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CHAMPAIGN, Ill. -- Researchers have developed new 3D-printed microlenses with adjustable refractive indices - a property that gives them highly specialized light-focusing abilities. This advancement is poised to improve imaging, computing and communications by significantly increasing the data-routing capability of computer chips and other optical systems, the researchers said.

The study was led by University of Illinois Urbana-Champaign researchers Paul Braun and Lynford Goddard and is the first to demonstrate the ability to adjust the direction in which light bends and travels through a lens with sub-micrometer precision.

The results of the study are published in the journal Light: Science and Application.

"Having the ability to fabricate optics with different shapes and optical parameters offers a solution to common problems faced in optics," said Braun, who is a professor of materials science and engineering. "For example, in imaging applications, focusing on a specific object often results in blurry edges. Or, in data-transfer applications, higher speeds are desired without sacrificing space on a computer chip. Our new lens-fabrication technique addresses these problems in one integrated device."

As a demonstration, the team fabricated three lenses: a flat lens; the world's first visible-light Luneburg lens - a previously impossible-to-fabricate spherical lens with unique focusing properties; and 3D waveguides that may enable massive data-routing capabilities.

"A standard lens has a single refractive index and therefore only one pathway that light can travel through the lens," said Goddard, who is a professor of electrical and computer engineering. "By having control over the internal refractive index and the shape of the lens during fabrication, we have two independent ways to bend light inside a single lens."

In the lab, the team uses a process called direct-laser writing to create the lenses. A laser solidifies liquid polymers and forms small geometric optical structures up to 100 times smaller than a human hair. Direct-laser writing has been used in the past to create other microlenses that only had one refractive index, the researchers said.

"We addressed the refractive index limitations by printing inside of a nanoporous scaffolding support material," Braun said. "The scaffold locks the printed micro-optics into place, allowing for the fabrication of a 3D system with suspended components."

The researchers theorize that this refractive index control is a result of the polymer-setting process. "The amount of polymer that gets entrapped within the pores is controlled by the laser intensity and exposure conditions," Braun said. "While the optical properties of the polymer itself do not change, the overall refractive index of the material is controlled as a function of laser exposure."

Team members said they expect that their method will significantly impact the manufacturing of complex optical components and imaging systems and will be useful in advancing personal computing.

"A great example of the application of this development will be its impact on data transfer within a personal computer," Goddard said. "Current computers use electrical connections to transmit data. However, data can be sent at a significantly higher rate using an optical waveguide because different colors of light can be used to send data in parallel. A major challenge is that conventional waveguides can only be made in a single plane and so a limited number of points on the chip can be connected. By creating three-dimensional waveguides, we can dramatically improve data routing, transfer speed and energy efficiency."

A person's genetic make-up can influence whether they might experience side effects from certain medications. Some laboratories now offer pharmacogenetic tests that allow patients to learn whether they carry genetic variants known to be associated with adverse drug effects. Such tests might help patients and their doctors choose safer, more effective treatments, but the U.S. Food & Drug Administration and other regulatory agencies have expressed concern that patients might make unproven, inappropriate decisions about their medications based on their pharmacogenetic results.

A new paper published December 3 in JAMA Network Open might help allay some of these concerns. Researchers at the VA Boston Healthcare System, Brigham and Women's Hospital, and Harvard Medical School conducted a randomized controlled trial of pharmacogenetic testing related to cholesterol-lowering medications called statins. Statins, such as atorvastatin and simvastatin, are used by millions of Americans to lower the risk of heart attack and stroke. However, in rare cases, patients might experience muscle damage from statins, which can sometimes be serious and life-threatening. Pharmacogenetic testing can identify whether a patient carries a genetic variant in the SLCO1B1 gene that puts them at a higher risk of such statin-associated muscle injury. Although this test might help patients avoid adverse drug effects, it might also have the unintended consequence of causing patients not to do enough to lower their risk of cardiovascular disease.

"This study provides reassurance that patients and providers can use pharmacogenetic testing in a way that maximizes its benefits while avoiding harmful unintendended consequences," said corresponding author Jason Vassy, MD, MPH, a clinician investigator at the Brigham, primary care physician at the VA Boston Healthcare System and assistant professor at Harvard Medical School. "Our findings do not support the idea that all patients should have pharmacogenetic testing before starting a statin, but they do provide rigorous, real-world evidence that the harms of such testing are minimal."

Vassy and colleagues enrolled 400 patients at the VA Boston Healthcare System who were not currently prescribed a statin but had cardiovascular disease risk factors that might make them candidates for statin treatment now or in the near future. The researchers conducted a controlled study in which statin pharmacogenetic results were given to a random half of the participants and their primary care providers at the beginning of the study, while the other half received their results after one year. After one year, the cholesterol levels in the group who received their pharmacogenetic results were not higher than those in the group who did not receive their results, and they were not less likely to receive medical care meeting recommended guidelines. In some cases, physicians may have used the results to choose an alternate, but equally effective, medication for the patient. Overall, the study results suggest that pharmacogenetic testing did not cause patients and their primary care providers to be less proactive in lowering their risk of cardiovascular disease.

