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The findings of a survey of adolescent cancer patients and their families at four tertiary care U.S. pediatric hospitals showed that parents had a poor understanding of their teens' preferences for the best time to bring up end-of-life decisions, dying a natural death, and being taken off life support. The findings, published this week in JAMA Network, suggest that family-centered pediatric advance care planning interventions are needed to close this gap.

Families wanted to know their child's treatment preferences, but did not know how to "break the ice." As one parent reported, "I'm glad we said yes to being in the study. Some things we 'know,' but we don't really know for certain and aren't quite sure how to bring them up, so having someone to do that has been really nice."

Having those conversations ahead of time may minimize the misunderstandings that can take place when an adolescent is close to death -- misunderstandings that can lead to ineffective communication, increased hospitalization, poor quality of life, and legal actions.

"Advance care planning interventions are needed to improve families' awareness and understanding of their teens' end-of-life choices," says Maureen E. Lyon, Ph.D., Children's National Hospital clinical psychologist and principal investigator on the study.

"Teens need to have a voice in their care and families are eager to know what their teens want, but those conversations can be difficult," says Dr. Lyon. Advance care planning interventions for parents and adolescents "create a space where they can ask questions and be honest with each other" before death is imminent.

The survey -- which enrolled the largest sample of teens with cancer and their families to date -- builds on earlier work by Dr. Lyon and her research colleagues. The findings are detailed in the article "Congruence Gaps Between Adolescents With Cancer and Their Families Regarding Values, Goals, and Beliefs About End-of-Life Care" published Wednesday, May 20, in JAMA Network.

The survey showed that family members' understanding of their adolescents' beliefs about the best time to bring up end-of-life decisions was poor. Among the teens, 86% wanted early timing (before getting sick, while healthy, when first sick from a life-threatening illness, when first diagnosed, or all of these), but only 39% of families knew that.

Families' understanding of what was important to their adolescents when dealing with their own dying was excellent when it came to wanting honest answers from their physician and understanding treatment choices. But their understanding was poor when it came to dying a natural death and being off life-support machines.

The study was conducted between July 16, 2016, and April 30, 2019, and included a 3-session intervention. The trial involved 80 adolescent-family dyads who were recruited from Akron Children's Hospital, Akron, Ohio; St Jude Children's Research Hospital, Memphis, Tennessee; University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota; and Children's National Hospital, Washington, D.C.

Family-centered pediatric advance care planning interventions offer a structured process that creates a safe space to contain the strong emotions that such conversations elicit. One parent said about the study, "Thinking about this makes me sad, but it's good to talk about them so we know what he wants."

The COVID-19 pandemic has led to a dramatic increase in advance care planning and the creation of advance directives, also known as living wills, in the United States. Now is the time to start having these conversations. People can use what's happening in the news as a trigger to begin the process of advance care planning. As one parent stated, "Everybody should talk about these topics, whether you are a teen or elderly or at any age."

While the initial coronavirus peak is starting to pass - in Europe, at least - without the ventilator shortages many feared, the spectre of a second wave or future outbreak means questions of medical rationing still hold sway.

New research suggests that current ICU protocols and ethical guidelines lack detail, and leave doctors exposed to legal liability if another contagion surge forces them to make painful snap decisions due to insufficient resources.

While the latest analysis focuses on ventilators, University of Cambridge researchers say that many of their arguments apply to other potential medical shortages e.g. a lack of properly staffed ICU beds, dialysis machines or related supplies or equipment.

If shortages lead to denial of treatment based on disability - including 'chronic illness' - or age, or treatment withdrawal during sedation, it could violate patient rights and cause unlawful death, argue the Cambridge lawyers.

They say that legal liability could extend to the UK Government if it is required to defend failures to purchase more medical supplies or publish ICU rationing guidance, despite knowledge of risks to life posed by the pandemic.

The study, published in the Journal of Medical Ethics, is based on UK law, but researchers say it is relevant to other European nations.

