Body

PARAMUS, N.J. (December 1, 2020) - Octapharma USA will present its most recent rare bleeding disorders research initiatives during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, a virtual medical congress to be held December 5 - 8.

Three scientific posters will be presented during the ASH meeting that focus on investigative treatment options utilizing NUWIQ®, Antihemophilic Factor (Recombinant) Lyophilized Powder for Solution for Intravenous Injection and WILATE®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection.

"Octapharma is committed to advancing clinical research that will help enhance the lives of people with bleeding disorders," said Octapharma USA President Flemming Nielsen. "We look forward to sharing the latest research developments with the medical community."

Ellis J. Neufeld, MD, PhD, of St. Jude Children's Research Hospital, Memphis, Tenn., will provide oral and poster abstracts for "Long-Term Prophylaxis with Simoctocog Alfa for the Management of Hemophilia A: Immunogenicity, Efficacy, and Safety Results from the NuProtect PUP Extension Study." The research is focused on evaluating the risk of factor VIII (FVIII) inhibitor development in pediatric patients during FVIII treatment. Prophylaxis with FVIII is the gold standard approach for management of hemophilia A, and long-term bleed prevention remains the key goal for patients and clinicians. The NuProtect extension study assessed the long-term immunogenicity, hemostatic efficacy and tolerability of NUWIQ® in 48 pediatric patients. No children with severe hemophilia A developed FVIII inhibitors during the study. Principal investigators: Ri Liesner, MD, Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children, London, United Kingdom, and Dr. Neufeld.

Another poster is entitled "Use of a Von Willebrand Factor/Coagulation Factor VIII Complex for Treatment of Refractory Inherited Platelet Disorders." Inherited platelet disorders are recognized as an important cause of mild to severe bleeding in both children and adults. Treatment of platelet disorders is mainly supportive. Normal hemostasis requires von Willebrand factor (VWF) and FVIII to support platelet adhesion and aggregation at sites of vascular injury. Four patients with qualitative platelet disorders, three with delta storage pool deficiencies and one with Bernard-Soulier syndrome achieved clinically relevant bleeding resolution with WILATE®. Notably, these patients were refractory to other therapies. Principal investigator: Amber Federizo, APRN, FNP-BC, Hemostasis and Thrombosis Center of Nevada, Las Vegas, Nev.

"Design of the Von Willebrand Factor in Pregnancy (VIP) Study" is a description of planned VWF in pregnancy research. This study will provide a better understanding of post-partum hemorrhage in women with von Willebrand disease (VWD) relative to VWD diagnosis, VWF levels, and other laboratory assessments of VWF associated parameters. The study evaluates the effectiveness of WILATE® in targeting VWF/FVIII during delivery and the immediate 72-hour postpartum period. Principal investigator: Jill M. Johnsen, MD, Bloodworks Research Institute and Department of Medicine, University of Washington, both in Seattle, Wash.

For more information on the ASH annual meeting, please visit hematology.org.

AUGUSTA, Ga. (Dec.1, 2020) - Results of standard laboratory tests performed on adult outpatients to provide an overall picture of their health are fairly consistent between those with obesity and their leaner counterparts, investigators report.

The finding negates one rationale behind what's called the "obesity paradox," which is that people with obesity are known to be at increased risk for a host of health problems like diabetes and hypertension, but tend to do better with these conditions than their leaner peers, including when they get admitted to critical care for reasons like heart attack or stroke.

One thought was that patients with obesity end up in intensive care sooner because their laboratory results were already out of line with their thinner peers, and these acute health events push them higher, they report in The Journal of Applied Laboratory Medicine.

"People who have obesity also have more hypertension, they get more diabetes, they get more cerebrovascular events like stroke and more heart attacks, but when they have these problems they tend to do better than when thin people get them," says Dr. Gurmukh Singh, vice chair of the Medical College of Georgia Department of Pathology and the study's corresponding author.

"We thought maybe laboratory tests would help provide an explanation," Singh says. "But they didn't."

In fact, investigators found the only significantly different lab values between the outpatients with obesity and those of normal weight was that those with uncomplicated obesity had fairly consistently higher levels of triglycerides, a fat, or lipid, in the blood, that indicates risk for heart and other blood vessel disease, and lower levels of high density lipoprotein, or HDL, cholesterol, which is considered protective of cardiovascular disease. Low HDL and high triglycerides are both linked to higher risk of death from cardiovascular diseases like heart attack, heart failure and stroke.

While what their findings do mean is not completely clear, they could indicate, that often regardless of lab results, individuals with obesity are sent to intensive care sooner, perhaps because of an unconscious bias, Singh says.

Just why they tend to do better in intensive care remains a mystery, and became the focus of this study by MCG investigators who compared results from a common, comprehensive metabolic profile -- things like total cholesterol, blood glucose levels and indicators of the health of white and red blood cells -- on 522 adult outpatients at AU Medical Center, the adult hospital affiliated with MCG, who were either normal weight or varying degrees of overweight.

Patients who were chronically or acutely ill were not included during the one-month testing timeframe, and the investigators looked at four categories of body mass index, or BMI, a measure of body fat based on height and weight including: 18.5 to 25, considered normal weight; 25.1 to 30, considered overweight; 30.1 to 35 and greater than 35, both considered obese, by the National Heart, Lung and Blood Institute. They did not factor in whether fat was fairly evenly distributed across the body or if it was more concentrated in the abdomen and abdominal cavity, called visceral adiposity, which is considered more inflammatory and dangerous.

Their premise was that people with overweight or obesity would have higher or more abnormal baseline laboratory results than their leaner peers generally, and it would take a smaller pathologic insult -- like a heart attack or stroke -- to push their lab values to the point that merited critical care. In other words: they looked sicker quicker, got intensive care faster and their outcome looked better.

However their findings were inconsistent with that theory and "effectively rules out this explanation of the obesity paradox," they write.

Health care providers were not surveyed about their attitudes toward patients with obesity for the study, but Singh says there may be a bias, albeit an unconscious bias, that may result in people with obesity being admitted to intensive care sooner than their trimmer counterparts, potentially because they are generally considered more difficult to manage. That bias could create an artifact of better outcomes, he and his colleagues write, and constitute an actual reason for some of the obesity paradox.

