Body

Researchers at the University of Nebraska Medical Center have identified a key cell signaling pathway that drives the devastating muscle loss, or cachexia, suffered by many cancer patients. The study, which will be published May 22 in the Journal of Experimental Medicine, suggests that targeting this pathway with a drug already in phase 2 clinical trials for diabetes could prevent this syndrome.

Cachexia reduces patients’ response to chemotherapy and can eventually result in respiratory or cardiac failure. It is thought to be the direct cause of death in up to one third of cancer patients. “However, there are no FDA-approved drugs to mitigate cancer-induced cachexia,” says Pankaj K. Singh, a professor from The Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center, Omaha. “There is therefore an urgent need to find more effective therapeutic targets against cancer cachexia.”

Muscle loss is particularly prevalent in patients with pancreatic cancer. Singh and colleagues found that the muscles of pancreatic cancer patients undergoing cachexia produce lower amounts of an enzyme called SIRT1. SIRT1 production was also reduced in mice with pancreatic cancer, and the researchers found that they could prevent these animals from undergoing cachexia by restoring the levels of this enzyme to normal.

Singh and colleagues determined that loss of SIRT1 causes muscle cells to produce increased amounts of an enzyme called NOX4 that generates toxic reactive oxygen species capable of inducing muscle degeneration. Treating mice with GKT137831, a drug that inhibits the NOX4 enzyme, prevented muscle loss and extended the life of mice with pancreatic cancer.

NOX4 levels were also elevated in patients undergoing pancreatic cancer­–induced cachexia, suggesting that GKT137831, which is already in phase 2 clinical trials for diabetes and primary biliary cholangitis, could also be used to treat cancer-associated muscle loss.

“Our study establishes the role of the SIRT1–NOX4 axis in mediating cancer cachexia and demonstrate the possibility of targeting this pathway to treat this devastating syndrome,” Singh says. “NOX4 activity is also elevated in muscular dystrophy and other muscle-wasting disorders, suggesting that GKT137831 could be effective in treating muscle loss induced by a variety of pathologies, a possibility that warrants further investigation.”

Developing safe and efficient bioformulations using approved materials and ingenious designs can accelerate the clinical translation process.

Scientists from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences have developed a new therapeutic tumor vaccine based on self-healing polylactic acid microcapsules, which can efficiently activate the immune system and inhibit tumor development.

This research was published in Science Advances on May 22.

Therapeutic cancer vaccines that harness the immune system to reject cancer cells have shown great promise for tumor treatment.

The research team, led by Prof. MA Guanghui and Prof. WEI Wei from IPE, already designed and fabricated a variety of tumor vaccines in their previous work. Theses vaccines have been proven effective in different tumor models, such as lymphoma, melanoma and breast cancer.

The researchers were impelled to improve the earlier tumor vaccines, however, due to certain limitations. For example, Prof. MA said that an unfavorable immunization microenvironment, along with a complicated preparation process and the need for frequent vaccinations significantly compromised their performance. "Therefore, we designed a novel microcapsule-based formulation for high-performance cancer vaccinations," said Prof. MA.

This study represents the first time researchers used self-healing microcapsules with post-encapsulation, multiple loading, and efficient modulation of immunization microenvironments in a tumor vaccine.

The special self-healing feature provides a mild and efficient paradigm for antigen microencapsulation. After vaccination, these microcapsules create a favorable immunization microenvironment in situ, wherein antigen release kinetics, recruited cell behavior and acid surrounding environment work in a synergetic manner.

Owing to synergetic effects, the vaccine succeeds in increasing antigen utilization, improving antigen presentation and activating antigen presenting cells. "As a result, effective T cell response, potent tumor inhibition, anti-metastatic effects and prevention of postsurgical recurrence are achieved with various types of antigens in different tumor models," said Prof. WEI.

Moreover, the researchers verified the availability of the novel vaccine platform used in the neoantigen vaccine, which conforms to precision medicine, said Prof. WEI. Due to the simple post-encapsulation process, the clinicians were able to prepare the neoantigen formulation by themselves at any time.

A peer reviewer from Science Advances described the study as "comprehensive and rationally designed." The reviewer also emphasized that the results are "impressive" and the work has "high value for therapeutic vaccines and cancer immunotherapy."

An improved urine-testing system for people suffering from kidney stones inspired by nature and proposed by researchers from Penn State and Stanford University may enable patients to receive results within 30 minutes instead of the current turnaround time of a week or more.

Kidney stones occur due to buildup of certain salts and minerals that form crystals, which in turn stick together and enlarge to form a hard mass in the kidneys. The stones move into the urinary tract and can cause blood in the urine, considerable pain and blockages in the urinary system.

Metabolic testing of a kidney stone patient's urine to identify metabolites such as minerals and solutes that cause stones to form is key for preventing future ones. This testing is currently done by requiring the patient to collect their urine over a 24-hour period in a large container. The container is then sent to a lab for analysis and the results normally come back in 7 to 10 days.

