Culture

CHICAGO --- For the first time, Northwestern Medicine scientists have pinpointed the location of dysfunctional brain networks that lead to impaired sentence production and word finding in primary progressive aphasia (PPA), a form of dementia in which patients often lose their language rather than their memory or thought process.

With this discovery, the scientists have drawn a map that illustrates three regions in the brain that fail to talk to each another, inhibiting a person's speech production, word finding and word comprehension. For example, some people can't connect words to form sentences, others can't name objects or understand single words like "cow" or "table."

The map can be used to target those brain regions with therapies, such as transcranial magnetic stimulation (TMS), to potentially improve an affected person's speech.

"Now we know where to target people's brains to attempt to improve their speech," said lead author Dr. Borna Bonakdarpour, assistant professor of neurology at Northwestern University Feinberg School of Medicine's Cognitive Neurology and Alzheimer Disease Center and a Northwestern Medicine neurologist.

PPA occurs in patients with neurodegenerative disorders, including Alzheimer's disease and frontotemporal degeneration.

Interactions among three main regions in the brain is responsible for how people process words and sentences. PPA occurs when there is a lack of connectivity among these areas. Different patterns of connectivity failure among these regions can cause different subtypes of PPA.

The findings will be published Sept. 1 in the journal Cortex. The large study (73 patients) recruited from the extensive pool of patients with PPA at Northwestern's Cognitive Neurology and Alzheimer Disease Center, one of the largest centers in the world.

The study used functional MRI, which monitors brain activity by detecting blood flow, to locate the regions of the brain that are talking to each other or not. That cannot be shown with structural MRI.

Previous research used structural MRI to locate only regions of the brain that had atrophied, and scientists did not clearly know how physiological impairment in these regions correlated with symptoms a patient was experiencing. This study is novel because it examined brain regions that were still functional (had not atrophied) and focused on the networks among the functional regions to see if they were connecting or not. This allowed the scientists to correlate the functional areas in the brain with symptoms of patients with PPA.

"Previous studies of structural changes in the brain were like archeology, in which scientists were locating areas of the brain that had already died," Bonakdarpour said. "But we are looking at the parts of the brain that are still alive, which makes them much easier to target with treatment."

Bonakdarpour and his colleagues have begun testing TMS on the three targeted brain regions in healthy individuals with the goal of applying it to patients with PPA in a future clinical trial.

The Endocrine Society and 10 other internationally esteemed medical societies have today issued the first Global Position Statement on the use of testosterone in the treatment of women. The statement was published in four leading international medical journals and has been authored by a diverse team of leading experts based around the world.

It follows years of debate regarding testosterone therapy for women and, for the first time, provides agreement among experts and medical societies about how testosterone could be prescribed for women.

"This position statement has far reaching global consequences. It not only reassures clinicians that a trial of testosterone therapy is appropriate for women with Hypoactive Sexual Desire Dysfunction (HSDD), but very emphatically states that, at present, the available evidence does not support the use of testosterone for any other symptoms or medical condition," said co-author Susan Ruth Davis, F.R.A.C.P.,Ph.D.,M.B.B.S., of Monash University in Melbourne, Australia. "It also clearly advises that when testosterone therapy is given, the resultant blood levels should not be above those seen in healthy young women. We hope this will allow women who may benefit to be offered treatment, and simultaneously protect women from receiving inappropriate testosterone therapy."

An international task force of experts from leading medical societies, brought together by the International Menopause Society, produced the Global Position Statement to provide clear guidance regarding the prescribing and measurement of testosterone for female testosterone therapy as well as advice on testosterone prescribing practices that have the potential to be ineffectual or cause harm.

They concluded that testosterone can be effective at improving sexual wellbeing for postmenopausal women with HSDD. Recognized benefits included improved sexual desire, arousal, orgasm and pleasure, together with reduced concerns and distress about sex.

HSDD is thought to affect around 32 percent of women at midlife; and, while it's common for women to lose interest in sex around the time of the menopause and after, the use of testosterone as a treatment offers women an approach that may significantly improve their sexual and related emotional wellbeing.

The international panel is calling on industry, researchers and funding organizations to recognize the need for further research into testosterone therapy for women of all ages and the development and licensing of products formulated specifically for women.

The statement was developed by a multinational, multidisciplinary task force, the members of which were delegates from leading medical societies, and was peer reviewed by expert committees of endorsing societies from across the world. It has been translated into 13 languages and aims to improve the sexual wellbeing of women on a global scale.

HAMILTON, ON (Sept. 1, 2019) - A major international study has shown that opening all clogged arteries with stents after a serious heart attack is much better than opening only the single clogged artery that caused the heart attack.

About half of all heart attack victims are found to have additional clogged arteries in addition to the one that caused their heart attack. Previously, doctors focused on opening the one artery responsible for the heart attack, leaving the other blockages for treatment with medication alone. The new study, a collaboration of 130 hospitals in 31 countries, has shown that opening all the blockages is better than treating only the one blockage causing the heart attack. This led to a 26 per cent reduction in the patient's risk of dying or having a recurrent heart attack.

The study, known as the COMPLETE trial, was published today in the New England Journal of Medicine and presented as a late-breaking clinical science session at the European Society of Cardiology Congress together with the World Congress of Cardiology in Paris, France.

