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A study of oncology staff carried out immediately after the spring peak of the COVID-19 pandemic in the UK indicates that many had been infected with the coronavirus as they tested positive for COVID-19 antibodies. This included staff who did not show any symptoms. [1]

The study also found that a substantial proportion of those with positive COVID-19 antibodies detected after the first peak had lost their positive antibody status after four weeks.

The research, presented at the NCRI Virtual Showcase, suggests that oncology staff should be routinely tested for signs of current or previous coronavirus infection as rates of COVID-19 begin to rise again.

Dr David Favara from Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, UK, led the Covid-19 Serology in Oncology Staff (CSOS) Study. He said: "We began work on this research in April 2020, when the UK was still under COVID-19 lockdown. At that time there was no widely available formal testing programme for NHS staff, symptomatic or asymptomatic, and I was concerned about the impact of transmission of the virus to our oncology patients. At that time, polymerase chain reaction testing was hampered by limited national testing capacity -- meaning that only individuals sick enough to be admitted to hospital with severe COVID-19 symptoms were being tested -- whilst antibody tests were not offered outside of the experimental setting.

"To the best of our knowledge, we believe this was the first study to specifically investigate exposure to the virus in patient-facing oncology staff who were at work during the peak of the COVID-19 pandemic in the UK between March and June 2020."

The study included 434 nurses, doctors, radiographers and administrators who had been at work in patient-facing roles during the peak of the first wave in oncology departments at three large East of England NHS Trusts: The Cambridge University Hospitals NHS Foundation Trust, The North West Anglia NHS Foundation Trust and the Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust .

At the start of June, participating staff were given both an antigen test (a nasopharyngeal swab tested with polymerase chain reaction) for signs that the virus was present and two different antibody tests (a blood sample tested with both a laboratory assay and a rapid point-of-care assay) for signs of a previous infection with the virus.

No one tested positive for the antigen, meaning they were probably not infected at the time of testing. However, 18.4% of staff tested in June were positive for antibodies specific to the virus (according to the laboratory assay), suggesting previous infection.

The highest rates were among oncology nurses (21.3%), followed by doctors (17.4%), administrators (13.6%) and radiographers (8.9%). Only some of those who tested positive for the antibodies reported previous symptoms suggestive of COVID-19 (38%).

Four hundred of the staff were re-tested four weeks later in July and 13.3% tested positive for the antibodies. Of these, 92.5% were previously positive and 7.5% were newly positive. Of those who tested positive for antibodies in June, 32.5% had become antibody-negative when re-tested four weeks later.

Dr Favara said: "The UK has guidance from the UK Royal College of Radiologists on testing patients for the virus antigen prior to their radiotherapy treatments, and broad advice for testing staff.

"Considering our findings, we propose that there should be a focus on routinely testing oncology nursing staff for both the virus antigen and antibodies until an effective vaccine becomes available. Testing for signs of previous infection alongside testing for current infection on a large scale would also help us better understand changes in immunity over time."

Dr Favara says he and his colleagues will continue collecting samples at intervals until a vaccine becomes widely available.

Dr Iain Frame, Chief Executive of NCRI, said: "This study gives us some important insights into levels of infection among oncology staff during the spring peak of COVID-19. As we see rates of the infection rise again around the world, it's crucial that we learn lessons to protect oncology staff and cancer patients and ensure patients get the best treatment now and in the coming months."

Liver cancer from too much fat accumulation in the liver has been increasing in many countries including Japan. In order to change this unfortunate state of affairs, it is important to improve the prognosis of non-alcoholic fatty liver disease. Most often the cause of fatty liver is overeating and lack of exercise. Fatty liver is often improved through eating less, getting more exercise, and reducing body weight. Therefore, the research group led by Shinshu University graduate student Fangping Jia posed the question, "Can eating less also suppress liver cancer caused by fatty liver?"

An international research team led by Shinshu University School of Medicine were able to show that reducing food intake by 30%, or eating until you are just 70% full is effective in reducing the likelihood of developing liver cancer from fatty liver. Fatty liver is a very common disease that can lead to liver cirrhosis and cancer. The team observed the incidence of fatty liver-related liver tumors in mice with the hepatitis C virus core gene and demonstrated the fall in the occurrence of liver cancer from 41% to 8% over a 15 month period, simply through dietary restriction.

Although there have been studies that showed the connection between obesity, fatty liver and hepatocellular carcinoma, the impact and mechanism of dietary restriction on cancer was not well understood before this study. Reducing food intake suppresses cell proliferation, oxidative/ER stress, inflammation, senescence and insulin signaling while increasing autophagy. Inflammation and oxidative/ER stress creates an environment in the body that is conducive to the development of abnormal cells. Autophagy is the mechanism in which the body cleans out damaged cells, reducing the likelihood of developing cancer.

Shinshu University School of Medicine Associate Professor Naoki Tanaka, corresponding author of the study hopes to eradicate liver cirrhosis and cancer from fatty liver through providing personalized dietary guidance and the promotion of the eating habit until you are just 70% full. In three other studies conducted by Associate Professor Tanaka using the same mouse model, the effect of the diet rich in cholesterol, saturated fats and trans-fats were shown to increase the incidence of liver tumors and elucidated the mechanism in which this occurs. Associate Professor Tanaka speculates that not only does the amount of fat intake matter, but the "quality" of dietary fats that lead to cancer. He hopes to elucidate this further in future studies.