The authors note that fewer than expected participants were prescribed statin therapy in general -- potentially a reflection of patient reluctance and physician prescribing patterns. Less than 16 percent of physicians documented talking to their patients about their SLCO1B1 in the intervention arm of the trial.

Vassy said the team's findings should allay stakeholders' concerns about the potential unintended consequences of pharmacogenetic results, a conclusion that he claims will become increasingly relevant as more and more patients undergo genetic testing as a part of their health care.

"Many health care systems have launched pharmacogenetic testing programs," said Vassy. Such a program exists at the Brigham through its Pharmacogenomics Clinic. "Our study offers empirical evidence that the clinical use of pharmacogenetic test results for SLCO1B1 do not worsen patient outcomes, which we hope will help inform the debate about utility and unintended harm for this kind of testing."

In the spring, scientists throughout the world were actively discussing whether there is a connection between vaccination against tuberculosis in early childhood and the mild course of the new coronavirus disease. However, at that time, statistics on patients with COVID-19 were still insufficient to draw reliable conclusions. Medical doctors throughout the world are currently beginning to find important patterns that will help protect public
health in the future.

An analysis of statistical data was conducted by experts from St Petersburg University. It showed that the incidence of COVID-19, the course of acute interstitial pneumonia caused by infection, and the mortality rate from it are associated with being vaccinated with bacilli Calmette-Guerin (BCG) according to the national vaccination schedule. The mortality rate turned out to be lower in those countries and areas where national vaccine immunisation programmes have taken place for a long time or continue today, especially if revaccinations were practiced. These countries are Finland, China, Japan, Korea, and also countries in Eastern Europe, Central and South Asia, Africa, and the former USSR. This figures are significantly higher where large-scale BCG vaccination has never been practiced or stopped more than 20 years ago, for example, in the USA, Italy, the Netherlands, Belgium, and Germany excluding the lands of the former East Germany.

The authors of the paper are young researchers: Alina Petyaeva, a student at St Petersburg University and a laboratory assistant researcher; Iana Ivashkevich, a graduate of the online course of St Petersburg University in General Pathophysiology, who carries out research at the University; and a physician Liubov Kazacheuskaya. The article is written under the supervision of Leonid Churilov M.D., Ph.D., Deputy Head of the Laboratory of the Mosaic of Autoimmunity and Head of the Department of Pathology at St Petersburg University.

'BCG vaccine in Russia is given once in a lifetime for newborns,' said Iana Ivashkevich. 'But it is the early and long-term influence of the vaccine strain on the developing immune system that provides an adjuvant effect - it enhances the body's immune reaction to various antigens, including many infectious ones. An adjuvant is a substance that enhances immune responses in a non-specific manner. Many adjuvants also enhance autoimmune processes. But the BCG vaccine has properties that are uncharacteristic for most adjuvants: for example, it acts as an immune response-modulating agent, and also reduces the risk of some autoimmune diseases and lymphoid tumours. COVID-19 can cause autoimmune complications, so the properties of BCG, which are so unusual for an adjuvant, can be of benefit in this regard. According to statistics, in countries practicing neonatal BCG vaccination, there has been an overall decrease in infant mortality.

Revaccination is a renewed vaccination throughout life. For BCG It is now practiced by only four countries: Belarus, Kazakhstan, Turkmenistan, and Uzbekistan. It is important that the effect of trained immune system response is achieved if the BCG vaccine is given to an immature immune system, scientists are certain. 'There is reason to believe that in adults and elderly people who were not vaccinated in early childhood, the effect of late vaccine administration will be significantly less,' explained Leonid Churilov. 'At the same time, there are research papers by scientists from the Netherlands, where BCG is not given in childhood. They indicate that BCG administration to adults does not worsen, and, perhaps, somewhat attenuates the course of the disease when infected with the new coronavirus.'

As the authors of the article said, the BCG vaccine activates a local immune response on the mucous membranes. It is through them that acute respiratory disease caused by SARS-CoV-2 spreads. According to the scientists, the BCG vaccine serves as a trigger for a 'trained' immune system response that activates monocytes, macrophages and natural killer cells - that power in the non-antigen-specific protective rogrammes of the body. Also, gamma-interferon, produced after BCG vaccination, and other mediators may ultimately attenuate the course of COVID-19.

'The causative agent of the new coronavirus infection and BCG have common peptides, which means that induction of cross-immunity is possible. Large clinical trials of the BCG vaccine and trials of its use for the prevention of the new coronavirus infection are currently underway, for example, in the Netherlands and Australia,' said Iana Ivashkevich. Additionally, the scientists explain that the viewpoint on the connection of BCG vaccine with a decrease in the spread of COVID-19 and a less severe course of the disease is confirmed by studies of international research teams from the USA, Germany, Canada, India, and Iran.

DANVILLE, Pa. - Using a single ventilator to support two patients could be feasible in crisis situations involving a ventilator shortage, researchers have found.

A team of clinical investigators from Geisinger partnered with Bucknell University and Kitware, a New York-based software research and development company, to develop a computational model to simulate varying scenarios in which two patients share one ventilator.

