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DALLAS, May 4, 2020 -- Women with cardiovascular conditions should be cared for during pregnancy by a cardio-obstetrics team or health care providers experienced in high-risk pregnancies to provide specialized maternity care for the mother and fetus, according to a new American Heart Association scientific statement, Cardiovascular Considerations in Caring for Pregnant Patients, published today in the Association's flagship journal Circulation.

"Cardiovascular diseases are the leading cause of pregnancy-related death and are increasing, possibly because women are having babies at older ages and are more likely to have preexisting heart disease or heart disease risk factors," said Laxmi Mehta, M.D., writing group chair for the statement, and professor of medicine and director of preventive cardiology and women's cardiovascular health at The Ohio State University Wexner Medical Center in Columbus, Ohio.

Advanced maternal age - defined as age 35 or above - is associated with a higher risk of premature birth, chronic hypertension, preeclampsia (pregnancy-related high blood pressure) and/or gestational diabetes.

Women who are planning to become pregnant and who have preexisting cardiovascular conditions, such as chronic high blood pressure, a history of preeclampsia, heart muscle disease (cardiomyopathies), diabetes, high cholesterol, previous heart attacks, heart valve disorders, aortic dilatation and/or congenital heart disease should receive preconception counseling by a cardio-obstetrics team or health care providers experienced in high-risk pregnancies.

"For each of these cardiac conditions, pregnancy can impact treatment as there are limitations in medication management and invasive procedures given the potential fetal risks. For example, statin medications should not be used to lower cholesterol during pregnancy because these drugs could cause fetal abnormalities, according to the most recent cholesterol guidelines. Women should understand fetal risks and the risks to their own health posed by heart conditions before becoming pregnant," said Mehta. "If a woman is taking statin drugs, they should be discontinued one to two months before pregnancy is attempted."

Blood pressure changes are normal during pregnancy, however, blood pressure should be monitored closely. The most common cardiovascular events during pregnancy are related to high blood pressure disorders such as preeclampsia, defined as systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg in women after 20 weeks of gestation who had normal blood pressure before pregnancy. It can lead to serious complications including liver or kidney dysfunction, headaches, vision changes and/or fluid overload in the lungs and is also a leading factor for premature birth and cesarean delivery.

Women with a history of preeclampsia have a 71% greater risk of dying from heart disease or stroke over their lifetime compared to women who have never had preeclampsia, according to the statement. There are effective treatments to prevent or manage preeclampsia; however, treatment must be carefully individualized.

The statement reports that several studies have proposed that regular exercise during pregnancy may improve the way blood vessels function and may even prevent preeclampsia; additional studies need to be conducted to verify these findings.

"The role of a healthy lifestyle during pregnancy - whether or not a woman has a cardiovascular condition - cannot be emphasized enough. Healthy diet, moderate exercise including walking, smoking cessation and other healthy behaviors are important tools for a healthy pregnancy for both mother and child," said Mehta.

Pregnant women who have valvular heart disease, which increases their risk of having an ischemic stroke (caused by blood clots), and women who are at high risk for ischemic stroke for other reasons may benefit from treatment with vitamin K antagonists or other blood thinners after the first trimester to help reduce blood clotting.

Arrhythmias - heart rhythm disorders - have been increasing among pregnant women. Data gathered between 2000-2012 on 57 million pregnancies in the U.S. shows a rise in the number of pregnancy-related hospitalizations for arrhythmias. This finding may be associated with the increasing number of women becoming pregnant at advanced maternal ages. While most arrythmias are benign and do not require treatment, more complex arrhythmias can lead to a cardiac arrest or stroke and require a cardio-obstetrics team for optimal care during pregnancy. Management strategies may include anti-arrhythmic medication therapy and/or consideration of performing a surgical procedure - radiofrequency ablation - that can stabilize the heart rhythm during pregnancy.

In addition to carefully managing their pregnancy, women with cardiovascular disease should have an individualized delivery plan. Vaginal birth is recommended most often because there are additional risks associated with cesarean delivery. However, there are individual situations where a cesarean section (where a baby is delivered surgically through an incision) is appropriate.

Ideally, a woman with preexisting cardiovascular disease should be cared for by a multidisciplinary cardio-obstetrics team, including an obstetrician, cardiologist, anesthesiologist, maternal-fetal medicine specialist and nurses. Women who don't have access to a cardio-obstetrics team can receive optimal care from health care providers experienced with high-risk pregnancies. In either scenario, the health care providers develop a comprehensive, individualized strategy for managing a woman's cardiovascular health during pregnancy, delivery and the postpartum period of at least one year. A comprehensive care plan that meets the needs of each individual patient and involves shared decision-making are essential to improving cardiovascular outcomes during and after pregnancy.

Additionally, women who have had adverse pregnancy outcomes - such as preeclampsia and/or gestational diabetes - are at increased lifetime risk of cardiovascular disease and should be closely monitored for development of cardiac risk factors and conditions. Between 1987 and 2015, pregnancy-related deaths have risen from 7.2 to 17.2 deaths per 100,000 live births in the United States, according to the statement.