Many previous studies have also shown that dietary restriction delayed the progression of cancer in humans through slowing down the rate of aging. There is a Chinese proverb that says, "to live a long and healthy life, eat until the stomach is 70 percent full." Then you will live healthy, and it might lead to longevity.

Novel approach to measuring antibodies against SARS-CoV-2
Current antibody testing strategies are known for their lack of specificity, leading to a large proportion of false positive results. German researchers lead by Prof. Anette-G. Ziegler at Helmholtz Zentrum München developed a novel approach to measuring antibodies against SARS-CoV-2 by defining antibody positivity as a dual-positive response against both the receptor binding domain and nucleocapsid proteins of the virus. This two-step approach allows for more accurate test results, close to a 100% specificity and greater than 95% sensitivity.

As Ziegler and her group have already been conducting a large-scale screening study for pre-symptomatic type 1 diabetes in children, "Fr1da", they could easily and quickly apply this novel testing approach for SARS-CoV-2 antibodies to their existing study infrastructure.

Results of the SARS-CoV-2 antibody screening
Between January 2020 and July 2020, the researchers tested blood samples of almost 12,000 children in Bavaria aged 1 to 18 (who were participants of the Fr1da study) for SARS-CoV-2 dual-antibody positivity. They detected an average antibody frequency of 0.87% from April to July. In comparison to the incidence of virus positive cases reported by the Bavarian Health and Food Safety Authority (in children in Bavaria aged 0 to 18 years from April to July), these antibody frequencies were six-fold higher.

The results showed no differences in sex or age. Almost half (47%) of the antibody-positive children were asymptomatic. In children with virus-positive family members, a third (35%) had antibodies, indicating a higher expected transmission rate in children compared to most previous studies. The regional results within Bavaria revealed substantial geographic differences, with the highest antibody frequency ("hot spots") in the south of Bavaria.

The children in this study were also tested for type 1 diabetes autoantibodies, an early marker for pre-symptomatic type 1 diabetes. The researchers found no increase in the frequency of these autoantibodies. This suggests that COVID-19 and type 1 diabetes in childhood are not associated.

Implications for COVID-19 measures
"Our study delivered important results revealing the discrepancy between reported virus positive cases and antibody prevalence", says Markus Hippich, who conducted the study as first-author and postdoc at Helmholtz Zentrum München. "As many individuals, in children almost half, do not show COVID-19 symptoms and therefore do not get tested, virus testing only is not a sufficient approach to receive reliable data on the actual virus exposure."

Prof. Anette-G. Ziegler who lead the study adds: "National antibody screening programs with high specificity and sensitivity could provide countries reliable data to prepare for the future, help them contain the virus spread and monitor the impact of their regional and national containment policies."

Dashboard
The study results including information on the geographical spread of antibody frequency is available on the study's dashboard: https://covid-dashboard.fr1da-studie.de/app_direct/covid-dashboard/. The numbers will be updated on a monthly basis.

Limitations
Antibodies against SARS-CoV-2 can take one to four weeks to manifest, which is why these measurements cannot be used for up-to-date prevalence screening. At present, there is no proof that SARS-CoV-2 antibodies lead to immunity. If this is shown to be the case, the results of this screening could provide relevant information on the immunity situation of children in Bavaria.

About the study
The work was supported by grants from the Federal Ministry of Education (BMBF) and the German Center for Diabetes Research (DZD). The Fr1da study is funded by the LifeScience-Stiftung, JDRF, and The Helmsley Charitable Trust.

Learn more about Fr1da: https://www.helmholtz-muenchen.de/en/aktuelles/latest-news/press-information-news/article/47571/index.html

Helmholtz Zentrum München
Helmholtz Zentrum München is a research center with the mission to discover personalized medical solutions for the prevention and therapy of environmentally-induced diseases and promote a healthier society in a rapidly changing world. It investigates important common diseases which develop from the interaction of lifestyle, environmental factors and personal genetic background, focusing particularly on diabetes mellitus, allergies and chronic lung diseases. Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,500 staff members. It is a member of the Helmholtz Association, the largest scientific organization in Germany with more than 40,000 employees at 19 research centers.

New Orleans, LA - A study conducted by Richard Vander Heide, MD, PhD, Professor and Director of Pathology Research at LSU Health New Orleans School of Medicine, and Marc Halushka, MD, PhD, Professor of Pathology at Johns Hopkins University School of Medicine, suggests myocarditis caused by COVID-19 may be a relatively rare occurrence. Their findings are published online in Cardiovascular Pathology, available here.

Reports of the rate of COVID-19 myocarditis have varied widely, ranging from 60% among middle-aged and elderly recovered patients to 14% among recovered athletes.

"Although it is clear that COVID-19 impacts the heart and blood vessels, to date, it has been difficult to know how reproducible any changes are due to the relatively small sample size of most autopsy series," notes Dr. Vander Heide.

The authors collected data from 277 autopsy cases to analyze cardiovascular pathological findings from patients who died from COVID-19 in nine countries around the world. The data from these autopsied hearts were published in 22 papers. After careful review, the authors determined that the rate of myocarditis found in these patients is between 1.4% and 7.2%.

"What we have learned is that myocarditis is not nearly as frequent in COVID-19 as has been thought," says Dr. Halushka. "This finding should be useful for our clinical colleagues to reconsider how to interpret blood tests and heart radiology studies."

