang, L., Liu, D. Abstract: In patients with diabetic microvascular complications, reduced vessel perfusion or vascular occlusion is a common characteristic which will cause the insufficient blood supply. However, identification of novel regulators involved in microvascular lumenization defects is hindered by the lacking of a model for imaging the blood vessels at high resolution in vivo. Taking advantage of the transparency of zebrafish, we observed the reduction of vascular diameter and compromised perfusion in high glucose treated embryos. RNA sequencing and whole-mount in situ hybridization analysis indicated that two aquaporins (aqp1a.1 and aqp8a.1) were significant down-regulated, which was further confirmed by endothelial specific Q-PCR. It was also shown that the two aqps were spatio-temporally enriched in the endothelial cells (ECs) of vascular system. Zebrafish with loss of aqp1a.1 or aqp8a.1 displayed lumenization defects in intersegmental vessels, recapitulating the phenotype in hyperglycemic zebrafish model. While overexpressing the aquaporins in zebrafish promoted the enlargement of the vascular diameter. Moreover, the defective vasculature induced by high-glucose treatment could be rescued by aqp1a.1 upregulation. In addition, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as in the ECs of sprouting ISVs, and loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Finally, we found that the expression of human AQP1 was downregulated in diabetic human retina samples and high-glucose treated human retinal microvascular endothelial cells. All these results suggest that EC-enriched aquaporins have a role in developmental and pathological blood vessel lumenization, and they might be potential targets for gene therapy to cure diabetes-related vascular lumenization defects. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Michael Sturek reviews features of macrovascular atherosclerosis and microvascular dysfunction that underlie ischemic events and the need for appropriate animal models for optimal translation.

Michael Sturek reviews features of macrovascular atherosclerosis and microvascular dysfunction that underlie ischemic events and the need for appropriate animal models for optimal translation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.23.517628v1?rss=1 Authors: Zhang, Q., Yang, Y., Cao, K. J., Chen, W., Paidi, S., Xia, C.-h., Kramer, R., Gong, X., Ji, N. Abstract: The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving synapses and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions and observed microglial migration in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode of the Award-winning PRS Journal Club Podcast, 2022 Resident Ambassadors to the PRS Editorial Board – Saïd Azoury, Emily Long, and Ronnie Shammas- and special guest Brett T. Phillips, MD, discuss the following articles from the November 2022 issue: “Risk Factors for Partial Flap Loss in a Free Flap: A 12-Year Retrospective Study of Anterolateral Thigh Free Flaps in 303 Lower Extremity Cases” by Min, Hong, and Suh. Read the article for FREE: https://bit.ly/PerforatorFlapLoss Special guest Brett T. Philips, MD, is an Assistant Professor and Program Director at Duke Integrated Plastic Surgery Program. He completed his General Surgery training at the State University Of New York At Stony Brook, Plastic Surgery training at Duke University, and Microvascular training at MD Anderson. He is the new Chair of the Young Microsurgeons Group Committee. READ the articles discussed in this podcast as well as free related content from the archives: https://bit.ly/PRSNov22Collection

In this episode of the Award-winning PRS Journal Club Podcast, 2022 Resident Ambassadors to the PRS Editorial Board – Saïd Azoury, Emily Long, and Ronnie Shammas- and special guest Brett T. Phillips, MD, discuss the following articles from the November 2022 issue: “Clinical Relevance of Sensory Nerve Coaptation in DIEP Flap Breast Reconstruction Evaluated Using the BREAST-Q” by Bijkerk, Buegels, van Kujik et al. Read the article for FREE: https://bit.ly/NerveCoapatationDIEP Special guest Brett T. Philips, MD, is an Assistant Professor and Program Director at Duke Integrated Plastic Surgery Program. He completed his General Surgery training at the State University Of New York At Stony Brook, Plastic Surgery training at Duke University, and Microvascular training at MD Anderson. He is the new Chair of the Young Microsurgeons Group Committee. READ the articles discussed in this podcast as well as free related content from the archives: https://bit.ly/PRSNov22Collection

In this episode of the Award-winning PRS Journal Club Podcast, 2022 Resident Ambassadors to the PRS Editorial Board – Saïd Azoury, Emily Long, and Ronnie Shammas- and special guest Brett T. Phillips, MD, discuss the following articles from the November 2022 issue: “Large-Volume Fat Grafting: Identifying Risk Factors for Fat Necrosis” by Chang, Lanni, Mirzabeigi, and Bucky. Read the article for FREE: https://bit.ly/LargeVolFatGrafting Special guest Brett T. Philips, MD, is an Assistant Professor and Program Director at Duke Integrated Plastic Surgery Program. He completed his General Surgery training at the State University Of New York At Stony Brook, Plastic Surgery training at Duke University, and Microvascular training at MD Anderson. He is the new Chair of the Young Microsurgeons Group Committee. READ the articles discussed in this podcast as well as free related content from the archives: https://bit.ly/PRSNov22Collection