"We're definitely not out of the woods," said Dr Kathy Liddell, Director of the Cambridge Centre for Law, Medicine and Life Sciences. "With lockdown easing, we might well see a second Covid-19 spike in intensive care units, and health services should be prepared legally as well as medically."

"The law requires more of hospitals, doctors and clinical commissioning groups than is currently set out in the guidelines provided by the British Medical Association, the Intensive Care Society and medical ethicists."

"The legal rights of patients matter, and they are not being given the attention they deserve," she said.

Around 2.5% of Covid-19 patients require mechanical ventilation to live while they fight the virus, and a patient can need assisted breathing for up to three weeks.

Early concerns that the virus would see patient demand overwhelm ventilator supply prompted researchers to investigate the legal limits of ventilator allocation.

They found "little concrete guidance" centrally in the UK, and argue that a shortage could see "postcode lotteries" of patient rights to life saving treatment - as decisions are taken at a local level by hospitals and doctors.

"The guidelines we reviewed differed in many ways," said co-author Dr Jeff Skopek, from Cambridge's Faculty of Law. "But they generally had the same goal: save as many lives as possible. While this is of course a worthy goal, it can lead to the violation of patients' rights - rights are not suspended merely because we are in a crisis."

The researchers argue that a ventilator cannot be denied on the grounds that a patient has a disability. "Denying treatment because of a disability, which includes chronic illness, violates the Equalities Act 2010. Denying treatment based on age may also do so," said Liddell.

"In fact, the Equalities Act requires efforts be taken not to disadvantage disabled people. This may mean giving people with disabilities longer assessment periods on ventilation, or actually not de-prioritising them," she said.

The analysis points out that if an initial trial of treatment is proposed, it must not be too short. No one should be taken off a ventilator for reallocation purposes until the trial has been long enough to generate reliable evidence for predicting the patient's outcome.

Any decision to withhold or remove ventilation must involve consultation with the patient or their family. Moreover, withdrawing a ventilator without bringing the patient out of sedation risks unlawful killing.

"Even though returning to consciousness would be deeply distressing, all patients must be given a chance to breathe independently if they have a meaningful chance of surviving until another ventilator is available," said Liddell.

If some of these scenarios occur during another virus spike, the researchers say doctors could be directly liable under criminal law for charges such as gross negligence manslaughter, criminal battery or willful neglect.

Even the UK Government could be held responsible. As Skopek highlights, the decision taken by government in April 2020 not to provide a national policy on handling ICU shortages - despite recommendations from its Moral and Ethical Advisory group - could result in a violation of its obligations under Article 8 of the European Convention on Human Rights.

"Without a national policy, the task of drawing up ICU rationing guidelines was left to individual CCGs and hospitals, and many lacked support to ensure their guidelines were legal and ethically sound," he said.

Added Skopek: "If we end up with another surge in patients that overwhelms our critical care infrastructure, hospitals and doctors may end up acting unlawfully - and worse, patients may end up dying unlawfully."

As we know, a malignant tumor is a complex system of mutated cells which constantly interacts with and involves healthy cells in the body. This specificity of malignant neoplasms greatly complicates the process of therapy, since the tumor quickly becomes resistant to chemotherapy drugs. Thus, there is a growing demand not only for new drugs, but also for new in vitro test systems that take into account the maximum possible number of tumor characteristics, and with the help of which it would be possible to select precisely those antitumor agents that would be quite effective under in vivo conditions and in the clinic.

The Gene and Cell Technology Lab team at Kazan Federal University has been working on this problem for five years.

In this paper, an explanation is offered of the existing in vitro test systems for the selection of potentially effective antitumor drugs, and potential research areas are proposed. Currently, there is a problem with conducting rational primary screening of substances with antitumor activity. The pharmaceutical industry is using mainly two-dimensional in vitro models, that is to say, cells growing on a flat surface. In particular, one of these models is the NCI60 panel, which consists of 60 different human cell lines of tumor origin. This is a simple and convenient tool for primary screening; however, two-dimensional models do not take into account the natural three-dimensional architecture of the tumor, complex intercellular interactions and, as a result, are not able to provide objective results. Thus, in preclinical screening, there are more and more requests for more complex models that take into account the entirety of tumor factors.