"Given its large size, international scope and focus on patient-centered outcomes, the COMPLETE trial will change how doctors treat this condition and prevent many thousands of recurrent heart attacks globally every year," said study leader Dr. Shamir R. Mehta of the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

He said that although it had been known that opening of the single blocked artery that caused the heart attack with stents was beneficial, it was unclear whether additional stents to clear the other clogged arteries further prevented death or heart attack. In most cases, doctors would just treat the additional blockages with medication alone.

"This study clearly showed that there is long term benefit in preventing serious heart-related events by clearing all of the arteries. There was also no major downside to the additional procedures," said Mehta.

The COMPLETE study, led by the PHRI and funded by the Canadian Institutes of Health Research, involved 4,041 patients and is the first large, randomized, international trial to show a reduction in major outcomes with this approach.

"The benefits emerged over the long term and were similar when the additional stent procedures were done anytime in the first 45 days after the heart attack," said Mehta who is also a PHRI senior scientist, a professor of medicine at McMaster University and an interventional cardiologist of Hamilton Health Sciences.

Over the median of three years, a second heart attack or cardiovascular death dropped to 7.8 per cent of the patients who had the complete revascularization compared to 10.5 per cent of those who had a stent only for the artery that caused the first heart attack, a highly significant difference, said Mehta. The benefit was even more sizable when factoring in other untoward events such as severe chest pain necessitating a repeat stenting procedure.

There was no difference between the groups on whether they experienced side effects, including stroke and major bleeding.

Paris, France - 01 Sept 2019: Caregivers of stroke survivors who show signs of depression may have a higher risk of suffering their own health challenges down the line, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

The findings highlight the importance of attending to the mental health of caregivers and bring to mind the airline-safety metaphor: 'Secure your own oxygen mask before helping someone else.'

"Caregiving is becoming more common and more demanding," says study first author Professor Misook L. Chung of the University of Kentucky College of Nursing in the United States. "More attention needs to be paid, especially early on, to managing depressive symptoms in caregivers. They must realise that self-care is not selfish."

Stroke is a leading cause of long-term disability around the world and often exerts a heavy toll on those in a supporting position. Providing assistance to patients, including helping the survivor with eating, dressing, going to the bathroom and showering, not to mention taking care of meals, organizing a home and supervising medical care, can become a full-time job - with a deep emotional component.

The current project is the first longitudinal study to address the issue of persistent depressive symptoms and their effect on physical health as well as changes in health during the first year of stroke caregiving.

The research team enrolled 102 caregivers with a mean age of 58. Two-thirds were female and about 70% were spouses. The rest consisted of other family members, although two or three were family friends, says study senior author Rosemarie King, a retired research professor at Northwestern University School of Medicine in Chicago, Illinois, USA.

Participants answered questionnaires at two points in time: six to ten weeks after the patient was discharged from the hospital and again one year later.

The overall proportion of individuals reporting symptoms of depression like poor appetite or trouble focusing, declined slightly over the course of the study: 32.4% versus 30.4 More than half the participants (57.8%) said they had no issues of mental distress at all, but 20.6% (or one in five) suffered persistent depressive symptoms in the first year of caregiving.

The mental health of people with chronic signs of depression was closely associated with their physical health. One-third of caregivers in the study reported their physical health as fair or poor after one year, while 43% said they felt their health had deteriorated. Compared to caregivers who did not have signs of depression, those with ongoing challenges were seven times more likely to report problems with their health after one-year of caregiving for stroke survivors.

Individuals with persistent symptoms of depression during the first year of caregiving reported heavier caregiving duties, poor family functioning and low interpersonal support.

One limitation of the study is that the researchers did not track primary health outcomes such as diagnoses of physical illness. Instead, they relied on self-reports of caregivers' health status and changes in health status. There was also a high attrition rate, with a third of study participants dropping out. Longer-term studies, with objective measures of caregiver health status, are required.

The conclusions suggest the need for earlier interventions and long-term follow-up of caregivers.

"We haven't paid enough attention to caregivers' health," stresses Prof Chung. "Self-care intervention programmes should include depressive symptom management for caregivers."

A pilot study conducted by Prof Chung found benefits in a more holistic approach incorporating stress management and self-care management for caregivers. "Cognitive behavioural therapy has shown promise, as have interventions that teach caregivers how to better manage patients' and their own emotions", she concluded.

Paris, France - 01 Sept 2019: Illicit performance-enhancing steroids can cause the heart to thicken and reduce its ability to function, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

Use of anabolic-androgenic steroids (AAS) has long been feared to have hazardous cardiovascular effects, but only recently has this been demonstrated in studies.

The study presented today examined the effects of long-term AAS use on left ventricular systolic function by assessing the size, thickness, mass and function of the heart in male weightlifters.

"Our study found that illicit steroid use is associated with a number of worrying effects on the heart. We demonstrated that AAS-using weightlifters have a thicker heart muscle and reduced ability to contract the ventricular chambers of the heart during a cardiac cycle," said Rang Abdullah, a third-year medical student at the University of Oslo, Norway.

"Having a heart that doesn't contract the way it should is associated with higher mortality," he added.

The study is part of a large multidisciplinary study on AAS use, which includes studies on brain imaging, cognitive, psychological, and other cardiovascular functions.