Enduring CME will expire on 11/2/2024. The presentation is originating from Northeast Georgia Medical Center Gainesville. Objectives: 1. To review sex differences in ischemic heart disease prevalence and outcomes 2. To understand new data regarding sex-specific ischemic heart disease pathophysiology in women 3. To evaluate sex-specific diagnosis and treatment strategies for ischemic heart disease in women Disclosures: Grant support*: NHLBI, Louis B Mayer Foundation, NIH-CTSI, CMDRP-DoD, NIH-Caladrius, California Institute for Precision Medicine (CIAPM), Sanofi-Vascular Consulting: Medscape*, Sanofi-Vascular*, NIH CSR and NIH ORWHAB*, iRhythm Honorarium*: Abbott Diagnostics Stocks: None Accreditation and Designation: The Northeast Georgia Medical Center & Health System, Inc. is accredited by the Medical Association of Georgia to provide continuing medical education for physicians. The Northeast Georgia Medical Center & Health System, Inc. designates this live activity for a maximum of 1 AMA PRA Category 1 Credit(s) TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The GRADE studies evaluated the pharmacotherapy of diabetes after initiation of metformin – for both micro- and macrovascular outcomes. Join host, Geoff Wall, and guest Jake Galdo as they examine these studies to determine if they are GameChangers in diabetes management.The GameChangerInsulin glargine and liraglutide had the biggest decrease in A1c; however, many patients still did not reach goal targets. Minor differences in microvascular and macrovascular outcomes were observed.Show Segments00:00 - Introductions1:40 - The GRADE Studies12:02 - Glycemic Outcomes16:08 - Microvascular and Cardiovascular Outcomes21:10 - The GameChanger: Selecting a Second Medication27:18 - Connecting to Practice: Realistic Diabetes Care33:17 - Closing RemarksHostGeoff Wall, PharmD, BCPS, FCCP, CGPProfessor of Pharmacy Practice, Drake UniversityInternal Medicine/Critical Care, UnityPoint HealthGuestJohn A Galdo, PharmD, MBA, BCPS, BCGP (Jake)Director, CEimpactPharmacist, Ross Bridge PharmacyCEO, SeguridadReferences and ResourcesGlycemia Reduction in Type 2 Diabetes - Glycemic OutcomesGlycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Redeem your CPE or CME hereCPE (Pharmacist)CME (Physician)Get a membership & earn CE for GameChangers Podcast episodes (30 mins/episode)Pharmacists: Get a membershipPrescribers: Get a membershipCE InformationLearning ObjectivesUpon successful completion of this knowledge-based activity, participants should be able to:1. Select a second medication after metformin in a patient with type 2 diabetes based on the data from the GRADE studies2. Discuss the results of the GRADE studies0.05 CEU/0.5 HrUAN: 0107-0000-22-401-H01-PInitial release date: 10/31/2022Expiration date: 10/31/2023Additional CPE and CME details can be found here.Follow CEimpact on Social Media:LinkedInInstagramDownload the CEimpact App for Free Continuing Education + so much more!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.24.505172v1?rss=1 Authors: Uruk, G., Ozcan, S. Y., Aktas, C. C., Taskiran-Sag, A., Donmez-Demir, B., Duran, J., Guinovart, J. J., Karatas-Kursun, H., Dalkara, T., Ozkan, M. Y. Abstract: Ischemic stroke results in sudden blood flow cessation, thus, unmet energy requirements. Although the clotted artery can be recanalized and blood flow is restored, brain perfusion may not be fully attained due to microvascular constrictions. Under glucose-deprived and hypoxic conditions, glucose derived from the glycogen stored around peri-microvascular astrocyte end-feet may serve as an emergency fuel to meet the metabolic demand during the acute period of ischemic stroke. To elucidate the impact of glycogen utilization on brain microcirculation, we administered glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) intracerebroventricularly. Transgenic mice in which glycogen synthase-1 expression was selectively knocked out in central nervous system (GYS1Nestin-KO) were also used. Both approaches caused microvascular constrictions mediated by CD13-positive pericyte contractions. When mice with disrupted glycogen utilization were subjected to MCA ischemia, pericyte-mediated microvascular constrictions and the infarct volumes were further increased compared to untreated controls or wild-type littermates. Peri-microvascular glycogen depletions were highly correlated with microvascular constrictions as shown by Periodic acid Schiff (PAS) staining and immunolabeling with anti-glycogen antibodies. Imaging of regional cortical blood flow changes during ischemia disclosed severely compromised blood flow dynamics in mice with disrupted glycogen metabolism. In conclusion, disrupting glycogen utilization causes ischemic-like microvascular constrictions under non-ischemic circumstances and increases susceptibility to brain ischemia. Understanding the role of glycogen at neurogliovascular level in brain may provide novel insight to the pathophysiology of ischemic stroke and therapeutic opportunities. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

The Journal RETINA is devoted exclusively to diseases of the retina and vitreous. These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.