The COVID-19 pandemic has created shortages of medical supplies and equipment, including life-saving ventilators, around the world. Earlier this year, the Federal Emergency Management Agency (FEMA) and the U.S. Department of Health and Human Services (HHS) issued guidelines for ventilator sharing in cases of ventilator shortage.

However, studies of this practice are few, and "the pace of conventional research is too slow when addressing a pandemic crisis," the research team wrote. "Computational simulation provides an opportunity to quickly develop guidance over a wide range of possible clinical scenarios without incurring patient risk."

Using Kitware's Pulse Physiology Engine software, the team created whole-body physiological simulations of 287 COVID-19 patients with varying levels of lung function and oxygen saturation index (OSI) that could be successfully managed using a dedicated ventilator. A whole-body physiological simulation allows researchers to observe secondary effects that would not be apparent when modeling mechanics of ventilation alone. The team then used the software to calculate outcomes for all possible modeled patient pairings to project the success of using a shared ventilator for each pair.

Patients with similar levels of lung function and comparable OSI were most likely to have satisfactory outcomes when paired to a single ventilator, the team found.

The study was published in PLOS ONE.

Sharing ventilators should be considered a last-resort approach in a situation where all available ventilators have been deployed, so it is most likely to be used in developing countries, researchers said.

"In resource-limited regions of the world, the COVID-19 pandemic has and will continue to create equipment shortages," said S. Mark Poler, M.D., anesthesiologist at Geisinger and a co-author of the study. "While single-patient ventilation is preferable, under extreme circumstances and in resource-challenged regions, multi-patient ventilation is a potentially viable option and can significantly increase the capacity to care for critically ill patients. Our simulations provide a conceptual framework and guidelines for clinical patient selection."

"This study shows that the Pulse Physiology Engine can simulate realistic equipment mechanics and patient physiology for a variety of illness severities," said Rachel Clipp, Ph.D., a technical leader on Kitware's Medical Computing Team and co-author of the study. "Having the ability to leverage these capabilities during a pandemic provides valuable clinical information that can be used to inform medical treatment in resource-constrained situations."

TORONTO, Dec. 03, 2020 -- Most countries are not fulfilling their international legal obligations during COVID-19 and other public health emergencies, reveals new research by a consortium of 13 leading global health law scholars, hosted by the Global Strategy Lab (GSL) at York University.

In 2019, members of the Global Health Law Consortium analyzed key aspects of the International Health Regulations (IHR) to authoritatively interpret what countries are legally allowed to do to each other during future public health crises like Ebola and SARS.

This work became even more relevant when the COVID-19 pandemic began spreading around the world early this year; the Global Health Law Consortium members reviewed how countries reacted to the outbreak based on the International Health Regulations that legally bind 196 countries in how they prevent, detect and respond to public health crises.

Subsequently, during a conference in South Africa, this group of legal experts developed consensus statements that authoritatively interpret Article 43 of the IHR, which identifies the additional health measures countries can legally enact when responding to public health risks, and Article 44, which outlines countries' legal duty to collaborate and assist one another in building national public health systems.

The consensus statements were published today in the prestigious International Organizations Law Review.

Professor Steven J. Hoffman, director of the Global Strategy Lab at York University, is senior author on both consensus statements, and Roojin Habibi, research fellow at the GSL and doctoral candidate at Osgoode Hall Law School, is lead author on the consensus statement that interprets Article 43 of the IHR.

"Many countries have taken overbroad measures, both in the past and now during the coronavirus outbreak, which indicate that the provisions within Article 43 of the International Health Regulations are not well understood and perhaps not fit for purpose," says lead author Habibi.

Under Article 43 of the IHR, countries are permitted to exercise their sovereignty in taking additional health measures to respond to public health emergencies, provided that these measures are proportionate to the risk at hand, aligned with human rights imperatives, and backed by scientific evidence.

"COVID-19 has clearly shown that proper international cooperation is required to prevent infectious diseases from spreading across borders," Habibi points out. "Based on our analysis, we believe that the global community needs a common understanding of the law at hand. We recommend revision and clarification of legal obligations contained in these Articles to facilitate collaboration and enhance pandemic responses in the future."

According to Article 44, there is a common and shared responsibility among countries to make it possible for every country to achieve the core public health capacities identified in the IHR, which is overseen by the World Health Organization.

"Most countries in the world are currently violating their international legal obligations under Articles 43 and 44 of the International Health Regulations," notes Hoffman. "This means that the rules that were supposed to guide governments' responses to pandemics like COVID-19 are either misunderstood, toothless, or insufficient - most likely a combination of all three. The Global Health Law Consortium's analyses of the International Health Regulations that were published today will help bring clarity to countries' legal obligations during global health emergencies, but ultimately these regulations need to be urgently updated to better reflect the realities of the globalized world in which we all live."

The two statements published today are the first consensus-based collaboration by members of the Global Health Law Consortium.

What impact has working from home as a result of the COVID-19 pandemic had on our health? In a new study, researchers from USC have found that working from home has negatively impacted our physical health and mental health, increased work expectations and distractions, reduced our communications with co-workers and ultimately lessened our productivity. The study finds that time spent at the workstation increased by approximately 1.5 hours, while most workers are likely to have less job satisfaction and increased neck pain when working from home. It also illustrates the differential impact of working from home for women, parents, and those with higher income.