Study authors recruited 100 male weightlifters - 58 with more than a year of cumulative AAS use and 42 who do not use steroids - with no difference in age or BMI between the two groups.

The size, thickness, mass and function of the heart were measured with echocardiography, which uses sound waves to monitor heart and valve function, and ejection fraction, which measures how much blood the left ventricle pumps out with each contraction.

AAS-using weightlifters had a thicker heart muscle - on average, a 2 mm thicker interventricular septum, which is the wall separating the lower chambers of the heart. The left ventricular posterior wall was also, on average, 1.2 mm thicker in the steroid group.

The steroid group also showed reduced ability to contract the ventricular chambers of the heart during a cardiac cycle. Both ejection fraction and ventricular global strain, a new method to assess systolic function, were decreased in AAS-exposed weightlifters as compared to the non-steroid group, 49% vs. 53%, on average, and -15.6% vs. -18.3%.

Abdullah said, surprisingly, only a minority of steroid users in the sample had experienced cardiovascular symptoms related to their AAS use.

"Continuous, long-term use of AAS might prove to be a 'silent killer' but it is too early to tell," he said.

"There are many case-studies out there on AAS-using weightlifters who end up dead or hospitalised from a heart attack or life-threatening cardiac arrhythmias. This is why prospective observational trials on this subject are so desperately needed," he concluded.

WASHINGTON (Sept. 1, 2019)--Despite its portrayal as a network that "champions free speech," users of the social media platform Gab display more extreme social hierarchy and elitism when compared to Twitter users, according to a new study published in the September edition of the online journal "First Monday." Researchers found a small number of Gab users hold a large amount of influence, sharing more homogeneous content than Twitter, some of which was associated with state-sponsored propaganda.

The ongoing debate surrounding content regulation and the censorship of social media platforms has grown increasingly contentious in recent years. Despite this, little research has been done to understand the impact regulation might have on online behaviors.

Researchers at the George Washington University, Northeastern Illinois University and Johns Hopkins University set out to examine the impact of content regulation by comparing two social media networks with similar technical structures, Twitter, a popular platform that occasionally removes content in violation of its terms of service, and Gab, a completely unregulated platform that advertises itself as championing "free speech, individual liberty and the free flow of information online." The results suggested that the complete absence of regulation did not lead to more fair and inclusive discourse, nor to a free marketplace of ideas.

"Governments and social media platforms around the world are trying to figure out how they can promote a free exchange of ideas without censoring content," David Broniatowski, an associate professor in GW's School of Engineering and Applied Science, said. "When compared to Gab, our results suggest that adherence to even relatively mild terms of service, such as Twitter's hateful conduct policy, may make a big difference in promoting the free exchange of ideas."

The team looked at millions of messages sent on each platform between August 2016 and February 2018 to determine who shared content and the types of content shared.

The researchers discovered that, despite its promotion of open and free discussion for all, a smaller numbers of users with substantial followings on Gab controlled a larger share of the content compared to Twitter. For example, most Gab users had less than five followers and did not post messages regularly, with 57% of the platform's approximately 150,000 users posting fewer than four messages during the 18-month study. In contrast, only 3,000 users posted more than 1,000 messages, thus creating a more extreme social hierarchy.

"With the perceived crackdown of far-right conservative accounts by mainstream social media, you would expect the far right to flock to platforms without elite users, and where everyone can be heard," Mark Drezde, an associate professor of computer science at Johns Hopkins University, said. "Surprisingly, Gab seems to be primarily a place where a small number of well-connected users broadcast their message to a larger group who already share their views."

Turning to the types of content users post and share, the research team identified several popular topic areas discussed on each platform. It found Gab users' content to be more homogeneous, with political topics making up 56% of all messages sent, and race and religion also being popular topics of discussion. On Twitter, while political topics were popular, they only made up a small percentage of posts compared to other topics, which included pop culture, business and sports. The researchers discovered Gab users were more linguistically homogeneous as well, with 89% of all messages written in English.

As with Twitter, Gab users also looked to share information through external content, with 74% of the most commonly shared URL domains on Gab linking to news websites. While the researchers found these links mostly led to far-right news websites, they also observed links to websites associated with conspiracy theories and state-sponsored messaging from non-U.S. governments.

"Unfortunately, Gab's stated mission of totally free speech creates an environment in which significant hateful and divisive rhetoric flourishes and paradoxically impedes debate. As a platform, it ultimately promotes the kind of hate which culminated in the shooting at a Pittsburgh synagogue in October 2018 shortly after the shooter posted on Gab," William Adler, an associate professor of political science at Northeastern Illinois University, said.

Dr. Broniatowski and his colleagues noted the results from the study, "Elites and Foreign Actors Among the Alt-Right: The Gab Social Media Platform," have implications for attempts by governments to regulate social media platforms and for platforms to regulate their own content. The researchers suggest possible options for regulation, including redesigning algorithms to ensure that a small number of voices do not dominate the debate, and removing the possibility for automated content to overwhelm genuine content by requiring users to provide evidence of whether their account is operated by humans or bots.

Paris, France - 1 Sept 2019: Home-based and personalised education keeps patients with atrial fibrillation out of hospital, according to late breaking results from the HELP-AF study presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

Principal investigator Professor Prash Sanders of the University of Adelaide, Australia said: "The initiative was designed to empower patients to understand and take control of their atrial fibrillation, i.e. to improve self-management. Its success in stopping hospital admissions has enormous implications for the delivery of care in atrial fibrillation. As healthcare costs grow due to hospitalisations, such programmes are essential."