"By bringing the data together from this large number of autopsy cases, we have better determined the spectrum of histologic findings," adds Dr. Vander Heide. "Even a low myocarditis rate of 1.4% would predict hundreds of thousands of worldwide cases of myocarditis in severe COVID-19 due to the enormous numbers of infected individuals. Low rates of myocarditis do not indicate that individuals infected with SARS-CoV-2 are not having cardiovascular problems, but rather those complications are likely due to other stressors such as endothelial cell activation, cytokine storms, or electrolyte imbalances."

The authors also created a "checklist" for pathologists to use going forward when evaluating COVID-19 at autopsy to provide consistency in investigating and reporting findings.

"This study demonstrates the importance of the autopsy in helping us determine what is occurring in the hearts of individuals passing away due to COVID-19," concludes Dr. Halushka.

Researchers in the University of Georgia's Center for Tropical and Emerging Global Diseases have found that a more intensive, less frequent drug regimen with currently available therapeutics could cure the infection that causes Chagas disease, a potentially life-threatening illness affecting up to 300,000 people in the United States.

Trypanosoma cruzi is a single-celled parasitic organism that causes Chagas disease. At least 6 million people are infected by T. cruzi, mostly in South America. Current drug therapies have been ineffective in completely clearing the infection and are associated with severe adverse side effects.

A single dose of benznidazole has been shown to be highly effective in killing more than 90% of parasites. However, after a CTEGD team found some of the parasites enter into a dormancy stage, the researchers hypothesized that an intermittent treatment schedule could be effective.

"In this system we can see what a single dose of drug does," said Rick Tarleton, Regents' Professor in UGA's department of cellular biology. "Does it make sense to give a drug twice daily when the remaining dormant parasites are insensitive to it?"

The investigators found that giving as little as two-and-a-half times the typical daily dose of benznidazole, once per week for 30 weeks, completely cleared the infection, whereas giving the standard daily dose once a week for a longer period did not.

"Current human trials are only looking at giving lower doses over a shorter time period, which is the exact opposite of what we show works," said Tarleton.

Since Tarleton's team worked with a mouse model, how this change in treatment regimen will translate in humans is yet unknown, as are any potential side effects of the higher doses. Adverse reactions already are a problem with current treatments; the hope is that side effects from a less frequent dosage would be more tolerable.

Assessing the success of treatments in Chagas disease is a significant challenge. Tissue samples from infected organisms might not be representative of the entire organ or animal, since low numbers of persistent, dormant parasites can be difficult to detect. Therefore, Tarleton's group used light sheet fluorescence microscopy to view intact whole organs from infected mice.

"With light sheet fluorescence microscopy, you have a broad view of potentially any tissue in the mouse that allows for dependable assessment of parasite load and persistence," said Tarleton. "It gives you an incredible view of the infection."

Using this technology, they learned something new about the dormant parasites: Some were still susceptible to drug treatment. This provides hope that new drug therapies could be developed to target these parasites.

"Discovery of new drugs should continue," Tarleton said. "We still need better drugs."

A Swansea University academic has helped draw up a landmark agreement amongst international experts, setting out the world's first standard guidance on how people with diabetes can use modern glucose monitoring devices to help them exercise safely.

The guidance will be a crucial resource for healthcare professionals around the world, so they can help people with type 1 diabetes.

The guidance, approved by an array of diabetes experts and organisations, was drawn up by a team including Dr Richard Bracken of the School of Sports and Exercise Sciences, College of Engineering and the Diabetes Research group, located in the Medical School at Swansea University.

Physical exercise is an important part of managing type 1 diabetes for people of all age groups. However, the blood sugar response can be difficult to predict, with exercise sometimes increasing the risk of falling blood sugar levels - known as hypoglycaemia - or other times causing blood sugar to rise. Levels of glucose therefore have to be closely monitored.

Fear of having a "hypo", which can lead to dizziness, disorientation, anxiety and many other symptoms, is one of the main barriers stopping people with diabetes from incorporating exercise into daily life.

Fortunately, modern real-time glucose monitoring systems are now available on the NHS or for purchase, so people can manage their glucose levels during exercise. The problem, however, is that these can be complex, and the information can be difficult for patients and health professionals to interpret.

This is where the new guidance will be invaluable. It looks at the evidence from glucose monitoring technology and uses it as the basis for clear guidance for exercise in adults, children and adolescents with type 1 diabetes.

The guidance covers areas like carbohydrate consumption and safe glucose thresholds. The idea is that it should serve as an initial guidance tool, which can then be tailored for the individual patient in consultation with health professionals.

The guidance, contained in a position statement, was published by the European Association for the Study of Diabetes and the International Society for Paediatric and Adolescent Diabetes. It is also endorsed by the global diabetes charity Juvenile Diabetes Research Foundation, and by the American Diabetes Association.

Dr Richard Bracken, one of the authors, and a diabetes expert from the A-STEM research team in Swansea University School of Sports and Exercise Sciences and the Lifestyle research group lead in the Diabetes Research Group, Medical School, said:

"This guidance is a landmark agreement which could end up making a real difference to people with Type 1 diabetes.

It is built on years of research into the strengths and limits of modern glucose monitoring devices. On the basis of that evidence, we can now recommend how to safely use these devices and support people with type 1 diabetes. It will help them to obtain the health benefits of exercise, whilst minimising wide fluctuations in their blood glucose level."

The guidance was simultaneously published in leading research journals Diabetologia and Pediatric Diabetes.

TAMPA, Fla. -- Children with multiple islet autoantibodies - biological markers of autoimmunity -- are more likely to progress to symptomatic type 1 diabetes (T1D) than those who remain positive for a single autoantibody.

