Podcasts about erasmus university medical center

Two new trials published in JAMA evaluate the efficacy of periprocedural intra-arterial thrombolytics after successful endovascular thrombectomy for patients with acute ischemic stroke. Diederik Dippel, MD, PhD, of Erasmus University Medical Center discusses this and more with JAMA Deputy Editor Christopher C. Muth, MD. Related Content: Intra-Arterial Thrombolytics During Thrombectomy for Ischemic Stroke—End of the Story or a New Beginning? Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke

A vast number of cancer patients will undergo radiotherapy during their treatment process. Because of this, experts are searching for ways to treat patients as effectively as they can through radiotherapy while also reducing the treatment's side effects as much as possible. One answer to this is adaptive radiotherapy. Recent advancements in AI and imaging technology have refined the process and made new solutions possible. These advancements have made it easier for healthcare professionals to adapt treatment to real-time images of the patient's anatomy. This helps to preserve the health of organs surrounding the targeted area and treat patients more effectively.Today, Sasa Mutic, Senior Vice President at Varian Medical Systems, a Siemens Healthineers company, is joined by Dr. Eric Horwitz, Chair of the Department of Radiation Oncology at Temple University and Fox Chase Cancer Center in Philadelphia; Jennifer Pursley, Medical Physicist and assistant professor at Harvard Medical School; and Kirsten Offereins-van Harten, a senior radiotherapeutic technician at Erasmus University Medical Center in Rotterdam, Netherlands. They discuss how advancements in adaptive radiology technology have transformed the patient experience and the field as a whole—and where it may take us in the future.What You'll Learn in This Episode:Adaptive radiotherapy allows real time scans of a patient in order to better, more precisely treat tumors.Improvement of imaging technology advances the ability to contour organs, which is a major aid in avoiding collateral damage around the target.Adaptive radiotherapy has the potential to reduce the ill effects of typical radiological treatments by focusing on a more precise target, therefore allowing patients to maintain their quality of life.Adaptive radiotherapy greatly changes the way that providers work together to create a treatment path. Artificial intelligence can potentially expedite the process of adaptive radiotherapy by allowing for a more accurate picture of the contours around affected organs. Connect with Sasa MuticLinkedInConnect with Dr. Eric HorwitzLinkedInConnect with Jennifer Pursley, PhDLinkedInConnect with Kirsten Offereins-van HartenLinkedIn Hosted on Acast. See acast.com/privacy for more information.

Michael S. Lloyd, MD, FHRS of Emory University discusses Catheter Ablation of Atrial Fibrillation in Adult Congenital Heart Disease: Procedural Characteristics and Outcomes with Natasja M. S. De Groot, MD, PhD, of Erasmus University Medical Center, and Jeremy P. Moore, MD, MS, FHRS, CCDS, CEPS-P, of UCLA Medical Center.   https://www.hrsonline.org/education/TheLead   Host Disclosure(s): M. Lloyd: Honoraria/Speaking/Consulting Fee: Medtronic, Baylis Medical Company, Boston Scientific   Contributor Disclosure(s): N. De Groot: Honoraria/Speaking/Consulting Fee: Biosense Webster J. Moore: No relevant financial relationships with ineligible companies to disclose.

Host Professor Majda Thurnher is joined by Prof. Meike Vernooij and Professor Sofie van Cauter. Meike Vernooij is Professor of Population Imaging at the Departments of Radiology & Nuclear Medicine and Epidemiology at Erasmus University Medical Center in Rotterdam. She is also a Chair of the Diagnostic subcommittee of the ESNR. Sofie van Cauter is a neuroradiologist, working in ZOL Hospital Genk in Belgium which is a tertiary non-university hospital with a special focus on neurosurgery and interventional neuroradiology and a Professor of Radiology and Neuroanatomy at Hasselt University.They discuss challenges female doctors may experience working in health care such as difficulty maintaining a work and life balance. Hosted on Acast. See acast.com/privacy for more information.

In this episode, host, Geoffrey Rubin, MD, MBA, FACR, talks with Dr. Gabriel Krestin, emeritus Professor of Radiology at Erasmus MC, University Medical Center Rotterdam, the Netherlands.  Dr. Krestin served as professor and chair of the Department of Radiology at Erasmus University Medical Center for 25 years.

Individualising drug dosing using model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin has been proposed as an alternative to standard dosing to optimise antibiotic efficacy in critically ill patients. However, randomised clinical trials (RCT) on clinical outcomes have been lacking.In this podcast, Drs Ewoldt and Abdulla relate how they conducted a multicentre RCT in 8 Dutch hospitals. It included patients admitted to the intensive care unit (ICU) treated with antibiotics and randomised to MIPD with dose and interval adjustments based on monitoring serum drug levels (therapeutic drug monitoring) combined with pharmacometrics modelling of beta-lactam antibiotics and ciprofloxacin. Original paper: Model‑informed precision dosing of beta‑lactam antibiotics and ciprofloxacin in critically ill patients: a multicentre randomised clinical trialSpeakersTim M. J. EWOLDT. Department Hospital Pharmacy, Erasmus University Medical Center, Rotterdam (NL).Alan ABDULLA. Department Hospital Pharmacy, Erasmus University Medical Center, Rotterdam (NL).Ana-Maria IOAN. Intensive Care Medicine Unit, Fundación "Jiménez Díaz" University Hospital, Madrid (ES). NEXT Committe member, ESICM.

Dean Clydesdale is a Project success Consultant at Blue Bricks. He has a Bachelor's degree of Medicine (Bachelor of Surgery) and a Master's degree in Health Economics. His experience includes working at the Dutch Healthcare Authority (NZa), PinkRoccade Healthcare, and the Erasmus University Medical Center. He is passionate about innovative health care solutions for better patient value and less work for medical staff. Find him at: https://www.linkedin.com/in/dean-clydesdale-442ab572/

We talk with Dr. Lisa Bauer, a postdoctoral researcher in the Van Riel lab at the Erasmus University Medical Center, who uses pluripotent stem cells differentiated into neurons and astrocytes to study how Influenza A virus and SARS-CoV-2 affect the brain.

Fat! This curious, wonderful and often misunderstood organ is the subject of today's podcast with Professor Liesbeth van Rossum, MD PhD and Dr Mariëtte Boon MD PhD authors of the incredible book “Fat. The Secret Organ”. And yes it is an organ.Professor Liesbeth van Rossum, MD, PhD is internist-endocrinologist at the Erasmus University Medical Center, Rotterdam. She is co-founder of the Obesity Center CGG, and has an internationally leading position in the field of obesity and biological stress research.Dr Mariëtte Boon, MD, PhD is an internal medicine specialist in training. Her research, per- formed at the Leiden University Medical Center, focuses on fat metabolism. Today's pod is a whirlwind of a conversation running through a fantastic variety of topics all to do with fat. You'll learn about:Why fat is an organWhat mechanisms drive hunger and satietyWhy too little as well as too much fat can be detrimentalHow you can stimulate your satiety to eat lessHow stress can cause fatThe number and size of fat cells and if they change throughout your lifeWhy liposuction doesn't workWhat brown fat is and how to increase itFat on inflammation, immune health and fertilityThe 6 categories of what causes weight gain from genetics and sleep to food and stressIf a virus can cause obesity?Their book “Fat. The Secret Organ” is a must read for anyone as interested in this subject. We didn't get time to properly dive deep into some other topics in the book, such as the evidence based lifestyle recommendations and how you can use simple hacks to increase metabolism as well as nutrition, so do grab a copy. I highly recommend it!Check out The Doctor's Kitchen website for full show notes and information on this and all other episodes. See acast.com/privacy for privacy and opt-out information.

We are confronted daily with complex ethical issues during the care of our patients in intensive care units. The principles of biomedical ethics may guide us with regard to concerns for ethical decision-making. Although globalisation brings enormous richness and diversity through multicultural structures, ethical issues may challenge intensivists in these conditions. However, the 'moral stresses' that health professionals experience are almost always ignored. Speakers: Dr Burcin Halacli.  Internist and intensivist at Hacettepe University, Faculty of Medicine, Department of Internal Medicine, Division of Intensive Care Medicine, Ankara, Turkey and ESICM NEXT Committee member. Prof Erwin Kompanje. Consultant in Clinical ethics at Erasmus University Medical Center, Department of Intensive Care in Rotterdam (NL), and interestingly he is Honorary curator and senior taxidermist at the Natural History Museum Rotterdam. He has lots of papers, more than 4000 citations about biomedical ethics, clinical ethics and intensive care medicine.