Over the last few decades, the number of people living with atrial fibrillation around the world has grown exponentially. This is because populations are getting older and acquiring lifestyle related conditions such as high blood pressure, obesity, sleep apnoea and diabetes that raise the risk of developing atrial fibrillation. Atrial fibrillation is now a more common cause of presenting to hospital than heart failure or heart attacks.

Prof Sanders said: "Some hospital admissions for atrial fibrillation are likely preventable through better education of those living with the condition. We believed that involving patients in their care, helping them understand their condition, and providing tools to manage it might avoid hospitalisations. This led us to do the HELP-AF study, which looked at the impact of home-based education on hospitalisation and quality of life."(2)

The study enrolled 627 patients with atrial fibrillation presenting to the emergency department of six hospitals in Adelaide, South Australia. Patients were randomised to the HELP-AF programme or usual care. Patients were approached to participate within two months of their emergency department presentation.

Patients allocated to the intervention received two educational home visits by a nurse or pharmacist: one approximately two weeks after enrolment and the second six weeks after that. Patients received a booklet for future reference. Education was delivered in a structured way and focused around four messages: 1) management of future atrial fibrillation episodes; 2) importance of medicines to manage symptoms and stroke risk; 3) appropriate use of stroke prevention medicines; and 4) role of lifestyle modification. Messages were personalised to target areas where behaviour change was needed.

Patients were followed up for two years for the primary endpoints of all-cause unplanned hospitalisation and health-related quality of life evaluated by the 36-Item Short Form Health Survey (SF-36).

At 24 months, total unplanned hospitalisations were 233 in the HELP-AF group and 323 with usual care with an incident rate ratio of 0.74 (95% confidence interval 0.62-0.89; p=0.001). After multivariable adjustment, the intervention reduced total unplanned hospitalisations by 26%, atrial fibrillation related hospitalisations by 31%, and other cardiovascular hospitalisations by 49%, while having no impact on non-cardiac hospitalisations.

There was no difference in health-related quality of life using the SF-36 survey, which is a generic health survey. Using a more specific questionnaire, the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT), there was gradual improvement in quality of life measures over time in both groups. This reached significance at 24 months in two subcategories of the "Symptoms" and "Treatment Concern" domains, in favour of the intervention.

Prof Sanders said several components of the scheme likely contributed to the fall in hospitalisations:

Education was delivered in the comfort of the patient's home using language they could understand and focusing on areas important to them.

Patients received a booklet as an ongoing reminder of the four messages.

The material listed questions patients could discuss with their physician to help manage their disease.

The booklet outlined the "REST plan" for patients to follow during atrial fibrillation episodes to avoid going to hospital. This included developing an emergency management plan with their physician and a dedicated telephone service for advice from a cardiologist.

Prof Sanders said: "The study shows that education delivered in a structured and individualised way within the patient's home has a dramatic impact not only on hospitalisations for atrial fibrillation but on all cardiovascular hospitalisations."

The design of the intervention makes it easy to replicate in other countries and settings, noted Prof Sanders. Nurses and pharmacists were trained in a structured educational visiting approach and upskilled in atrial fibrillation management. "It was personalised education using a structured delivery method," he said.

In this study, the research team conducted a large-scale epigenome-wide association study of LTL using seven large cohorts the Framingham Heart Study, the Jackson Heart Study, the Womens Health Initiative, the Bogalusa Heart Study, the Lothian Birth Cohorts of 1921 and 1936, and the Longitudinal Study of Aging Danish Twins.

Dr. Steve Horvath from the Department of Human Genetics, David Geffen School of Medicine at the University of California Los Angeles in Los Angeles, CA 90095, USA as well as the Department of Biostatistics, Fielding School of Public Health, at the University of California Los Angeles in Los Angeles, CA 90095, USA said, "Telomeres are the (TTAGGG)n repeats located at the ends of each chromosome."

Telomere length is reported to be shorter in leukocytes of men than women, but this sex difference may depend on the measurement method.

Further, leukocyte TL is significantly but weakly associated with atherosclerotic cardiovascular disease and exhibits a complex U-shaped association with certain cancers: longer telomeres are associated with an increased risk of certain kinds of cancer.

High heritability estimates for LTL have been reported irrespective of the methods used for measuring LTL; reported heritability estimates are between 36% and 82% based on Southern blot, and between 51% and 76% based on qPCR.

Genome-wide association studies conducted in large observational cohorts have identified 11 loci associated with LTL.

Previous studies have explored the association between DNAm and LTL, but these studies were somewhat limited due to moderate sample sizes or the focus on specific regions in the genome.

The Horvath research team concluded, "We identified over 800 genome-wide significant Cp G sites that are located in or near genes with links to circadian rhythm, blood coagulation and wound healing. These findings link two hallmarks of aging: epigenetic changes and telomere biology."

The arrival of refugees in eastern German communities has had no effect on local residents' voting behavior or on their attitudes toward immigration, finds a new study of citizens in more than 200 regional municipalities.