For example, using the Boyden chamber and microfluidic chip, it is possible to assess the ability of tumor cells to migrate and invade, that is, to predict how aggressively the tumor will behave in the body. Of great interest are three-dimensional tumor models, which are created with the use of several techniques. These include the use of a matrix framework in which the cells are located; the spheroid technique, in which the cells are "hanged" in the medium and form spheres; as well as the organoid method, which is based on the cultivation of embryonic stem cells or tumor explants (pieces of tissue isolated from the patient). Another promising technique is three-dimensional bioprinting, which opens up great opportunities for the creation of realistic models of tumor tissue. Moreover, in each of the techniques, it is possible to use not only tumor cells but also cells that are usual components of tumor tissue in the body - fibroblasts, stem cells, immune cells, etc. Thus, this review gives an idea of the screening of potential antitumor drugs using in vitro models, which is of interest to researchers and clinicians from various fields, including pharmaceutics, preclinical studies, and cell biology.

The development of new approaches to the screening of anticancer drugs is pertinent in light of the growing prevalence of cancer. The selection of an appropriate tumor model at the stage of in vitro drug testing provides a reduction in financial and time costs for the search and testing of promising antitumor drugs.

One of the trends of the last decade has been the use of 3D bioprinting, thanks to which, in theory, it is possible to print fabric with the desired architecture with a sufficiently high resolution. Although at the moment there is no universal protocol for such printing or that of a standard type of tumor tissue used with it, the importance of its further development is indisputable.

The inherited disease of phenylketonuria is expressed in the inability of the body to absorb certain amino acids, mainly phenylalanine.

A person affected by this disease has to follow a low-protein diet all his life. Otherwise, phenylalanine will accumulate in the body and can lead to severe damage to the central nervous system.

Recently, the scientific journal Pharmaceuticals published an article written by researchers of the Institute of Living Systems of the IKBFU and Kemerovo State University, which offers an effective way to treat this disease.

Olga Babich, Director of the Institute of Living Systems:

- The most promising medicine here is L-phenylalanine ammonium-liasis (PAL). However, this enzyme is unstable, it quickly dissolves in the acidic environment of the stomach before having had time to produce a positive effect.

Therefore, scientists have developed a stable capsule shell for PAL, which is broken down mainly in the upper parts of the intestine, which allows the enzyme to work as efficiently as possible.

Natural polysaccharides are proposed to create such a shell: agar-agar, carrageenan, carboxy-methylcellulose.

Experiments were conducted over a three-year period. The main difficulty was the correct interpretation of the results obtained using model biological fluids, since the behavior of the enzyme preparation in vitro (i.e. in a test tube) and in vivo can vary significantly.

According to Olga Babich, the obtained results will find application not only in the treatment of phenylketonuria, but also in the development of new methods for the treatment of other hereditary diseases associated with defects of amino acid metabolism.

It should be noted that the team of authors of the scientific article has good experience in implementing joint projects. In particular, it is the creation of food for children suffering from phenylketonuria and histidynemia, a hereditary disease caused by impaired histidine metabolism.

Besides, there have been implemented projects on the development of capsules for pharmaceutical preparations based on plant components (alternative to gelatin capsules). Thus, the development of the capsule form of L-phenylalanine-ammonium-liazyase is a part of complex research in the field of health saving conducted by a consortium of scientific organizations from Kaliningrad and the Siberian Federal District.

Research completed in NUI Galway has shown that lowering blood pressure by taking blood pressure medications reduces the risk of developing dementia and cognitive impairment by 7%. The findings are published today in a leading international medical journal, the Journal of the American Medical Association (JAMA).

Fourteen randomised controlled trials (96,158 participants) were included in this systematic review and meta-analysis. Blood pressure lowering with antihypertensive medications reduced the risk of developing dementia or cognitive impairment by 7%, and cognitive decline also by 7% over a four-year period.