"The lengthy process, cumbersome collection procedure and delay in obtaining the results render 24-hour urine testing to be underutilized in clinical practice despite guideline recommendations," said Pak Kin Wong, professor of biomedical engineering and mechanical engineering and principal investigator on the study. The research was published today (May 22) in Science Advances.

Wong said that expensive special equipment is required to detect urinary solutes and minerals for a test result. The urine sample, therefore, has to be shipped to a commercial diagnostic lab for testing. To solve this, the research team developed a biomimetic detection system called slippery liquid-infused porous surface (SLIPS)-LAB.

SLIPS is a dynamic, extremely low-friction smooth surface created by locking lubricating liquids in micro/nanostructured substrates. This is inspired by nepenthes pitcher plants, which are carnivorous plants that have unique leaves shaped like pitchers and are filled with digestive liquid. The plants have evolved extremely slippery liquid-infused micro-textured rims that cause insects to fall into the "pitcher."

"There are many aspects we can learn from nature and our environment, and our research is an example how biomedical engineers can make good use of it," Wong said.

SLIPS-LAB works by enabling reagent and urine droplets to easily move over the slick surface of the testing device's fluid addition channel and not get stuck. The droplet is driven by a Laplace pressure difference, a small pressure force due to surface tension, induced by the geometry of the device. This enables the reactants to combine with the urine at the necessary timed rate for reaction.

"We demonstrated that SLIPS-LAB enables the reagent and sample to move themselves and perform the reactions for us," Wong said. "It means the technology doesn't require a technician to run any test machinery, so it is possible to do the test in non-traditional settings, like a physician's office or even the patient's home."

The test results can then be read using a scanner or a cell phone, and the scanned image can then be analyzed using a computer algorithm. All these steps, according to Wong, would take approximately 30 minutes in a physician's office. An added benefit, Wong said, is that SLIPS-LAB is more cost-effective than regular, 24-hour testing.

"The low cost, rapidity and simplicity of SLIPS-LAB would reduce the barrier for the clinician and patient to undergo stone risk metabolite analysis," Wong said. "This would improve the management of patients with urinary stone disease and open new possibilities for stone patients to test their urine samples in mobile health settings."

The lead author of the study, Hui Li, graduate student in biomedical engineering, said another promising result of their research was demonstrating that the test also works as a spot test, which means a patient can monitor certain levels in their urine without 24-hour collection.

"SLIPS-LAB may open new opportunities in on-demand monitoring of urinary analytes and may potentially transform metabolic evaluation and clinical management of urinary stone disease," Li said.

Although heart disease is the leading cause of death in women, and older adults are more likely to have heart and vascular disease than young people, randomized clinical trials testing medications to lower cholesterol have historically underenrolled both groups. Randomized clinical trials generate the best evidence regarding the benefits or harms of given drug, and their results are used to shape guidelines for patient management in clinical practice. Due to a push from the U.S. National Institutes of Health and the U.S. Food and Drug Administration, the pharmaceutical industry had begun efforts to enroll more women and seniors into their trials.

However, after analyzing the trends in the types of 485,409 people enrolled in 60 studies from 1990 to 2018, Johns Hopkins Medicine researchers report that ¾ although some progress has been made -- women and older adults are still vastly underrepresented in lipid lowering therapy trials compared with their disease burden. The findings, published on May 21, 2020, in the journal JAMA Network Open, suggest that trials still aren't reflecting real-world patient populations.

"We want to ensure that the types of patients who will be using these drugs are the ones included in the clinical trials, so that we can determine if these medications are safe and effective for the people who are prescribed them," says senior author Erin Michos, M.D., M.H.S., associate professor of medicine at the Johns Hopkins University School of Medicine. "Although we did see an improvement over the years in representation of women and older adults, that progress was rather modest. Clearly more still needs to be done to shift the balance to represent our patient demographics."

For their study, the researchers reported an increase in the number of women participants from about 20% in the early 1990s to about 33% in the most recent trials analyzed. However, many trials included only women who were past menopause or who were unable to have children, particularly excluding people who were pregnant or breastfeeding. Only slightly more than half of the 60 trials reported results based on effectiveness by gender.

"Heart diseases have been increasingly on the rise among younger women," says lead author Safi U. Khan, M.D., an assistant professor of medicine at West Virginia University. "The exclusion of women of childbearing age into these lipid-lowering trials results in missed opportunities to understand about important cardiovascular disease prevention measures in this group."

In the report on these studies, the percentage of trial participants 65 or older increased from 32% from the early 1990s, compared with 42% in the most recent trials examined. As with gender, only slightly more than half of the 60 studies reported their findings specifically for older adults.

The researchers say older Americans must be included in trials because as people age over time, the way they metabolize drugs may change, or they may develop other health conditions that could alter the effectiveness of the treatment.