"Our analysis shows widespread anti-immigrant sentiments after the arrival of refugees in 2015, but these are unaffected by the presence of refugees in these citizens' hometowns," explains Delia Baldassarri, a sociologist at New York University and one of the researchers. "This is likely because those in this part of Germany are more focused on the wider impact of immigration on society rather than on local impact. Their personal experience with refugees, then, is relatively unimportant to their views and voting behavior."

The research, co-authored with Max Schaub of the Berlin Social Science Center and Johanna Gereke of the Mannheim Center for European Social Research, was presented at the American Political Science Association's annual meeting in Washington, DC.

The study examined communities in eastern Germany that had few immigrants prior to 2015, but faced a large influx of refugees from conflict-torn countries such as Afghanistan, Iraq, and Syria beginning that year.

Baldassarri and her colleagues sought to understand if the inhabitants of these communities became more friendly towards immigrants or, conversely, rejected them.

The question is a significant one in light of political changes in Germany. Between the beginning of the refugee crisis in 2015 and the team's data collection in 2018, support for Germany's anti-immigrant party Alternative for Germany (AfD) surged from 6 percent to 16 percent nationwide and from 7 percent to 27 percent in eastern Germany.

These developments raise questions regarding the impact of refugees on German politics: How much of this shift can be attributed to the arrival of immigrants in people's hometowns? And, more specifically, do those Germans exposed to refugees in their municipality show political attitudes and behavior that are different from those without local exposure?

To address this, the researchers examined electoral records and conducted surveys with 1,320 German citizens from 236 municipalities in the states of Mecklenburg-Vorpommern, Sachsen-Anhalt, Brandenburg, Thüringen, and Sachsen. Half of these municipalities received refugees beginning in 2015 (a treatment community) and half did not (a control community), but all of them had an immigrant population of less than 1.5 percent before 2015. This allowed the researchers to compare analogous towns--with an average population of approximately 3,000--with measurable differences in exposure to refugees in their communities.

Crucially, in a study survey, the perceived number of refugees in the participants' home communities was much higher in the treatment towns than in the control towns, indicating that individuals in the treatment areas are aware that their municipality has received refugees.

Overall, the study's measurements showed no significant changes between the treatment community, which experienced the arrival of refugees, and the control community, which did not:

* An analysis of voting behavior in the 2013 and 2017 elections showed no meaningful differences between treatment and control municipalities in the share of votes for the AfD or any other party (e.g., Christian Democratic Union, Social Democratic Party). Even though support for the AfD increased dramatically from 2013 to 2017, it did so at the same rate in both communities. Thus, the presence of refugees in one's community appears to have had no role in affecting vote change between the 2013 and 2017 elections.

* Overall, the study's survey (conducted in the period between March and June 2018) showed notable support for right-wing positions and parties--for example, 36 percent supported the statement that foreigners only come to Germany to exploit the welfare state and 34 percent supported the idea that child support should only be given to native Germans. However, the differences in these views between the treatment and control communities were insignificant.

"Our work does not show that the arrival of refugees, in general, has no effect on natives' attitudes and behavior," explains Baldassarri. "Undoubtedly, consensus for right-wing parties in eastern Germany has dramatically increased partly because of the refugees' arrival. Rather, this study shows that the physical presence of refugees in a municipality does not affect local citizens' vote and political attitudes on immigration."

Paris, France - 31 Aug 2019: Bleeding during the first six months after discharge from hospital for a heart attack is linked with a subsequent cancer diagnosis, according to research presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

"Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack," said study author Isabel Munoz Pousa of Alvaro Cunqueiro Hospital, Pontevedra, Spain. "Particularly if the bleeding is of gastrointestinal, pulmonary or genitourinary origin, without any obvious reason, and occurs in the first six months. If the cause is cancer, early detection can improve prognosis."

Following discharge for an acute coronary syndrome (heart attack or unstable angina), patients are typically treated with dual antiplatelet therapy for around one year. This treatment inhibits the formation of blood clots but raises the risk of bleeding. Previous research has suggested that post-discharge bleeding may have negative consequences. This study examined its association with a new diagnosis of cancer.

The researchers retrospectively reviewed the hospital records of 3,644 acute coronary syndrome patients discharged with dual antiplatelet therapy from Alvaro Cunqueiro Hospital. Patients were followed-up for a median of 56.2 months for bleeding events and cancer. The researchers analysed associations between bleeding and the absolute risk of a new cancer diagnosis.

Bleeding occurred in 1,215 patients (33%) during follow-up and 227 patients (6%) had a new diagnosis of cancer. After adjustment for factors known to influence bleeding or cancer, post-discharge bleeding was associated with a threefold higher risk of new cancer diagnosis. The median time from bleeding to cancer was 4.6 months. The link with cancer increased as the severity of bleeding worsened.

Spontaneous bleeding with no apparent cause was linked with a four times higher risk of cancer diagnosis while there was no relation with bleeding due to trauma such as injury or bladder catheterisation.

Regarding the location, blood in the faeces was associated with a nearly fourfold risk of cancer diagnosis, while coughing up blood or blood in the urine were linked with four and eight-times greater risks, respectively.

There was a relationship between bleeding and cancer regardless of whether patients were still on dual antiplatelet therapy or not.

Ms Munoz Pousa said: "Most of the bleeding episodes in the study were mild. The bleeding events more strongly related with a new cancer diagnosis were severe haemorrhages of unknown cause requiring surgery - for example digestive bleeding needing endoscopic treatment. We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual antiplatelet therapy or not."