Improving Cancer Imaging and Treatment The Anne Klibanski Visiting Lecture Series was created to support and advance the careers of women. These lectures bring together faculty from institutions that have hosted Anne Klibanski Scholars with MGH scholars, on topics that overlap both research areas. This lecture was given by Meenal Datta, PhD, AACR-Loxo Oncology Postdoctoral Research Fellow, Radiation Oncology, MGH/HMS and Simone Dalm, PhD, Assistant Professor of Radiology & Nuclear Medicine, Erasmus University Medical Center. Webinar available: https://youtu.be/G9VrvR0PiuA 

This week on Womanity-Women in Unity, Dr. Amaleya Goneos-Malka talks to Professor Hanneke Takkenberg, who is co-executive director of the Erasmus Centre for Women and Organisations (ECWO) at Rotterdam School of Management at Erasmus University. She is also a clinical epidemiologist and professor of clinical decision making in cardiothoracic interventions at the department of Cardio-Thoracic Surgery in Erasmus University Medical Center. Additionally, she chairs the Dutch Network for Women Professors (LNVH) board, which consists of a network of over 1300 women professors and associate professors. We discuss gender stereotyping and the influence this has on perceptions of leaders, which exerts a limiting effect on women’s advancement in the workplace. Some of the research ECWO is undertaking to help empower women to drive their careers forwards include i) network analysis – to teach women to more effectively navigate both visible and invisible organisational networks; and ii) advocacy and awareness raising – focussing on listed companies, specifically the composition of boards and representation of women as well as imaging and language utilised by these entities. We also consider other factors that contribute to gender imbalances in organisations, such as hierarchy, remuneration, non-financial benefits, promotion, culture and social safety. Prof. Takkenberg reminds us that women are generally underrepresented across the spectrum and to help address this gap colleagues should use opportunities to support and help amplify women’s voices. Tune in for more…

"Theranostics in Glioma" The Anne Klibanski Visiting Lecture Series was created to support and advance the careers of women. These lectures bring together faculty from institutions that have hosted Anne Klibanski Scholars with MGH scholars, on topics that overlap both research areas. This lecture was be given by Zohreh Amoozgar, PharmD, PhD, Research Fellow, Radiation Oncology, MGH/HMS and Esther Warnert, PhD, Assistant Professor of Radiology & Nuclear Medicine, Erasmus University Medical Center. Webinar available at https://youtu.be/FlyHsFMUtWg

"Analysis of neurodevelopment and neurodegeneration on brain imaging using machine learning" The Anne Klibanski Visiting Lecture Series was created to support and advance the careers of women. These lectures bring together faculty from institutions that have hosted Anne Klibanski Scholars with MGH scholars, on topics that overlap both research areas. This lecture was given by Lilla Zöllei, PhD, Assistant Professor of Radiology, MGH/HMS and Esther E. Bron, PhD, Assistant Professor of Radiology & Nuclear Medicine, Erasmus University Medical Center. Webinar available at https://youtu.be/fH5ctBA41-U

While not featured in Hollywood blockbuster films like some universities from the UK, Boston, or California, Belgium’s KU Leuven University has topped the Reuters ranking as Europe’s most innovative university for four of the last six years. This Belgian innovation engine boasts more than 135 spin-off companies and has a dominant focus on healthcare innovation. In this podcast we discuss the role that KU Leuven plays in Flanders with Professors Maarten De Vos and Inge De Prins, who introduce the latest effort to broaden the EU’s innovation capacity through their new initiative focused on health innovation fellowships. Named The Institute for Biodesign, it will open its doors this spring in collaboration with TU Delft and Erasmus University Medical Center in the Netherlands. The institute’s Health Fellowship Network will be further supported by the European Institute of Technology (EIT), whose input in ensuring that KU Leuven’s new project comes to fruition is also discussed in the podcast. Lastly, the podcast details how interested researchers, healthcare professionals, and industry partners can join the new Institute for Biodesign and offers some insights into what the programme will deliver in the future. We touch on the broad macroeconomic competitive challenges that the EU currently faces and how the fellowship network hopes to overcome these to keep breakthrough technologies and the value they create within Europe.

“The black box of cancer therapy” The Anne Klibanski Visiting Lecture Series was created to support and advance the careers of women. These lectures bring together faculty from institutions that have hosted Anne Klibanski Scholars with MGH scholars, on topics that overlap both research areas.  This lecture was given by Kerry Reynolds, MD, Assistant Professor of Medicine, MGH/HMS and Julie Nonnekens, PhD, Assistant Professor and Group Leader of Radiobiology of Radionuclide Therapy, Erasmus University Medical Center. Webinar available at https://youtu.be/RRCbigbNDnA

Date: October 2nd, 2020 Guest Skeptic: Dr.Barbra Backus is an emergency physician at the Emergency Department of the Erasmus University Medical Center in Rotterdam, the Netherlands. She is the creator of the HEART Score and an enthusiastic researcher. Reference: Claiborne Johnston S et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. NEJM […]

This episode features Kim de Nooijer and Sophie van Dongen (Erasmus University Medical Center, Rotterdam, Netherlands).   Self-management has predominantly been studied in the context of chronic diseases, where it has been defined as ‘the ability to manage the symptoms, treatment, physical and psychosocial consequences, and lifestyle changes inherent in living with the condition’. Patients with advanced cancer experience severe, multidimensional symptoms and challenges and are increasingly expected to actively manage their health and care. There still is a lack of insight into the full range of self-management experiences of patients with advanced cancer and the attitudes of relatives and healthcare professionals towards self-management of these patients. This study demonstrates that self-management strategies of patients with advanced cancer span many domains: medicine and pharmacology, lifestyle, psychology, social support, knowledge and information, navigation and coordination and medical decision-making. Patients’ self-management strategies and experiences are highly individual and divergent and may be substitutional, additional and distinctive or conflicting compared to care provided by healthcare professionals. Healthcare professionals perceive self-management as both desirable and achievable if based on sufficient skills and knowledge and solid patient–professional partnerships. Self-management support programmes for patients with advanced cancer can benefit from an individualised approach that re-evaluates patients’ needs and wishes, is embedded in solid partnerships with relatives and healthcare professionals, and is incorporated into existing models of care. Future studies on self-management of patients with advanced cancer need to further examine attitudes of relatives and healthcare professionals and investigate effectiveness and working mechanisms at the levels of patients, communities and healthcare organisations and policy.