"When you consider how common dementia is in the population (50 million people worldwide), effective treatment and control of hypertension would have a major impact on preventing dementia. Our findings emphasize the need for more effective screening, prevention, and treatment of hypertension, which remains suboptimal in Ireland", explains Dr Conor Judge, joint first author and Wellcome Trust Health Research Board Irish Clinical Academic Training (ICAT) fellow.

Dr Judge continued: "We know from The Irish Longitudinal Study on Aging that two thirds of people aged over 50 in Ireland have hypertension (high blood pressure), of which half are unaware of the diagnosis, and one third are not on treatment. This is a major care gap."

This study aimed to gather all the evidence from previous trials of blood pressure lowering medications and estimate how much the risk of dementia can be reduced by taking blood pressure lowering medications in people who are diagnosed with high blood pressure. Blood pressure lowering reduces the risk of stroke and heart disease. Prevention of dementia can now be added to the benefits of treating hypertension. Importantly, there are no available therapies that directly prevent dementia, so this study highlights the critical importance of blood pressure in the risk of dementia.

Dr Michelle Canavan, Consultant Geriatrician at Galway University Hospital, and senior author of the paper, commented: "Prevention of dementia is a major health priority. We know from previous research that a major concern of older people is developing dementia. The message from this study is simple: Get your blood pressure checked. If it is high, it can be readily treated with lifestyle changes and medications. We would hope that our study will heighten awareness of the importance of controlling blood pressure to maintain "brain" health, combined with a healthy lifestyle."

Berkeley -- Residents of states with limited access to contraceptives and high rates of unplanned pregnancies are more likely to turn to the internet for information about abortion. These are the findings of a new study of Google search data across all 50 states by researchers at the University of California, Berkeley.

The results suggest that policies that limit access to birth control -- such as the Title X gag rule, which restricts federal funding from clinics that provide birth control if they also provide abortion information or referrals -- lead people to seek out family planning information online.

"What is surprising is that the opinions that people have toward abortion might influence whether they search for abortion, but we found that these opinions don't make a difference, once you control for health and legal factors," said Sylvia Guendelman, a professor of maternal, child and adolescent health at UC Berkeley and co-principal investigator of the study. "What encourages or incentivizes people to search seems to be far more pragmatic than just ideological."

The same results hold regardless of statewide opinions toward abortion or legal restrictions on abortion access. In fact, some states with the most restricted access to abortion care and the most negative opinions toward abortion, such as Alabama, Louisiana and Mississippi, actually had the highest Google search volume for abortion, the study found. In 2019, these three states all attempted to pass legislation banning the procedure after the sixth week of pregnancy or banning it outright.

"It's not that abortion restrictions don't make any difference. People in highly restrictive states search for abortion more. However, when you control for other factors, namely access to contraceptives and the rates of unplanned pregnancies, we found the latter are far more important determinants of what people are searching for when it comes to abortion," Guendelman said.

This study appeared online on Thursday, May 21, in the journal PLOS ONE.

Online search data can give researchers a unique glimpse into consumers' concerns regarding contentious issues like abortion, Guendelman said, because stigma and lack of access to reproductive health care may prevent people from seeking the information more publicly. However, navigating the internet can be perilous, due to the amount of misinformation there on both birth control and abortion.

The study analyzed the relative search volume, or proportion, of all Google searches containing the words "abortion" or "abortion pill" in each state in 2018. The researchers then compared these numbers to state-level, reproduction-related policies and attitudes, including legal restrictions on and protections for abortion, availability of abortion facilities, health care costs, access and health outcomes, opinions about abortion, concern about birth control and prevalence of unplanned pregnancies.

Many states impose significant restrictions on people seeking to obtain an abortion, including mandatory waiting periods and counseling. In some areas, the number of clinics that provide abortions is also severely limited: A recent study found that people in 27 U.S. cities with populations greater than 50,000 had to travel more than 100 miles to reach a clinic.

While Google search volume for "abortion" was not predicted by state restrictions on abortion, the research team did find that people in states with fewer abortion facilities were more likely to search for the term "abortion pill."