She added: "A possible explanation is that there is a pre-existing subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack. This hypothesis needs to be tested and patients should ensure they take antiplatelets as prescribed to avoid having another heart attack."

Paris, France - 31 Aug 2019: The European Society of Cardiology (ESC) Guidelines on acute pulmonary embolism are published online today in European Heart Journal(1), and on the ESC website.(2) They were developed in collaboration with the European Respiratory Society (ERS).

Acute pulmonary embolism is the third most common cause of cardiovascular death in Europe, after heart attack and stroke, contributing to more than 350,000 deaths each year. A blood clot (thrombus) in a deep vein, usually in the legs, is dislodged and travels to the lungs where it blocks one or more vessels. This typically occurs if the vein wall is damaged, blood flow is too slow, or the blood becomes too thick.

Major surgery such as knee or hip replacement, serious injury, prolonged bed rest and cancer are common risk factors for acute pulmonary embolism. It can also happen after long travel and in women who are pregnant or taking the oral contraceptive pill.

"Symptoms including shortness of breath and chest pain resemble other diseases so the diagnosis is often missed, or the severity of the situation is underestimated, and many patients die before getting appropriate therapy," said Professor Stavros Konstantinides, Chairperson of the guidelines Task Force and medical director, Centre for Thrombosis and Haemostasis, Johannes Gutenberg University Mainz, Germany.

The guidelines clarify how to diagnose acute pulmonary embolism step by step. The process begins with clinical suspicion based on symptoms combined with blood tests (D-dimers). Depending on the severity and urgency of the scenario, a computed tomography (CT) scan may be used to visualise the lung vessels, or cardiac ultrasound to look at the heart chambers.

A new table shows how CT scans and lung scans compare in their ability to diagnose or exclude pulmonary embolism, and how much radiation the patient receives with each of these tests.

"The aim is to get to the diagnosis as reliably and quickly as possible, in order to start lifesaving therapy and prevent other clots from reaching the lungs," said Professor Guy Meyer, Co?Chairperson of the guidelines Task Force and respiratory medicine physician, Hôpital Européen Georges-Pompidou, Paris, France.

Anticoagulant drugs (blood thinners) help the body dissolve clots and reopen the blocked vessels. If the patient is in shock and about to collapse, the clot must be removed immediately, and this can be achieved using thrombolytic drugs (clot busters), catheters, or surgery.

The guidelines recommend how to judge the severity of pulmonary embolism based on a combination of clinical, imaging and laboratory results. This will dictate whether blood thinners alone are sufficient or if clot busters, a catheter intervention, or surgical removal is necessary. There is new advice on how to distinguish, in the CT scan, fresh thrombi in the lungs from chronic obstructions due to a disease called chronic thromboembolic pulmonary hypertension (CTEPH), which requires a different type of therapy.

Also new is the guidance on which drugs to use in a patient with pulmonary embolism and cancer. Patients with cancer have a high risk of recurrence, and indefinite anticoagulation is often necessary.

Acute pulmonary embolism is a leading cause of maternal death in high-income countries, but diagnosis can be challenging because symptoms often overlap with those of normal pregnancy. Novel recommendations outline how to diagnose and treat pulmonary embolism in the pregnant patient.

Updated instructions state when it is safe to send patients home from the hospital. Some have a lifelong increased risk of another event. Anticoagulants are used to treat the acute episode and prevent recurrence but raise the risk of bleeding. The guidelines describe how to decide the duration of treatment. They also specify when and how (with which tools and tests) to follow patients, and which findings suggest chronic disease (CTEPH) requiring diagnosis and treatment in an expert centre.

Last but not least, the 2019 ESC Guidelines endorse a multidisciplinary approach to pulmonary embolism after the acute phase and discharge of the patient. Teams should include physicians, appropriately qualified nurses, and other allied health professionals, aiming to ensure smooth transitions between hospital specialists and practitioners, optimised long term care and prevention of recurrence.

Advice for patients

Be aware of conditions that predispose to acute pulmonary embolism.

If you are at increased risk or have previously had pulmonary embolism or deep vein thrombosis, and are admitted to hospital for another disease, ask what is being done to prevent thrombosis.

If you have one or more risk factors for pulmonary embolism and feel shortness of breath, chest discomfort or chest pain, lightheaded or faint, call a doctor or ambulance immediately. Lie down and do not move around. Do not walk or drive to the hospital or physician's practice.

If you had an acute pulmonary embolism and are on blood thinners, when you are discharged from hospital ask when you need to see a doctor again. At the follow-up visit, report any bleeding and whether you have returned to normal or still have symptoms such as shortness of breath.

Paris, France - 31 Aug 2019: Low-dose aspirin does not prolong disability-free survival of healthy people over 70, even in those at the highest risk of cardiovascular disease. The late breaking results of the ASPREE trial are presented today at ESC Congress 2019 together with the World Congress of Cardiology.(1)

On behalf of the ASPREE Investigators, Professor Christopher Reid of Curtin University, Perth, Australia said: "An ever-increasing number of people reach the age of 70 without overt cardiovascular disease (CVD). This analysis suggests that improved risk prediction methods are needed to identify those who could benefit from daily low-dose aspirin."