DALLAS, May 22, 2020 -- It's inappropriate to consider blanket do-not-resuscitate orders for COVID-19 patients because adequate data is not yet available on U.S. survival rates for in-hospital resuscitation of COVID-19 patients and data from China may not relate to U.S. patients, according to a new article published today in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

There is a presumption that COVID-19 patients have a low survival rate after resuscitation, based on a recent study from Wuhan, China, that found an overall survival of 2.9% in 136 COVID-19 patients who underwent cardiopulmonary resuscitation for in-hospital cardiac arrest. However, that prognosis should not be applied to the U.S., said Saket Girotra, M.D., S.M., assistant professor of medicine in the division of cardiovascular diseases at the University of Iowa Carver College of Medicine, on behalf of the American Heart Association's Get With The Guidelines®-Resuscitation (GWTG-R) investigators.

In the study, "Survival After In-Hospital Cardiac Arrest In Critically Ill Patients: Implications For Covid-19 Outbreak?," investigators report data from the GWTG-R registry of in-hospital cardiac arrest patients. They examined data from 2014-2018 on patients similar to the COVID-19 population: 5,690 adult patients who underwent CPR for in-hospital cardiac arrest while being treated in an intensive care unit (ICU) for pneumonia or sepsis and were receiving mechanical ventilation at the time of cardiac arrest.

While researchers noted an overall survival rate of only 12.5% in the U.S. simulation, there were many variables that could affect survival and neurologic outcomes. The probability of survival without severe neurological disability ranged from less than 3% to more than 22%, across key patient subgroups. The probability of mild to no disability ranged from about 1% to 17% across key patient subgroups.

While survival rates were low in older and sicker patients in whom the initial heart rhythm was non-shockable, survival rates were much higher (more than 20%) in younger patients with an initial shockable rhythm who were not being treated with vasopressor medications prior to the cardiac arrest. Vasopressor medications are generally used to improve blood pressure and cardiac output in emergency situations such as septic shock or cardiac arrest.

"Such large variation in survival rates suggests that a blanket prescription of do-not-resuscitate orders in patients with COVID-19 may be unwarranted. Such a blanket policy also ignores the fact that early experience of the pandemic in the U.S. reveals that a about a quarter of COVID-19 patients are younger than 50 years of age and otherwise healthy. Cardiac arrest in such patients will likely have a different prognosis," the researchers said.

The article concludes that "... in a cohort of critically ill patients on mechanical ventilation, survival outcomes following in-hospital resuscitation were not uniformly poor. These data may help guide discussions between patients, providers and hospital leaders in discussing appropriate use of resuscitation for COVID-19 patients."

Co-authors are Yuanyuan Tang, Ph.D.; Paul S. Chan M.D., M.Sc.; and Brahmajee K. Nallamothu, M.D., M.P.H. Nallamothu is the Editor-in-Chief of Circulation: Cardiovascular Quality and Outcomes. This manuscript was reviewed by an external guest editor: Dennis T. Ko, M.D., M.Sc. Disclosures and funding sources are listed in the manuscript.

The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public's health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for nearly a century. Connect with us on heart.org, Facebook, Twitter or by calling 1-800-AHA-USA1.

Journal

Circulation

An elevated pre-pregnancy hemoglobin A1c--which measures average blood glucose concentration--is associated with a higher risk of adverse pregnancy outcomes even in women without known diabetes, according to a new study published this week in PLOS Medicine by Joel Ray of ICES and the University of Toronto, Canada, and colleagues.

Diabetes mellitus and obesity are both associated with adverse pregnancy outcomes but the relationship between pre-pregnancy A1c and severe maternal morbidity or maternal mortality is unknown. In the new study, researchers used data from the Canadian province of Ontario spanning 2007 through 2015. The study included data on 31,225 women aged 16 through 50 years with a hospital live birth or stillbirth and who had an A1c measured within 90 days before conception. 28,075 of the women (90%) did not have a known diagnosis of diabetes mellitus.

Overall, the risk of severe maternal morbidity (SMM) or death from 23 weeks gestation to 6 weeks postpartum was 2.2%. For each 0.5% absolute increase in A1c, the relative risk of SMM or death was 1.16 (95% CI 1.14-1.19, p

The authors note that most women do not undergo A1c testing, which may have led to selection bias among the cohort. Additionally, pre-pregnancy body mass index was unknown for 77% of the participants. Therefore, the potential interaction between BMI, A1c and risk of SMM should be investigated further. Still, these findings have implications for pre-pregnancy health screening.

"Given its convenient and widespread use, A1c testing may identify those women with preexisting diabetes mellitus at risk of severe maternal mortality, in a manner similar to its current use in recognizing those at higher risk of fetal anomalies, preterm birth and pre-eclampsia," the authors say. "As there is no current recommendation about A1c testing in nondiabetic pregnant women, especially those with obesity and/or chronic hypertension, our findings may enhance research about the benefits of A1c screening in these women."

Scientists have identified metabolites in the blood that accurately predict whether a woman will develop type 2 diabetes after experiencing a transient form of illness during pregnancy. This discovery could lead to a test that would help doctors identify patients at greatest risk and help them potentially avert the disease through interventions including diet and exercise.