Other theories are that people with obesity have greater fat reserve to see them through critical illness and that some of their "leaner" peers have actually lost a lot of weight because of illness so are really emaciated, not trim. For that reason, the investigators excluded individuals who had more than a 10% weight loss or gain in the prior three months.

Next steps might include a difficult study to manage: blinding health care providers to a patient's weight so only other health parameters, like objective lab values, are used to determine who gets admitted to intensive care and when, Singh says.

WHAT:
An experimental vaccine developed in Europe to prevent infection by Crimean-Congo hemorrhagic fever virus (CCHFV) has protected cynomolgus macaques in a new collaborative study from National Institutes of Health scientists. The animals received the DNA-based candidate vaccine through intramuscular injection immediately followed by electroporation--a process in development for human vaccines that helps cells absorb DNA. The study, published in Nature Microbiology, comes about three years after the same research group developed the macaque model for CCHFV. No specific treatments or vaccines for CCHFV exist.

Crimean-Congo hemorrhagic fever, first described in 1944, is spread primarily by the bite of Hyalomma ticks found in the Middle East, Asia, Africa and parts of Europe. The virus also can be transmitted to people by direct contact with infected fluids or tissue from people or certain livestock species. CCHFV infects up to 15,000 people annually, according to the World Health Organization. About 1 in 8 of those who are infected develop severe disease, which leads to about 500 deaths each year. CCHFV also is considered a possible agent of bioterrorism.

Scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) in Hamilton, Montana, tested the candidate vaccine on six cynomolgus macaques, each of which received three inoculations, followed by electroporation, at three-week intervals. No animals experienced significant adverse reactions upon vaccination. Through regular blood tests, the researchers confirmed that the candidate vaccine generated protective antibodies against the virus. They then infected the vaccinated animals with CCHFV and monitored them for clinical signs for six days, after which they looked for virus in their organs. Six control animals infected with CCHFV but not given the experimental vaccine showed signs of disease throughout the study. The vaccinated animals did not. Their blood tests remained largely unchanged with no indication of progressive virus infection and no virus shedding. Virus was nearly undetectable in their liver, kidneys, lungs and adrenal glands, all targets of CCHFV.

Collaborators at the Karolinska Institute in Sweden developed the candidate vaccine with colleagues from the Public Health Agency of Sweden, the National Veterinary Institute of Sweden, the Justus Liebig University in Germany and NIAID's Rocky Mountain Laboratories in Montana. The candidate vaccine uses two proteins from CCHFV to generate protection.

The researchers next plan to study if the vaccine candidate is effective with fewer than three doses and whether it offers long-term protection. They also plan to continue evaluating the use of electroporation to make vaccination more effective.

UNIVERSITY PARK, Pa. -- Having children doesn't just make you feel like you've aged overnight -- a new study led by Penn State researchers found that the number of times a person gives birth may also affect the body's physical aging process.

The researchers examined several different measures that represent how a person's body is aging and found that people who had few births -- or many -- seemed to have aged quicker than those who had given birth three or four times. However, these effects were found only after a person had gone through menopause.

"Our findings suggest that pregnancy and birth may contribute to the changing and dysregulation of several different physiological systems that may affect aging once a person is post-menopause," said Talia Shirazi, a doctoral candidate in biological anthropology at Penn State. "This is consistent with the metabolic, immunological, and endocrinological changes that occur in the body during pregnancy and lactation, as well as the various disease risks that are associated with pregnancy and reproductive investment more generally."

According to the researchers, pregnancy and breastfeeding use a large amount of the body's energy and can affect many of its systems, including immune function, metabolism, and blood pressure, among others. Additionally, people who have given birth are more likely to die from diabetes, kidney disease, and hypertension, among other conditions, than those who have not.

The researchers were curious about how the body balances these "costs of reproduction" and whether it affects how the body ages.

"We think there's something going on, some sort of trade-off, between aging and reproduction," Shirazi said. "This makes sense from an evolutionary biology point of view, because if you're spending energy in pregnancy and breastfeeding, you probably don't have as much energy to allocate towards things like physiological maintenance and defense."

For the study, the researchers used data on 4418 participants from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey. Data included information about reproductive health including the number of live births and whether they had gone through menopause or not.

The researchers measured biological aging in several ways based on nine biomarkers designed to assess metabolic health, kidney and liver function, anemia and red blood cell disorders, and immune function and inflammation.

"We wanted to look at measures that would help capture the age and functioning of the body's major organ systems, instead of looking at aging at the cellular level," said Waylon Hastings, postdoctoral researcher at Penn State. "When we think about pregnancy, we don't think about changes to individual cells but instead about how the immune system or metabolism changes, for example."

The researchers found a "U?shaped relationship" between the number of live births and accelerated biological aging. Those reporting zero or few live births, or reporting many live births, had markers of quicker biological aging than those who reported three or four live births. This was true even when controlling for chronological age, lifestyle, and other health?related and demographic factors.

Shirazi said that because the data was taken at one point in time, it's not currently possible to know what caused these associations. But she said one possible explanation for the findings -- recently published in Scientific Reports -- is the presence, or lack, of ovarian hormones in post-menopausal people.

"Previous research has found that generally, ovarian hormones are protective against some cellular level processes that might accelerate aging," Shirazi said. "So it's possible that in pre-menopausal women the effect of hormones are buffering the potential negative effect of pregnancy and reproduction on biological age acceleration. And then perhaps when the hormones are gone, the effects can show themselves."

Hastings said the study also suggests that additional research can be done to understand the processes that may be involved in the connection between aging and having children, as well as how these processes work over time.

"This transition into menopause, and female reproductive health in general, is very much under researched and not as well understood as it should be at this time," Hastings said. "So if we can see that there are these changes in aging as a function of reproduction and menopause, and we don't have a great explanation for why, then that's a sign we should investigate this more."