Now, new findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study in the U.S. and Europe show that detailed information about the order, timing and type of autoantibodies appearing after the first autoantibody can significantly improve prediction of which children are most likely to progress to type 1 diabetes more rapidly.

The TEDDY analysis was published in the September 2020 issue of Diabetes Care.

"A better understanding of distinct autoantibody spreading is important, because it will allow us to identify at-risk children earlier in the disease process," said the study's lead author Kendra Vehik, PhD, a professor of epidemiology at the University of South Florida Health (USF Health) Morsani College of Medicine's Health Informatics Institute. "That means while children are still asymptomatic, we can start to look at interventions and strategies that may reduce, delay or stop the progression of type 1 diabetes."

While antibodies are molecules produced by the body's immune system to detect and destroy specific viruses, bacteria and other harmful substances, autoantibodies are antibodies that target a person's own healthy tissue. In the case of T1D, a misdirected autoimmune response attacks the pancreas and gradually destroys the organ's insulin-producing beta cells.

Without the hormone insulin the body cannot regulate its blood sugar levels, which can cause serious, long-term medical complications such as cardiovascular disease, nerve and kidney damage, and vision loss. Children (and adults) with T1D must monitor their dietary intake and exercise and take insulin injections, or use an insulin pump, daily to help control their blood sugar levels.

"Physically and psychologically, it's a very burdensome disease that needs to be managed every day over a lifetime," Dr. Vehik said.

For this TEDDY analysis, eligible children with increased genetic risk for T1D, were followed every three months, from the age of 3 months up to 15 years, for the development of a first-appearing autoantibody directed against pancreatic insulin-producing cells: glutamic acid decarboxylase antibody (GADA), insulin autoantibody (IAA), or insulinoma-associated-protein-2 autoantibody (IA2-2A). The researchers also looked for the subsequent appearance of a second autoantibody and further progression to T1D. Zinc transporter 8 autoantibody(ZnT8A) was only measured in children who developed an IAA, GADA, or IA-2A. These four different autoantibodies are so far the most reliable biological indicators of early T1D, before symptoms become apparent.

Of the 608 study participants - all testing positive for either a first-appearing IAA or GADA -- more than half (336) developed a second autoantibody. Furthermore, 53% of these 336 children with a second antibody progressed to T1D within about 3.5 years. Only about 10% of the 272 children testing positive for a single autoantibody at the end of the follow-up for this study (Dec. 31, 2019) had transitioned to T1D.

Among the key study findings:

All study participants had high-risk genotypes for T1D. However, those increased-risk children who also had a parent or sibling with T1D were more likely to develop a second-appearing autoantibody than those without a family history.

The younger the child at the time they tested positive for a first autoantibody, the greater their risk for developing a second autoantibody. Conversely, the risk for T1D decreased if the first autoantibody appeared when the child was older.

Children testing positive for a second autoantibody, regardless of the type, had at least a five-fold increased risk of progressing to T1D, compared to children who stayed single autoantibody positive. IA-2A, as a second autoantibody, conferred the highest risk, compared with GADA, IAA, or ZnT8A.

Risk of progression to T1D was influenced by how quickly the second autoantibody appeared. Emergence of a second autoantibody within a year of the first doubled the risk of progression to T1D. Children's likelihood of developing T1D declined as the months between the first and second-appearing autoantibodies increased.

Better stratifying the risk of progression from the start of autoimmunity to symptomatic disease could help diagnose T1D earlier and offers the opportunity to prevent diabetic ketoacidosis (DKA) and its serious complications by educating parents to watch for early signs, Dr. Vehik said.

"For instance, if a clinician knows that a young child testing positive for IA-2A as their second-appearing autoantibody will be at a higher risk to more rapidly progress to type 1 diabetes, they can reduce the risk of symptomatic onset of disease. Clinicians can also educate the parents about the early signs of disease, such as, weight loss, extreme thirst, more frequent urination, or other DKA symptoms," she said. "If that happens, the parents will know they should get their child to a doctor or hospital as soon as possible."

Specific antibody risk profiling can also help identify those at-risk children most likely to benefit from recruitment for T1D prevention trials, Dr. Vehik added.

Dr. Vehik next plans to build upon a previous TEDDY study linking viral behavior with T1D diabetes to test whether prolonged viral infections may environmentally trigger the transition from first- to second-appearing islet autoantibodies in children genetically susceptible to diabetes.

More than a dozen U.S. Immigration and Customs Enforcement (ICE) detention centers experienced large, repeated outbreaks of vaccine-preventable illnesses in the last three years, according to a new study by researchers at UC San Francisco.

Between Jan. 1, 2017, and March 22, 2020, the researchers identified 1,280 cases of influenza, 1,052 cases of chickenpox, and 301 cases of mumps. There were 41 flu outbreaks, 26 chickenpox outbreaks, and 12 mumps outbreaks.

"These numbers are pretty shocking, and very concerning," said Nathan C. Lo, MD, PhD, the first author, who is a resident physician and public health scientist at UCSF. "They suggest this vulnerable population is being placed at very high risk for these infections while being detained."

Given how widespread the outbreaks were, Lo said federal authorities should offer vaccination to both adult and child migrants as soon as they are brought to the detention centers, which is not currently being done. The vaccines should protect people, even if they have already been exposed. Chickenpox, in particular, can be very serious and even life-threatening.

"Crowding people together and giving them poor access to health care or vaccines makes these detention centers ripe for facilitating infectious outbreaks," Lo said.