The research was led by Michael Wheeler, a professor of physiology at U of T's Faculty of Medicine, in collaboration with Hannes Röst, an assistant professor of molecular genetics and computer science at the Donnelly Centre for Cellular and Biomolecular Research, Feihan Dai, a research scientist of physiology and Erica Gunderson, a research scientist at the Kaiser Permanente Division of Research in Northern California. Mi Lai, a post-doctoral fellow in Wheeler's group performed much of the analyses.

"There is a metabolic dysregulation that occurs in the group of women that will go on to develop type 2 diabetes that is present in the early postpartum period, suggesting that there is an underlying problem that exists already and we can detect it," says Wheeler, who is also a senior scientist at Toronto General Hospital Institute at University Health Network.

The identified metabolic signature can predict with over 85 per cent accuracy if a woman will develop type 2 diabetes (T2D), as described in a study published in the journal Plos Medicine.

About one in 10 women will develop gestational diabetes (GD) during pregnancy which puts them at higher risk of T2D, with 30 to 50 per cent of these women developing the disease within 10 years after delivery. The disease hampers the body's ability to regulate blood sugar levels and can lead to serious complications including vision loss, neurological problems, as well as heart and kidney disease.

Women with GD are recommended to have an annual oral glucose tolerance test after delivery, which measures the body's ability to remove sugar from the bloodstream. But the procedure is time and labor consuming and fewer than half of the women follow through with it.

"If you've got a newborn at home one of the last things you are thinking about or have time for is your own health," says Wheeler. "This is one of the main reasons why we performed this study, to potentially develop a simple blood test reducing the number of hospital visits."

Wheeler and Gunderson first uncovered metabolic signatures predictive of T2D in their 2016 pilot study of 1033 women with GD Gunderson recruited for the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT), one of the largest and most diverse studies of its kind. All of the women delivered their babies at Kaiser Permanente Northern California hospitals between 2008 and 2011.

The new study builds on prior research, following the same cohort of women over a longer time period during which more women developed T2D.

Baseline blood samples were collected between six and nine weeks after birth and then twice over two years. The women's health was followed through their electronic medical records for up to 8 years. During this time, 173 women developed T2D and their blood samples were compared to 485 women enrolled in the study, matched for weight, age, race and ethnicity, who had not developed the disease.

"This study is unique as we are not simply comparing healthy people to people with advanced disease," says Röst, who holds Canada Research Chair in Mass Spectrometry-based Personalized Medicine and led the statistical data analysis. "Instead, we are comparing women who are clinically the same--they all had GD but are back to being non-diabetic post-partum.

"This is the holy grail of personalized medicine to find molecular differences in seemingly healthy people and predict which ones will develop a disease," says Röst.

Röst said that, unsurprisingly, sugar molecules feature prominently among the identified compounds. But amino-acids and lipid molecules are also present, indicating underlying issues in protein and fat metabolism, respectively. In fact, the predictive power of the test dropped if amino-acids and lipids were excluded, suggesting that processes beyond sugar metabolism may occur very early in the development of the disease. The finding may help explain why complications occur in T2D patients even when blood sugar is tightly controlled with medications.

The researchers hope to turn their discovery into a simple blood test that women could take soon after delivery, perhaps during an early visit to the doctor with their baby.

The women from the SWIFT study are being invited back for a 10-year follow-up visit, where they will be tested for T2D. "The information we glean from this study will bring us even closer to our goal of developing this blood test," says Gunderson.

"It will also help us to identify metabolic differences among race and ethnic groups that this test will need to take into account. The test is intended to help obstetricians and primary care providers identify the women with recent gestational diabetes who are most at risk for developing type 2 diabetes and to support them with breastfeeding and other healthful lifestyle habits during the first year postpartum that may reduce their risk."

Over the past twenty years, huge efforts by a broad coalition of stakeholders, coordinated by the World Health Organization have curbed the latest epidemic of human African trypanosomiasis, a lethal disease transmitted by tsetse flies. Now, public health officials report in PLOS Neglected Tropical Diseases that the elimination of the disease as a public health problem is within reach, with fewer than 1,000 new cases reported in 2018.

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic infection that has wreaked havoc across Africa at different times in the 20th century. A slow-progressing form of the pathogen, Trypanosoma brucei gambiense, is found in western and central Africa, while a faster-progressing form, T. b. rhodesiense, occurs in eastern and southern Africa. Following a resurgence of the disease in the late 1990s, strengthened control and surveillance activities were put in place with the coordination of the World Health Organization. In 2012, the WHO's Neglected Tropical Diseases roadmap targeted HAT for elimination as a public health problem by 2020.

In the new work, Jose Ramon Franco of the World Health Organization in Geneva, Switzerland, and colleagues studied global indicators and milestones collected between 2017 and 2018 to monitor progress toward the 2020 goal of HAT elimination. The team also developed new country-level indicators to be used by endemic countries to track HAT and validate their elimination status.

977 cases of HAT were reported in 2018, down from 2,164 in 2016, and the area at moderate or high risk of HAT has shrunk to less than 200,000 square kilometers, the team reported. More than half of this area is in the Democratic Republic of the Congo. Eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem. In addition, health facilities providing diagnosis and treatment for gambiense HAT have increased since the last survey, while rhodesiense HAT facilities decreased in number.