Nearly 1,000 respondents participated in the survey regarding the impact of working from home on physical and mental well-being. Authored by Ph.D student Yijing Xiao, Burcin Becerik-Gerber, Dean's Professor of Civil and Environmental Engineering, Gale Lucas, a research Assistant Professor at the USC Institute for Creative Technologies and Shawn Roll, Associate Professor of Occupational Science and Occupational Therapy, the study was published in the Journal of Occupational and Environmental Medicine. Becerik-Gerber and Lucas are co-directors of The Center for Intelligent Environments at USC.

The survey was conducted during the early days of the pandemic. Responses regarding lifestyles, home office environments, and physical and mental well-being revealed the following about that first phase of the pandemic's "work from home" period:

Over 64 percent of respondents claimed to have one or more new physical health issues

Nearly 75 percent of those surveyed experienced one new mental health issue

Female workers with annual salary less than 100k were more likely than male workers or workers with higher income to report two or more new physical and mental health issues

Female workers had higher incidence of depression

Parents with infants tended to have better mental well-being but also a higher chance of reporting a new mental health issue

Having toddlers was affiliated with physical well-being but was also associated with more physical and mental health issues

Living with at least one teenager lowered the risk of new health issues

Nearly 3/4 of workers adjusted their work hours and more than 1/3 reported scheduling their work hours around others

Workers who adjusted their work hours or schedule work around others were more likely to report new physical or mental health issues

Pets did not appear to have impact on physical or mental health

Workers decreased overall physical activity and physical exercise, combined with increased overall food intake

Decreased physical and mental well-being was correlated with increased food or junk food intake

Only one-third had a dedicated room for their work at home; at least 47. 6 percent shared their workspace with others

The authors suggest that having a dedicated work from home space would mitigate a number of negative impacts.

Becerik-Gerber, the study's corresponding author said,"The quality of your home workspace is important; having a dedicated workspace signals to others that you are busy, and minimizes the chances of being distracted and interrupted. Increased satisfaction with the environmental quality factors in your workspace, such as lighting, temperature, is associated with a lower chance of having new health issues. In addition, knowing how to adjust your workspace helps with physical health."

MINNEAPOLIS- December 3, 2020 - University of Minnesota Medical School and UnitedHealth Group (NYSE: UNH) researchers found that metformin was associated with significantly reduced COVID-19 death risks in women in one of the world's largest observational studies of COVID-19 patients.

Metformin is an established, generic medication for managing blood sugar levels in patients with type 2 diabetes. It also reduces inflammation proteins like TNF-alpha that appear to make COVID-19 worse.

The study, published in The Lancet Healthy Longevity, is a retrospective cohort analysis based on de-identified patient data from UnitedHealth Group. The team analyzed about 6,000 individuals with type 2 diabetes or obesity who were hospitalized with COVID-19 and assessed whether or not metformin use was associated with decreased mortality. They found an association that women with diabetes or obesity, who were hospitalized for COVID-19 disease and who had filled a 90-day metformin prescription before hospitalization, had a 21% to 24% reduced likelihood of mortality compared to similar women not taking the medication. There was no significant reduction in mortality among men.

"Observational studies like this cannot be conclusive, but contribute to growing bodies of evidence. Seeing a bigger association with protection in women over men may point towards inflammation reduction as a key way that metformin reduces risk from COVID-19. However, more research is needed," said principal investigator Carolyn Bramante, MD, MPH, who is an assistant professor in the Department of Medicine at the University of Minnesota Medical School. "A large database covering different geographic areas is rarely available. We were fortunate to have the opportunity to do this research alongside UnitedHealth Group."

"While effective therapies to mitigate the harm of the SARS-CoV-2 virus are being developed, it is important that we also look to, and evaluate commonly used medications with good safety profiles for their potential to combat the virus," said Deneen Vojta, MD, executive vice president, Enterprise Research and Development, UnitedHealth Group.

The results provide new directions for research against COVID-19. In collaboration with Christopher Tignanelli, MD, assistant professor in the Department of Surgery at the University of Minnesota Medical School, Bramante submitted an investigational new drug application to the Food and Drug Administration for use of metformin for COVID-19 treatment and prevention. The FDA approved this application. Bramante and Tignanelli received a donation from the Parsemus Foundation to conduct a multi-site prospective, randomized pilot study in collaboration with the Executive Director of Clinical Research for UnitedHealth Group R&D, Ken Cohen, MD. This pilot trial will begin enrolling the week of Dec. 8 and will lead into a larger trial that is fully powered for important clinical outcomes if additional funding becomes available. These collaborators are still seeking this funding.

FAIRFAX, Va.-- The final 2021 Medicare Physician Fee Schedule (MPFS) issued this week by the Centers for Medicare & Medicaid Services (CMS) will result in reimbursement cuts in the range of 10% for neurointerventional procedures, according to a detailed analysis published last week in the Journal of NeuroInterventional Surgery™, the leading international peer-reviewed journal for the clinical field of neurointerventional surgery. Practitioners warn that this measure will jeopardize access to lifesaving care for individuals experiencing strokes, aneurysms and other deadly conditions.