Jane Ferguson:                Hello, welcome to Getting Personal: Omics of the Heart, Episode 22. This is a podcast from Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. I am Jane Ferguson and it's November 2018.                                            Our first article comes from Carlos Vanoye, Alfred George and colleagues from Northwestern University Feinberg School of Medicine and is entitled, High Throughput Functional Evaluation of KCNQ1 Decrypts Variance of Unknown Significance.                                            So a major growing problem in clinical genomics is that following the identification of a variant that is potentially linked to a disease phenotype, without further interrogation, it's really hard to make sense of the functional significance of that variant. Right now, the large number of variants of unknown significance lead to confusion for patients and clinicians alike. To allow for accurate diagnoses and the best treatment plans, we need a way to be able to screen variants to assess their function in a fast and cost-effective manner.                                            In this paper, the authors decided to focus in the KCNQ1 gene, a cardiac ion channel, which can affect arrhythmias. They aim to assess whether a novel high-throughput functional evaluation strategy could identify functional mutations, as well as an in vitro electrophysiological approach. Which is effective, but expensive and time-consuming. Their approach capitalized on an existing automated electrophysiological recording platform that had originally had been developed for drug discovery essays.                                            They selected 78 variants in KCNQ1 and assessed their function using the High-Throughput platform, which coupled high efficiency, cell electroporation with automated plain or patch clamp recording. They compared the results to traditional electrophysiological essays and find a high rate of concordance between the two methods. Overall, they were able to reclassify over 65% of the variants tested, with far greater efficiency than traditional methods.                                            While this method will not work for all genes and phenotypes, the authors have demonstrated an efficient method for functional interrogation of variants. Which may greatly accelerate discovery and conditions such as Long QT or other congenital arrhythmias.                                            The next paper, Nocturnal Atrial Fibrillation Caused by Mutations in KCND2 Encoding Poor Forming Alpha Subunit of the Cardiac KV 4.2 Potassium Channel, comes from Max Drabkin, Ohad Birk, and colleagues at Soroka University Medical Center in Israel. This paper also focuses on cardiac ion channels and the role of mutations in atrial fibrillation.                                            In a family with early-onset peroxisomal AF across three generations, whole XM sequencing revealed a variant in KCND2 encoding the KV 4.2 Potassium Channel, which segregated consistent with autosomal dominant heredity. This variant resulted in a replacement of a conserved [inaudible] residue with an arginine. To investigate functional consequences of this novel variant, they conducted experiments in xenopos laevis oocytes and found that there is decreased voltage depended channel and activation and impaired formation of the KV 4.2 Homotetramer and the KV 4.2, KV 4.3 Heterotetramer.                                            Overall, this study shows that a novel mutation in a conserved Protein kinase C Phosphorylation site within the KV 4.2 Potassium Channel underlies the phenotypes observed in a family of peroxisomal atrial fibrillation. The targeting Atrial KV 4.2 might be an effective therapeutic avenue.                                            Next up, Michael Levin and Scott Damrauer and colleagues from the University of Pennsylvania published an article entitled, Genomic Risks Stratification Predicts All-Cause Mortality After Cardiac Catheterization.                                            They were interested in understanding the utility of polygenic risk scores for disease prediction. They constructed a genome Y genetic risk score for CAD and applied it to individuals from the Penn Medicine Bio-bank who had undergone Coronary angiography and genotyping.                                            They included over 139,000 variants for the 1,500 ancestry subjects who were included and classified them as high or low polygenic risk. Individuals who were classified as high polygenic risk were shown to have higher risk of All-Cause mortality than low polygenic risk individuals despite no differences in traditional risk factor profiles. This was particularly evident in individuals with high genetic risk but no evidence of angiographic CAD.                                            Adding the polygenic risk score to a traditional risk assessment model was able to improve prediction of five year All-Cause mortality. Highlighting the utility of a polygenic score and underscoring traditional risk factors do not yet fully capture mortality risk.                                            The next article entitled, "Bio-marker Glycoprotein Acetyls is Associated with the Risk of A Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients" comes from Johannes Kettunen, Scott Ritchie, Peter Würtz and colleagues from the University of Oulu Finland.                                            GlycA is a circulating biomarker that reflects the amount of Glycated proteins in the circulation. It has been associated with cardiovascular disease, Type 2 Diabetes, and all-cause mortality. In this paper, the authors used electronic health record data from over 11,000 adults from the finish general population previously included in the "FINRISK" and "Dilgom" studies and they tested for a associations between GlycA and 468 different health outcomes over an 8-12 year follow up. They report new associations between GlycA and multiple conditions including incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthric disease and hypertension.                                            These associations held true even after adjusting for CRP suggesting that GlycA represents an independent biological contributor to inflammation and disease. Their findings highlight potential utility for GlycA as a biomarker of many diseases and underscore the importance future functional and mechanistic studies to understand how GlycA is linked to disease risk.                                            Our last original research article entitled, "Tissue Specific Differential Expression of Novel Jeans and Long Intergenic Non-coding RNAs in Humans with Extreme Response to Endotoxic glycemia comes from Jane Ferguson, Murdock Riley, and colleagues from Vanderbilt University, Columbia University, and the University of Pennsylvania. That first author is none other than me, so I'm not unbiased reader of this particular manuscript, but I'd like to tell you a little bit about it anyway.                                            We were interested in understanding the transcriptional changes that occur in tissues during acute inflammation. As part of the genetics of evoked responses to Niacin and Endotoxemia, or gene study, we recruited healthy individuals and performed an inpatient endotoxin challenge where we administered a low dose of LPS and looked at the systemic inflammatory response. Individuals vary greatly in the degree of their inflammatory response to LPS and we identified high and low responders, men and women, of African and European ancestry, who had responses in the top or bottom 10% for cytokines and fever.                                            We conducted RNA seek and adipose tissue in 25 individuals and CD-14 positive monosites for 15 individuals in pre and two or four hours post LPS samples. We found that the differences in transcriptional response between high or low responders are mostly explained by magnitude rather than discrete sets of genes.                                            So some core genes were altered similarly, in both groups, but overall the high responders mounted a large transcription of response to LPS or low responders rather than mounting an anti-inflammatory response actually just barely responded on the transcription level. We saw clear tissue specificity between manosites and adipose tissue we identified several long non-coding RNAs that were up or down regulated in response to LPS and validated these independent samples one of these link RNAs which we have now named Monosite LPs induced link RNA regulator vile six or Mahler Isle six, with highly regulated by LPs and monosites but not in adipose tissue.                                            We [inaudible] THP-1 monosites and find a significant effect on iOS six expression suggesting that this is a novel link RNA that regulates Isle six expression in manosites potentially through a cd-86 dependent pathway. Overall our data revealed tissue specific transcriptional of changes that correlate with clinical inflammatory responses and highlight the role of specifically incarnate and inflammatory response.                                            Next up is a research letter entitled "Reduced Sodium Current in Native Cardiomyocytes of a Regatta Syndrome Patient Associated with Beta Two Central Mutation" published by Constance Schmidt, Felix Wiedmann, Ibrahim El-Battrawy, Dierk Thomas, and co-authors from University Hospital Heidelberg. They obtained cardiomyocytes from a patient with Regatta Syndrome previous whole XM sequencing had implicated a variant in the Beta Two Syntrophin or "SNTB2" gene as potentially causal in this individual. Expression analysis showed lower SNTB2 expression and atrial tissue of the affected individual compared with controls.                                            They performed electrophysiology on the Microcytes and found reduced peak sodium density and reduced late sodium current. They co-express wild type or mutant SNTB2 in heck 293 T cells and [inaudible] with the cardiac sodium channel NAV-1.5 and found a significant effect on binding which adversely affected sodium currents. This study nicely demonstrates the functional effect of this SNTB2 mutation underlying Regatta Syndrome in this patient.                                            A second research letter comes from A.T. van den Hoven and Jolien Roos- Hesselink and colleagues from Erasmus University Medical Center in the Netherlands and is entitled "Aortic Dimensions and Clinical Outcome in Patients with SMAD three mutations, they were interested in understanding how the Aortic dilation comment individuals with SMAD three mutations compared to individuals with other syndrome and causes of Aortic dilation.                                            In 28 patients with SMAD three mutations, there were significant growth in the Sinotubular Junction the ascending Aorta on the diaphragm over an average of 10 years of follow up at reads far higher population averages but lower than might be seen in other syndromes, such as [inaudible]. Intensive management and preventive surgery and many of the patients prevented any mortality in this group.                                            Rounding out this issue is a clinical letter entitled "Concealed Arrhythmogenic  Right Ventricular Cardiomyopathy in Sudden unexplained Cardiac Death events from Jodie Ingles, Chris Semsarian, and colleagues from the University of Sydney, Australia. They report on for clinical cases where individuals presented in early adulthood with unexplained cardiac arrest, which was later found to be attributable to mutations in the PKP2 gene. PKP2 or, Plakophilin 2, encodes an integral component of the Desmosome, which is important and Cell-Cell adhesion. Further PKP2 is involved in transcriptional activation of genes controlling intracellular calcium cycling. This gene has been implicated arrhythmogenic right ventricular cardiomyopathy in individuals with cardiac structural abnormalities. These four cases where unrelated individuals were all fans to have loss of function variants and PKP2 underlying sudden cardiac death or events, despite structurally normal hearts. This prompts questions on the clinical management of such cases of concealed ARVC.                                            That's all from us for November, thanks to all of you out there listening. We'll be back in December for the final episode of 2018.                                            This podcast was brought to you by Circulation Genomic and Precision Medicine and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2018.                                             