"The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status," the authors say. "Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal) by preparing for both the expected challenges and the unexpected ones."

In public health emergencies--including the current COVID-19 pandemic--local media are important sources of information for the public. In a paper published this week in PLOS Neglected Tropical Diseases, researchers have interviewed Sierra Leonean journalists about their experiences reporting during the 2014-2015 Ebola outbreak. The experiences of these journalists may be able to help inform current efforts to communicate about COVID-19.

When disaster strikes, people have a direct and strong need for information. Risk communication is one of the vital parts of any disaster, be it an earthquake, a gas leak or a disease outbreak. It has been suggested that local journalists can be directly mobilized or even commissioned by governments to disseminate public health information. In 2014 and 2015, Ebola virus disease (EVD) infected more than 28,000 people in West Africa.

In the new work, Maike Winters of Karolinska Institutet in Stockholm Sweden, and colleagues conducted semi-structured interviews with 13 Sierra Leonean journalists a few weeks after the last two EVD cases were reported in Sierra Leone in 2016. Radio is the most used medium for the large majority of the public in Sierra Leona and 11 of the 13 journalists interviewed worked for radio stations.

The thematic analysis showed that journalists adapted different roles over the course of the outbreak. In the early months of the outbreak, most were skeptical about the existence of an outbreak at all. They cited a lack of forthcoming information from official sources as leading to a mix of uncertainty and confusion. As the virus spread, the journalists became eyewitnesses, educators and public mobilizers. During this time, many struggled with their own fear for the virus, and say that targeted training helped them identify safe reporting practices in the field. Collaboration between local radio stations and with outbreak experts and local leaders helped the journalists make the transition to becoming instructors for the local communities and convey practical tips to the public.

"Our results show that it is possible to effectively partner with local media to disseminate public health messages," the researchers say. "This might be challenging in settings with problematic press freedom, but Sierra Leonean journalists actually felt that the outbreak helped improve their practices."

More than half of mums-to-be who are at risk of the dangerously high blood pressure condition, pre-eclampsia, are missing out on preventive aspirin treatment, says an expert in an editorial published online in Drug and Therapeutics Bulletin.

Making aspirin available from local pharmacies could help ward off the condition, says consultant obstetrician Dr Joanna Girling of West Middlesex University Hospital, London.

Pre-eclampsia is the leading cause of premature birth, restricted fetal growth, and stillbirth and it increases the risk of hospital admission for the expectant mother before the birth.

Risk factors include: chronic high blood pressure; underlying kidney disease; autoimmune disease such as rheumatoid arthritis; high blood pressure in a previous pregnancy; diabetes; older age (40+); obesity; more than 10 years since the previous pregnancy; or a family history of pre-eclampsia.

National guidelines recommend that women at risk of pre-eclampsia should begin to take preventive low dose aspirin at 12 weeks of pregnancy.

"So why is it that despite compelling evidence for its benefit and safety, more than 50% of eligible pregnant women never start aspirin?" asks the author.

Concerns about taking any drugs during pregnancy and logistical issues, such as midwives in most maternity units not having legal powers to prescribe or supply aspirin, may account for the figures, she suggests.

When midwives can't prescribe, they advise mums-to-be to see their local GP to get a prescription, but this obviously takes time, risking delays in the start of preventive treatment, or not starting it at all, says Dr Girling.

The easiest option would be to enable at-risk women to obtain supplies of low dose aspirin from their local pharmacy. It could be a lot cheaper than the "unnecessary branded pregnancy related nutrients and supplements that many women choose to buy," she suggests.

But the snag is that many pharmacists can't legally sell aspirin to ward off pre-eclmapsia because it is not officially marketed for the treatment of the condition.

While some may be concerned that this suggests the use of aspirin for pre-eclampsia is unsafe, the absence of an official license for this indication is most likely for commercial reasons, because it's unlikely to be financially worthwhile, explains Dr Girling.

But it makes no medical, financial, or common sense to disallow access to the drug in local pharmacies, she contends.

"If we are serious about increasing uptake of a nationally recommended, evidence-based, life-saving, low-cost intervention, how about developing a national [protocol] to allow community pharmacists to supply low-dose aspirin to women who are at risk of pre-eclampsia," she suggests.

We can't, and shouldn't, expect healthcare professionals without adequate personal protective equipment (PPE) to risk their lives to care for patients with COVID-19 infection, contends an expert in a stinging rebuke, published in the Journal of Medical Ethics.

Governments in the developed world knew full well what they were doing when they chose to underfund health service infrastructure and ignore repeated warnings about the advent of a pandemic, such as SARS-CoV2, the coronavirus responsible for COVID-19 infection.

And so did we, by voting for them, claims Dr Udo Schuklenk, of Queen's University, Kingston, Ontario, Canada. We've only got ourselves to blame.

Many healthcare workers across the globe have resigned, staged protests, or gone on strike over the lack of PPE. Hundreds have already lost their lives while on the frontline of COVID-19 care.