BOSTON - During the early days of the COVID-19 pandemic in New England, emergency department visits for medical emergencies - including psychiatric problems, trauma and heart attacks - declined by nearly a third, raising concerns among clinicians that critically ill patients were not seeking the care they needed for fear of coronavirus infection.

Comparing emergency department (ED) visits in two major urban hospitals and three community hospitals in the Mass General Brigham system for the months of March and April 2020 with the same period in 2019, Joshua J. Baugh, MD, MPP, Sayon Dutta, MD, MPH, and colleagues in the Department of Emergency Medicine at Massachusetts General Hospital (MGH) found that ED volumes - the total number of patients treated - declined by 30.9% from one year to the next.

"Our health system experienced decreases in nearly all non-COVID-19 conditions presenting to EDs during the initial phase of the pandemic, including those requiring specialty consultation and urgent inpatient procedures. Findings have implications for both public health and health system planning," Baugh and colleagues wrote in a study in the American Journal of Emergency Medicine.

"While more people with less serious conditions may have stayed away from the emergency department, many cases that we would not have expected to decrease went down as well," Baugh says. "For example, people requiring catheterization of their hearts for potential heart emergencies, people requiring appendectomies for appendicitis, people requiring consultation for an acute psychiatric episode - across the board we saw that patients with other conditions weren't coming in at the rate that they usually do."

As was widely reported at the time, some patients who might otherwise have sought care for non-emergency conditions opted not to go to a hospital out of fear of contracting COVID-19 during the first surge of the pandemic, and some may have sought care at primary care practices or urgent care clinics.

"Some of the changes we saw may have been attributable to reductions in risk from lockdowns, people driving less, and being outside less, but we don't think that lifestyle changes adequately account for the full effect that we saw," says Baugh.

"Obviously, we saw many more patients with COVID-19 who otherwise wouldn't have been there," Dutta adds, "and a lot of the resources that those patients needed were available because those other patients did not show up. So this expectation that COVID-19 would add to the overall hospital volume or emergency department volume didn't turn out to be true."

The retrospective study included data on all ED patients at five hospitals in the Mass General Brigham health system (formerly Partners HealthCare). The hospitals included MGH and Brigham and Women's Hospital, both Harvard-affiliated quaternary-care referral hospitals with designated centers of excellence for emergency care of patients with trauma, heart attacks and strokes. The three other hospitals are community-based centers that included one that is a designated level-three trauma center, heart attack center and stroke center, and two others that are designated stroke centers.

The investigators drew on electronic health records for data on patient demographics, Emergency Severity Index, primary diagnosis in the ED, bedside procedures performed, subspecialty consultations requested, and related procedures occurring during each patient's hospital stay.

For Evie Junior, living with sickle cell disease has been like running a marathon.

"But it's a marathon where as you keep going, the trail gets rockier and then you lose your shoes," the 27-year-old said. "It gets harder as you get older. Things start to fail and all you can think about is how much worse it's going to get down the road."

In sickle cell disease, a genetic mutation causes the blood-forming stem cells -- which give rise to all blood and immune cells -- to produce hard, sickle-shaped red blood cells. These misshapen cells die early, leaving an insufficient number of red blood cells to carry oxygen throughout the body. Because of their sickle shape, these cells also get stuck in blood vessels, blocking blood flow and resulting in excruciating bouts of pain that come on with no warning and can leave patients hospitalized for days.

The disease affects 100,000 people in the United States and millions around the world, the majority of whom are of African or Hispanic descent. It can ultimately lead to strokes, organ damage and early death.

As a child growing up in the Bronx, New York, Junior had to have his gall bladder and spleen removed due to complications from the disease, but he refused to let his condition limit him. He played football, basketball and baseball during the day, even though on some nights he experienced pain crises so severe he couldn't walk.

"It was just really routine if I had a sickle cell crisis," he said. "Going to the emergency room, staying in the hospital, coming out in a few days and then getting back to normal life."

'I want to create a better future'

When he was 24 and living in Portland, Oregon, Junior began working as an emergency medical technician. He adopted the same mentality -- trying to treat his pain episodes the best he could, and hoping they would resolve overnight so he could get back to work. Around that time, though, the crises became harder to manage. He developed pericarditis, an inflammation in the layers of tissue around his heart, and needed six weeks to recover.

"The big worry with sickle cell disease is that you're going to die young from some type of complications or damage to your organs," he said. "In the last couple of years, I've been seeing that slowly happen to me and I can only suspect that it's going to keep getting worse. I want to create a better future for myself."

In July 2019, in pursuit of that future, Junior enrolled in a clinical trial for an experimental stem cell gene therapy for sickle cell disease. The study is led by UCLA Broad Stem Cell Research Center physician-scientists Dr. Donald Kohn and Dr. Gary Schiller and funded by the California Institute for Regenerative Medicine.

The therapy, developed by Kohn over the past 10 years, is intended to correct the mutation in patients' blood-forming stem cells to allow them to produce healthy red blood cells. Kohn has already applied the same concept to successfully treat several immune system deficiencies, including a cure for a form of severe combined immune deficiency, also known as bubble baby disease.

But sickle cell disease has proven more difficult to treat with gene therapy than those other conditions. Junior volunteered for the trial knowing there was a chance the therapy wouldn't cure him.

"Even if it doesn't work for me, I'm hoping that it can be a cure later down the road for millions of people," he said.

In July 2020, Junior received an infusion of his own blood-forming stem cells that had been genetically modified to overcome the mutation that causes his disease.

"The goal of this treatment is to give him a future, let him plan for college, family or whatever he wants without worrying about getting hospitalized because of another pain crisis," said Kohn, a distinguished professor of microbiology, immunology and molecular genetics, pediatrics, and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Reason for optimism

Three months after his treatment, blood tests indicated that 70% of Junior's blood stem cells had the new corrected gene. Kohn and Schiller estimate that even a 20% correction would be enough to prevent future sickle cell complications. Junior said he hasn't had a pain crisis since undergoing the treatment and he has more energy and feels out of breath less often.

"I noticed a big difference in my cardiovascular endurance in general -- even going for a light jog with my dogs, I could feel it," he said.

Junior and his doctors are cautiously optimistic about the results.