Dr Carolyn Lam:                Welcome to Circulation On the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.                                                 In this day and age of endovascular treatment for acute ischemic stroke, does time to treatment really matter? Well, we will be discussing results of the MR CLEAN Registry from real-world clinical practice, coming right up after these summaries.                                                 The first original paper this week describes the first mouse model of progerin-induced atherosclerosis acceleration. Progerin is an aberrant protein that accumulates with age, causes a rare genetic disease known as Hutchinson-Gilford Progeria Syndrome. Patients with Progeria Syndrome have ubiquitous progerin expression and exhibit accelerated aging and atherosclerosis, dying in their early teens mainly from myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part due to the lack of appropriate animal models. First author Dr Hamczyk, corresponding author Dr Andrews, and colleagues from CNIC in Madrid performed an elegant series of experiments and generated not only the first mouse model of progerin-induced acceleration of atherosclerosis, but also provided the first direct evidence that progerin expression restricted to vascular smooth muscle cells but not to macrophages was sufficient to induce premature atherosclerosis and death. Progerin-induced loss of vascular smooth muscle cells caused atherosclerotic plaque destabilization that led to myocardial infarction. Ubiquitous and vascular smooth muscle cell specific progerin expression increased LDL retention in aortic media, likely accelerating atherosclerosis.                                                 The next original paper implicates dysregulation of mitochondrial dynamics as a therapeutic target in human and experimental pulmonary arterial hypertension. Now, mitotic fission is increased in pulmonary arterial hypertension. The fission mediator, dynamin-related protein 1, or Drp1, must complex with adaptor proteins to cause fission. In the current paper from co-first authors Dr Chen and Dasgupta, corresponding author Dr Archer from Queens University in Ontario Canada, and colleagues, the authors examined the role of two recently discovered but poorly understood Drp1 adaptor proteins known as mitochondrial dynamics protein of 49 and 51 kilodalton. They found pathological elevation of these mitochondrial dynamic proteins in pulmonary artery smooth muscle cells and endothelial cells in both human and experimental pulmonary arterial hypertension that accelerated mitotic fission and supported rapid cell proliferation. Mitochondrial dynamics protein's expression was epigenetically upregulated by a decreased expression of microRNA-34a-3p. Circulatory microRNA-34a-3p expression was decreased in both patients with pulmonary arterial hypertension and preclinical models, silencing the mitochondrial dynamics proteins or augmenting microRNA-34a-3p regressed experimental pulmonary arterial hypertension, thus, proving to be potential new therapeutic targets for pulmonary arterial hypertension.                                                 Dyslipidemia guidelines currently recommend that non-HDL cholesterol and apolipoprotein B, or apoB, are secondary targets to the primary target of LDL cholesterol. However, how frequently does non-HDL cholesterol guideline targets change management, and what is the utility of apoB targets after meeting LDL and non-HDL targets?                                                 Well, answers are provided in the next paper from first author Dr Sathiyakumar, corresponding author Dr Martin, and colleagues from Johns Hopkins University School of Medicine. These authors analyzed more than 2,500 adults in the US National Health and Nutrition Examination Survey, as well as more than 126,000 patients from the Very Large Database of Lipids Study with apoB. They identified all individuals as well as those with high-risk clinical features, including coronary disease, diabetes, and metabolic syndrome who met the very high and high-risk guidelines targets of LDL cholesterol of less than 70 and less than 100 mg/dL, respectively, and this was measured using either the Friedewald estimation or a novel, more accurate method. They found that after using the more accurate method of estimating LDL cholesterol, guidelines suggested non-HDL targets could alter management in only 1 to 2% of individuals, including those with coronary disease and other high risk clinical features.                                                 However, using the Friedewald estimated LDL cholesterol gave a much higher percentage. Among all individuals with both LDL cholesterol less than 100 and non-HDL cholesterol less than 130 mg/dL, only 0-0.4% had an apoB above or equal to 100 mg/dL. Thus, the utility of current non-HDL targets appears to be contingent on the accuracy of LDL cholesterol estimation. When using a novel, more accurate estimation method to assess LDL cholesterol, the non-HDL cholesterol is infrequently above current guidelines' suggested targets after the LDL target is met. Current guidelines suggest that apoB targets also provide only modest utility after cholesterol targets are met. These findings were robust to high-risk clinical features, sex, fasting status, and presence of lipid-lowering therapies.                                                 The final paper tells us that HIV infection increases the risk of developing peripheral artery disease. Dr Beckman from Vanderbilt University Medical Center and colleagues studied almost 92,000 participants in the Veterans Aging Cohort Study from 2003-2014 over a median follow-up of nine years. They excluded participants with known prior peripheral artery disease or prevalent cardiovascular disease. They found that infection with HIV was associated with a 19% increased risk of incident peripheral artery disease beyond that explained by traditional atherosclerotic risk factors. Once peripheral artery disease had developed, HIV infection increased the risk of mortality compared to uninfected patients. Whereas for those with sustained CD4 cell counts above 500, there was no excess risk of incident peripheral artery disease events compared to uninfected people. Furthermore, worsening HIV infection as measured by CD4 cell count and HIV viral load was associated with increased incident peripheral artery disease and mortality. In summary, HIV infection increased the risk of developing peripheral artery disease and mortality. The findings also suggest that aggressive antiretroviral therapy to reduce viral load and increase CD4 cell counts may reduce the risk of developing peripheral artery disease. Furthermore, clinicians should solicit clinical complaints and physical signs consistent with peripheral artery disease to facilitate the diagnosis of peripheral artery disease in patients with HIV and ensure the addition of guideline-based anti-atherosclerotic therapies in these patients.                                                 Well, that wraps it up for our summaries. Now for our feature discussion.                                                 When it comes to acute ischemic stroke treatment, we've learned from trials of intravenous thrombolytics that time is brain. But what about the situation with endovascular treatment of strokes? Also, what's the situation like in the real world? Well, today's featured paper really provides precious data telling us about time-to-endovascular treatment and outcomes in acute ischemic stroke. I am so delighted to have with us the first and corresponding author of the MR CLEAN Registry, Dr Maxim Mulder from Erasmus University Medical Center, as well as our editorialist, Dr Micheal Hill, from University of Calgary, and our associate editor, Dr Graeme Hankey, from University of Western Australia, all here to discuss this hugely important topic.                                                 Maxim, could we start with you? So, MR CLEAN Registry means there was a MR CLEAN trial. Could you tell us a little bit more about your paper? Dr Maxim Mulder:           Sure, well to start with, I think it's important to make sure all the people know the difference between the MR CLEAN trial and the registry since of course the trial was to show whether the intra-arterial treatment is effective when it comes to acute ischemic stroke treatments and then, of course, for people treated within six hours. When the MR CLEAN trial finished we continued in the Netherlands with all the participating centers from the trial to gather all the data from everybody who is treating in the whole country with the intra-arterial treatment, but they're not anymore in the light of the trial but in the clinical practice. We've had a lot of trials, but we don't have a lot of clinical practice date yet of the intra-arterial treatment, so that's where it all started.                                                 So, what we found is we consider our data, so with the least possible selections or the only selection was basically to treat within six and a half hours and have patients that had a proven large vessel occlusion that were treated in the Netherlands and of course as we also know from when intravenous therapy was introduced that what happens in clinical trials doesn't necessarily happen when a new treatment is introduced into clinical practice. There are less strict criteria for patients to get treated, and you know everybody, of course, there is a lot of debate about which patients should be treated. In clinical trials it is very strictly coordinated, but in clinical practice there's a lot more room to have an interpretation and also treat a different population. So, we also see that our population is somewhat older and has more comorbidities than in all the trials. Also what we found, of course, our most important finding was that when compared to all the trials or the large trials combined together in the Emberson analysis about time that when we look at the influence or the association of time with functional outcome of intra-arterial treatment that this association is clearly stronger than we found in the previous, the trial data.                                                 So, I think that's a very important finding. Also, for everybody who's now treating this patient in clinical practice. Dr Carolyn Lam:                Exactly. I mean this is really stunning results. If I could paraphrase from your paper, every hour delay in time from stroke onset to the start of endovascular treatment resulted in a 5.3% decreased probability of functional independence and a 2.2% increase in mortality. This is stunning. Thank you, thank you for publishing these results with us in Circulation. I would like to ask Michael, I love the point you made in the editorial that time of stroke onset is really quite a difficult thing to determine. Could you tell us your thoughts about that, Michael? Dr Micheal Hill:                  I mean, it's something like 15-20% of the time stroke is unwitnessed, either because stroke occurs in sleep and the patient is discovered with their stroke symptoms on awakening. Or the patient is simply alone and has their stroke unwitnessed by any bystander. Even in so-called witness stroke, there are probably significant errors in determining the exact time of stroke onset because it's an emergency, and everybody's flustered and time anchors are not necessarily well known. And, so, I think it's an important point that the actual measurement of time is challenging, yet it's still an easier clinical tool for us to use in gauging the extent or evolution of stroke. That's the most important thing to point out here is that this population effect that Max has observed in the MR CLEAN registry is certainly concordant with clinical trial data.                                                 I certainly think it's correct, and, as you pointed out in your comments, dramatic, but a really important issue is that for the individual patient, there's quite a lot of variance in the evolution of stroke. So, whereas, on a population basis, it's absolutely true that the average time from estimated time of stroke onset to treatment initiation is absolutely critical; in some patients, the individual might be still a good candidate for treatment even in late time windows, and some patients, even after a couple hours, the damage is already extensive, and they may not be good candidates for treatment. It still requires individual decision making, and it still leaves a lot of room for clinical judgment largely based on imaging. Dr Carolyn Lam:                True, and I think you've really succinctly put that solid take-home message in the title really, which is acute ischemic stroke biology really demands fast treatment. I think that's the one thing that we'd really like clinicians to come away with. You agree? Dr Micheal Hill:                  Absolutely. Especially, I think, the advantage of looking at whole populations and large, I mean this is a large registry, the MR CLEAN registry, and the group should be congratulated because it's clearly the biggest registry in the world right now of available data, and it's only getting larger week by week as they carry on with their work. You know the whole Netherlands group, the MR CLEAN group, are a fantastic group, but absolutely right, on a population basis, we absolutely have to get our systems in place so that on average we're treating patients incredibly fast. On an individual basis, the clinicians and the teams treating an individual patient still need to make judgments about that patient's eligibility for treatment. It's easy when the times are fast, so if you're an hour and a half from onset, nearly everybody's gonna be a good candidate for treatment, but as time elapses you need to make judgements on the basis of imaging. Dr Carolyn Lam:                Well put. You know, Graeme, you're over there in Australia. What are your take-home messages about how generalizable these findings are to places outside perhaps of the Netherlands? Dr Graeme Hankey:        I think you're asking about the external validity. I think the internal validity is certainly there. As Michael said, this is the largest registry that we have that's been published data on this before. It's certainly novel, and we're very confident that the results are valid, although this is an observational study and not a randomized trial. The association between time and outcome seems to be independent of the major patient factors that may influence time to endovascular therapy. For example, younger people who are less frail and they're alert and they're mobile can get to treatment earlier. So, you might say, well of course they're gonna have a better outcome. But these factors were adjusted for. And, of course, there are procedural factors that could influence the association between time and outcome, but we're very confident in the results and the novelty of them in supporting and building on the randomized trial data.                                                 We're also very confident in the registry and the nature of the population. The results are likely to be generalizable beyond the Netherlands population where this was conducted in routine clinical practice, certainly across Caucasian populations that are similar and with similar stroke interventional and assessment protocols, and I would hope to see this sort of study validated externally in other populations. But, also, as Michael said, I think this study not just highlights the importance of time as a factor and its implications for systems of care and recognizing people with disabling stroke and ensuring they’re assisted urgently to the appropriate imaging but also to acknowledge that time isn't the only factor. And as Michael has alluded to, our brain tissue has different collateral circulations and different probable genetic factors and metabolic factors. So, someone with a stroke at one hour, it might be all over for them. Whereas, another person with a stroke at 24 hours ago, they might have salvageable tissue.                                                 So, although, generally time is an important prognosticator as we've learned here, there are probably other factors that need to be considered and accounted for. But this certainly takes us a step forward, and, in answer to your question, I think we have confidence in its generalizability. Dr Carolyn Lam:                Thank you Graeme. Maxim, in line with that, are there any next steps you plan? Dr Maxim Mulder:           In light of the most recent trials, the DAWN and DEFUSE 3 trial about 6 to 25-hour, 24-hour window, I think that both of the trials are very exciting, and they shine a new light into a new set of patients that are still able to offer a great benefit intra-arterial treatment. In my opinion, the most important thing, especially in those two trials, those are highly selective patients, especially selected on all the extra imaging parameters, and I guess that there's a whole larger population that could still benefit in this time window and that's also one of the things we're currently studying in one of our new trials in the Netherlands in the MR CLEAN-LATE trial, and that is randomizing patients who are having a large vascular occlusion 6 to 24 hours, and the only extra criteria they should meet is they should have at least a little bit of collateral circulation on the ischemic brain side. Dr Carolyn Lam:                Michael and Graeme, what do you think are the priorities for next steps in research. Dr Micheal Hill:                  I guess overall in the field, I don't think there's any doubt that faster treatment is better. What we need to do across the world is make sure that everybody's receiving it on a system-wide basis. Right? I think there needs to be a lot of more careful work done on getting systems of care in place to make sure that patients are getting the treatment they can get. We have very many weaknesses. Some are related to lack of accreditation. Some are related to the resources required to get people treated quickly. Some are related to continuing resistance in some specialties to even giving intravenous thrombolytic drugs. So, I think faster treatment in general for acute stroke is a theme; it's not just limited to endovascular treatment. It's treatment for patients for intravenous thrombolysis. It's also actually true for TIA and minor stroke. We've had recent data on fast antiplatelet therapy, so, it's not an emergency in the same way in terms of minutes, but it's still a general theme of acute stroke care.                                                 We need to be like the Ferraris and the Formula One, right? And get ourselves moving. That's a big challenge for people. Right? It's a big stress on systems. But, I think there are other examples in medicine. We've seen this evolution in acute coronary care, and we've seen the evolution in acute trauma care. In many ways, the next things that need to really continue to happen are publications like this and getting the message out that people need to start changing their mind. The biggest thing that I find when I talk to people or talk at meetings or talk to administrators is that they say, "Well, we can't do this many CTs that fast. We can't respond that fast." And the answer is actually that you can't change the biology of the disease, so if you decide you wanna treat stroke patients, you better figure out how to change your systems. It's a question of will here rather than trying to bend the disease to the system. Dr Carolyn Lam:                Wonderfully put. Can't change the biology so we better change the systems. How about you, Graeme? Any last words? Dr Graeme Hankey:        Just to concur with Michael’s comments there and Max's underlying theme that time is very important. And as Michael alludes to, it's not just acute ischemic stroke due to large vascular disease, it's also acute intracerebral hemorrhage. We're learning now really if we're gonna have an effect in the bleeding brain probably we have to do that within the first three hours and maybe not be waiting so late. And as Michael alludes to, someone with a minor ischemic stroke who's had a hot volcano gone off in their neck, as you know, ruptured atherosclerotic plaque, it's like those volcanoes in Hawaii, they're gonna keep going off again. And the risk is 5% in the next two days and 10% in the next week. So, a TIA and a mild ischemic stroke, it is a medical emergency to find the cause and to get it treated, and that's why the synopsis of this message from Max's study is that people, if they do avail themselves of acute assessment early, even if they don't have a large vessel occlusion causing an ischemic stroke, they may actually have their intracerebral hemorrhage treated quickly or, more evidence based at the moment, their TIA or mild ischemic stroke have the cause ascertained and treated emergently and reduce that early risk of recurrence should they survive. Dr Carolyn Lam:                Excellent points. Thank you so much, gentlemen. This has been an amazing podcast.                                                 Thank you so much for joining us today. Don't forget to tune in again next week, listeners.  