The abortion pill refers to medication that can be used to induce abortion. The higher search volume for "abortion pill" in states with a limited number of abortion facilities may imply that people who cannot access clinics are instead seeking out abortion information online, researchers said.

Restrictions and access barriers to contraceptives and abortion are particularly concerning during the COVID-19 pandemic, Guendelman said, as many people are now without work and struggling financially, child care centers and schools have shut down or gone remote, and many medical centers are limiting their in-person services.

However, medication abortion provides an opportunity to make abortion services available through telemedicine, as the drug regimen is easy to follow for self-administration, said Ndola Prata, co-principal investigator of the study.

"Before COVID-19, women were being redirected and restricted in terms of the reproductive choices that they could make and, as a result of that, they had to go online to find the right resources and to understand their options," Guendelman said. "Now, COVID-19 is impoverishing our population at a dramatic rate, and I think this is a time when the majority of women are looking for ways to plan their families in a way that is far more consistent with their values and their economic means than ever before. This is a time to ramp up the investment in prevention and good family planning."

A new study finds rates of advanced prostate cancer continued to increase in men aged 50 and over in the United States, five years after the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen-based screening for all men. The study, led by American Cancer Society investigators, says the rise in cancers that had spread beyond the prostate gland was accompanied by drops in early-stage disease during the same time period. The study appears in JNCI, the Journal of the National Cancer Institute.

The USPSTF began recommending against prostate-specific antigen-based screening for men 75 and older in 2008 and for all men in 2012. In 2018, the USPTF recommended individual decision-making for men 55 to 69 and said men 70 and over should not be screened.

National self-reported survey data found past-year routine PSA testing rates among men aged 50 and over declined from 40.6% in 2008 to 38.3% in 2010, to 31.5% in 2013, and remained unchanged in 2015.

Previous studies reported that prostate cancer incidence rates in the U.S. declined for local-stage disease and increased for regional- and distant-stage disease soon after the USPSTF recommendations against routine screening. The new study looked at whether these patterns persisted in the longer-term, through 2016.

Researchers led by Ahmedin Jemal, DVM, Ph.D. used data from the U.S. Cancer Statistics Public Use Research Database to look at trends- annual percent change- in invasive prostate cancer incidence from 2005 to 2016 in men 50 and older stratified by stage, age group, and race/ethnicity.

They found that for all races/ethnicities combined, incidence for local-stage disease decreased by 6.4% per year from 2007-2016 in men 50 to 74. In men 75 and older, incidence declined by 10.7% per year from 2007-2013 then stabilized during 2013 to 2016.

In contrast, incidence for prostate cancer spread beyond the gland (regional- and distant-stage disease) increased in both age groups during the study period. For example, distant-stage incidence in men 75 and older increased by 5.2% per year from 2010-2016.

"These data illustrate the trade-off between higher screening rates and more early-stage disease diagnoses (possibly overdiagnosis and overtreatment) and lower screening rates and more late-stage (possibly fatal) disease," write the authors. "Several modeling studies, however, showed that the harms associated with higher PSA screening rates can be mitigated while preserving the benefit of screening through PSA-stratified strategies including longer screening interval based on baseline PSA, higher PSA threshold for biopsy referral in older men, and restricting routine testing to men aged ?70 years."

The study did not cover the period after 2018, when USPTF recommendations changed again to include screening as an option for men 55 to 69, and against screening for men 70 and over. The impact of that most recent change on prostate cancer rates has yet to be seen, as cancer registry data is not yet available.