European guidelines on the prevention of CVD do not recommend aspirin for individuals free from CVD due to the increased risk of major bleeding.(2) This advice was subsequently supported by results in moderate risk patients (ARRIVE),(3) diabetic patients (ASCEND),(4) and in people over 70 (ASPREE) which demonstrated that modest reductions in CVD risk were outweighed by the increased bleeding hazard.(5)

The primary finding from the ASPREE randomised trial was that in people aged 70 years or over with no known CVD, there was no effect of 100 mg of daily aspirin on the composite primary endpoint of disability-free survival (defined as those not reaching a primary endpoint of dementia or persistent physical disability or death).(6) The primary endpoint was chosen to reflect the reasons for prescribing a preventive drug in an otherwise healthy elderly population.

This analysis examined whether the results for the primary endpoint of disability-free survival might vary by the baseline level of CVD risk. Analyses were also conducted for the secondary endpoints of all-cause mortality, major haemorrhage, and prevention of CVD (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalisation for heart failure).

The investigators calculated ten-year CVD risk probabilities at baseline for the 19,114 ASPREE participants using the Framingham score (up to 75 years) and the atherosclerotic cardiovascular disease (ASCVD) pooled cohort risk equations (up to 79 years) and divided them into thirds. As there are no CVD risk scores available beyond the age ranges specified in the equations, they also classified participants according to the presence of 0 to 1, 2 to 3, or more than 3 CVD risk factors. Overall rates of disability-free survival, mortality, major bleeding and CVD were examined for each risk group and outcomes were compared for those treated with aspirin or placebo.

For participants in the lowest third of CVD risk, by both Framingham and ASCVD scores, there was no disability-free survival or cardiovascular benefit from aspirin. This group also had the highest likelihood of bleeding.

In contrast, those in the highest third of CVD risk, by both Framingham and ASCVD scores, had significantly lower CVD event rates on aspirin with similar rates of bleeding. Hazard ratios for CVD reduction with aspirin version placebo were 0.72 (95% confidence interval [CI] 0.54-0.95) for the group classified as high risk by the Framingham score and 0.75 (95% CI 0.58-0.97) for those defined as high risk by the ASCVD equations.

However, this reduction in CVD did not translate to a significantly improved disability-free survival. Hazard ratios for disability-free survival with aspirin versus placebo were 0.86 (95% CI 0.62-1.20) for the group designated high risk by the Framingham score and 0.89 (95% CI 0.62-1.28) for those considered high risk by the ASCVD equations.

Prof Reid said: "The findings emphasise that the risk-benefit trade-off for aspirin use in healthy older men and women varies across levels of cardiovascular risk. It also indicates that the reduction in CVD events in the highest risk groups using current stratification methods does not identify individuals in whom this advantage translates into longer disability-free survival."

New ways to identify groups at increased CVD risk, beyond the use of conventional risk factors and current prediction models, will be investigated in the ASPREE longitudinal follow-up study. Genetic and biomarker information will be included from the ASPREE biobank.

Prof Reid concluded: "Based on the results of the main ASPREE trial, daily low-dose aspirin cannot be recommended in healthy people over 70 - even in those at the greatest CVD risk. Today's analysis indicates that more refined methods are needed to pinpoint a subgroup who might gain from preventive therapy."

TORONTO, August 31, 2019 - A new study from St. Michael's Hospital in Toronto, Canada shed lights on how a class of medications that help regulate blood sugar for patients with Type 2 diabetes can also protect against heart disease.

The findings from the EMPA-HEART CardioLink-6 Trial, presented today at the ESC Congress 2019, organized by the European Society of Cardiology, and simultaneously published in Cell Metabolism, focus on the effect of a diabetes medication - empagliflozin - on cell repair in blood vessels and the resulting risks of heart disease. Empagliflozin is a medication that falls under a category of drugs called SGLT2 inhibitors, which lower blood sugar.

The research suggests that circulating progenitor cells - which are found in bone marrow and play a role in heart health - along with inflammatory cells are regulated with this diabetes medication. For patients who have diabetes and are at risk of heart disease, such medications may provide heart protection by relieving damaged cells that would otherwise perpetuate heart disease by causing faulty vessel repair.

"We have seen large-scale clinical trials giving us clear evidence that SGLT2 inhibitors can also protect our patients who have diabetes from heart disease," said Dr. Subodh Verma, a cardiac surgeon and scientist at the Keenan Research Centre for Biomedical Science (KRCBS) of St. Michael's Hospital. "Before our study, it wasn't known why this was happening."

According to the World Health Organization, an estimated 1.6 million deaths were caused by diabetes in 2016. It is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. Heart disease is a major concern for people with diabetes as they often have compromised blood vessel repair, making them more susceptible to cardiovascular issues.

The team at St. Michael's collaborated with Dr. David Hess, an associate professor at Western University's Schulich School of Medicine & Dentistry and a scientist at Robarts Research Institute. Dr. Hess is an expert in the identification and quantification of blood vessel progenitor cells. Using blood samples from the EMPA-HEART CardioLink-6 Trial, Dr. Hess was able to show that in diabetes, regenerative progenitor cells were reduced. In patients who took empagliflozin, however, these progenitor cells were restored.

"We found that in people with diabetes, not only were beneficial progenitor cells increased but we saw indications of reduced inflammation and oxidative stress, which can also contribute to cardiovascular disease," said Dr. Hess.