16 July 2013: In this episode, Dr. Robert Dellavalle speaks with Dr. Tamar Nijsten, from the Erasmus University Medical Center, about important aspects of epidemiology, such as the prevalence and incidence of events and their associated factors, which lead to a better understanding of skin disease.

Conversamos coa divulgadora e profesora de matemáticas da Universidade de Sevilla Clara Grima sobre grafos, redes sociais, Rosalind Franklin, vacinas, divulgación e teatro. Esta semana o Grupo Interdisciplinario de Bioestatística da Universidade de Santiago organizou unha reunión científica sobre Modelado Conxunto de Datos Lonxitudinais e de Supervivencia. Grazas a esta técnica estatística é posible facer determinadas predicións tomando de base medicións tomadas repetidamente no tempo. Isto é algo que pode ser moi útil en disciplinas como bioloxía ou nas finanzas, pero especialmente no campo da medicina. En dúas pílulas reproducimos as impresións de varios dos participantes no seminario internacional que impartiu Dimitris Rizopoulos da Erasmus University Medical Center de Holanda.

Conversamos coa divulgadora e profesora de matemáticas da Universidade de Sevilla Clara Grima sobre grafos, redes sociais, Rosalind Franklin, vacinas, divulgación e teatro. Esta semana o Grupo Interdisciplinario de Bioestatística da Universidade de Santiago organizou unha reunión científica sobre Modelado Conxunto de Datos Lonxitudinais e de Supervivencia. Grazas a esta técnica estatística é posible facer determinadas predicións tomando de base medicións tomadas repetidamente no tempo. Isto é algo que pode ser moi útil en disciplinas como bioloxía ou nas finanzas, pero especialmente no campo da medicina. En dúas pílulas reproducimos as impresións de varios dos participantes no seminario internacional que impartiu Dimitris Rizopoulos da Erasmus University Medical Center de Holanda.