The JNIS article outlines the potential impact of the new fee schedule and raises the alarm that this action by CMS could further compound current challenges to the viability of neurointerventional practices, which already have been severely impacted by the COVID-19 pandemic.

The catalyst for this potentially devastating change is Medicare's budget-neutrality requirements, which require substantial reductions to offset payment increases approved in other areas of the health care system. The authors of the JNIS analysis point to the fact that these impacts will almost certainly be compounded in upcoming years. JNIS Editor-in-Chief Felipe Albuquerque, MD, says the article authors predict even more severe economic impacts as private payers follow Medicare's lead.

"This rule originates in Medicare, but we know that private insurers often base their own rates on those set by CMS. Together, that represents about 80% of the patient population," says Albuquerque. "Some practices will not be able to withstand that level of reimbursement reduction for very long."

To combat this draconian change, the Society of NeuroInterventional Surgery (SNIS)--an association representing neuroendovascular care professionals and the sponsor of JNIS--has joined a coalition of professional societies urging Congress to provide a legislative fix.

"We've been working for more than two decades to increase access to neurointerventional therapies that actively save lives," says co-author Joshua A. Hirsch, MD, FSNIS, chair of the SNIS health policy committee, "but the thoughtlessness of CMS' approach put practices at risk in the midst of fighting a pandemic. It is inexcusable. Congress needs to move quickly and add stability to the system without diminishing access to critical diagnostic tests and surgical procedures."

For heavy (ex-)smokers, lung cancer screening using low-dose computed tomography (low-dose CT, LDCT) offers more benefit than harm: The procedure can save a number of people from dying of lung cancer; for some of them, it might also prolong overall survival. This is the conclusion drawn by IQWiG in its final report commissioned by the Federal Joint Committee (G-BA).

Overall, the IQWiG project team sees a hint of a benefit of low-dose CT for lung cancer screening versus no screening for the outcome "mortality". This benefit is accompanied by harm from false-positive screening results and overdiagnosis. For the high-risk group of heavy (ex-)smokers, however, the benefit outweighs the potential harm.

Low-dose CT for lung cancer screening under evaluation

Lung cancer is one of the leading causes of cancer deaths worldwide. Men are diagnosed at a median age of 70, women at 69. Lung cancer is usually discovered at a late stage, so that five years after diagnosis, only one fifth to one sixth of people affected are still alive.

At present, there is no systematic screening for lung cancer in Germany and LDCT is not part of the scope of services provided by statutory health insurance. Pursuant to the Radiation Protection Act, the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) is currently evaluating whether radiation exposure due to several years of LDCT screening (including follow-up diagnostics) is permissible.

Low-dose CT screening reduces lung cancer mortality

The results of eight randomized controlled trials (RCTs) with more than 90,000 people provide an indication of a benefit of LDCT screening for heavy (ex-)smokers: Within about ten years, it can prevent about 5 out of every 1,000 people from dying of lung cancer.

In contrast, no statistical advantage of LDCT screening is shown for all-cause mortality. This could be because people saved from death by lung cancer die from other tobacco-related diseases instead, such as other types of cancer or cardiovascular diseases. However, the results of meta-analyses of all pooled study data suggest a reduction in all-cause mortality.

In the overall weighing of disease-specific mortality and all-cause mortality, in its final report IQWiG therefore concludes that there is a hint of a benefit of low-dose CT for lung cancer screening versus no screening.

Misdiagnosis and overdiagnosis are rather rare

A false-positive result alone means harm to the people affected. The diagnosis of lung cancer also requires histological or cytological confirmation, which - like any diagnostic procedure and treatment - carries the risk of side effects and complications. For instance, surgical interventions are performed without a lung tumour always being present, sometimes with serious side effects. However, the risk of harm in the studies included varies: 1 to 15 out of every 1000 people underwent unnecessary surgery due to false-positive screening results.

Overdiagnosis detects lung tumours that would never have been noticed without screening and would never have required treatment. The risk of being overdiagnosed also varies greatly in the studies analysed: Out of every 1000 people invited to screening, 0 to 22 might be affected by an overdiagnosis. The risk of overdiagnosis for people diagnosed with lung cancer during the screening phase ranged between 0 and 63 percent in the studies. This highlights the importance of an optimized screening strategy to keep the risk of overdiagnosis low.

For the high-risk group of heavy (ex-)smokers, however, the benefit outweighs these aspects of harm. In summary, there is a hint of a benefit of low-dose CT screening versus no screening.

Screening strategy is important

An optimal screening strategy is the basis for a positive benefit-harm ratio of low-dose CT for lung cancer screening. For this purpose, the high-risk population to be examined must be defined as precisely as possible by means of smoking behaviour and remaining life expectancy. As in the studies analysed, lung cancer screening should be supported in practice by specific quality assurance measures (diagnostic algorithm, types of devices, follow-up, etc.).