"It's too early to declare victory, but it's looking quite promising at this point," Kohn said. "Once we're at six months to a year, if it looks like it does now, I'll feel very comfortable that he's likely to have a permanent benefit."

After a lifetime of dealing with the unwelcome surprises of the disease, Junior is even more cautious than his doctors. But as the weeks pass, he's slowly allowing a glimmer of hope that he could soon be someone who used to have sickle cell disease. For him, that hope feels like "a burst of happiness" that's followed by thoughts of all the things he could do with a healthy future: pursue his dream of becoming a firefighter, get married and start a family.

"I want to be present in my kids' lives, so I've always said I'm not going to have kids unless I can get this cured," he said. "But if this works, it means I could start a family one day."

Decision-makers are failing to harness young people's potential to help shape pandemic responses, according to a major study that features the views of young people from around the world.

The report, titled: To lockdown and back: young people's lived experience of the COVID-19 pandemic reveals the impact of the virus' first wave on 14-to-18-year-olds from seven countries, including the UK, from the perspectives of young people.

The study, which includes the expertise of the University's Professor Barry Percy-Smith and researcher Dr Leanne Monchuk, is the initial report from the 18-month Growing up Under COVID-19 project.

Funded by the Nuffield Foundation and conducted with the independent research institute Ecorys, the study explores how young people experience the crisis and outlines how to promote their rights and wellbeing during and after the pandemic.

As well as arguing that their experiences could drive more inclusive, democratic COVID-19 approaches, the report shows their rights have been marginalised through lack of access to quality education, healthcare, and other services.

The international study says that political, public and media discourses feature young people as 'victims' of educational upheaval or rule-breaking 'villains'. Yet this population is overlooked in decisions about how the pandemic is handled.

Professor Percy-Smith, who is the Director of the University's Centre for Applied Childhood, Youth and Family Research, said the Centre is committed to research that makes a difference in the lives of young people and families.

"So often research messages are reported to adult decision makers in the hope they will listen and respond. But what happens when politicians don't listen to what young people are saying?", said Professor Percy-Smith.

"In this report, with their insightful observations and commentaries, young people are telling us how politicians and public officials so often are failing to act in the best interests of children and young people.

"This really is the time for us to start taking young people seriously, listen to what they are telling us, value their contributions and support their involvement as a force for change. This report and the research will contribute to that endeavour," he added.

The research involved 70 young people from the four UK nations and Italy, Singapore and Lebanon. The diverse participants, who contributed to the study between July and September 2020, included BAME, LGBTQ+ young people and teenagers with experience of care or mental health issues.

Each participant was mentored by the project team to undertake research and commentary on the crisis, according to their own priorities and terms of reference. Thus meaning, they were not seen simply as research subjects but as active 'experts by experience'.

Findings of the study

While there were differences between the seven countries, the young people shared a common frustration towards the media for dismissing younger people as irresponsible in contrast to examples of individuals embracing volunteering or greater family responsibility.

"I think there's been a lot of this about, 'oh young people feel like they're invincible so they're not socially distancing'... and I think it's quite a generalisation from unfair stereotypes about young people."

Anonymous participant

There were significant concerns about how politicians ignore younger people and why there was a lack of opportunity to speak out about their experiences in strategies decided by local schools or services. For example, participants had to be over the age of 18 to ask a question in the televised COVID-19 briefings.

There was also disappointment in participatory processes such as youth councils or surveys due to their failure to impact on a national level.

"We were saying, 'Well, young people have questions, too'; why can't we? There's been no address to us, we can't ask questions. Where are we at all in this pandemic?"

Anonymous participant

The report also discovered the polarising impact of COVID-19. Just as some teenagers experienced moments of self-reflection and resilience, others struggled with a lack of support services. The need for a holistic strategy when managing global public health emergencies was also made clear.

Lessons to be learnt

Ultimately moving forward, the report suggests government and public authorities must improve young people's representation on participatory platforms and review access to support. Furthermore, it challenges schools, youth organisations and service providers to review opportunities intended for engaging young people in decision-making.

The report highlighted the importance of the media removing negative stereotypes and said they need to balance the portrayal of young people during the pandemic, from involving them in reporting roles to covering their personal stories.

Two further reports are scheduled for spring and autumn 2021, with the project set to conclude a month later. There will also be additional outputs and communications from young people released throughout the year.

Download the full list of findings and recommendations from phase 1 of the Growing Up Under Covid-19 research project: https://www.guc19.com/pdf/resource-bank/to-lockdown-and-back-research-report.pdf

Patients with liver cirrhosis display a wide range of clinical symptoms. A prospective study conducted by MedUni Vienna has now shown that blood levels of biomarkers for systemic inflammation increase over the various stages of the disease and can predict the development of complications, even in previously asymptomatic patients.

Every year, liver cirrhosis is responsible for approximately 170,000 deaths in Europe and recent epidemiological data show Austria to be in second place in regard to prevalence of cirrhosis in Europe. Excessive alcohol consumption, poor dietary habits, and metabolic comorbidities are the most common causes of cirrhosis in the Western world.

Liver cirrhosis is characterized by chronic liver damage, which leads to fibrosis and loss of functioning liver tissue. These changes to the liver tissue result in increased resistance to the blood flow to the liver via the portal vein and cause so-called 'portal hypertension'. In addition, experimental studies have shown that the intestinal barrier is weakened in cirrhosis, so that pathogenic germs and bacterial products can pass into the bloodstream and cause a chronic inflammatory response in the body, in other words 'systemic inflammation'. All these factors drive the progression of the liver disease, which can manifest clinically as the transition from asymptomatic (compensated) to symptomatic (decompensated) cirrhosis. This goes hand-in-hand with an increased risk for death.