Dr Carolyn Lam:     Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. And Dr. Carolyn Lam, Associate Editor from the National Heart Center, and Duke National University at Singapore.                                 What is the effect of obesity and underweight status on perioperative outcomes of congenital heart operations?                                 Our feature paper this week sheds light from the Society of Thoracic Surgeons Database. More soon, right after these summaries.                                 The first original paper highlights the role of micro RNAs in metabolic remodeling and heart failure. As a reminder, micro RNAs are small, noncoding RNAs important in post transcriptional modification and influencing many cellular processes simultaneously.                                 First author, Dr. Heggermont, corresponding author, Dr. Heymans, and colleagues from Maastricht University in the Netherlands use mice subjected to pressure overload by means of endotension to infusion or transverse aortic constriction. They show that micro RNA 146A was up regulated in whole-heart tissues in these murine pressure overload models, as well in left ventricular biopsies of aortic stenosis patients. Over expression of micro RNA 146A in cardio cardiomyocytes provoked cardiac hypertrophy and left ventricular dysfunction in vivo, whereas genetic knockdown or pharmacological blockade of micro RNA 146A blunted the hypertrophic response and attenuated cardiac dysfunction in Vivo.                                 Mechanistically, micro RNA 146A reduced its target dihydrolipoyl succinyltransferase or DLST, a mitochondrial protein that functions as a TCA cycle transferase. DLST protein levels were reduced in pressure overload mice, while they were partially maintained in micro RNA 146A knockout mice. Furthermore, overexpression of DLST in wild type mice, protected against cardiac hypertrophy and dysfunction in Vivo. Thus, micro RNA 146A and its target DLST are important metabolic players in LV dysfunction. These results also opened the door to novel therapies to treat metabolic disturbances and improve energy efficiency of a failing heart.                                 Program cell death is critically involved in ischemic cardiac injury, pathologic cardiac remodeling, and heart failure progression. Our next paper sheds light on the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure. Using genetic mouse models, first authors Dr. Guo and Yin, corresponding author Dr. Liu, and colleagues from University of Washington in Seattle, identified a critical role for a tumor necrosis factor receptor associated factor 2 or TRAF2 in myocardial survival and homeostasis by suppressing necroptosis.                                 The authors delineated an important TRAF2 mediated NF-KB independent pro-survival pathway in the heart by suppressing necroptotic signaling. They identified novel molecular mechanisms whereby TRAF2 suppressed TNF receptor 1 mediated, receptor interacting protein 3 dependent necroptosis, which is critical for myocardial survival and homeostasis. Thus, this finding suggests that the necroptosis suppressing TRAF2 signaling pathway and its effectors may serve as novel therapeutic targets for pathologic cardiac remodeling and heart failure.                                 Our next paper tells us that cerebral hyperperfusion may be associated with accelerated cognitive decline and an increased risk of dementia in the general population. First author Dr. Walters, corresponding authors Dr. Ikram, and colleagues from Erasmus University Medical Center in Rotterdam, The Netherlands, measured cerebral blood flow by 2D phase contrast MRI in non-demented participants of the population based Rotterdam study. A 4,759 participants with a median age of 61 years, and a median follow up of 6.9 years, 123 participants developed dementia.                                 Lower cerebral perfusion was associated with higher risk of dementia and this risk was even higher with increasing severity of white matter hyperintensities on MRI. At cognitive reexamination after an average of 5.7 years, lower baseline perfusion was associated with accelerated decline in cognition, which was similar after excluding those with incident dementia, and again, most pronounced in individuals with higher volumes of white matter hyperintensities.                                 Thus, lower cerebral perfusion was associated with accelerated cognitive decline and increased risk of dementia in the general population. This association was modified by hypertension and cerebral small vessel disease, possibly reflecting impaired arteriola and capillary function. This paper calls for further long term study and evaluation of optimizing cerebral perfusion as a means to prevent cognitive deterioration, for example, in patients with heart failure or carotid artery stenosis.                                 Well, that wraps it up for our summaries. Now for our feature discussion. For today's feature discussion, we will be looking at data from the Society of Thoracic Surgeons Database. This time looking at the effect of body mass index on perioperative outcomes of congenital heart operations in children, adolescents, and young adults. To discuss this, we have none other than the first and corresponding author, Dr. Michael O'Byrne from Children's National Medical Center in Washington D.C., as well as Dr. Naveed Sattar, Associate Editor from University of Oxford. Welcome gentlemen. Dr Michael O'Byrne:       Good morning. Dr Naveed Sattar:            Good morning. Dr Carolyn Lam:                Michael, we know that extreme body mass indices, very high or very low, has been associated with increased risk of at first, perioperative outcomes in mainly older adults undergoing cardiac surgery. We also know about the obesity paradox in conditions like heart failure, so why was it important to look at this specific group of patients? Congenital heart patients and children, adolescents, and young adults? Dr Michael O'Byrne:       Yeah, I think that as a pediatric cardiologist, a lot of the data that we use to guide our management is extrapolated from adult studies. However, in this particular case, it wasn't clear necessarily that adult data would necessarily be applicable to children and adolescents and young adults. We are aware that there are epidemiologic trends that congenital heart disease population ages and there are also in increasing problems of obesity among children in the United States.                                 The convention wisdom among surgeons in the United States is that obesity would increase perioperative risk and the thought is that some combination of exposure to hypertension and diabetes and peripheral vascular disease might impede wound healing and that body habit as itself might be a risk for the technical approach in wound healing. Acknowledging that there's a lot of evidence both for extreme BMI being a risk in surgical patients and adults, but also the idea that obesity paradox might be important in children because the biological mechanisms might be different.                                 Children themselves are exposed, their sort of dose response or dose exposure is less, they're younger, and so haven't been obese for a prolonged period of time, so that the integrated effect of having diabetes, hypertension, and obesity might be less. At the same time, we also acknowledge that in children with heart disease, we have congenital cardiac disease, the same issues with cachexia and frailty are present. i.e. that children with very low body mass index might be assigned to their own medical frailty, or a part of a heart failure cachexia syndrome.                                 One of the challenges in dealing with children with congenital heart disease, however, as you know is that its rarer than cardiac disease of the aging and additionally, that the population is very heterogenous in terms of the actual defects that are present and the surgeries that are performed. It was relevant to look and see over a wide range of sort of technical complexity surgeries with a wide range of sort of intrinsic preoperative risk of perioperative outcome, whether or not BMI would be associated with an adverse outcome. Either operative mortality in this case, or a composite outcome of mortality, major adverse events, and wound infection. Dr Carolyn Lam:                Wow, that makes a lot of sense and congratulations. This is not just the first, it's huge and really comprehensive. Could you just tell us a little bit more about what you did and what you found? Dr Michael O'Byrne:       I think as this point, I'd have to acknowledge that the challenges that we described in terms of both a sample size and in terms of getting a representative sample, is a constant challenge in our field and we have to give credit to my co-authors Marshall and Jeff Jacobs for their work in developing the collaboration that allowed for the STS Congenital Heart Surgery Database to exist. Also, on top of shepherding the database, their research, along with the people at Duke Clinical Research Institute, they've developed a robust risk stratification model for mortality that we utilize as part of this study. Without that, this would be really be very challenging.                                 What we did is performed an observational cohort study using the STS Congenital Heart Surgery Database to look at the risk of perioperative mortality and composite outcome in patients undergoing surgery in the United States between 2010 and 2015. We looked at both the actual events, the sort of observed events, in terms of mortality and adverse events, and then created multivariate models to adjust for the known covariance.                                 We hypothesized that extreme BMI, either very high or very low, would be associated with increased risk of mortality and increased risk of that composite outcome. What we found that operative mortality and that perioperative adverse events occurred more frequently in obese and severely underweight subjects. However, because they have an unequal distribution of potentially important covariance, we used multivariate modeling to adjust for those covariance.                                 Our multivariate models for death, however, the severely underweight subjects had an odds ratio of 1.4 and obese subjects had an odds ratio of 1.3, but neither was specifically significant in that context. We sort of anticipated that with a possibility given the very low event rate. That's the reason we've used a composite outcome, a higher event rate.                                 For that composite outcome, in both different versions of the multivariate model that we used, the severely underweight subjects had an odds ratio of 1.5, underweight subjects had an odds ratio of 1.3, and obese subjects had an odds ratio of 1.2. An increased risk in all three of those populations of interest relative to normal weight or just overweight subjects. Dr Carolyn Lam:                We're always saying that at circulation we do want to publish papers that have direct and important clinical implications, so Naveed, could you share some thoughts on what this means clinically? Dr Naveed Sattar:            Yeah, I think they went through the review process and I think the paper was very well written. I think Michael and his colleagues clearly understood the strength and the limitations of the data so that you can only ever itself prove associations here and therefore, clinically when we push them on trying to make clinical inferences, I think clearly they recognize that once they find associations between obesity and adverse outcomes and underweight.                                 What they need to do next, now this is a paper that then leads you to think, "Well actually, I need to do some clinical trials to prove that module ..." You're preventing these outcomes or in very under knowledge where they're actually increasing the BMI but improving their nutrition, cannot also improve outcomes following surgery. Now those are tough things to do. Michael, what do you think from some of the clinical inference? My inferences were the associations were there, particularly for the normal [inaudible 00:12:35] outcomes, but actually to prove that, to make a difference, you probably might need to do some intervention trials or is that how you take it as well? Dr Michael O'Byrne:       I agree with you 100%. I think that as an epidemiologist, I think that what we see in an observational study like this is an association. The two next levels of research that are necessary at this point are to see whether or not in this population BMI is a modifiable factor in the short run before surgery, or even in the long run. And the second question to answer is whether those adjustments in BMI, if they are achievable, affect outcome with surgery. Absolutely.                                 It's a tremendous challenge, both logistically in organizing a study, and honestly, in terms of capturing a cohort that would be large enough, given that this is almost 100% of the surgeries that occurred over a six year period in the United States. Dr Naveed Sattar:            I looked at it and thought, "Well, the mortality association once you adjusted were not quite significant but are there any individuals you would not do surgery on based on their BMI based on these results? Dr Michael O'Byrne:       The motivation for the study is exactly to try to begin to shed light on that kind of question. I think that it might be what I would call a tiebreaker potentially, if you have a situation where a patient is near meeting criteria but isn't quite at a place where you need to do surgery at that point. It might dissuade you from proceeding immediately potentially pursuing a course that might adjust their BMI in the correct direction.                                 At the same time also, in a patient who's underweight particularly to evaluate whether their medical regimen has been optimized and if there are other residual lesions that can be addressed in a non-surgical or medical fashion. Dr Naveed Sattar:            I suppose the other trick with this type of research research is always trying to make sure that people understand these are the associations and not trying to attribute causality because it's always physical, isn't it? But I think you and your team did that very well and I'm sure we had a back and forth with review but I think your discussion section, your limitation section, is beautifully written and covers those kinds of caveats, which I think is important as well. Dr Michael O'Byrne:       I thank you for that. That's very complimentary and we certainly strived for that, but I think that you as an editor, and also in terms of the reviewers also, were very helpful in that sort of collaborative process to try to make sure that we're communicating it. It's not always clear in a project that takes months and years to finish when you're writing it necessarily, you may be constantly aware of trying to be clear in your communication but it's also helpful to have a reviewer from the outside carefully read the study. Dr Carolyn Lam:                That's wonderful and Michael, may I just join Naveed in congratulating you on beautiful paper? And maybe just one other little question, did you have any insights into the mechanisms of increased risk for composite events in the extremes of BMI? Dr Michael O'Byrne:       I think it's an important question. There's been a tremendous amount of research in adult cardiac disease about whether it is the BMI as a steady state or BMI changes immediately before and after surgery that are relevant in this case. From this kind of observational study, it's very hard and very challenging to try to make any sort of inferences about the causes. It would be an important part of any study moving forward to include ways to investigate that, and honestly, as an interventional cardiologist and epidemiologist, I probably would defer to Naveed, he might have more cogent and logical ideas about that than I do. Dr Naveed Sattar:            We've had lots of research from a whole variety of researchers. We all understand it's finally serious but recognize it's difficult, so one of the ways moving forward and I think Michael and his colleagues have this is if you have serial BMI data prior to surgery, that could try and inform on reverse causality because of the low BMI, but in terms of the mechanisms, remember these are associations, but I think mechanisms are well covered if you are obese and clearly you have risk factors for death, across the vasculature, across the cardiac functions, across the whole variety of things.                                 We know those mechanisms, question is, to what extent are they actually operating and causing increased risk in the surgical arena and that's a really tough ask. I think people can come up with a multitude of mechanisms. I think the key things, like this particular paper, is that there are potential mechanisms but these are associations ... Look, this is what we found, and clinically now we need to try and address this within the following types of interventions or at least provide some guidance to colleagues and clinicians.                                 Exactly as Michael says, if there is somebody who is approaching surgery whose quite obese, perhaps they should try and intervene to try and lessen their weight for a short period of time prior to [inaudible 00:17:07], you know what happens. It would be nice to do some big trials but I think doing trials in this area is going to be really tough, but with imagination, with good collaboration across centers, trials are not impossible. I think they can be done. Dr Michael O'Byrne:       Naveed, I think, actually articulated what I think is both the difficulty of doing that trial but also the importance of it. I think that looking at ... In these databases, we don't have a serial BMI and I think that's an important missing piece of information that we tried to address in our discussion and I think it's something that would be really valuable moving forward. And certainly testing interventions, whether they're medical, interventional, or surgical, to help these patients who are obese either lose or maintain an appropriate weight is the next step.                                 On the converse side, this research highlighted to me the prevalence of chachectic or underweight patients in our population and it's something that outside of the infant period, we don't necessarily think about tremendously and we don't think about it as a modifiable factor. I think that's another group of patients who also deserve some attention. Dr Carolyn Lam:                Listeners, you've been listening to Circulation on the Run. I'm sure you learned a lot as I did. Don't forget to tune in again next week.  

Senescent cells play a uniquely dual role in the body: in the younger stages of life, they are crucial in helping heal wounds, yet later in life, they contribute to certain aspects of aging. The powerful influence senescence cells have on the body is what drives Peter de Keizer, an anti-aging researcher at Erasmus University Medical Center in the Netherlands. In this Future Tech “Almost Here” podcast, Anti-Aging, de Keizer takes us deep into his research. His goal is to find a way to purge these senescent cells before they cause irreparable damage. When a cell reaches its damage threshold, it either dies (apoptosis) or hibernates (senescence). de Keizer discusses what happens when the cells that refuse to die begin to accumulate and how he and his team have found two different ways to disrupt cell senescence. While this seems like great news, de Keizer explains that if done in the wrong way or at the wrong time, the cells can turn toxic and cause unintended damage. He also describes the results from experiments on aging mice and what it might mean for humans. Since the effects on both long-term health and on healthy people in their 50s and 60s still need to be determined, de Keizer also cautions against people who are understandably eager to acquire this at any cost and describes what's happening to people who are going about it the wrong way. You'll also learn: * Why cell death is more common when you're younger and cell senescence more common when you're older as well as what determines cell death or senescence * The science behind why this is not the Elixir of Life to make you immortal but instead is a method to improve your health span (i.e., quality of life) in your later years; even so, though our lifespans are increasing, there might actually be an age cap that humans cannot surpass * What's in store for the rest of 2017 and into 2018: despite all the challenges, are we really this close to a breakthrough? So make sure to listen to it and subscribe to the podcast. Keep donating Bitcoins to Future Tech Podcast so we keep bringing you the stuff you love and want to know more about.

  Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore.                                                 In today's episode, we are discussing very important new data regarding stroke risk stratification in patients with atrial fibrillation. First though, let me give you the highlights of this week's journal.                                                 The first paper provides mechanistic evidence that endothelial-derived microparticles may play a key role in the development of endothelial dysfunction following acute coronary syndrome. In this paper from first author, Dr. Abbas, co-corresponding authors, Dr. Toti and Morel from the University of Strasbourg in France, authors expose core sign coronary artery endothelial cells to microparticles shed from senescent cells, or circulating microparticles from patients with acute coronary syndrome.                                                 They showed that exposure to these microparticles induced increase senescence-associated beta-galactosidase activity, oxidative stress, and early phosphorylation of MAP kinases and AKT, and upregulation of p53, p21 and p16. Depletion of endothelial-derived microparticles from acute coronary syndrome patients reduced the induction of senescence.                                                 On the other hand, pro-senescent microparticles promoted endothelial cell thrombogenicity. These microparticles exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and ACE in endothelial cells. Losartan and AT1 receptor antagonist and inhibitors of either MAT kinases or PI3-kinase prevented the microparticle-induced endothelial senescence.                                                  In summary, these findings indicate that endothelial-derived microparticles from acute coronary syndrome patients induce premature endothelial senescence and thrombogenicity suggesting that targeting endothil-derived microparticles and their bioactivity may be a promising therapeutic strategy to limit the development of endothelial dysfunction post-acute coronary syndrome.                                                 The next study is the first large and prospective study showing that NT-proBNP is associated with cardiovascular events in patients with adult congenital heart disease independent of multiple clinical and echocardiographic variables.                                                 This is a study from first author, Dr. Bekan; and corresponding author, Dr. Roos-Hesselink and colleagues from the Erasmus University Medical Center in Rotterdam, the Netherlands. The author studied 595 clinically stable patients with adult congenital heart disease who attended the outpatient clinic between 2011 and 2013.                                                 All patients underwent clinical assessment, electrocardiography, echocardiography and biomarker measurement, including NT-proBNP, high-sensitivity troponin T and growth differentiation factor 15. Patients were prospectively followed over a median of 42 months for the occurrence of cardiovascular events including death, heart failure, hospitalization, arrhythmia, thromboembolic events and reintervention.                                                 They found that of the three evaluated biomarkers, NT-proBNP was most strongly associated with cardiovascular events. Importantly, patients with a low-risk of death and heart failure could be accurately identified with a high negative predictive value.                                                 In patients with elevated NT-proBNP, elevations of high sensitivity troponin T and growth differentiation factor 15 identified those patients at highest risk of cardiovascular events.                                                 In summary, these biomarkers may play an important role in the monitoring and management of patients with adult congenital heart disease.                                                 The next study describes heart failure stages among older adults in the community. Dr. Shah and colleagues from the Brigham and Women's Hospital in Boston Massachusets classified more than 6,000 participants in the atherosclerosis risk and community study into heart failure stages. These were stage A; asymptomatic individuals with heart failure risk factors, but no cardiac structural or functional abnormalities. Stage B; asymptomatic individuals with structural abnormalities such as left ventricle hypertrophy, dilation, dysfunction, or valve disease. Stage C1; clinical heart failure without prior hospitalization. Stage C2; clinical heart failure with prior hospitalization.                                                 They found that only 5% of examined participants were free of heart failure risk factors or structural heart disease. 52% were categorized as stage A, 30% stage B, 7% stage C1, and 6% stage C2. Worst heart failure stage was associated with a greater risk of incident heart failure hospitalization or death at a median follow up of 608 days.                                                 Left ventricular ejection fraction was preserved in 77% of stage C1 and 65% of stage C2 respectively. In corporation of longitudinal strain measurements and diastolic dysfunction into the stage B definition, reclassified 14% of the sample from stage A to B.                                                 Abnormal LV structure, systolic function, whether based on ejection fraction of longitudinal strain, and diastolic dysfunction, were each independently and additively associated with the risk of incident heart failure hospitalization or death in stage A and B participants.                                                 The authors concluded that the majority of older adults in the community are at risk of heart failure, appreciably more compared to previous reports in younger community-based samples. The study also highlighted the burden of heart failure with preserved ejection fraction in the elderly and provided evidence that left ventricular diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and ejection fraction in identifying patient at risk of heart failure hospitalization or death.                                                 The next study sheds light on the association of the LPA gene, ethnicity and cardiovascular events. First author, Dr. Lee; corresponding author Dr. Tsimikas and colleagues from University of California San Diego studied 1,792 black, 1,030 white, and 597 Hispanic subjects all enrolled in the Dallas Heart Study. They measured LPA snips, apolipoprotein A isoforms, LP(a) and oxidized phospholipids on apolipoprotein B100.                                                 These individuals were also followed for a median of 9.5 years for major adverse cardiovascular events. The authors found that the prevalence of LPA snips and apolipoprotein A isoforms were very different across ethnic groups. LPA snips that were associated with elevated LP(a) in whites were associated with low LP(a) in Hispanics mainly due to differences in apoliproprotein A isoforms size.                                                 After multi-variable adjustment, LP(a) and oxidized phospholipids on apolipoprotein B were both predictors of major adverse cardiovascular events. Conversely, LPA snips and apolipoprotein A isoforms did not add predictive value to models and did not show clinical utility in this study.                                                 These data suggests that much of LP(s) mediated major adverse coronary events is driven by oxidized phospholipids. Importantly, elevated LP(a) and oxidized phospholipids on apolipoprotein B must be recognized as important predictors of major adverse cardiovascular events across racial groups.                                                 The final study addresses the question of the optimal antithrombotic regimen for longterm management of patients with symptomatic peripheral artery disease, or PAD, with a history of limb revascularization. To answer this question, Dr. Jones and colleagues from Duke Clinical Research Institute looked at the EUCLID trial, or examining use of ticagrelor in PAD trial, which randomized patients with PAD to treatment with ticagrelor 90 milligrams twice daily, or clopidogrel 75 milligrams daily.                                                 As a reminder, patients in EUCLID were enrolled based on a normal ankle-brachial index of less .8, or a prior lower extremity revascularization. The current paper really focus on the subset of 7,875 patients who were enrolled based on a prior lower extremity revascularization criterion.                                                 The authors found that after adjustment for baseline characteristics, patients enrolled based on prior revascularization for PAD had higher higher rates of myocardial infarction and acute limb ischemia with similar composite rates of cardiovascular death, myocardial infarction and stroke when compared with patients enrolled based on the ankle brachial index criterion.                                                 Overall, there were no significant differences between ticagrelor and clopidogrel for the reduction of cardiovascular or acute limb events.                                                 Those were your highlights. Now, for our featured discussion.                                                 On today's podcast, we are discussing the very, very important issue of stroke risk in patients with atrial fibrillation. Most of us use the international guidelines for anticoagulation in atrial fibrillation that mostly suggest that we use the CHADS VASc scoring system to determine the stroke risk in a particular patient and then determine whether or not this patient meets the threshold for anticoagulation.                                                 This assumes that the CHADS VASc score corresponds to a fixed stroke rate. Today, in our journal, we have very, very interesting results from a paper with corresponding author, Dr. Daniel Singer who really suggest that we may need to rethink that. Dr. Daniel Singer joins us today from Massachusets General Hospital.                                                 Welcome Daniel. Dr. Daniel Singer:             Thank you for having me. Dr. Carolyn Lam:               Great. Today, we also have Dr. Sana Al-Khatib who's the associate editor from Duke University who managed this paper. Welcome Sana. Dr. Sana Al-Khatib :         Thank you Dr. Carolyn, I'm happy to be here. Dr. Carolyn Lam:               Daniel, could we start by you letting us know what you sought to do in your study and what you found? Dr. Daniel Singer:             We all know that anticoagulants are extraordinarily effective at preventing stroke in patients with atrial fibrillation, but they also raise the risk of bleeding, and sometimes that bleeding could be quite serious and even fatal. As a result, for that past 10, 15 years, we have used a risk-based approach to the decision about whether to start a patient on anticoagulation, and that risk is the stroke risk that a patient faces if they weren't taking anticoagulants. Then we figured that anticoagulants will reduce it by about two-thirds.                                                 There are formal decision analysis and then a more informal sense that a patient has to face an anticoagulated risk of stroke of about 2%, some people might say 1% to 2% before anticoagulation results in an expected net clinical benefit that the effect in reducing ischemic stroke will exceed the risk of increasing bleeding.                                                 While the CHADs VASc score has been widely accepted as the basis for estimating that risk, it became apparent to us as we looked across the studies that were underlying that assumption, that the risk that were associated with various CHADs VASc scores were extremely variable. Many of these risks actually were less than that 1% or 2% threshold for anticoagulation.                                                 What I mean is that the stroke risk associated with CHADs VASc score of one, or two, which is the basis for the guideline threshold for anticoagulation actually corresponded to risk less than 1% in many of these very large studies. We have conducted a systematic review just to be sure that we were capturing the overall evidence base for this, and that's what we report in our paper. Dr. Carolyn Lam:               Perhaps you could start by letting us know exactly how far off are we in our stroke risk estimation. Dr. Daniel Singer:             We looked at 34 studies that were quite large and then we zeroed in on the largest one. If you looked at the rate for stroke overall, they varied enormously in terms of the overall stroke rate. Then when we focused down on CHADs VASc score of 1, or 2, we found that the majority of these studies, actually, for CHADs VASc 1, was less than 1% per year. For CHADs VASc 2 score was in the majority these studies less than 2% per year.                                                 Both of those stroke risks have raised us the question where are these patients could gain in that clinical benefit from being anti-coagulated, because those stroke risk, if they were reduced by two-thirds, would really be a very small reduction in risk and yet they'd still face the bleeding risk.                                                 Among the most interesting findings actually is that we found that a Swedish national database and the large Danish national database came up with threefold difference in their estimate of stroke rates. The Swedish database produced lower risk, and the Danish database produced substantially higher risk.                                                 If you think about it, there are probably no two countries in the world that are more similar in terms of gene, social environmental, medical care systems, and that raises the specific question of, "Is it underlying rates that vary across different cohorts and different geographies, or is it a different in methodology?"                                                 We think a lot of the differences are due to methodologic difference, and that we need to standardize these differences together, better handle on what the real stroke rate is among patients with these low CHADs VASc scores. Dr. Carolyn Lam:               The variability that you pointed on your paper is really striking, but another possibility, do you think, is that maybe stroke risk isn't static. Dr. Daniel Singer:             Yeah. If that's the case, we face a great difficulty in developing predictions rules of what the stroke risk could be. I think most people feel it's the function of their age, and whether they've had a prior stroke, and whether they have the comorbidity, hypertension, and diabetes, and so on, that are incorporated into the various stroke risk scores, in particular, CHADs VASc.                                                 We tend to think that that's pretty fixed until you get older or until you accumulated another comorbidity. I think the striking difference is that, one, that we actually anticipated in the beginning, was that the stroke rates in people with atrial fibrillation were also coming down. The stroke rates in general have been dramatically decreasing for decades now.                                                 One issue is whether that applies as well to atrial fibrillation associated stroke. There is a suggestion of that, but the variability across the cohorts is so great that you can't pick up a strong signal in terms of calendar time. Although I suspect that there is a strong calendar effect. Exactly why that is, we could speculate. I suspect a lot of it is control of blood pressure, but that's speculation. Dr. Carolyn Lam:               Daniel, congratulations again for that fascinating and really very sobering findings.                                                 Sana, you managed this paper. It's very important paper. In fact, important enough that you invited an editorial. Could you please share some of your thoughts? Dr. Sana Al-Khatib :         Oh, yeah. Absolutely. First, I'd like to start by congratulating Daniel and his team on conducting this really important study. I enjoyed reading it and managing it. Definitely, congratulations.                                                 A couple of thoughts that I have. I completely agree with this really important finding, that there is a lot of variability in the rates of stroke that come from different patient populations and databases. As you pointed out Daniel, I think this is indeed largely due to differences in methodology in terms of how the information was selected, how certain things were defined.                                                 I agree with you there. You called for standardization of this, and I wonder if you have any thoughts about how we can go about doing that. I also want to bring up some of the newer studies now that are showing some significance in terms of biomarkers. Is that really adding significantly to the predictive ability of risk prediction models? I wanted to get your thoughts on that as well. Dr. Daniel Singer:             Let me address your last question, which is simply you state that the CHADs VASc score, the CHAD score and so on, are based on very simple clinical features, and it would be unusual for them to be highly predictive. In fact, they're only mediocrely predictive, and the addition of biomarkers high-sensitivity troponin proBNP, now, people have suggested the imaging biomarkers like magnetic resonance to asses fibrosis in the left atrium. These are all very, very promising in terms of getting better models.                                                 The problem is to do that on a very scale such that we can get precise and well-calibrated predictions. We've found when we're analyzing to pair risk scores, we found that the most important issue is the underlying risk, so that, yes, you can get a great model, but if you have high variability in the underlying rate, you can have a problem specifying an individual with a stroke risk.                                                 We have to standardize and improve the quality of bringing people into these cohorts, and of interrogating the cohorts and databases and making sure that we have the same approach to assessing outcomes.                                                 This could probably be best done in very big scientific prospective registry studies, but it's tough to get all that information. There are some registry studies now ongoing, the ORBIT registries, the GARFIELD registries that may help us a lot with specifying stroke risk, but they don't have the biomarkers embedded in them. I'm hopeful that with better message, and large studies, and incorporating biomarkers, that we'll really get down to very accurate and generalizable stroke risk.                                                 I think the CHADs VASc and similar simple stroke risk scores will be in the rear-view mirror. Dr. Sana Al-Khatib :         That's great. Can I ask one other question, because I completely agree with you looking at your numbers and the data that you presented, is that when you look, especially at the CHADs VASc score 1 patient, the risk seems to be pretty low.                                                 As you very well know, the guideline documents don't really ... At least, for the American AHA/ACC guideline document, they don't really verbalize very definitively the need to anticoagulate patients with a CHADs VASc score of 1.                                                 If you look at the numbers related to a CHADs VASc score of 2, I'm not sure that I completely agree that the risk is very low. Certainly, there was 33% of the studies reported stroke rates of greater than 2% per year. I think maybe different people have different thresholds. While I completely agree with you on the CHADs VASc score of 1 patients, I find that the findings on patients with a CHADs VASc score of 2 a bit more concerning.                                                 In fact, if anything, I would want based even on your data, not on the guidelines to offer anticoagulation to patients with CHADs VASc score of 2. What would you say to that? Dr. Daniel Singer:             I'm looking at our table that has this, and a lot of the CHADs VASc 2 scores are under 2%, but they're in mid 1%. In the North American cohorts in particular, the rates tend to be lower. That said, I think the heart of the problem here is that we have focused on the threshold for anticoagulation. I think there's an argument to be made that you lay out the risks and benefits to the patients and engage them in a decision, particularly with regards to these lower CHADs VASc scores.                                                 At least you make a lot of, perhaps, even more emphasis on being sure that the higher CHADs VASc scores, that anticoagulation is the net benefits of anticoagulation are made very clear to the patient, and that we don't have large fractions of patients who can take anticoagulants not taking them.                                                 We know from the pinnacle registry and other registries, that even at high CHADs VASc scores, we have 40% plus of atrial fibrillation patients who are not getting anticoagulants. I think that's where we have a lot more assurance that the net benefit is positive and that we can make a different both in terms of a patient in front of us, and in terms of the overall public health aspects of atrial fibrillation and stroke. Dr. Sana Al-Khatib :         I do believe that this is really important, but it is also important to keep in mind that with the novel novel oral anticoagulants, I think the whole landscape has changed. Not only do patients have different options to consider, but certainly, the risk of bleeding, which is the other part of this equation, has gone down significantly with the novel agents.                                                 I think as we engage in shared decision making with patients, I think it is really important to highlight these really very remarkable features about the agents that have really changed the care of patients with atrial fibrillation.                                                 One thing to add to this whole topic is, really, all the new advances that we're seeing in this field that has been really life-changing for us and for our patients. Dr. Carolyn Lam:               Indeed Sana. I was about to bring up the bleeding risk part, the flip side of the coin as well. Also, the point that most of my patients with atrial fibrillation, they really strongly value the avoidance of stroke even more than avoidance of bleeding. Someone, that needs to be taken into consideration as well.                                                 Daniel, I'd love to give you the last words. You mentioned that you like to highlight, maybe, some more of the implications of your findings. Dr. Daniel Singer:             I guess I would say there's a scientific implication, which is what we've ben discussing, which is the importance of trying to get these rates down correctly and accurately, and maybe we have to get people together to say how they're doing these studies.                                                 The second is, for the individual patient, that we should engage them in this discussion. Maybe patients who are perfectly willing to a novel anticoagulant and CHADs VASc score of zero. That would come out of a discussion with the patient. That our emphasis at this point since we're a little unsure about the threshold level, our emphasis both at the individual patient level, and then from the public heath perspective should be on the higher CHADs VASc scores where we know that we can expect a net clinical benefit from the vast majority of patients with AF.                                                 I agree with Dr. Al-Khatib, that the novel anticoagulants post an important advantage in the sense not so much in their overall bleeding, but particularly in terms of their intercranial bleeding, which is the lethal bleeding we most want to avoid. Dr. Carolyn Lam:               Thank you both for joining us. Thank you listeners for joining us. Don't forget to tune in next week.  