Further optimization of low-dose CT for lung cancer screening is currently ongoing. For example, up to the end of 2024, a European study is investigating the safety of risk-based examination intervals and strategies for implementation: The EU project "4-IN THE LUNG RUN", in which German research institutions are also involved, is to include a total of 24,000 people in an RCT.

Black and Hispanic populations are disproportionately affected by COVID-19, according to a systematic review published this week.

The disparities were likely related to minority populations being at higher risk of exposure to the coronavirus as opposed to underlying health conditions or other factors, according to the review led by researchers at Oregon Health & Science University and the VA Portland Health Care System.

The review confirms health disparities that have been widely reported in a series of observational studies nationwide.

"It's likely rooted in social determinants of health and longstanding inequalities in terms of housing, transportation, occupation and access to health care," said lead author Katherine Mackey, M.D., a staff physician in the Department of Hospital and Specialty Medicine at the Portland VA and assistant professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine.

The review published this week in the Annals of Internal Medicine.

Funded and conducted at the behest of the U.S. Department of Veterans Affairs, the study closely examined 52 observational studies conducted since the beginning of the year.

"This is the first paper to comprehensively examine the literature about COVID-related health disparities and the factors leading to disparities in health outcomes," said senior author Devan Kansagara, M.D., a staff physician in the Department of Hospital and Specialty Medicine with the Portland VA and an associate professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine. "The information we've seen so far suggests the disparities were likely related to exposure-related factors rather than other factors, like underlying health issues."

Kansagara added that he expects further clarity as evidence continues to build over the course of the pandemic.

The review highlights the fact that racial and ethnic minority populations are disproportionately harmed by the virus primarily because they are at heightened risk of being exposed in the first place. Underlying health conditions did not appear to be a factor driving higher rates hospitalizations and deaths.

Instead, the evidence suggests disparities in housing, transportation and occupations are likely raising the risk of exposure and transmission of the virus. In Oregon, for example, several outbreaks have affected workers in food processing and agriculture, with a labor pool comprised to a large degree by Latino workers. Some efforts are underway to reduce the risk of exposure, including a longtime health outreach program operated by OHSU Health Hillsboro Medical Center.

"We need to double down on efforts to reduce exposure to the virus in the first place among vulnerable populations," Kansagara said.

Researchers from Tokyo Medical and Dental University (TMDU) find that stimulating a group of cellular receptors called β-ARs can halt the progression of oral cancer

Tokyo, Japan - Affecting almost 600,000 people worldwide every year, and with only a 50% survival rate, oral squamous cell carcinoma (OSCC) is one of the more common and deadly forms of cancer. The poor prognosis of OSCC patients is mainly attributed to a lack of therapies that block the metastasis, or spread, of cancer cells from the primary tumor to other sites in the body.

Prior to metastasis, cancer cells undergo a series of changes that cause them to become motile and more invasive. This process, called epithelial?mesenchymal transition (EMT), equips cancer cells with everything they need to travel through the lymphatic system and form secondary tumors. Furthermore, recent reports imply that EMT also confers cancer cells with tumor initiation activity and drug resistance.

Working on the theory that disrupting EMT should prevent cancer progression and therefore reduce OSCC mortality rates, researchers from Tokyo Medical and Dental University (TMDU) screened a panel of small chemical compounds for their ability to reverse the process of EMT in oral cancer cells. The results, published this month in Cancer Science, may represent an exciting new avenue for the treatment of OSCC.

"We identified a β2?adrenergic receptor (β2?AR) agonist called isoxsuprine that effectively interfered with EMT," says lead author of the study Shintaro Sakakitani. "Interestingly, previous studies have provided conflicting results regarding the involvement of β-ARs in tumorigenesis--some reports suggest that β-AR signaling is important in tumor progression, while others point to a protective role for β-AR induction."

After treating a range of oral cancer cell types with isoxsuprine, the researchers found that the resulting increase in β2-AR expression significantly impaired EMT and reduced cell motility. A non-selective agonist called isoprenaline, which enhances the expression of all types of β?adrenergic receptor not just β2, produced a similar result.

Confirming the protective role of β-AR activation, the researchers then pre-treated cells with a chemical that prevents receptor expression, resulting in enhanced EMT. Further, deletion of the gene coding for β2?AR completely abolished the protective effects of isoxsuprine.

As a further test of treatment efficacy, the researchers established tumors in mice and provided daily treatment with either isoxsuprine or a placebo. Not surprisingly, at the end of the treatment period, mice that received isoxsuprine had significantly smaller tumors compared with the placebo group, confirming the tumor-suppressive effects of isoxsuprine.

"These results are hugely encouraging," says senior author Katarzyna Anna Podyma-Inoue. "The efficacy of β-AR-agonist therapy in both the in vitro and in vivo models suggests that this group of compounds may be the answer to preventing metastasis in OSCC and could potentially even inhibit tumor growth, offering a much better prognosis for OSCC patients worldwide."