This episode features Dr. Ofer Azoulay. He serves as  Assistant Professor and Chief of Robotic and Microvascular Head and Neck Reconstruction at SUNY Downstate Health Sciences University. Be sure to check out the Downstate ENT Patient Stories we discuss in this week's episode: Matthew Racies: https://www.youtube.com/watch?v=dwYra708wF4&ab_channel=DownstateTV John Rodriguez: https://www.youtube.com/watch?v=aV3BLG_eZOw&ab_channel=DownstateTV Natalia Plaza: https://www.youtube.com/watch?v=Os5zRSVRQW0&ab_channel=DownstateTV Mary Williams: https://www.youtube.com/watch?v=8q_FYXrdCSQ&ab_channel=DownstateTV 

In this episode, Associate Editor Amanda LeBlanc (University of Louisville) interviews authors Lacy Alexander and Gabrielle Dillon (The Pennsylvania State University) along with content expert Melissa Witman (University of Delaware) about a new study by Dillon et al. With their lab closed due to the pandemic, the Alexander Lab continued to hold journal club meetings virtually to discuss two articles published previously in AJP-Heart and Circ – Ratchford et al. and Nandadeva et al. The intriguing results in these studies became a catalyst for new research questions which the Alexander Lab began to pursue as soon as they could return to human research post-pandemic. In contrast to both Ratchford et al. and Nandadeva et al., Dillon et al. found that healthy young adults who had recovered from mild to moderate COVID-19 did not display alternations in nitric oxide-mediated cutaneous microvascular. The authors hypothesized that methodology, onset of symptomology, and the role of vaccine-generated antibodies are key reasons their results differed from other recent studies. In addition, the authors found that having vaccine-generated antibodies was not detrimental to the microvasculature. The authors navigated numerous roadblocks in undertaking this study—stringent COVID-19 health and safety measures, scarce PPE, difficulty enrolling participants, and required COVID-19 testing protocols prior to participation. When faced with the decision on how to handle enrolling fully vaccinated, partially vaccinated and unvaccinated subjects, the authors opted to include all and stratify their results. This is an episode as much about resilience as it is about research. In search of inspiration for how to pivot and keep moving forward? Listen now.   Gabrielle A. Dillon, S. Tony Wolf, and Lacy M. Alexander Nitric oxide-mediated cutaneous microvascular function is not altered in young adults following mild-to-moderate SARS CoV-2 infection   Am J Physiol Heart Circ Physiol, published January 28, 2022. DOI: doi.org/10.1152/ajpheart.00602.2021

On Episode 12 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the January 2022 issue of Stroke: “Efficacy of Intravenous Mesenchymal Stem Cells for Motor Recovery After Ischemic Stroke: A Neuroimaging Study” and “Cumulative Concussion and Odds of Stroke in Former National Football League Players.” She also interviews Dr. Mike Sharma about his article “Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.” Dr. Negar Asdaghi: 1) Can repeated concussions increase the risk of stroke in professional athletes? 2) Does stem cell therapy enhance the recovery from ischemic stroke? 3) ESUS stands for “embolic stroke of unknown source.” Is ESUS just a fancy new term, or is there more to it than meets the eye? These are some of the topics that we will discuss in today's podcast. We're covering the best in Stroke. Stay with us. Dr. Negar Asdaghi:         Welcome to a new year of Stroke podcasts. 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. The January 2022 issue of Stroke covers a host of topics, from molecular biomarkers and drug targets in brain arteriovenous malformation to examining the role of calcium in atherosclerotic carotid disease, which I encourage you to review in addition to listening to today's podcast. Later in the podcast, I have the honor of interviewing Dr. Mike Sharma from McMaster University in Hamilton, Ontario, on his work with embolic stroke of unknown source and some of the therapies to soon be studied in this population, including the new Factor XI inhibitors. But first with these two articles. Dr. Negar Asdaghi:         Stem cells are truly the new kids on the block of therapies to potentially enhance stroke recovery. There's now four decades worth of experience with preclinical research and studies with animal models to evaluate the safety and efficacy of stem cell therapies and stroke. Now, this is a complex topic, and I will try to simplify it as much as possible. So, what are the things that we need to know about stem cell therapy and ischemic stroke? Well, first, in humans, the bone marrow has emerged as the widely used source of stem cells, primarily because of its long track record of safety profile. In fact, bone marrow derived cell populations, some examples being mesenchymal stem cells, mononuclear cells, endothelial progenitor cells, are the leading candidates for stem cell therapies in ischemic stroke. Number two, stem cells can be practically delivered to the brain through a variety of pathways. Intravenous and intra-arterial treatments have been and are currently being studied, but stem cells can also be delivered intranasally and, of course, surgically transplanted in the brain. Dr. Negar Asdaghi:         So, with these in mind, there are two recently concluded clinical trials of mesenchymal stem cells in adult stroke patients. The STARTING-2 trial, which stands for the Stem Cell Application Researches and Trials in Neurology-2, was one of those two trials. This trial evaluated the safety and efficacy of intravenous autologous, meaning from the same individual, mesenchymal stem cells in patients with moderate to severe neurological deficit originating from the middle cerebral artery territory infarct within 90 days of symptom onset. The primary results of the trial was