For patients with diabetes, this is an important step forward to reduce their risk of heart disease, Dr. Verma said.

The team at St. Michael's included: Dr. Verma; Dr. Rotstein; Dr. David Mazer, an anesthesiologist and scientist at the KRCBS; Dr. Mohammed Al-Omran, a heart surgeon and scientist at the KRCBS; Dr. Kim Connelly, a cardiologist and scientist at the KRCBS; Dr. Andrew Yan, a cardiologist; and Dr. Lawrence Leiter, an endocrinologist and scientist at the Li Ka Shing Knowledge Institute.

The researchers say these novel findings may provide the basis for new therapies for patients who have heart disease complicated by diabetes.

Older people who have never taken part in sustained exercise programmes have the same ability to build muscle mass as highly trained master athletes of a similar age, according to new research at the University of Birmingham.

The research shows that even those who are entirely unaccustomed to exercise can benefit from resistance exercises such as weight training.

In the study, published in Frontiers in Physiology, researchers in the University of Birmingham's School of Sport and Exercise Science compared muscle-building ability in two groups of older men. The first group were classed as 'master athletes' - people in their 70s and 80s who are lifelong exercisers and still competing at top levels in their sport. In the second were healthy individuals of a similar age, who had never participated in structured exercise programmes.

Each participant was given an isotope tracer, in the form of a drink of 'heavy' water, and then took part in a single bout of exercise, involving weight training on an exercise machine. The researchers took muscle biopsies from participants in the 48 hour periods just before and just after the exercise, and examined these to look for signs of how the muscles were responding to the exercise. The isotope tracer showed how proteins were developing within the muscle.

The researchers had expected that the master athletes would have an increased ability to build muscle due to their superior levels of fitness over a prolonged period of time. In fact, the results showed that both groups had an equal capacity to build muscle in response to exercise.

"Our study clearly shows that it doesn't matter if you haven't been a regular exerciser throughout your life, you can still derive benefit from exercise whenever you start," says lead researcher, Dr Leigh Breen. "Obviously a long term commitment to good health and exercise is the best approach to achieve whole-body health, but even starting later on in life will help delay age-related frailty and muscle weakness.

"Current public health advice on strength training for older people is often quite vague. What's needed is more specific guidance on how individuals can improve their muscle strength, even outside of a gym-setting through activities undertaken in their homes - activities such as gardening, walking up and down stairs, or lifting up a shopping bag can all help if undertaken as part of a regular exercise regime."

Artificial intelligence has been used to analyse high-resolution digital x-ray images of the world famous Ghent Altarpiece, as part of an investigative project led by UCL.

The finding is expected to improve our understanding of art masterpieces and provide new opportunities for art investigation, conservation and presentation.

Researchers from the National Gallery, Duke University and UCL worked with technical images acquired from the brothers Van Eyck's Ghent Altarpiece, a large and complex 15th-century altarpiece in St Bavo's Cathedral, Belgium.

The paper, 'Artificial Intelligence for Art Investigation: Meeting the Challenge of Separating X-ray Images of the Ghent Altarpiece', demonstrates how academics used a newly developed algorithm to study mixed x-ray images containing features from the front and back of the painting's double-sided panels, which scientists have deconstructed into two clear images.

These images are part of a comprehensive set of high resolution pictures acquired using different imaging techniques as part of the altarpiece's on-going conservation by the Royal Institute for Cultural Heritage (KIK-IRPA), providing a wealth of data to interrogate and interpret.

"This approach demonstrates that artificial intelligence-oriented techniques -- powered by deep learning -- can be used to potentially solve challenges arising in art investigation," commented lead academic Dr Miguel Rodrigues (UCL Electronic & Electrical Engineering).

"We'd like to see the impact that the development of similar AI-oriented approaches will have on our ability to reveal other hidden features in a painting, such as earlier concealed designs," he continued.

The Ghent Altarpiece originally consisted of twelve panels. The two wing sections, each originally made of four panels - painted on both sides - could be opened fully on feast days to reveal the four central panels. The painting has survived near destruction over the centuries and seizure by the Nazis in the 1940s.

X-ray images are a valuable tool for examining and restoring paintings as they can help to establish a piece's condition and provide insights into an artist's technique.

However the penetrating nature of x-rays means that everything in its path will contribute to the resulting image, which is informative but can produce images that are difficult to interpret. This is particularly true for panels painted on both sides, or where an artist has re-used a canvas.

By separating the complex x-ray images, the new algorithm enables art historians, conservators and heritage scientists to better understand Old Master paintings, and the information revealed can help experts when protecting and restoring delicate pieces.

Deep learning approaches are now being used to address challenges arising in other sectors including healthcare, fintech, defence and security.

Hélène Dubois, Head of the Conservation Project of the Ghent Altarpiece, Royal Institute for Cultural Heritage (KIK-IRPA) said: "The application of AI to x-ray image processing will provide very useful tools to decrypt complex technical images. The structural weaknesses of the wooden supports and of the ground and paint layers could be diagnosed with more precision.

"These images will also help to understand the brothers Van Eyck's techniques and the changes carried out in the course of the successive execution of this unique masterpiece. This new development of the use of the traditional x-ray has great potential for countless applications in conservation of irreplaceable works of art."