The study is published October 29, 2020 in JAMA.

When the study began in January of 2017, only a handful of centers reported cases of chickenpox, flu or mumps. By the time it ended in March of 2020, 17 of the 22 ICE detention centers under review had outbreaks of one or more of the three viruses.

One facility had a chickenpox outbreak that lasted for 33 months, and also had year-round transmission of the influenza virus. Many centers had outbreaks of mumps. Both chickenpox and mumps are relatively rare in the general population, and flu typically circulates in the winter, but not all year round.

Nearly half of the infections--44.7 percent--occurred in the South Texas Family Residential Center. Another 16.5 percent occurred at the Port Isabel Service Processing Center, also in Texas.

Given how many outbreaks they found, and how long they lasted, experts said it was very likely the viruses were being spread by transfers of migrants between detention centers, which bring infected people into close contact with others who are highly susceptible to these diseases, either because they have never been vaccinated against them, or because their immunity has waned.

"Typically, migrants are detained, held for a few days, then moved to another center," Lo said. "That moving around of people is likely a big contribution. Otherwise, how would you get so many outbreaks in so many centers with infections that are not so common?"

The study most likely underestimates the number of infections. The scientists were only able to get data from the 22 centers that have the ICE electronic health record system and are served by ICE Health Service Corps. That is a small subset of the 315 facilities around the country, some of which are privately managed, that house detained migrants.

Also, the data came from ICE officials at those 22 detention centers who searched the medical charts of detained migrants to see which of them had been diagnosed with chickenpox, flu or mumps, so any cases that went undiagnosed would have been missed.

"These are infectious diseases that can be prevented through vaccination," Lo said. "These detention centers are high-risk environments for infectious diseases, so we should change policy to offer vaccines that can minimize preventable suffering."

The United States has become the epicenter of the world in the ever increasing pandemic of COVID-19. While public health prevention strategies of social distancing, crowd avoidance, masking and frequent hand washing are of proven benefit, effective drug therapies for treatment are sparse. Not surprisingly, remdesivir has attracted worldwide attention, first receiving an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) and especially with U.S. President Donald Trump taking the drug for COVID-19 earlier this month. Last week, the World Health Organization (WHO) published the largest randomized trial showing no benefit on reducing hospital stays or mortality. Nonetheless, remdesivir has received approval from the FDA for standard of care use for patients who are hospitalized.

In a commentary published in the journal Contemporary Clinical Trials Communications, researchers from Florida Atlantic University's Schmidt College of Medicine and a collaborator reviewed the totality of available evidence, in particular, the most reliable data from randomized trials to detect the plausible small-to-moderate effects of remdesivir. They concluded that the current totality of evidence that they compiled before the WHO trial results justifies compassionate use of remdesivir for severely ill patients with COVID-19.

"Remdesivir significantly decreased mean recovery time with no suggestion of a mortality benefit in a smaller trial in China. Subsequently, the larger Adaptive Covid-19 Treatment Trial or ACTT-1, found the same improvement in mean recovery time and a suggestion of a mortality benefit, which did not achieve statistical significance," said Richard D. Shih, M.D., first author, a professor of emergency medicine and division director and founding program director for the emergency medicine residency program in FAU's Schmidt College of Medicine.

According to the researchers, Dexamethasone is the only other drug having received FDA approval based on a large randomized trial showing a mortality benefit among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. This drug also was used by President Trump.

"The U.S. accounts for less than 5 percent of the world's population but more than 20 percent of the global cases and deaths. We need far wider utilization of the preventive strategies of proven benefit of social distancing, crowd avoidance, masking, and frequent hand washing," said Charles H. Hennekens, M.D., Dr.PH, senior author, first Sir Richard Doll Professor and senior academic advisor to the dean in FAU's Schmidt College of Medicine. "While vaccine development and further research on other drug therapies to treat and prevent COVID 19 are a necessity, don't let the 'perfect be the enemy of the possible.'"

The authors also believe that in the U.S., cases and deaths in the fall and winter will far exceed those of last spring without effective implementation of nationally coordinated efforts at preventive strategies to mitigate and contain COVID-19 and which are well known to public health professionals.

Dennis G. Maki, M.D., co-author and professor in the Department of Medicine at the University of Wisconsin School of Medicine and Public Health, has been a collaborator with Hennekens since 1969, when they served as lieutenant commanders in the U.S. Public Health Service as epidemic intelligence service officers with the U.S. Centers for Disease Control and Prevention. They served under Alexander Langmuir, M.D. and Donald A. Henderson, M.D., who first promulgated these public health strategies of proven benefit.

DALLAS - Oct. 28, 2020 - An X-ray test commonly used to assess hardening of the arteries could help doctors decide whether the benefits of taking aspirin to prevent a first heart attack or stroke outweigh the risks of bleeding from its use, UT Southwestern research suggests.

The findings, published online today in JAMA Cardiology, could give doctors and patients more concrete guidelines for making this important decision.

Due to its anti-clotting properties, aspirin is widely prescribed as a preventive measure to patients who have already had cardiovascular events, such as a heart attack or ischemic stroke. However, aspirin's role in primary prevention - averting first heart attacks and strokes - has been unclear, explains study leader Amit Khera, M.D., professor of internal medicine and director of the

After decades of commonly prescribing aspirin for primary prevention, recent guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) recommend more select use for those with the highest risk of cardiac events due to the increased risk of bleeding.

"We used to say for aspirin, generally yes, occasionally no," Khera says. "With these new guidelines, we've flipped that on its head and are saying that we should not use aspirin for most people in primary prevention."