published in Neurology very recently in February of 2021, and if you missed it, well, luckily, you are listening to the podcast today. So, here's a quick recap of the trial. Fifty-four patients were enrolled in the trial with mean stroke onset to randomization of 20 days. Patients were randomized 2:1 to either receive intravenous mesenchymal stem cell treatment or placebo. Dr. Negar Asdaghi:         Well, in terms of the primary outcome, stem cell therapy did not improve the primary outcome, which was improvement of modified Rankin Scale at 90 days after treatment. So, disappointing, but secondary analysis showed a significant improvement in lower extremity motor function in the stem cell group as compared to the control group. So, in the current issue of the journal, in the study titled "Efficacy of Intravenous Mesenchymal Stem Cells For Motor Recovery After Ischemic Stroke: A Neuroimaging Study," the STARTING-2 collaborators, led by Dr. Jungsoo Lee from the Department of Physical and Rehabilitation Medicine from Sungkyunkwan University School of Medicine in Seoul, South Korea, aimed to look at this improved motor recovery in more detail using advanced neuroimaging. So, of the original 54 patients in the trial, 44 were eligible for the current neuroimaging study. Participants underwent a variety of testings, including diffusion tensor imaging and resting-state functional MRI studies, at the time of enrollment and then 90 days afterwards. Dr. Negar Asdaghi:         So, not surprisingly, at baseline, patients in both the stem cell and control group had comparable demographics, clinical characteristics and infarct volumes, as well as similar motor function, which was measured by the Fugl-Meyer, or the FMA, score. So here's a look at their main findings. So, number one, the FMA scores that were comparable at baseline were significantly higher at follow-up in the stem cell-treated group. Number two is the interesting results; they looked at the motor pathways using diffusion tensor imaging. So, they looked at fractional anisotropy values of the corticospinal pathways and the posterior limb of the internal capsule. Now, just a quick review of a somewhat complex concept of the fractional anisotropy for our listeners. In general, FA is one of the calculated parameters in DTI with a value between zero to one, and what it does is that it defines the degree of diffusion directionality. Dr. Negar Asdaghi:         A value of zero means that the diffusion is isotropic, meaning it is unrestricted or equally restricted in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all the other directions. So, it's easy to understand in terms of axons creating white matter tracts. When the tracts are intact, then the FA values would be high because the diffusion is occurring only in one direction as the tract is intending it to do so, whereas if the white matter tracts are damaged, then the uni-directionality of the tract would be disrupted and the molecules would diffuse freely in various directions and the FA values for that white matter tract is then, as expected, reduced. So, in the stroke model, for example, if a neuron in the motor cortex is damaged, the white matter tract related to that region will, over time, degenerate, a process which we know as Wallerian degeneration and, as such, the FA values of that tract is expected to decrease as we go from the acute to the chronic stages of stroke. Dr. Negar Asdaghi:         So, back to the current study. At time zero, FA values for the corticospinal tract and the posterior limb of internal capsule were fairly similar between the two groups, but interestingly, at 90-day follow-up, those in the control group had a significant and expected drop in their FA values, whereas those who had received stem cell therapy did not show a significant drop, meaning that intravenous administration of mesenchymal stem cells did modulate and perhaps prevented degeneration of the motor tracts after stroke. The third and final interesting finding of the study was the findings of the resting-state functional MRI. They used RS, or resting-state, fMRI as a measure of functional motor connectivity and found that stem cell treatment increased the strength of ipsilesional connectivity in the motor network and prevented a drop in the strength of intrahemispheric connectivity, whereas these findings were not seen in the control group. Dr. Negar Asdaghi:         So, what does this all mean? We now have some detailed neuroimaging evidence that indeed stem cell treatment can facilitate motor recovery possibly by reducing degeneration, which is what their DTI data showed, and potentially by leading to positive motor network organization or reorganization, which is what the resting-state fMRI findings showed. So, obviously, lots still to come in this topic and a reminder to our listeners that there are ongoing clinical trials on this topic. So, we will stay tuned as the neuroprotection and regeneration paradigm is truly changing for ischemic stroke with stem cell therapy. Dr. Negar Asdaghi:         Sports-related concussive symptoms typically resolve within a few weeks of the injury, but there is now ample scientific evidence to suggest that repeated concussion can cause long-term neurological disorders extending way beyond the short-term post-concussive period. How can traumatic brain injury, or TBI, be a cause for stroke? Well, in the more severe forms of TBI, it can actually cause damage to the large vessels and cause dissection, but there is more and more research showing that even milder trauma can lead to microvascular disruptions and even alterations in coagulation pathway, which will then increase the risk of stroke. So, how about repeated mild trauma or repeated concussion in professional athletes? Is concussion a risk factor for stroke in this population? Dr. Negar Asdaghi:         Well, in the current issue of the