MedUni Vienna's Hepatic Hemodynamic Laboratory as an international showcase model

In the recent MedUni Vienna study, portal vein pressure measurements were performed in nearly 170 patients, while simultaneously taking a blood sample to determine biomarkers for systemic inflammation. "Portal pressure measurement via hepatic vein catheterisation is currently the gold standard for assessing the severity of portal hypertension," explains Thomas Reiberger, Head of the outpatient clinic for liver cirrhosis and the Vienna Hepatic Hemodynamic Laboratory at University Hospital Vienna. "At MedUni Vienna, we have established one of the largest hepatic hemodynamic laboratories in the world and are therefore able to offer this valuable prognostic test at our centre at the University Hospital Vienna, in order to optimise the treatment of our patients with cirrhosis." The international standing of the Vienna Hepatic Hemodynamic Laboratory is also evidenced by regular shadowing placements, such as that of Dalila Costa from Portugal, who shares lead authorship of the study with Benedikt Simbrunner from the Division of Gastroenterology and Hepatology of MedUni Vienna and Vienna General Hospital.

Inflammation as a significant disease mechanism and prognostic factor

New findings produced by the study show that the severity of portal hypertension increases predominantly in patients with asymptomatic (compensated) cirrhosis, while biomarkers for systemic inflammation increase predominantly in more advanced (decompensated) stages of the disease. Interleukin-6, a biomarker for inflammation, can predict the risk of complications and mortality both in compensated and decompensated cirrhosis. "These data underline the significance of systemic inflammation for the course of cirrhosis. The mechanisms underlying the inflammatory signals and potential interactions of the gut and the liver need to be further elucidated in humans", observes Simbrunner. The study has been published in the Journal of Hepatology (Impact factor 2019: 20,582), the number one journal in the field of gastroenterology and hepatology.

A mass screening programme of more than 10 million Wuhan residents identified 300 asymptomatic cases, but none were infectious - according to a study involving the University of East Anglia.

The mass testing project took place over two weeks at the end of May - after the city's stringent lockdown was lifted in April.

The study found no 'viable' virus in the asymptomatic cases and the close contacts of these positive asymptomatic cases did not test positive.

But the research team warn that their findings do not show that the virus can't be passed on by asymptomatic carriers.

Rather, strict non-pharmaceutical interventions such as mask-wearing, hand washing, social distancing and lockdown have helped reduce the virulence of Covid-19.

The study, published in Nature Communications, was led by researchers at the Huazhong University of Science and Technology (HUST) in Wuhan, China - in collaboration with researchers at UEA's Norwich Medical School.

Prof Fujian Song, from UEA's Norwich Medical School, said: "Wuhan was the most seriously affected city in China by the Covid-19 pandemic.

"After stringent non-pharmaceutical interventions and lockdown measures from 23 January 2020, the city's lockdown was lifted on 8 April 2020.

"To assess the post-lockdown risk of Covid-19 in the city, a mass screening project of nearly 10 million Wuhan residents was carried out between May 14 and June 1.

"This screening programme identified 300 asymptomatic cases. But the virus cultures indicated no viable virus in the identified asymptomatic cases. This means that these people were not likely to infect anyone else."

The asymptomatic cases were found among people aged between 10 and 89, however the asymptomatic positive rate was the lowest in children and teens aged under 17 and highest among people aged over 60.

Further swab testing of 1174 close contacts of these 300 asymptomatic positive cases were all negative.

Prof Song said: "What this tells us is that the infection prevalence of Covid-19 was very low five to eight weeks after the end of lockdown in Wuhan.

"This work confirms that transmission of Covid-19 can be successfully controlled by well implemented non-pharmaceutical interventions, including face covering, hand hygiene, safe social distancing, contract tracing, and lockdown restrictions. Actually, mask wearing remains common in public places now in Wuhan."

However, the research team say that it is important to emphasise that the results of this study should be correctly interpreted.

Prof Song said: "The asymptomatic cases identified in the screening programme in Wuhan were truly asymptomatic, as none of them showed clinical symptoms before or during their follow-up isolation.

"But there is plenty of evidence elsewhere showing that people infected with Covid-19 may be temporarily asymptomatic and infectious before going on to develop symptoms.

"It's also very important to say that these asymptomatic cases were identified shortly after the relaxation of a very stringent lockdown in Wuhan that lasted more than 70 days. By then, the epidemic in Wuhan had been effectively brought under control.

"The virulence of Covid-19 may be weakening over time. And it is likely that the viral load of Wuhan's asymptomatic cases may be low, compared with cases in locations with a high level of virus transmission.

"Antibody testing showed that almost two thirds of the asymptomatic cases had previously had Covid-19.

"Because the risk of residents being infected in the community was greatly reduced, when susceptible residents are exposed to a low dose of virus, they may tend to be asymptomatic as a result of their own immunity.

"So, it would be problematic to apply the results of our research to countries where Covid-19 outbreaks have not been successfully brought under control.

"Actually, the existence of asymptomatic cases remains a concern even in Wuhan. It is too early to be complacent, because of the existence of asymptomatic positive cases and high level of susceptibility in residents in Wuhan.

"Public health measures for the prevention and control of Covid-19 epidemic, including wearing masks, keeping safe social distancing in Wuhan should be sustained. And vulnerable populations with weakened immunity or co-morbidities, or both, should continue to be appropriately shielded."

Induced pluripotent stem cells (iPS) have the potential to convert into a wide variety of cell types and tissues for drug testing and cell replacement therapies. However, the "recipes" for this conversion are often complicated and difficult to implement. Researchers at the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden, Harvard University (USA) and the University of Bonn have found a way to systematically extract hundreds of different cells quickly and easily from iPS using transcription factors, including neurons, connective tissue and blood vessel cells. Researchers can use this transcription factor source through the non-profit organization Addgene. The results have now been published in the journal Nature Biotechnology.

The researchers used human induced pluripotent stem cells (iPS), which were reprogrammed from connective tissue cells into a quasi-embryonic state. In principle, iPS cells can be used to obtain all kinds of differentiated cells, from neurons to blood vessel cells, with each recipe being individually adapted. "Most differentiation protocols are very laborious and complicated. It's not possible to obtain different cell types from iPS simultaneously and in a controlled manner in a single culture," explains Prof. Dr. Volker Busskamp, who works at the Eye Clinic and the ImmunoSensation2 Cluster of Excellence at the University of Bonn the Excellence Cluster Physics of Life (PoL) and at the CRTD at TU Dresden.