Stress hormones and immune cells called neutrophils may contribute to the recurrence of tumors years after treatment by awakening dormant cancer cells, suggests a study of mice and data from 80 patients with lung cancer. The experiments help answer the enduring question of why cancers can return long after seemingly being cured with chemotherapy or surgery; the results also hint that targeting stress hormones with approved drugs known as beta-blockers could potentially help prevent tumors from returning. The recurrence of tumors is one of the biggest causes of deaths in cancer patients, but it's unclear exactly what biological mechanisms prompt tumors to recur. However, studies have suggested that recurrence unfolds as dormant tumor cells, which initially spread during the early stages of cancer, become active once more. Michela Perego and colleagues discovered that stress hormones such as norepinephrine reactivated dormant lung and ovarian cancer cells in mice. Specifically, the scientists found that exposing the mice to stressful situations elevated levels of stress hormones, which caused neutrophils to release S100A8/A9 proteins and fatty molecules that in turn prompted tumor cells to reawaken from dormancy. However, tumor cells remained dormant in stressed-out mice that received an experimental beta-blocker. The team also studied serum samples from 80 patients who had their lung cancers surgically removed and saw that patients who harbored higher concentrations of S100A8/A9 were more likely to have experienced recurrence 33 months after surgery. Perego et al. say that beta blockers or compounds that target S100A8/A9 proteins should be evaluated as potential therapies to disrupt the reactivation process, but stress the need for more sophisticated models of tumor cell dormancy.

Targeted therapies are currently available for about one-third of people with lung adenocarcinoma, the most common kind of lung cancer. These drugs inhibit cancer cells by thwarting the molecular changes that drive them to grow while largely sparing healthy tissues. But for the other two-thirds of people with this type of cancer, there are fewer treatment options.

A team from Memorial Sloan Kettering is reporting new findings about a particularly aggressive subset of lung adenocarcinomas that are driven by two mutations that frequently occur together, in genes called KEAP1 and STK11. The molecular changes characteristic of these tumors were surprising to the investigators who discovered them: they block a type of cell death called ferroptosis. Cancers with these changes require this blockade to stay alive and grow. The study was published December 1, 2020, in Cell Reports.

Ferroptosis is a type of programmed cell death that is dependent on iron. Ferroptosis was discovered less than a decade ago, but it has already emerged as an important target for cancer therapies as well as drug treatments for other diseases. When ferroptosis fails to occur when it should, cells can grow uncontrollably.

"We really didn't know what particular vulnerabilities we would find in these cancer cells," says MSK physician-scientist Charles Rudin, Chief of the Thoracic Oncology Service, Co-Director of the Fiona and Stanley Druckenmiller Center for Lung Cancer Research, and the paper's senior author. "But all of the work we report in this study pointed toward ferroptosis as a key player."

Two Mutations Working Together

The genetic change that allows the cancer cells to block ferroptosis is called a co-mutation: alterations in two genes called STK11 and KEAP1 work together to create an environment in which tumor cells are able to grow even when they are receiving signals that would otherwise induce cell death. The combination of mutations in these two genes is found in more than 10% of lung adenocarcinomas, so a drug that could successfully target this alteration would have a meaningful impact.

MSK biostatistician Ronglai Shen was the first to discover that the STK11/KEAP1 co-mutation is often found in lung adenocarcinomas that are very aggressive and hard to treat. She made the discovery when doing an analysis of lung cancer using data from MSK-IMPACTTM, a test that looks for hundreds of mutations in tumors at the same time. Dr. Shen is a co-author on the new study.

The connection to ferroptosis was unexpected. "Our findings suggest that targeting certain proteins that play a role in the regulation of ferroptosis could lead to new treatments for this cancer," Dr. Rudin says.

CRISPR Helps Create Useful Lab Models

In the current study, first author Corrin Wohlhieter, a graduate student in the lab that's co-led by Dr. Rudin and Triparna Sen, used the gene editing tool CRISPR -- which allows researchers to make very specific changes to the genetic code -- to create three types of cells: some of these cells had the gene STK11 knocked out, some had KEAP1 knocked out, and some had both genes knocked out. She then isolated each of the three cell types and studied them in the lab, including in mouse models. By analyzing the cells' behaviors, she was able to figure out which other genes were activated when STK11 and KEAP1 were lost.

"Lung cancers tend to be very heterogeneous, so if you don't do these kinds of controlled experiments it's hard to isolate changes attributable to a particular gene or set of genes," Dr. Rudin says. "By creating these knockouts, it allows us to really focus on cells with these mutations and to link any behaviors we observe to the presence or absence of these factors."

The team's observations helped them make the connection to ferroptosis. They found that cells with both the STK11 and KEAP1 mutations also had high levels of proteins already known to make cells resistant to ferroptosis. Dr. Rudin and his colleagues pinpointed one of these proteins, called SCD1, as a particularly good target for these tumors.

"Although the current SCD1 inhibitors that we have are not likely to make good drugs," he explains, "there are many labs at MSK that are actively investigating strategies for targeting ferroptosis in cancer cells."

Dr. Rudin says he plans to work with other researchers to learn more about these interactions and to look for compounds that could be developed into drugs. "We hope to find drugs that inhibit the pathways in these tumor cells, ultimately developing a targeted therapy strategy for these particularly difficult cancers," he concludes.