journal, in the study titled "Cumulative Concussion and Odds of Stroke in Former NFL Players," Dr. Benjamin Brett and Zachary Kerr from Department of Neurosurgery, Medical College of Wisconsin, and Department of Exercise and Sports Science, University of North Carolina at Chapel Hill, and colleagues report on a cross-sectional study that included professional football players who had at least played for one year in the National Football League and were over the age of 50 at the time of the study. Dr. Negar Asdaghi:         Now, before we go over the results, there are a few important definitions from this study to note. Number one, concussion was defined as a blow to the head followed by a variety of neurological symptoms, such as headache, dizziness, loss of balance, etc. Getting knocked out or being unconscious was not necessary to define concussion. For our listeners, this is an important shift from the original definition of concussion that required some alteration of level of consciousness. Number two, the participants were asked as part of the study survey about a history of stroke, which was defined as any health provider giving the participant the diagnosis of stroke at some point in their life. So, there were no mandates of any neuroimaging or particular testings to confirm this diagnosis as part of the study. So, with these in mind, 979 participants met the study inclusion criteria and were included in the study. The mean age was 65 years ranging from 50 to 99, self-reported lifetime concussion history was recorded, and the participants were then divided into five categories of zero, meaning never had experienced concussion, to those with over 10 concussions. Dr. Negar Asdaghi:         So, the first important finding was that over a quarter of their study population actually were in the over 10 concussions category. The second finding was the overall prevalence of stroke was 3.4% amongst the pro-NFL players, which was significantly lower than that expected from age-matched normative population, meaning the prevalence of stroke amongst U.S. men over age of 50. So, in simple words, being athletic is a good thing and not surprisingly is associated with a lower risk of vascular disease. But what they found was that NFL players with a history of 10 or more prior concussions had five times the odds of stroke as compared to those with no prior concussions in the adjusted models. So, what we learned from this study is that traumatic brain injury, specifically repeated TBI, however mild, seems to be an independent risk factor for stroke. Microvascular disruptions and potentially alterations in coagulation pathways have been proposed as potential mechanisms for this association. Dr. Negar Asdaghi:         About a quarter of patients with ischemic stroke do not have a clear cause for the stroke and fall under the cryptogenic or unknown category. In 2014, an international panel of experts developed a criteria to define a group of patients with cryptogenic stroke that are likely to have an embolic, but yet undefined source for their ischemic event and called them ESUS, which stands for "embolic stroke of unknown source." These were operationally defined as non-lacunar brain infarcts without significant proximal arterial stenosis or known cardioembolic sources of infarct. Now, the idea behind the development of this new term, ESUS, was to identify a more homogenous subgroup of cryptogenic stroke patients that would perhaps benefit from preemptive anticoagulation therapy over the standard antiplatelet treatment for secondary prevention of stroke. Dr. Negar Asdaghi:         Indeed, since 2014, ESUS has become a rather commonly used terminology in the stroke literature with multiple ongoing and a few already completed randomized trials examining the efficacy and safety of the newer oral anticoagulants in patients with ESUS over antiplatelet therapy. Similarly, much has been done to further study the clinical and radiographic characteristics of patients with ESUS. In this issue of the journal, in the study titled "Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source," the NAVIGATE ESUS randomized control trial investigators set out to examine the radiographic characteristics and infarct patterns of ESUS patients enrolled in the NAVIGATE ESUS randomized trial. Dr. Negar Asdaghi:         Joining me now is the first author of the paper, Dr. Mike Sharma, to discuss the findings of this paper. I always say that my guest needs no introduction, and today's guest is, of course, no exception to that. Dr. Sharma is well known to our Stroke readership. He is a stroke neurologist and a scientist at the Population Health Research Institute at McMaster University in Ontario, Canada. He is truly a leader in the field of clinical epidemiology in secondary stroke prevention with an interest in randomized trials, covert stroke, and economics of stroke care. He holds the Michael G. DeGroote Chair in Stroke Prevention and is the immediate past chair of the Canadian Stroke Consortium and also leads the Hamilton McMaster Stroke Program. Good morning, Mike. It's so good to connect with you after so many years. Thanks for being with us. Dr. Mike Sharma:            Good morning, Negar. It's a pleasure to talk to you again, and thank you for that kind introduction. Dr. Negar Asdaghi:         Well, thank you so much. Can you please start us off with a brief summary of what the NAVIGATE ESUS trial set out to do, and what were the main findings of the trial? Dr. Mike Sharma:            So, in NAVIGATE, we really wanted to advance the care of patients with cryptogenic stroke. Cryptogenic has been a somewhat nebulous term for decades, and care really hasn't advanced beyond using aspirin. The problem with that term is, there is no agreed upon criteria to define cryptogenic stroke. Sometimes it means that the workup is incomplete, where there are multiple