Together with a team from Harvard University, TU Dresden and the University of Bonn, he aimed to replace the complicated procedures with simple "recipes". Using a large-scale screening process, the researchers found a total of 290 DNA-binding proteins that quickly and efficiently reprogram stem cells into target cells. The researchers were able to demonstrate that just a single transcription factor is sufficient in each case to derive differentiated neurons, connective tissue, blood vessel and glial cells from the stem cells within four days. The latter coat neurons as "insulators".

A genetic switchboard for stem cell differentiation

Using automated procedures, the researchers introduced the DNA sequence for the respective transcription factor and other control elements into the stem cell genome. The transcription factors could be activated by adding a small molecule, causing some of the transgenic stem cells to be converted into differentiated cells. It was then possible to distinguish and automatically sort stem cells and differentiated cells using cell markers. The researchers subsequently investigated how much of a certain transcription factor was present in the differentiated cells compared to the stem cells. "The greater the difference, the more important the respective transcription factor seems to be for the conversion of iPS into differentiated cells," explains Busskamp.

The team used this method to test a total of 1732 potential transcription factors on three different stem cell lines. The researchers found an effect for 290 different transcription factors that caused the iPS to convert into differentiated cells. This is new territory, because this property of the iPS programming of 241 of the discovered transcription factors was previously unknown. Using the example of neurons, connective tissue, blood vessel and glial cells, the researchers performed various tests to show that the converted cells are very similar to human body cells in their functional ability.

The results open new possibilities in research

"The advantage of the identified transcription factors is that they are able to convert iPS into body cells particularly quickly and easily and that they can potentially also be used to form more complex tissues," says Busskamp. What took weeks or even months now happens within days. Instead of costly and time-consuming protocols, a single transcription factor is sufficient for the hits identified in mass screening.

"These results open new possibilities," says Prof. Dr. George M. Church of Harvard University. "The variety, simplicity and speed of stem cell programming using transcription factors makes stem cell research possible on a large scale. Worldwide, 50 other groups are already working with our programmable stem cell lines and with the transcription factor library". The two lead authors Alex H.M. Ng and Parastoo Khoshaklagh from Harvard University have now founded the start-up GC Therapeutics in Cambridge (USA), which provides programmable stem cells with customized, integrated transcription factors.

"The cooperation between the different research institutions was very successful, because the different disciplines complemented and interlinked with each other very well," says Busskamp. Researchers worldwide can now use the transcription factor resource that is available by the non-profit organization Addgene.

Particularly as an expert in degenerative retinal diseases, Busskamp sees great potential for stem cell technology in ophthalmology. "For diseases in which the retina degenerates, such as age-related macular degeneration (AMD), there is hope that at some point, it will be possible to replace the affected photoreceptors with the help of iPS conversion," says Busskamp. "My team is working towards this goal."

BOSTON - Adding exercise to a genetic treatment for myotonic dystrophy type 1 (DM1) was more effective at reversing fatigue than administering the treatment alone in a study using a mouse model of the disease. In fact, exercise alone provided some benefit whereas the genetic treatment alone did not. This study, carried out by researchers at the Massachusetts General Hospital (MGH) and collaborators, has implications for patients who experience fatigue due to genetics-related musculoskeletal diseases as well as other types of illness-induced fatigue. The study appears in Molecular Therapy - Nucleic Acids.

"It's encouraging that exercise makes a noticeable difference on its own and in combination with a genetic treatment specifically tailored for the disease," says Thurman M. Wheeler, MD, an investigator in the department of Neurology at MGH and at Harvard Medical School. Wheeler was the senior author of the study.

DM1 is the most common muscular dystrophy in adults, and one of several genetic conditions that cause muscle wasting and progressive weakness. Patients with DM1 report that chronic fatigue is the most debilitating symptom of their condition, although the biological underpinning of this effect is not known. Wheeler and his colleagues wanted to test the value of exercise in reversing this symptom.

The disease is caused by a gain-of-function mutation that leads to the expression of higher levels of a genetic element called an expanded microsatellite CUG repeat. The researchers used mice genetically engineered to carry the same defect and treated some of them with an antisense oligonucleotide, which is essentially a strand of genetic material that sticks to RNA to repair specific gene defects.

Then they studied the effects of exercise on old mice with the gene defect who received only the oligonucleotide, some that were only compelled to exercise, some that had both the treatment and exercised, and a group that received a placebo (a saline solution). They compared the post-exercise activity levels of mice in each of those arms of the trial. They also measured the responses of young mice with the defect who just received the placebo. The mice's activity was measured using a special type of enclosure that records the mouse's movement.

This study provides preliminary answers to at least two questions: How effective should scientists expect gene therapy for this disease will be in actual patients? And could exercise benefit such patients?

"We were surprised that even on its own, exercise helped the mice recover from exertion more quickly," says Wheeler. "Exercise plus the antisense treatment had an even greater effect. But the antisense alone was of no measurable benefit."

While it seems like common sense that exercise would help patients suffering from muscle weaknesses, some clinicians and researchers wondered if it could also have the opposite effect and actually hasten patients' decline. Wheeler and his colleagues' study suggests that is not the case and that the effects of exercise could be beneficial to these patients and others with similar conditions.

OAK BROOK, Ill. - Researchers at Massachusetts General Hospital (MGH) have developed a deep learning model that identifies imaging biomarkers on screening mammograms to predict a patient's risk for developing breast cancer with greater accuracy than traditional risk assessment tools. Results of the study are being presented at the annual meeting of the Radiological Society of North America (RSNA).

"Traditional risk assessment models do not leverage the level of detail that is contained within a mammogram," said Leslie Lamb, M.D., M.Sc., breast radiologist at MGH. "Even the best existing traditional risk models may separate sub-groups of patients but are not as precise on the individual level."

Currently available risk assessment models incorporate only a small fraction of patient data such as family history, prior breast biopsies, and hormonal and reproductive history. Only one feature from the screening mammogram itself, breast density, is incorporated into traditional models.