However, he adds, it's been unclear how to select which patients might still benefit most from aspirin therapy, taking into account the risk of bleeding. "We need tools to find that sweet spot where aspirin is most beneficial and offsets the associated risks," he says.

In the study, Khera and his colleagues looked to a diagnostic test - coronary artery calcium (CAC) scanning - to see if it could help doctors make this important decision. CAC scanning, a CT scan that scores the amount of calcium that lines the heart's arteries, is commonly performed to detect hardening of the arteries and risk of a heart attack or stroke.

The researchers gathered data from the Dallas Heart Study, an ongoing study that tracks the development of cardiovascular disease in more than 6,000 adults in Dallas County. Initially, participants were invited to three visits for the collection of health and demographic information, laboratory samples, and various imaging studies, including CAC scanning. These volunteers were then followed for 12 years on average to track those who had heart attacks, died from heart disease, or had a nonfatal or fatal stroke - medical problems collectively called atherosclerotic cardiovascular disease - and/or who had a bleeding event that caused hospitalization or death.

The researchers used data from 2,191 participants with a mean age of 44 years who had CAC scans and follow-up information available. About 57 percent were female and 47 percent were Black.

Overall, about half of the participants had a CAC score of 0, suggesting little to no calcium buildup in their arteries. About 7 percent had a CAC score of more than 100, suggesting heavy calcium buildup. The rest had values in the middle (1-99).

When Khera and his colleagues examined the rates of atherosclerotic cardiovascular disease (ASCVD) and bleeding in the study group, they found that both events increased in a graded fashion as CAC scores rose. However, when they used statistical modeling to see how many of the ASCVD events may have been prevented by aspirin use - based on values gleaned from a recent meta-analysis that informed the AHA and ACC guidelines - they found that aspirin's benefits only outweighed its risks for those with CAC scores above 100. For this group, the risk of ASCVD was about 15-fold and the bleeding risk about threefold of those with a CAC score of 0.

Yet, this effect only held true for those whose inherent risk for bleeding was already low, Khera says, meaning that in practice, as mentioned in the guidelines, if someone has had prior significant bleeding episodes, risk factors for bleeding, or was on medications that increase bleeding, they should not take aspirin for primary prevention regardless of their CAC score.

Together, Khera says, the findings reinforce new guidelines suggesting that aspirin for primary prevention is only appropriate for select patients and that CAC scanning can help doctors and patients make that decision.

"Aspirin use is not a one-size-fits-all therapy," says Khera, who holds the Dallas Heart Ball Chair in Hypertension and Heart Disease. "CAC scanning can be a valuable tool to help us tailor care to help more patients avoid a first heart attack or stroke."

Aim to detect cancer at an earlier, more treatable stage

700,000 in U.S. living with brain tumors

CHICAGO --- A new three-dimensional imaging technique has been developed that greatly improves the visibility of brain tumors in magnetic resonance imaging (MRI) scans. The technique, invented by a scientist at Northwestern University Feinberg School of Medicine, will potentially enable earlier diagnosis of tumors when they are smaller and more treatable.

The study will be published Oct. 28 in Science Advances.

In a study of 54 patients with brain tumors, the technique was found to provide a two-fold improvement in the contrast between tumors and normal brain tissue, compared with existing MRI techniques in widespread use. It greatly improved tumor visibility and ease of detection.

"Our goal is for the new technique -- T1RESS -- to help thousands of patients by allowing malignant tumors to be detected at an earlier, more curable stage," said inventor and lead author Dr. Robert Edelman, a professor of radiology at Northwestern.

The benefit of the new technique is particularly noticeable for very small malignant tumors, which are difficult to see and may be missed with standard imaging techniques. For patients undergoing treatment by surgery or radiotherapy, it is hoped the improved visibility of the tumor margins on contrast-enhanced scans will ensure the entire tumor is treated and result in better outcomes, Edelman said.

To better understand the mechanism by which T1RESS improves tumor visibility on MRI scans, consider the challenge of trying to see stars during the daytime.

"There just isn't enough contrast between the stars and the sunlit sky to make them visible," Edelman said. "In the case of brain tumors, T1RESS doubles the contrast between tumors and normal brain, so the tumors are more easily detected. It's like looking at the stars on a dark night instead of on a sunny day."

While the current study focused on imaging brain tumors, the investigators plan to apply the technique to detect cancer in the breast and prostate.

More than 700,000 Americans are living with a brain tumor and nearly 16,000 will die from their tumor this year, according to the American Brain Tumor Association.

MRI techniques for cancer imaging have evolved relatively slowly over the past decade. T1RESS applies the radio waves and magnetic fields used to generate the MRI signal differently from existing cancer imaging techniques. As a result, T1RESS is able to manipulate the signals from various brain tissues in a unique way so as to produce a very significant improvement in tumor visibility.

The findings of this initial study will need to be confirmed in a larger multi-site trial, Edelman said.

If the benefits are confirmed, it will be straightforward to make the technology widely available on MRI scanners throughout the world, Edelman noted. This is because the technology only involves installation of a specialized software package.

A tiny device the size of a small paperclip has been shown to help patients with upper limb paralysis to text, email and even shop online in the first human trial.

The device, Stentrode™, has been implanted successfully in two patients, who both suffer from severe paralysis due to amyotrophic lateral sclerosis (ALS) - also known as motor neuron disease (MND) - and neither had the ability to move their upper limbs.