competing causes or indeed there is a disagreement as to what the cause is. So, in NAVIGATE, we took a different approach, which was to look for markers which would identify patients who had strokes which were embolic. Our feeling was that they might respond better to anticoagulation than antiplatelet therapy. So that was the main goal in NAVIGATE, was to use this construct of ESUS to test the hypothesis that anticoagulation will be more effective in preventing stroke recurrence than antiplatelet therapy. Dr. Negar Asdaghi:         And what did the trial find? Dr. Mike Sharma:            So, NAVIGATE randomized over 7,000 patients with ESUS, and it was stopped, unfortunately, at the time of the second interim analysis after about 67% of primary events had occurred. At that point in time, our mean follow-up was only about 11 months. It was stopped because there was a difference in the risk of bleeding between the rivaroxaban arm and the aspirin arm and, at that point in time, no evidence of benefit. So, the DMC reasonably halted the trial. So, at that point, we saw an excess of hemorrhage with rivaroxaban without an offsetting benefit in preventing recurrent ischemia. Dr. Negar Asdaghi:         Okay, so to recap for our listeners, NAVIGATE is an early terminated randomized trial that basically looked at the safety and efficacy of rivaroxaban over aspirin in secondary prevention of stroke in ESUS. Now, the dose of rivaroxaban used in NAVIGATE ESUS was slightly lower than the current standard of care for treatment of embolic stroke patients with known atrial fibrillation. So, you used 15 milligrams per day rivaroxaban, whereas the standard is 20 milligrams per day. Was there a reason why a slightly lower dose of rivaroxaban was chosen for the trial? Dr. Mike Sharma:            That's a great question. So, 20 milligrams a day in atrial fibrillation is approved in the U.S. I must say that many guidelines, including the AHA guidelines, suggest 15 milligrams for patients with renal impairment and creatinine clearance that is less than 50. Now, in other countries, as the label is slightly different recommending the lower dose. So, in planning this very large international trial, we had a variability in dosing and the complexity of possibly having to change the dose during the course of the trial if a patient's renal function changed. When we looked at the drug exposure between the 15 and 20 milligrams, it turns out that they were very similar. So, taking 15 milligrams, you get very close to the drug exposure with 20 milligrams. The lower dose, we felt, would eliminate the need for dose adjustments during the course of the trial and make running the trial simpler and possibly have a slightly lower risk of hemorrhage than the 20 milligram dose. So, for all those reasons, 15 milligrams was chosen. Dr. Negar Asdaghi:         Mike, I love these interviews mainly because of these valuable background information we get on trials that is otherwise impossible to easily access. Now, coming back to your current paper, the current paper in the January issue actually is an MRI sub-study of the NAVIGATE ESUS trial. Can you please walk us through the details of the current study? Dr. Mike Sharma:            Sure. You know, in NAVIGATE, in the parent trial, we included people who had embolic strokes of uncertain source, and those were operationally defined as either visible on imaging, the majority were, or having symptoms that lasted greater than 24 hours. You couldn't have atrial fibrillation, and we required at least 20 hours of monitoring. Now, 20 hours sounds like a funny time period to request. Originally, we asked for 24 hours, but it turns out that when you put a monitor on for 24 hours, it's never exactly 24 hours. It's often just slightly less. So, we had to make a practical decision as to how much was enough, and in addition, you had to have less than 50% extracranial stenosis. We didn't require imaging of the intracranial vasculature; however, if it was imaged, the stenosis had to be less than 50% to the affected area. Dr. Mike Sharma:            You needed an echocardiogram. We didn't specify a transesophageal echo. Most were transthoracic, which excluded left ventricular thrombus or left atrial appendage thrombus. People who had prosthetic mitral valves were excluded as well. So, from that population of about 7,000, our aim was to select 1,000 patients who met those criteria, but in addition had no contraindication to MRI, and the plan in the MRI sub-study was to look at what happened to covert infarcts, infarcts we didn't identify clinically during the course of the trial, if there was a treatment effect on those and also with MRI, a very sensitive, I would say, exquisite measure of hemorrhage that occurs in the brain. Because the trial was closed early, we ended up at baseline having 918 usable images and participants from 87 sites across the world, less than our original target. You know, our goal really was to see what would happen to these MRI lesions and if treatment affected them. Dr. Negar Asdaghi:         Okay. So we are talking about baseline MRIs of a subpopulation of the patients who were enrolled in NAVIGATE ESUS, and I think we are ready now to hear about your main results. Dr. Mike Sharma:            Thanks very much. I'm bursting to talk about them. You know, in spite of the fact that this was a subset of the whole ESUS population, 918 out of 7,000, roughly 13%, the characteristics of these patients was very similar to the main trial. So, I think that with the usual caveats of the subgroup, I think it's reasonable to think that what we found is representative of the ESUS population in general. The most exciting finding for us was that, so we set out to define clinically a group that would be embolic. The majority of the MRIs that we had first off had visible infarcts, and secondly, 70% of these were multiple infarcts often