And "there can be no doubt that the death toll among healthcare professionals caring for COVID-19 patients all over the world will be significant," warns the author.

Amid rising concerns about the human cost of inadequate PPE supplies, some governments have considered introducing a compulsory service obligation for healthcare professionals as they grapple with the issue of whether clinicians have a professional duty of care "under the circumstances," points out Dr Schuklenk.

"During the early days of the HIV pandemic, when an infection with that virus meant certain death, regulatory bodies in most countries eventually decreed that healthcare professionals had an obligation to treat," he explains.

The risk of death from COVID-19 is lower, but what makes it different is that the regulatory response was predicated on the availability of PPE. "With SARS-CoV2, we are, in most countries, in a very different situation," he insists.

Taxpayers in many countries in the global north* that have some form of publicly funded healthcare have voted for governments that favoured low tax regimes and austerity measures, effectively crippling services, he says.

"The endpoint was the same: democratically elected governments across the global north have left hospitals woefully unprepared for the onslaught of patients, not only in terms of ICU beds and ventilators, but also in terms of PPE," he writes.

"The unavailability of PPE to efficiently maintain universal precautions while on the job was a foreseeable consequence of the race to the public services bottom that globalisation motivates," he contends.

"It's not as if governments and their experts did not know that the occurrence of an agent like SARS-CoV2 or worse was likely," he points out, adding that there's no excuse for the shortage of PPE.

"[It] does not constitute hi-tech expensive equipment; all of it can be produced relatively cheaply, and it can be stored in large quantities without taxing a given healthcare system unreasonably financially," he writes.

Except that now, of course, it is much more expensive, because no one prepared properly and invested in it when it was readily available.

"We live in democracies, and we elected politicians who promised us time and again that we could have our cake and eat it. It turns out, unsurprisingly, we cannot have that," he points out.

"There is no reason why doctors, nurses, and other healthcare workers should be seen to be professionally obliged to risk their wellbeing during pandemic outbreaks in the global north, because we chose governments that starved the healthcare delivery infrastructure sufficiently of resources to permit them to do their job safely or with minimal increases to their average on-the-job risk," he concludes. "Elections have consequences."

Patients with heart failure have substantially shorter life expectancies than people without this condition. Approximately 6.5 million people in the U.S. and over 64 million people worldwide have heart failure, and about half of them have heart failure with reduced ejection fraction (HFrEF). In the last three decades, there have been many advancements in the treatment of HFrEF with several new drugs showing promising results in randomized, controlled clinical trials. However, uptake of new therapies has been slow. A team led by investigators from Brigham and Women's Hospital has conducted an analysis to estimate the potential benefits of using a comprehensive regimen that incorporates newer therapies into clinical practice compared to using a more conventional regimen. The team found that comprehensive therapy could extend lifespan up to six years and eight years free from cardiovascular death or first hospital admission for HFrEF. Results are published in The Lancet.

"There's been some resistance to adopting comprehensive therapy for heart failure patients," said corresponding author Scott Solomon, MD, of the Brigham's Cardiovascular Division. "What we did here was to say, 'What might the benefit be over a patient's lifetime?' And the benefit we're seeing is pretty dramatic."

"Across a broad range of ages, these therapies, when implemented in combination, may meaningfully improve life expectancy and help patients remain out of the hospital," said lead author Muthiah Vaduganathan, MD, MPH, also of the Brigham's Cardiovascular Division.

To conduct their analysis, Solomon, Vaduganathan and colleagues leveraged data from three previously conducted randomized, clinical trials. Each trial evaluated a therapy for heart failure patients: mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNI), and sodium/glucose cotransporter (SGLT2) inhibitors. Drawing on the data from these trials, the team conducted an actuarial analysis to estimate the lifetime benefit of taking all three drugs in addition to a conventional regimen.

Their analysis found that over the course of a lifetime of use, assuming consistent treatment benefits, the comprehensive regimen could add up to eight years of survival free from cardiovascular events and hospitalization due to heart failure. While younger patients with HFrEF would stand to benefit the most, the researchers reported gains in life expectancy for all age groups analyzed.

Offering readily understandable metrics for clinicians and patients to be able to refer to when discussing treatment options was important to the authors, especially amid the COVID-19 pandemic.

"Patients with heart failure are especially vulnerable during COVID-19 and ensuring effective preventive care for this high-risk segment of the population is a top priority in the next phase of the pandemic planning," said Vaduganathan.

The authors note that their analysis has certain limitations, including assumptions about the therapy, adherence, and that benefits would continue to accrue over time. In addition, the analysis does not examine the costs of heart failure drugs or the potential side effects -- such as kidney toxicity -- of taking these drugs in combination.

Amsterdam, May 21, 2020 - Bladder cancer is associated with significant illness and mortality, particularly if treatment is delayed. Writing in the journal Bladder Cancer, researchers have outlined recommendations for treatment of both muscle invasive (MIBC) and non-muscle invasive (NMIBC) bladder cancer during the COVID-19 pandemic based on data from trials and prior studies, and taking into account the current strains on the healthcare system.