Noninvasive pulses of ultrasound waves aimed at specific regions in the brains of macaque monkeys can give some control over the monkeys' choices, scientists report. These findings indicate that ultrasonic brain stimulation could provide a noninvasive, drug-free avenue to study and potentially treat decision-making disorders such as addiction. Previous research has shown that low-intensity ultrasound waves applied to rodent brains from outside the head can stimulate neurons - including deep, compacted neurons - and cause corresponding muscle movements elsewhere in the body. However, more recent studies have yielded less definitive results, suggesting the technique may have little or no effect. Moreover, effects on behavior in larger animals and humans have not been well studied. Jan Kubanek and colleagues had two macaque monkeys engage in an experiment widely used to investigate choice behaviors: the monkeys looked at a target at the center of the screen and were then presented with targets on the left and right sides of the screen, one shortly after the other. Monkeys usually choose to look at the target that appears first. However, by briefly applying ultrasonic waves to the monkeys' frontal eye fields (FEF), brain regions that control eye movement, the researchers influenced which target the monkey looked at. When the researchers targeted the left FEF, the monkeys were more likely to choose the right target, and vice versa. No effects were observed when ultrasound was applied to the motor cortex, which is not involved in perceptual decision-making. The scientists rewarded the monkeys differently for the task. Monkey A was rewarded with juice for selecting either target whereas monkey B was only rewarded for selecting the first target. That the researchers controlled the monkeys' choices regardless of the reward suggests that this technique could be used to study disorders such as addiction, binge eating and compulsive behaviors. The authors note the study provides several recommendations for future applications of ultrasonic neuromodulation in animals and humans, including avoiding anesthesia and applying stimulation relatively infrequently, as repetition appears to diminish the effects

What The Study Did: This study combined the results of seven studies and compared the risk of melanoma among 34,000 patients treated with biologics and 135,000 patients treated with conventional systemic therapy for rheumatoid arthritis, psoriasis or inflammatory bowel disease.

Authors: Shamarke Esse, M.Res., of the University of Manchester in the United Kingdom, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamadermatol.2020.1300)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Viewpoint Says: This Viewpoint discusses the challenges that arise for patients with cancer who are undergoing immune-engaging therapeutic treatment during the coronavirus disease 2019 (COVID-19) pandemic.

Authors: Muhammad Bilal Abid, M.D., M.R.C.P., of the Medical College of Wisconsin in Milwaukee, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamaoncol.2020.2367)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

In an innovative study, Radboudumc and LUMC jointly tested a candidate vaccine based on a genetically weakened malaria parasite. The results of this clinical trial, published in Science Translational Medicine, show that the vaccine is safe and elicits a defense response against a malaria infection.

Malaria is a major infectious disease, caused by a parasite with a complicated life cycle in humans and mosquitoes (see "About Malaria" below). The first stage in humans takes place in the liver, the second in the blood. Since the liver phase does not cause any symptoms of disease, but the blood phase does, the purpose of the vaccine is to stop the parasite in the liver.

Weakening malaria

For the malaria vaccine in this study, researchers made a weakened malaria parasite by removing two genes and developed it into a vaccine together with the American company Sanaria Inc. This parasite reaches the first liver stage in humans, but the genetic weakening means that it does not continue to later stages or lead to infection of the blood. In earlier phases of the research, important genes were identified that, in their absence, prevented the parasite from developing in the liver. In a joint clinical study, 67 volunteers in Leiden and Nijmegen received injections of the vaccine made from the genetically modified parasite (called PfSPZ GA1) - a first in the world for an injectable, genetically weakened malaria vaccine. A high and a low dose were administered.

Safe and partially effective

The results of the trial show that the vaccine is safe. It does not lead to infection of the blood and therefore does not cause malaria symptoms. It was also observed that the vaccinated volunteers developed an immune defense against a malaria infection, although this protection was not complete. This means that the disease is delayed but not prevented. According to the researchers, the measured immune responses and demonstrated safety are strong incentives to further develop a vaccine based on genetically attenuated malaria parasites.

About malaria

Malaria is one of the major infectious diseases of our time with around 216 million cases and 400,000 deaths annually. In recent years there has been an increase in the number of infections, especially in Sub-Saharan Africa and South America.

The most deadly form of malaria is caused by a single-celled parasite, Plasmodium falciparum, which is transmitted by mosquitoes. Once in humans, the parasite first develops in the liver for about seven days. The parasite transforms and shifts from the liver into the blood where it can infect red blood cells. Subsequently, the parasite develops from asexual cells into mature male and female germ cells which can then be sucked up by mosquitoes, after which fertilization of the parasites takes place in the mosquito stomach. The offspring can return to humans after another mosquito bite.