in multiple vascular territories. So, the clinical construct, I would say, worked. We did identify a group of patients who have embolic lesions and often proximal sources, as we see with these multiple vascular territories affected. Dr. Mike Sharma:            So, this clinical construct works really very well in identifying them. The second thing we found, which shouldn't have been overly surprising but really stood out, were the number of lesions that these people had. The ones with multiple lesions, on average, had four infarcts visible on their MRI, and these were present even in patients who did not have a previous history of TIA or stroke. So, this was their first symptomatic event, and I think that tells us a lot about what's happening in this condition. It's an embolic disease with multiple events, which seems to be very active over time, even when these lesions aren't identified symptomatically. Dr. Negar Asdaghi:         So, Mike, you've already alluded to what I was going to ask you in this question, but I want to recap and repeat for our listeners again, some very pretty impressive findings you have in the study, 93% of ESUS patients with evidence of infarcts, 70% in multiple vascular territories. What I find very interesting is that two-thirds of your patients without even a history of TIA or stroke had multiple infarcts on their neuroimaging. Does that represent to you this clinical radiographic dissociation in the ESUS population? Dr. Mike Sharma:            You know, I think that's a really great question. So, it certainly does. What we know in the number of other covert studies and some other work that colleagues have done epidemiologically is the proportion of covert infarcts. These are infarcts without clinical symptoms that have been identified as stroke, is roughly 5 to 10 times symptomatic events. And we are seeing this recapitulated in this population. Dr. Mike Sharma:            In looking across literature, I suspect that some of these and perhaps a majority had symptoms which were transient, which they didn't appreciate the significance of, or were not identified as stroke at the time. So, this is similar to what's been seen in other populations, just more striking, I think, because of the embolic nature of this condition. You know, I think this really points to the significance of identifying these patients. We expect them to continue to have these covert infarcts, and I prefer the term "covert" to "silent." Silent means it's not really having any manifestation, whereas covert indicates a hidden and nefarious purpose. So, these things do detract from cognition, from motor function, they correlate with disability and recurrent stroke. So, this condition seems to us to be very dynamic and really needs to be addressed. Dr. Negar Asdaghi:         So, striking indeed and definitely concerning findings, Mike, as you pointed out. I think it goes along with all the continuous efforts of increasing public awareness about mild or transient neurological symptomatology along the lines of what you were mentioning. For our listeners, what should be the top two takeaway messages from your study? Dr. Mike Sharma:            So, you know, I think from this study, the really important things are when you identify one of these patients where there is an infarct that you cannot comfortably identify the etiology of, please know that it is likely to be embolic often from a proximal source, but not exclusively, and that patient has an ongoing risk of recurrent infarcts, which may not present symptomatically. So, I think that what this underscores is the need to pay a very serious attention to these patients, look carefully for underlying causes, and we really do need a better treatment. Dr. Negar Asdaghi:         Fair enough. Now I want to end by something that I derived from your study, and I wanted your opinion on that. ESUS is truly proving to encompass a more heterogeneous group of ischemic stroke patients than I think previously recognized. Can you please tell us what's the future for the ESUS trials? Are you going to more elaborate on the etiology of ESUS, again truly cardioembolic versus others, and can you please share with our listeners some of the work that you are currently doing in this field? Dr. Mike Sharma:            Very exciting future, I think, for this. If you consider where we are with this condition, it's similar to where we were with mechanical thrombectomy with the early trials, which were negative but taught us a lot, and so has this one. Our approach with mechanical thrombectomy, we did two things. First, we honed in on the patient population that was likely to respond, and secondly, we improved the treatments, and I think our approach to ESUS, and this goes along with what we are doing currently, is along the same lines. So, in terms of honing down on the population likely to respond, there is now a number of interesting trials being done. One of these is ARCADIA, and I would encourage everybody to refer patients for this trial. In a post hoc analysis of NAVIGATE, we found that patients with markers of atrial myopathy, particularly a large left atrial diameter, seemed to respond to anticoagulation. Dr. Mike Sharma:            So, in ARCADIA, which is being run from Columbia University through NIH StrokeNet, is looking for patients with ESUS who have markers of atrial myopathy, randomizing to anticoagulation or aspirin. So, really honing in on a population likely to respond. The other thing that we are working on are better treatments. So, at the same time NAVIGATE was being done at our institute, we were doing COMPASS. Now, COMPASS used low dose rivaroxaban 2.5 milligrams BID with aspirin, and one of the startling findings in COMPASS was a 50% reduction in ischemic stroke occurrence in that trial. And if you think about it, emboli can be fibrin rich or platelet rich or some combination and we