The COVID-19 pandemic has disrupted the paradigm of healthcare in many ways. Hospital resources are stretched thin as the number of cases continue to climb daily. In cancer care, treatment must be weighed against the issues of viral transmission, resource utlization, healthcare access, and community safety.

"The COVID-19 epidemic has forced doctors to prioritize patients with time-sensitive illnesses and defer those with conditions that can wait. We know some patients with bladder cancer simply can't wait on treatment without compromising their oncologic outcomes," explains senior author Lambros Stamatakis, MD, Director, Urologic Oncology - MedStar Washington Hospital Center, Assistant Professor of Urology - Georgetown University, Washington, DC, USA. "Our hope with this paper is to provide a framework that can help clinicians navigate treatment decisions for their bladder cancer patients in the setting of the COVID-19 epidemic."

First author Filipe L.F. Carvalho, MD, PhD, MedStar Georgetown University Hospital, Washington, DC, USA, adds "Many institutions have stopped performing elective surgery and outpatient procedures during the COVID-19 epidemic. This can be problematic for patients with NMIBC who need frequent cystoscopies, bladder biopsies/tumor resections, and intravesical therapy. For patients with MIBC, delay of treatment may unfortunately result in missing the window of opportunity for cancer cure."

Risk stratification is key in helping clinicians manage this cancer. The authors note that several studies recommend that patients with low risk NMIBC can be safely managed with active surveillance after transurethral resection of bladder tumor (TURBT), generally the first treatment for bladder cancer. "Given the inevitable shift of resources diverted to treat patients with COVID-19, and to prevent viral exposures during medical visits, we propose surveillance for all patients with a history of low risk tumors, and those with non-high-grade intermediate risk NMIBC, reserving TURBTs for symptomatic patients." says Dr. Stamatakis.

On the contrary, patients with high risk NMIBC should proceed with active treatment. Since hospitalization after TURBT is uncommon, and the risk of aerosolization of virus during these procedures is low, the authors recommend that these surgeries should be continue if possible, within a hospital system.

MIBC is a more lethal disease, and studies show that delayed treatment leads to significantly worse outcomes. One of the standard therapies is radical cystectomy with urinary diversion. However, the authors observe that the COVID-19 pandemic has forced the urologic community to reconsider standard practices. Radical cystectomy is resource intensive, with the need for ventilators, masks, and other equipment. Moreover, the need for human resources is extensive when a hospital system is performing major surgeries. These factors all need to be considered during this period when material and human resources are scarce and may be needed elsewhere.

The authors believe that radical cystectomy is one of the procedures that should be prioritized during the COVID-19 epidemic. They recommend that the choice of treatment for MIBC should be individualized, with specific consideration given to patient symptoms, tumor volume, access to cancer treatments such as infusion centers and radiation centers, access to post-hospitalization care (i.e., rehab/skilled nursing facilities), and the current status of the virus in the community. They note that enhanced recovery after surgery protocols should be implemented to allow for improved convalescence. Telemedicine should be feasible for pre- and postoperative visits in most instances.

Currently there are multiple clinical trials available for patients with NMIBC and MIBC, however, recommendations from governments and other institutions regarding these trials are evolving. The authors recommend that for patients already enrolled in therapeutic trials, all efforts should be made to continue providing the appropriate treatment if safe for the patient and local healthcare community.

While non-therapeutic trials focused on biomarker discovery or relying on tissue banking should be placed on hold, "we encourage clinical investigators to consider novel approaches to patient monitoring and disease management. Looking forward, recommendations will inevitably need to evolve with the quickly changing landscape of medicine during the COVID-19 epidemic," comments Dr. Carvalho.

Results of a comprehensive analysis of exercise and its protective role for high-risk breast cancer patients show that women who exercise not only live longer, but also are more likely to remain cancer-free after their treatment. What's more, the study suggests that even a modest amount of exercise can be beneficial.

"Aiming for as little as two and half hours a week of exercise - the minimum under federal guidelines - can have a big impact for women with high-risk breast cancer," said study lead Rikki Cannioto, PhD, EdD. "Our research shows that some physical activity is far better, in terms of cancer survival, than no activity at all and it is just as beneficial as longer workouts."

Cannioto's study was part of a clinical trial run by SWOG Cancer Research Network, a cancer clinical trials network funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and a member of the oldest and largest publicly-funded research network in the nation. Study results are published in the Journal of the National Cancer Institute, and featured in the most recent edition of the NCI's Cancer Currents blog.

Research has long shown a positive correlation between exercise and cancer survival. People who exercise more- before or after cancer treatment - appear to live longer. What makes the SWOG study unique is that it also showed, among the high-risk breast cancer patients it studied, those who exercised had a lower chance of their breast cancer returning after treatment. Another new twist is the time scale of the study. Patients were not only asked about their exercise before and after cancer treatment - but during chemotherapy, too.