"Why should we limit ourselves to only breast density when there is such rich digital data embedded in every woman's mammogram?" said senior author Constance D. Lehman, M.D., Ph.D., division chief of breast imaging at MGH. "Every woman's mammogram is unique to her just like her thumbprint. It contains imaging biomarkers that are highly predictive of future cancer risk, but until we had the tools of deep learning, we were not able to extract this information to improve patient care."

Dr. Lamb and a team of researchers developed the new deep learning algorithm to predict breast cancer risk using data from five MGH breast cancer screening sites. The model was developed on a population that included women with a personal history of breast cancer, implants or prior biopsies.

The study included 245,753 consecutive 2D digital bilateral screening mammograms performed in 80,818 patients between 2009 and 2016. From the total mammograms, 210,819 exams in 56,831 patients were used for training, 25,644 exams from 7,021 patients for testing, and 9,290 exams from 3,961 patients for validation.

Using statistical analysis, the researchers compared the accuracy of the deep learning image-only model to a commercially available risk assessment model (Tyrer-Cuzick version 8) in predicting future breast cancer within five years of the index mammogram. The deep learning model achieved a predictive rate of 0.71, significantly outperforming the traditional risk model, which achieved a rate of 0.61.

"Our deep learning model is able to translate the full diversity of subtle imaging biomarkers in the mammogram that can predict a woman's future risk for breast cancer," Dr. Lamb said.

Dr. Lamb said the new deep learning model has been externally validated in Sweden and Taiwan, and additional studies are planned for larger African-American and minority populations.

At MGH, deep learning risk information is available on reporting software when the radiologist reads a patient's screening mammogram.

"Traditional risk models can be time-consuming to acquire and rely on inconsistent or missing data," Dr. Lamb said. "A deep learning image-only risk model can provide increased access to more accurate, less costly risk assessment and help deliver on the promise of precision medicine."

DALLAS, Nov. 30, 2020 -- Women face a 20% increased risk of developing heart failure or dying within five years after their first severe heart attack compared with men, according to new research published today in the American Heart Association's flagship journal Circulation.

Previous research looking at sex differences in heart health has often focused on recurrent heart attack or death. However, the differences in vulnerability to heart failure between men and women after heart attack remains unclear.

To study this gap, researchers analyzed data on more than 45,000 patients (30.8% women) hospitalized for a first heart attack between 2002-2016 in Alberta, Canada. They focused on two types of heart attack: a severe, life-threatening heart attack called ST-segment elevation myocardial infarction (STEMI), and a less severe type called Non-STEMI or NSTEMI, the latter of which is more common. Patients were followed for an average of 6.2 years.

Women were older and faced a variety of complications and more risk factors that may have put them at a greater risk for heart failure after a heart attack.

In addition to the elevated risk for heart failure among women, researchers found:

A total of 24,737 patients had the less severe form of heart attack (NSTEMI); among this group, 34.3% were women and 65.7% were men.

A total of 20,327 patients experienced STEMI, the more severe heart attack; among this group, 26.5% were women and 73.5% were men.

The development of heart failure either in the hospital or after discharge remained higher for women than men for both types of heart attack, even after adjusting for certain confounders.

Women had a higher unadjusted rate of death in the hospital than men in both the STEMI (9.4% vs. 4.5%) and NSTEMI (4.7% vs, 2.9%) groups. However, the gap narrowed considerably for NSTEMI after confounder adjustments.

Women were more likely to be an average 10 years older than men at the time of their heart attack, usually an average age of 72 years versus 61 for the men.

Women also had more complicated medical histories at the time of their heart attacks, including high blood pressure, diabetes, atrial fibrillation and chronic obstructive pulmonary disease, risk factors that may contribute to heart failure.

Women were seen less frequently in the hospital by a cardiovascular specialist: 72.8% versus 84% for men.

Regardless of whether their heart attacks were the severe or less severe type, fewer women were prescribed medications such as beta blockers or cholesterol-lowering drugs. Women also had slightly lower rates of revascularization procedures to restore blood flow, such as surgical angioplasty.

"Identifying when and how women may be at higher risk for heart failure after a heart attack can help providers develop more effective approaches for prevention," said lead study author Justin A. Ezekowitz, M.B.B.Ch., M.Sc., a cardiologist and co-director of the Canadian VIGOUR Centre at the University of Alberta in Edmonton, Alberta, Canada. "Better adherence to reducing cholesterol, controlling high blood pressure, getting more exercise, eating a healthy diet and stopping smoking, combined with recognition of these problems earlier in life would save thousands of lives of women -- and men."

Based on these findings, study co-author Padma Kaul, Ph.D., co-director of the Canadian VIGOUR Centre, said the next step is to further examine if all patients are receiving the best care, particularly women, and where interventions can address oversights.

"Close enough is not good enough," said Kaul, who is also the Sex and Gender Science Chair from the Canadian Institutes of Health Research. "There are gaps across diagnosis, access, quality of care and follow-up for all patients, so we need to be vigilant, pay attention to our own biases and to those most vulnerable to ensure that we have done everything possible in providing the best treatment."

DALLAS, Nov. 30, 2020 — The menopause transition, the years leading up to menopause, is a time of increasing heart disease risk for women. Monitoring women’s health and lifestyle, while integrating early intervention strategies for good cardiovascular health, are important, especially during midlife and during menopause to help prevent heart disease, according to a new Scientific Statement from the American Heart Association, “Menopause Transition and Cardiovascular Disease Risk: Implications for Timing for Early Prevention,” published today in its flagship journal, Circulation.

“Over the past 20 years, our knowledge of how the menopause transition might contribute to cardiovascular disease has been dramatically evolving,” said Samar R. El Khoudary, Ph.D., M.P.H., FAHA, chair of the statement writing committee and associate professor of epidemiology at the University of Pittsburgh’s Graduate School of Public Health and the Clinical and Translational Science Institute. “We have accumulated data consistently pointing to the menopause transition as a time of change in cardiovascular health. Importantly, the latest American Heart Association guidelines that are specific to women, which were published in 2011, did not include the data that is now available on menopause as a time of increased risk for women’s heart health. As such, there is a compelling need to discuss the implications of this accumulating body of literature on this topic.”