really don't know. So, if there is a safe dose to combine aspirin with an anticoagulant, that is a promising approach. So, currently what we are doing is a trial using Factor XI inhibitors. Dr. Mike Sharma:            Now, you know, if you think broadly across stroke prevention, we have made advances using dual antiplatelet therapy, but they seem to be hitting a ceiling in terms of efficacy with some risk of hemorrhage, and it certainly seems to be the case from NAVIGATE and also RE-SPECT ESUS, which used dabigatran, that anticoagulation by itself won't work. So, from COMPASS, we have this dual pathway approach combining anticoagulation and antiplatelet agents. The novelty here that we are pursuing is using anticoagulants, which have a much lower risk of hemorrhage. So, Factor XI, unlike Factor X, which is affected by rivaroxaban, is not involved in hemostasis, but rather amplifies thrombi, and we know that Factor XI-deficient patients have a low rate of stroke, lower than matched controls, and really no significant spontaneous hemorrhage. Dr. Mike Sharma:            So, there's a number of trials currently in DVT. We are running really the first trial ever done in stroke at phase two to develop an appropriate dose of anticoagulation for these patients. So, I think the future is going to be combining anticoagulants with antiplatelet agents to reduce these patterns of embolic stroke. Holds a lot of promise after what we saw in COMPASS, and indeed we did a similar MRI study in COMPASS, which taught us a lot about how to do these trials. So, currently, we are working on those, and the first results from two trials using Factor XI inhibition. This approach should be available to us next year. Dr. Negar Asdaghi:         So, wow, a lot of information, and we look forward to reading about all of this and perhaps collaborating with you on this. Now, Mike, one question that came up along the lines of what you were mentioning is that, what about the duration of therapy? Do you think that much like CHANCE and POINT, where dual antiplatelet therapy is beneficial for shorter period of time and not for long period of time, that you might choose that as well for ESUS patients, that a short period of anticoagulation or combined anticoagulation and antiplatelet therapy might be beneficial and then not continuing them indefinitely for this population? Dr. Mike Sharma:            You know, it's an entirely reasonable approach to consider. The problem really is what we found in the MRI study, which is that infarcts continue to occur over the long period. We have data now for about a year. But, in other trials and COMPASS, we saw it over many, many years. So, I think that if we focus on the short term, we will have success in reducing the recurrence rate, and the payoff might be a lower risk of hemorrhage, but at the cost of leaving patients vulnerable to recurrences over the long term, you know, and NAVIGATE, we saw recurrence rate of about 5% per year. So quite a significant recurrence rate of symptomatic stroke, and we won't have touched the occurrence of covert infarcts and all that means for the brain. Dr. Negar Asdaghi:         Dr. Mike Sharma, thank you so much for joining us on the podcast this morning. We look forward to covering more of your work in the future. Dr. Mike Sharma:            It's a pleasure, Negar, very nice to talk to you. Dr. Negar Asdaghi:         And this concludes our podcast for the January 2022 issue of Stroke. Please be sure to check out this month's table of contents for a full list of publications, including an organizational update from the European Stroke Conference, which highlights some of the top science presented as part of the plenary sessions at this year's meeting to give us that extra motivation to start the year. Now, speaking of motivation, starting the year, in my view, is much like running a long distance race. Anyone who has done it would tell you that this is as much about mental fitness as it is about physical fitness. So, I think it's only fitting to end the beginning of this year's podcast remembering one of America's inspirational distance runners, Steve Prefontaine. Dr. Negar Asdaghi:         As a kid, he was told that he's too short and perhaps too slow to be played in any of his school's sport teams. Later, when he became a runner, people would say that they had never seen anyone run like him, a runner who never slowed down nor paced himself. And he famously said "to give anything less than your best is to sacrifice a gift." All of 2022 is now ahead of us. Let's not sacrifice the gift. There is no time to pace ourselves, and what better way to do this than staying alert with Stroke Alert? Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. 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

The post Episode 044: Microvascular Health appeared first on Rehab U Practice Solutions.

This podcast highlights original research published in the November 2021 issue of Otolaryngology–Head and Neck Surgery, the official journal of the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) Foundation. The objective was to review long-term clinical and quality-of-life outcomes following free flap reconstruction for osteonecrosis. In conclusion, the majority of patients maintained or had advancement in diet following reconstruction, with low rates of osteonecrosis or cancer recurrence and above-average scores on UW-QOL survey suggesting good return of function and quality of life.   Click here to read the full article.

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

The University of Texas MD Anderson Cancer Center's Microvascular Reconstruction Surgery is designed to provide advanced postgraduate training for plastic surgeons in microvascular reconstructive surgery for oncology patients. In this episode, two fellows, Jessie Z. Yu, M.D., and Stefanos Boukovalas, M.D., share their experiences.