Cannioto, an assistant professor of oncology in the Department of Cancer Prevention and Control at Roswell Park Comprehensive Cancer Center, wanted to determine the impact of the amount of exercise, and its timing, on women with breast cancers that are high-risk, or likely to return. She addressed this question in the context of the Diet, Exercise, Lifestyle and Cancer Prognosis Study (DELCaP), led by Christine Ambrosone, PhD, from Roswell Park and her SWOG collaborators. The DELCaP study was part of S0221, a randomized phase III SWOG trial determining the best dose and schedule for three chemotherapy drugs. S0221 included patients with stage II or III breast cancer, or high-risk stage I cancer, all of which have a higher rate of returning because, among other features, the primary tumor was large or the cancer had spread to the lymph nodes. S0221 enrolled 2,716 patients - and 1,607 consented to responding to the DELCaP questionnaire. It included questions about study subjects' habits, including exercise. They were asked about current habits, as well as routines prior to their breast cancer diagnosis. The questionnaire was administered when patients enrolled in the study, when they were undergoing chemotherapy, one year after their study treatment, and again two years after treatment, for a total of four responses. More than 80 percent responded in each round.

For exercise, patients were asked what type of physical activity they did, for how long, and how often. Responses were categorized based on the U.S. Department of Health and Human Services' Physical Activity Guidelines for Americans, which call for at least two and half hours of moderate-intensity activity a week or one and a quarter hours of vigorous activity per week. Cannioto and her team then looked at post-treatment outcomes for different groups.

Here's what they found:

Patients who met the minimum federal exercise guidelines, before and after treatment, had a significantly reduced risk of their cancer returning - a 55 percent decrease in risk.

Patients who met the minimum federal exercise guidelines, before and after treatment, had a significantly reduced risk of death - a 68 percent decrease in risk.

Patients who started exercising only after treatment still saw big benefits - a 46 percent decreased chance of recurrence and a 43 percent decreased chance of dying.

A few hours of consistent, weekly exercise result in the same survival benefits as longer periods of weekly activity.

"What these results suggest for doctors - and patients - is that even a modest exercise routine, taken up after cancer treatment, can help women with high-risk breast cancer live longer and healthier lives," Cannioto said. "It's never too late to start walking, doing yoga, cycling, or swimming - and that activity certainly appears to pay off."

Leesburg, VA, May 21, 2020--Remote reading of imaging studies on home PACS workstations can contribute to social distancing, protect vulnerable radiologists and others in the hospital, and ensure seamless interpretation capabilities in emergency scenarios, according to an open-access article published ahead-of-print by the American Journal of Roentgenology (AJR).

"Transitioning from on-site interpretation to remote interpretation requires a careful balancing of hospital and departmental finances, engineering choices, and educational and philosophical workflow issues," wrote lead author Srini Tridandapani of the University of Alabama at Birmingham, which uses iSite (Philips Professional Healthcare) for its PACS.

Financial Challenges and Engineering Choices

Given the difficulty of funding acquisition in the present environment, several radiologists from Tridandapani's institution offered computers from their laboratories or offices for redeployment as PACS workstations. "Unfortunately," Tridandapani et al. acknowledged, "many of the offered computers either did not have the processing or memory capacity to serve as PACS workstations or did not have the requisite connections to support all the peripherals needed." Moreover, hardware and software standardization for every remote workstation proved essential for efficient remote maintenance. "Ultimately," the authors continued, "our financial request from hospital administration mainly consisted of support for the hardware VPN (virtual private network) system and the standard display monitors, which we were able to secure within a week after conceptualization of the project."

Workstation Assignments

"Because we did not have the funding to equip all of our radiologists with remote PACS workstations, we had to make difficult choices regarding who would benefit the most from these workstations, and conversely who, if equipped with these workstations, could benefit the department the most," Tridandapani and colleagues explained. Providing remote reading for emergency radiologists was "the easiest part of this decision," as they interpret across a spectrum of modalities (radiography, ultrasound, CT, MRI) and organ systems (abdominal, cardiothoracic, musculoskeletal, neuroradiologic). However, to achieve equity between the radiologists assigned remote workstations and those needed for on-site reading, the former may be required to work more shifts than the latter. Due to curtailed outpatient imaging and the higher-quality monitors necessary for Mammography Quality Standards Act certification, workstations were not provided for the mammography section. Nuclear medicine was provided a secondary route for remote access to run its specialized PACS solution.

Workflow Redesign

Remote reading, coupled with the decline in imaging volume nationwide, significantly reduced the number of on-site interpreters at Tridandapani and team's institution--"three or fewer readers per reading room, depending on the size of the rooms," the authors noted. "We make sure that each section has at least one radiologist on-site to provide technologists with backup and to reassure them of our constant presence and availability," Tridandapani et al. continued. Limiting the presence of resident trainees, too, program directors scattered them across reading rooms at various off-site locations and within clinic buildings that were ostensibly closed to other functions. "We check in with residents periodically using the Primordial communication tool on the PACS workstation," Tridandapani and colleagues wrote, adding that the reduced workload has provided unique opportunities for both telephone and videoconferencing discussions regarding interesting cases.