For many women, the menopause transition — the change from the reproductive to the non-reproductive phase of life marked by changes in menstruation — begins when they are in their late 40s to mid-50s. Before this transition, women produce estrogen, the female sex hormone, which may also have cardio-protective effects. When women go through the natural menopause transition, their ovaries stop producing as much estrogen. This can also occur through surgical menopause (a partial or full hysterectomy, which includes removal of one or both ovaries). Significant changes in a woman’s cardiometabolic and vascular health, which lead to higher heart disease risk, occur during the menopause transition.

Since the increase in heart disease risk during menopause is associated with a decrease in the production of the hormone estrogen, health care professionals and scientists have studied if hormone therapy might help reduce cardiovascular risk. There is research indicating potential cardiovascular benefits of certain combinations of hormone therapy when initiated in early but not late menopause. Further research is needed to evaluate the role of other hormone therapies, and how long these interventions impact cardio-metabolic health.

Additionally, some studies show the benefits of hormone therapy, including a decreased risk of type 2 diabetes and protection from bone loss, seem to outweigh the risks for most women in early menopause. Current recommendations from leading professional medical societies endorse the use of hormone therapy for women who have recently begun the menopause transition, with appropriate indications.

“This Scientific Statement aims to raise awareness for both health care professionals and women about the significant adverse cardiovascular health changes accompanying midlife and the menopause transition and point out the importance of adopting prevention strategies early during this stage,” said El Khoudary. “As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a heathy heart and reduce the risk of heart disease. Thus, health care professionals may consider an aggressive, prevention-based approach for women during this stage in their lives to decrease the probability of a future cardiovascular disease occurrence, such as heart attack or stroke.“  

In addition to summarizing research focused on the use of hormone therapy, the Scientific Statement provides an overview of risks related to the stages of menopause, age at menopause and lifestyle factors that affect women’s risk during this time.

Key takeaways in the statement include the following:

Some of the common symptoms felt with menopause have a correlation with cardiovascular disease. Hot flashes and night sweats  are associated with worse cardiovascular disease risk factor levels. Depression and sleep disturbances, linked in some studies to an increased risk of heart disease, are also common among women during this time.  
Physiological changes during menopause, such as increased abdominal fat and visceral fat (body fat around the organs), are associated with a heightened risk of all-cause, cardiovascular disease and cancer mortality, even among those with normal body mass index levels.
Cholesterol levels, metabolic syndrome risk and vascular vulnerability appear to increase with menopause beyond the effects of normal aging. Metabolic syndrome is diagnosed when a person has three or more of the following measurements: abdominal obesity, high triglycerides, low HDL cholesterol (the good cholesterol), high blood pressure and/or high blood glucose levels (blood sugar).
Novel data show a reversal in the associations of HDL cholesterol (the good cholesterol) with heart disease risk over the menopause transition, suggesting higher good cholesterol levels may not consistently reflect good heart health in all stages of life in women.
Data about the use of cholesterol-lowering medications remains limited for women going through the menopause transition and requires further study so evidence-based recommendations can be developed.
Women who experience menopause at an earlier age have a higher risk of heart disease. A woman’s age at menopause can be influenced by factors such as length of menstrual cycle, poor cardiovascular risk profile during reproductive years and socioeconomic factors. Race and ethnicity also play a role, with many Hispanic and Black women experiencing menopause at younger ages.
Physical activity and nutrition may play a role in the timing of menopause for all women. Women who drink little to moderate amounts of alcohol may have later onset of menopause, and those who smoke cigarettes are likely to start menopause about a year earlier than non-smokers.
There is, however, limited information on what is ideal in terms of lifestyle changes (such as the AHA’s Life’s Simple 7) for women during menopause. Data does indicate though that only 7.2% of women in menopause meet physical activity guidelines, and fewer than 20% of those women consistently maintain a healthy diet.

“Lifestyle and behavioral interventions are critical to maintaining cardiovascular health and reduce heart disease. However, we do not have adequate randomized clinical trials testing these interventions specifically during the menopause transition,” said Matthew A. Allison, M.D., M.P.H., FAHA, vice chair of the statement writing committee and professor and chief of the Division of Preventive Medicine in the Department of Family Medicine and Public Health at the University of California San Diego. “Similarly, we need randomized clinical trials of therapeutic interventions, like cholesterol-lowering medications and menopause hormone therapy, in women who are transitioning through menopause. This at-risk population has not been the focus of previous clinical trials, thus leaving us with questions about how the results from these studies might apply to women during this earlier phase of menopause.”

New research confirms men and teens are affected by Instagram influencers who set global benchmarks for ideal body shape, fashion and even facial trends.

While perhaps not as focused on 'thinness' as women appear to be from female influencers, the Flinders University study confirms males are responding to the body image and fitness messages shared by Instagram leaders, some with millions of followers.

This may mean men are less exposed to some of the negatives of social media but confirms the influence of fitspiration ('fitspo') and body image on this online platform, says psychology Professor Marika Tiggemann and Isabella Anderberg in a new paper in Body Image.

"Despite the rise in use of social media, there haven't been many studies into its effect on men and our new study found there are similarities and differences between women and men," says lead author Professor Tiggemann, who has extensively researched the power of social media images on body image, eating and other behaviours in women.

"While participants all had some vulnerable responses to some types of social media imagery, results typically obtained for women cannot simply be generalised to men."

Co-author Isabella Anderberg says the new study shows there is a high level of response to fitspiration goals via Instagram influencers.

"It is interesting that both the fitspiration and fashion images made participants feel more inspired to exercise, and we have certainly seen a rise in men following international fitspo and professional sporting hero influencers."

The Flinders research studied responses from 300 US adult men aged 18-30 who were randomly shown images of bare-chested (fitspiration), clothed (fashion) and control images, similar to those posted by Instagram influencers.

It was found that exposure to bare-chested and muscular images resulted in significantly lower body satisfaction relative to viewing clothed fashion images or scenery images.

"It's important to expand this research, including on the 'Brotox' facial ideals set in social media which is leading to more men reportedly using skin products and even cosmetic fillers and botox to keep up to influencers," Ms Anderberg adds.