Dr Kirstin De Bruijn talks to ecancer at the 2013 European Cancer Congress (ECC2013) about the link between diabetes and an increased risk of developing cancer. Researchers performed a unique meta-analysis that excludes all other causes of death and found that diabetic patients not only have an increased risk of developing breast and colon cancer but an even higher risk of dying from them. Dr De Bruijn, a PhD student in the Surgery Department at the Erasmus University Medical Center in Rotterdam (The Netherlands), and colleagues analysed results from 20 trials that had taken place between 2007 and 2012, involving more than 1.9 million patients with breast or colon cancer, with or without diabetes. They found that patients with diabetes had a 23% increased risk of developing breast cancer and a 38% increased risk of dying from the disease compared to non-diabetic patients. Diabetic patients had a 26% increased risk of developing colon cancer and a 30% increased risk of dying from it compared to non-diabetic patients.

Dr Sepideh Saadatmand reports on a study at a press conference during the 8th European Breast Cancer Confernce in Vienna which conludes that adding magnetic resonance imaging (MRI) to standard breast cancer screening approaches is expensive, though it could be cost effective for a group of women who may not have inherited the breast cancer susceptibility genes.

Mrs Gelder presents findings from a Dutch study on the effectiveness of breast cancer screening at a press confernce at the 8th European Breast Cancer Conference. Results from the study show that, even with improved treatments for the disease, population-based mammography programmes still save a significant number of lives.

Mr Jacques Fracheboud presents results from one of the longest-running national breast cancer screening programmes at a press conference at the 8th European Breast Cancer Conference in Vienna. The results show that the screening programme has contributed to a drop in deaths from the disease, that any harm caused by the screening, such as false positives and over-diagnosis, has been limited, and that the costs have been reasonable.