Viruses have an exceptional ability to circumvent the body's immune system and cause diseases. The majority of people recover from a viral infection such as influenza, although the current COVID-19 pandemic demonstrates how dangerous viruses are when there is no effective vaccine or treatment.

Professor and virologist Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark, has been leading a research partnership between Aarhus University, the University of Oxford and the University of Gothenburg, which has brought us one step closer to understanding the tactics used by viruses when they attack the immune system.

Søren Riis Paludan heads a laboratory which carries out research into the immune system's ability to fight diseases caused by the herpes virus, influenza viruses and, most recently, SARS-CoV2, more commonly known as coronavirus.

In the new study, which has just been published in the scientific journal Journal of Experimental Medicine, the researchers have investigated how the herpes simplex virus circumvents the immune system in order to cause infections of the brain. This is a rare infection but one which has a high mortality rate among those who are affected.

"In the study, we found that the herpes simplex virus is capable of inhibiting a protein in the cells, known as STING, which is activated when there is a threat. When STING is inhibited, the body's immune system is also inhibited - the virus thereby puts the brakes on the body's brake, which is supposed to prevent us from becoming ill. Other viruses also make use of the same principle," says Søren Riis Paludan.

Søren Riis Paludan points out that though the study focuses on herpesviruses, there are parallels to the coronavirus. Interestingly, the same protein is also inhibited by many different viruses, including the coronavirus.

"This suggests that we have found an Achilles heel in the virus and the way it establishes infections in the body. Our results lead us to hope that if we can prevent viruses from blocking STING, then we can prevent the virus from replicating. That could pave the way for new principles for treatment of herpes, influenza and also the coronavirus," says Søren Riis Paludan.

He hopes that the research results can be used in the development of antiviral drugs and vaccines in the future.

"Previous studies have also shown that the coronavirus inhibits STING in the same way as the herpes virus. This suggests that we have found a common denominator for several types of virus, and that this is probably an important element in the development of treatment," he says.

A new study from Lund University in Sweden has shown no correlation between obesity and how close you live to fast food restaurants or gyms. Studies from other countries have previously indicated that these factors may be important in adult obesity.

The areas where we live are known to be important for our health. For example, obesity is more prevalent in deprived neighborhoods. Deprived neighborhoods are typically defined by low socio-economic levels, e.g., low average income and high unemployment rates.

The reason why obesity is more prevalent in such neighborhoods have been a topic of interest among both researchers and policy makers for a long time, and commercial facilities, like fast food outlets and physical activity facilities, have attracted much research attention and debate.

"However, our large-scale study in Sweden, using longitudinal national registry data of more than 1,5 million adults, did not find a statistically significant association between these two types of facilities and obesity", explains Kenta Okuyama, PhD student at Center for Primary Health Care Research at Lund University.

The researchers say it is unlikely that the availability of fast food outlets or lack of gyms are causes of obesity in Swedish adults.

"Although reducing fast food outlets or introducing physical activity facilities might in theory promote healthy eating and exercise, it may not be very effective in all countries and regions, because the contexts vary by its culture and lifestyle that may affect how often people utilize these facilities in their daily lives", says Kenta Okuyama.

The study did show a correlation between neighborhood deprivation and obesity.

"The next goal is to investigate further what other factors can possibly impact the risk of obesity in Sweden", concludes Kenta Okuyama.

Access to targeted therapies for lung cancer depends on accurate identification of patients' biomarkers through molecular testing, but survey results published today in the Journal of Thoracic Oncology suggest that many international clinicians are unaware of evidence-based guidelines that support the use of molecular testing.

Current evidence-based standards for molecular testing of lung cancer have been established, but the global frequency and practice of testing are not well understood. To address this knowledge gap, the International Association for the Study of Lung Cancer (IASLC) conducted an international survey to evaluate current practice and barriers to molecular testing.