Published in the Journal of NeuroInterventional Surgery, the results found the Stentrode™ was able to wirelessly restore the transmission of brain impulses out of the body. This enabled the patients to successfully complete daily tasks such as online banking, shopping and texting, which previously had not been available to them.

The Royal Melbourne Hospital's Professor Peter Mitchell, Neurointervention Service Director and principal investigator on the trial, said the findings were promising and demonstrate the device can be safely implanted and used within the patients.

"This is the first time an operation of this kind has been done, so we couldn't guarantee there wouldn't be problems, but in both cases the surgery has gone better than we had hoped," Professor Mitchell said.

Professor Mitchell implanted the device on the study participants through their blood vessels, next to the brain's motor cortex, in a procedure involving a small 'keyhole' incision in the neck.

"The procedure isn't easy, in each surgery there were differences depending on the patient's anatomy, however in both cases the patients were able to leave the hospital only a few days later, which also demonstrates the quick recovery from the surgery," Professor Mitchell said.

Neurointerventionalist and CEO of Synchron - the research commercial partner - Associate Professor Thomas Oxley, said this was a breakthrough moment for the field of brain-computer interfaces.

"We are excited to report that we have delivered a fully implantable, take home, wireless technology that does not require open brain surgery, which functions to restore freedoms for people with severe disability," Associate Professor Oxley, who is also co-head of the Vascular Bionics Laboratory at the University of Melbourne, said.

The two patients used the Stentrode™ to control the computer-based operating system, in combination with an eye-tracker for cursor navigation. This meant they did not need a mouse or keyboard.

They also undertook machine learning-assisted training to control multiple mouse click actions, including zoom and left click. The first two patients achieved an average click accuracy of 92 per cent and 93 per cent, respectively, and typing speeds of 14 and 20 characters per minute with predictive text disabled.

University of Melbourne Associate Professor Nicholas Opie, co-head of the Vascular Bionics Laboratory at the University and founding chief technology officer of Synchron said the developments were exciting and the patients involved had a level of freedom restored in their lives.

"Observing the participants use the system to communicate and control a computer with their minds, independently and at home, is truly amazing," Associate Professor Opie said.

"We are thankful to work with such fantastic participants, and my colleagues and I are honoured to make a difference in their lives. I hope others are inspired by their success.

"Over the last eight years we have drawn on some of the world's leading medical and engineering minds to create an implant that enables people with paralysis to control external equipment with the power of thought. We are pleased to report that we have achieved this."

The researchers caution that while it is some years away before the technology, capable of returning independence to complete everyday tasks is publicly available, the global, multidisciplinary team is working tirelessly to make this a reality.

The trial recently received a $AU1.48 million grant from the Australian commonwealth government to expand the trial to hospitals in New South Wales and Queensland, with hopes to enrol more patients.

It's no secret that loneliness and social isolation have a negative impact on the mental and physical health of older adults. Now, researchers at the University of British Columbia are discovering that social isolation affects the health of men and women in different ways--including placing women at higher risk of high blood pressure.

In a study recently published in the Journal of Hypertension, researchers discovered that middle aged and older women who lacked social ties were much more likely than men to suffer from hypertension--a known risk factor for heart disease, which is the leading cause of death among women--and stroke.

"Among older adults, social isolation is the largest known risk factor for mortality, equal only to smoking," said principal investigator Annalijn Conklin, assistant professor in the faculty of pharmaceutical sciences at UBC and researcher with the Centre for Health Evaluation and Outcome Sciences. "Less well known is how social isolation affects men and women differently, or how it affects biomarkers of longevity. Our research indicates that women, in particular, are more likely to be hypertensive when they experience isolation in middle and older age."

Using data from the Canadian Longitudinal Study on Aging, these researchers analyzed the social ties of 28,238 adults aged 45 to 85, and found that women who were non-partnered, engaged in fewer than three social activities a month, or had a small social network (fewer than 85 contacts) had higher odds of hypertension. Average systolic blood pressure was highest among widowed, lone-living and socially inactive women, and the largest difference in blood pressure was between widowed and married women. Widowed women were found to have the strongest likelihood of hypertension across all categories.

Among men, the picture was quite different. Those who were single, shared a home with others, and had the largest social networks had the highest blood pressure, while those who had smaller networks and lived alone had lower blood pressure.

The researchers found that combinations of different social ties also mattered. Regular social participation appeared to have a protective effect among non-partnered women, suggesting that health care providers may want to screen for the number of monthly social activities, and include these alongside healthy diet and exercise when treating non-partnered older women.

"Among women, the increase in blood pressure that was associated with the lack of social ties was similar to that seen with non-steroidal anti-inflammatory use, increased sodium diets pollution or weight gain," said Conklin. "This represents a significant women-specific risk factor for heart disease or stroke."

Previous research by Conklin using the same data set found that women who were single, widowed, divorced or separated had higher odds of abdominal and general obesity, while men were less likely to be obese if they lived alone and had a smaller social network.

"Taken with our previous research, our new findings underline how social isolation affects health in men and women differently," said Conklin. "At a time when COVID-19 is forcing us to limit our social interactions, it's important for those working in health care and public health to encourage older women, in particular, to find new ways to be socially active."

Zeinab Hosseini, the lead author who contributed to the work as a former postdoctoral fellow at UBC says more studies are needed on how exactly social connections impact cardiovascular risk factors. "Prospective and intervention studies can help us understand this as well as why the associations are different for women compared to men," she said.