OAK BROOK, Ill. - Automated deep learning analysis of abdominal CT images produces a more precise measurement of body composition and predicts major cardiovascular events, such as heart attack and stroke, better than overall weight or body mass index (BMI), according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).

"Established cardiovascular risk models rely on factors like weight and BMI that are crude surrogates of body composition," said Kirti Magudia, M.D., Ph.D., an abdominal imaging and ultrasound fellow at the University of California San Francisco. "It's well established that people with the same BMI can have markedly different proportions of muscle and fat. These differences are important for a variety of health outcomes."

Unlike BMI, which is based on height and weight, a single axial CT slice of the abdomen visualizes the volume of subcutaneous fat area, visceral fat area and skeletal muscle area. However, manually measuring these individual areas is time intensive and costly.

As a radiology resident at Brigham and Women's Hospital in Boston, Dr. Magudia was part of a multidisciplinary team of researchers, including radiologists, a data scientist and biostatistician, who developed a fully automated method using deep learning--a type of artificial intelligence (AI)--to determine body composition metrics from abdominal CT images.

"Abdominal CT scans that are routinely performed provide a more granular way of looking at body composition, but we're not currently taking advantage of it," Dr. Magudia said.

The study cohort was derived from the 33,182 abdominal CT outpatient exams performed on 23,136 patients at Partners Healthcare in Boston in 2012. The researchers identified 12,128 patients who were free of major cardiovascular and cancer diagnoses at the time of imaging. Mean age of the patients was 52 years, and 57% of patients were women.

The researchers selected the L3 CT slice (from the third lumbar spine vertebra) and calculated body composition areas for each patient. Patients were then divided into four quartiles based on the normalized values of subcutaneous fat area, visceral fat area and skeletal muscle area.

In this retrospective study, it was determined which of these 12,128 patients had a myocardial infarction (heart attack) or stroke within 5 years after their index abdominal CT scan. The researchers found 1,560 myocardial infarctions and 938 strokes occurred in this study group.

Statistical analysis demonstrated that visceral fat area was independently associated with future heart attack and stroke. BMI was not associated with heart attack or stroke.

"The group of patients with the highest proportion of visceral fat area were more likely to have a heart attack, even when adjusted for known cardiovascular risk factors," said Dr. Magudia. "The group of patients with the lowest amount of visceral fat area were protected against stroke in the years following the abdominal CT exam."

"These results demonstrate that precise measures of body muscle and fat compartments achieved through CT outperform traditional biomarkers for predicting risk for cardiovascular outcomes," she added.

According to Dr. Magudia, this work demonstrates that fully automated and normalized body composition analysis could now be applied to large-scale research projects.

"This work shows the promise of AI systems to add value to clinical care by extracting new information from existing imaging data," Dr. Magudia said. "The deployment of AI systems would allow radiologists, cardiologists and primary care doctors to provide better care to patients at minimal incremental cost to the health care system."

This paper is the recipient of an RSNA 2020 Trainee Research Prize.

Co-authors are Christopher P. Bridge, D.Phil., Camden P. Bay, Ph.D., Florian J. Fintelmann, M.D., Ana Babic, Ph.D., Katherine P. Andriole, Ph.D., Brian M. Wolpin, M.D., and Michael H. Rosenthal, M.D., Ph.D.

INDIANAPOLIS -- Returning home after a stay in the hospital and a skilled nursing facility is often overwhelming. New research from Regenstrief Institute and Indiana University shows that individualized treatment plans and instructions would be beneficial to both patients and their caregivers.

"Patients who are discharged from the hospital to a nursing facility before being able to go home are an extremely vulnerable population," said Jennifer Carnahan, M.D., MPH, M.A., who is the study's first author, a research scientist at Regenstrief Institute and an assistant professor of medicine at Indiana University School of Medicine. "These patients often have more comorbidities and medically complex situations. The first few days at home are crucial to prevent adverse events, but we found that period is where the biggest gaps in care exist."

Care transitions are burdensome for patients and are the points in time where errors and gaps in care are more likely. The transitions can affect quality of life and cause the patient to lose progress made during their stay at the care facility.

The research team interviewed two dozen patients and 15 caregivers about their experience returning home after spending time in the hospital and then a skilled nursing facility. The patients reported not having enough information about plans for the transition in care. They found informational paperwork they received overwhelming or not useful. Many had challenges managing medication, and some experienced a gap in physical and occupational therapy.

"I think I've missed the therapy ... I've gotten kind of stiff and everything so I think if we could have started the therapy sooner it would have been better," one patient told researchers.

"We need to develop a way to bridge this gap between nursing facilities and the home environments to set individuals up for a successful transition and a return to their normal lives," said Dr. Carnahan. "Patients need very tailored and specific instructions, because they face many changes and adjustments.

"COVID-19 has exacerbated nearly all of these transitional challenges," she continued. "It will be hard to meet face to face; occupational therapy may be difficult due to restrictions or risk of exposure to the virus. These are issues we need to consider moving forward in these transitions."

Dr. Carnahan is currently conducting research on an intervention that provides nurses to communicate treatment plans to patients and their caregivers and facilitate the necessary steps, whether it's helping to schedule doctors' appointments or making sure patients have proper medications.