The IASLC developed a seven-question introduction, with 32 questions for those requesting tests and treating patients, 45 questions on performing/interpreting assays, and 24 questions on tissue acquisition. All respondents were asked to provide three to five barriers that impede their country's ability to offer molecular testing.

There were 2537 survey responses representing more than four practice specialties in 102 countries. More than six of 10 respondents (61%) report that molecular testing rates are less than 50% in their country, with the lowest rates reported in Latin America. Nearly four in 10 surveyed (39%) were not satisfied with the conditions of molecular testing in their country, citing concerns with the time it takes to receive results, the reliability of samples and trouble understanding results. Other findings include:

67% were aware of the most recent CAP/IASLC/AMP guidelines for molecular testing.

75% reported that they had multidisciplinary tumor boards, but 23% said that board met less than once a month.

47% stated there is no policy or strategy to improve the quality of the tissue samples in their country.

17% reported patients are not satisfied with the state of molecular testing in their country, 35% are unsure.

The most frequent barrier to molecular testing was cost, followed by quality/standards, turnaround-time, access and awareness.

"The risk of death for patients with non-small cell lung cancer is substantially reduced when a gene alteration is identified and the available targeted therapy is administered," said Dr. Matthew Smeltzer, IASLC committee member, and lead author from the University of Memphis, Memphis, Tenn. "But one-third of respondents were unaware of evidence-based guidelines that recommend using these therapies."

Smeltzer recommended that continuous education around molecular testing in lung cancer should be intensified on national and international levels to ensure patients receive optimal therapy.

PrECOG, LLC is reporting clinical efficacy and biomarker analyses from its single-arm phase two study PrE0505 for the initial treatment of patients with malignant pleural mesothelioma. The trial evaluated adding durvalumab, an immune checkpoint antibody targeting PD-L1, to chemotherapy consisting of pemetrexed and cisplatin (Pem-Cis), the only FDA approved regimen, in 55 patients of any histologic subtype. The study met its primary endpoint with a median overall survival (OS) of 20.4 months (one-sided P=0.0014) as compared to historical control (Vogelzang et al. J Clin Oncol 2003) of 12.1 months. OS rates at 12 and 24 months were 70.4% and 44.2%, respectively. The combination was well-tolerated with no unexpected toxicities.

The American Society of Clinical Oncology (ASCO) is highlighting these data in an oral session (Abstract 9003) at its virtual Annual Meeting, May 29-31.

"Durvalumab plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma," said lead investigator Patrick Forde, MD, of Johns Hopkins University. "The data signal us to move forward with a phase three study."

PrE0505 study investigators at 15 US clinical sites rapidly enrolled 55 patients into the study over 13 months, between June 2017 and June 2018. Eligible patients received the combination of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) with durvalumab (1120 mg) every three weeks for up to six cycles. Substitution of carboplatin (AUC 5) for cisplatin was permitted if toxicity occurred during the initial treatment. After up to six cycles of concurrent chemotherapy with durvalumab, patients who had a partial response or stable disease could continue on durvalumab until disease progression. The maximum duration of durvalumab treatment was 12 months from the start of therapy.

"This is a remarkable result in mesothelioma, and warrants confirmation in a randomized phase three trial, which is already in the planning," said Peter J. O'Dwyer, MD, CEO and Chair, PrECOG, LLC.

The secondary endpoints in the PrE0505 trial are safety and tolerability, PFS, and objective response rate. PFS at six months was 69.1%. Best responses to treatment were measured by the RECIST criteria and included 31 patients (56.4%) with partial response, 22 (40%) with stable disease, and one (1.8%) who progressed during the evaluation period. One patient was not evaluable for response. All patients were evaluated for safety, and there were no unexpected toxicities. Adverse events reported by investigators as associated with durvalumab were generally mild in severity (Grade 1 and 2).

In analyses of exploratory objectives, researchers saw no statistically significant associations between tumor sample expression of PD-L1 or tumor mutational burden and progression or survival. They observed neoantigen-specific T-cell responses in some selected cases. Analytical work for the study is ongoing.