A genetic analysis of non-small cell lung cancer (NSCLC) patients on the phase III NRG Oncology RTOG 0617 clinical trial assessing radiation dose discovered that high dose radiation therapy is associated with shorter survival times among patients with a radiation-sensitive genotype in DNA repair pathway. These findings were presented at the virtual edition of the American Society for Radiation Oncology's (ASTRO) Annual Meeting in October 2020.

The NRG-RTOG 0617 analysis reviewed blood and DNA samples from the 321 eligible patients who participated in the study. The primary focus was to externally validate blood cell ERCC1 and ERCC2 genetic signatures as a radiosensitivity biomarker for tumor and normal tissues. Previous findings in stage I and IV NSCLC patients indicate that high dose radiotherapy typically leads to improved survival, better tumor control, and better survival in inoperable NSCLC.

"Single nucleotide polymorphisms (SNPs) signature in DNA repair pathway and its interaction with radiation dose could provide personalized radiation prescriptions to patients depending on their genotypic signature, and this could improve survival outcomes," stated Feng-Ming (Spring) Kong, MD, PhD, FACR, FASTRO of the Clinical Oncology Center, the University of Hong Kong - Shenzhen Hospital; and Li Ka Shing Faculty of Medicine, The University of Hong Kong; Department of Radiation Oncology, Case Western Reserve University, and the lead author of the NRG-RTOG 0617 abstract. "Previously, the data that indicated the potential for ERCC1 and ERCC2 genes to be biomarkers for normal and tumor tissue in NSCLC patients had only been performed in single institution trials. It was imperative to validate these findings in a multi-institutional clinical setting."

Patients who participated on the initial NRG-RTOG 0617 trial were randomly assigned to receive either standard radiation (RT) dose (60 Gy) or high RT dose (74 Gy). Among the 321 eligible patients, 275 patients had both ERCC1 and ERCC2 SPNs signatures conducted. The median follow up time for the trial was 68 months. Of the 163 patients assigned to 60 Gy arm, 67 patients carried the resistant genotype signature and had a median survival time (MST) of 22 months compared to the radio-sensitive genotype's MST of 31 months (P=0.076, HR= 1.4 [95%CI: 0.96-2.01]). There were 112 patients assigned to the 74 Gy arm and 36 of these patients were carrying the resistant genotype signature and had a MST of 31 months (95% CI, 20-52). This was significantly better than the MST of 20 months for the sensitive signature type patients on the 74 Gy arm (p=0.025, HR= 0.59 [95% CI: 0.37-0.94]). These results confirm the hypothesis that patients with the radio-sensitive genotype have better survival with 60 Gy, whereas patients with the radiation-resistant genotype fair better in the 74 Gy arm with regard to survival. Interestingly, 63% patients from this study were classified as radiation sensitive according to this signature, and this at least partially explains the result of better survival in patients in the 60 Gy arm.

These findings could benefit from further prospective validation through a study with a larger sample size, and suggest the need of future study on personalized radiation prescription in treating patients with lung cancer.

Researchers involved in the phase II NRG Oncology RTOG 0526 trial studying low dose rate (LDR) prostate brachytherapy (BT) following local recurrence (LR) after external beam radiotherapy (EBRT) for patients with low-to-intermediate risk prostate cancer reported late Grade 3 gastrointestinal and genitourinary adverse events (AEs) occurring in 14% of trial participants. Results from a follow up of a minimum of 5-years of patients that participated on the trial suggest that 5-year freedom from biochemical failure (BF) stands at 68% and remains steady with the 10-year rate being 54%. This report was presented at the virtual edition of the American Society for Radiation Oncology's (ASTRO) Annual Meeting in October 2020.

"Low and intermediate risk prostate cancer typically recurs locally in 10-30% of men following EBRT. Prior to this study, most data available on salvage brachytherapy in prostate cancer was retrospective and stemmed from single-center studies with multiple variables regarding doses and technique. With such a high recurrence rate afflicting this patient population, it was crucial to expand data on this modality in a multicenter study with defined methods," stated Juanita M. Crook, MD, FRCPC, of the Cancer Centre for the Southern Interior at the University of British Columbia and lead author of the NRG-RTOG 0526 abstract.

In order to be eligible for NRG-RTOG 0526, prostate cancer patients needed to have low or intermediate risk prostate cancer prior to EBRT in addition to having a proven LR thirty or more months following their EBRT. 92 patients were analyzed for the study and followed for a minimum of 5 years after their salvage brachytherapy. Participants on NRG-RTOG 0526 received a minimum dose of 140 Gy with I-125 or 120 G with Pd-103. Researchers followed clinical outcomes at 5 year or greater including objectives such as disease-specific survival, overall survival, time to biochemical failure, and patterns of recurrence.

As initially reported, 14% of participants experienced late Grade 3 gastrointestinal and genitourinary AEs at a median follow up of 6.9 years. The median prior EBRT dose was 74 Gy and the median interval since EBRT was received was 85 months. Androgen deprivation therapy was combined with salvage BT in only 16% of cases. The 5-year freedom from biochemical failure rate was 68%, which is comparable to other salvage modalities. At 10 years, the biochemical failure rate was 54% (95% CI: 43-66). Disease-free survival at 5 years was 61% but fell to 33% at 10 years. Nineteen patients died. Four patients had local recurrence (5% at 10 years), and 14 had distant failure with a 10-year rate of 19% (95% CI:10-29). None of the clinical or treatment factors was significantly associated with participants' overall survival, disease-free survival, or local, distant, or biochemical failure.