Before becoming pregnant, the authors say all women should discuss their nutrition, weight, exercise and cardiac risks with their doctor. "For women with existing heart disease, proper medical care and a healthy lifestyle are essential for these women to have a healthy pregnancy," said Mehta.

New research from The George Institute for Global Health at the University of Oxford has found that there is substantial overlap in symptoms - such as chest pain - experienced by women and men upon clinical presentation, as well as crucial differences, the like of which have been established in literature for over a decade. While women had lower odds of presenting with chest pain, the study found that both sexes presented most often with this symptom.

Women are more likely to present with fatigue, pain between the shoulder blades, neck pain, nausea, vomiting, and shortness of breath than are men. These symptoms are often labelled as 'atypical' as they are different to those generally experienced by men.

Researchers analysed 27 studies comprising over 1.2 million individuals who had experienced a heart attack and concluded that in order to ensure timely diagnosis and treatment, medical professionals need to be familiar with the well-established sex differences as well as the overlap in symptoms experienced by patients with suspected and confirmed cases of acute coronary syndrome.

Acute coronary syndrome (ACS) is the umbrella term for angina (when the heart muscle doesn't receive sufficient oxygen-rich blood to function normally) and heart attack, and is a substantial component of ischemic heart disease which is the greatest cause of death worldwide, claiming an estimated 9 million lives in 2015 [1].

The first-line treatment for ACS, reperfusion, restores blood flow to the heart following a heart attack, and is most effective when initiated in a timely manner to minimise damage to the heart muscle tissue [2].

"Delayed symptom recognition, by either patients or medical professionals, is a key reason for delay in potentially life-saving treatment. By shedding further light on sex differences in clinical presentation with ACS, this research will hopefully lead to more timely and equitable treatment and outcomes," said Dr Sanne Peters, Research Fellow in Epidemiology at The George Institute UK, who led the research.

"As the study only looked at those with confirmed ACS, further studies should be conducted in those with suspected ACS as they may help doctors to pick up cases earlier, saving critical time and heart muscle," Dr Peters added.

The authors concluded that future research should also focus on the development and validation of a diagnostic tool, with a comparison of symptoms among women and men with and without confirmed ACS.

WINSTON-SALEM, N.C. - May 4, 2020 - Intensive blood pressure control may reduce the risk of atrial fibrillation (AFib), an irregular heartbeat that can lead to serious complications such as stroke, heart failure and heart attacks, according to scientists at Wake Forest School of Medicine.

In a study published in the May 4 edition of the American Heart Association journal Hypertension, the researchers found that lowering a systolic blood pressure to less than 120 resulted in a 26% lower risk of AFib compared to systolic blood pressure of less than 140.

"This is the first evidence from a randomized controlled trial that showed benefit in reducing the risk of atrial fibrillation as a result of aggressive blood pressure control to a target of less than 120 mm Hg," said the study's lead author, Elsayed Z. Soliman, M.D., professor of epidemiology and prevention at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

This analysis, using data from the National Institutes of Health Systolic Blood Pressure (SPRINT) trial, included 8,022 study participants who were randomized into one of two groups: 4,003 participants in an intensive blood pressure control group (target less than 120 mm Hg) and 4,019 participants in a standard lowering group (target less than 140 mm Hg).

Participants were followed for up to five years. During that time, only 88 AFib cases occurred in the intensive blood pressure lowering group while 118 cases occurred in the standard blood pressure lowering group. Soliman's team showed that the benefit of intensive blood pressure lowering on reducing the risk of AFib was similar in all groups of the participants regardless of sex, race or levels of blood pressure.

"Hypertension is the most common modifiable risk factor for atrial fibrillation," Soliman said. "And now, we have a potential pathway for prevention."

The landmark SPRINT study, which published its main results in 2015, enrolled participants with hypertension who were at increased risk of cardiovascular disease. The trial was designed to answer how aggressive blood pressure control affects cardiovascular health and showed that intensive treatment significantly reduced the rates of death and cardiovascular disease. As a result of the trial, the American Heart Association and American College of Cardiology updated their clinical guidelines for high blood pressure.

Previous SPRINT findings published by Wake Forest Baptist researchers have shown that lowering blood pressure reduces risk of cognitive impairment and may slow age-related brain damage.

Obese mice with unhealthy lifestyles gain significantly less weight and avoid type 2 diabetes when they receive viruses transplanted from the stool of lean mice. These are the findings of a new University of Copenhagen study.

In recent years, faecal transplants from healthy donors to sick patients have become a popular way of treating a serious type of diarrhoea caused by the bacterium Clostridioides difficile in humans. Recent trials in mice suggest that a similar treatment, in which only the virus in stool is transplanted, may help people suffering from obesity and type 2 diabetes. The majority of virus particles transmitted are so-called bacteriophages -- viruses that specifically attack other bacteria and not humans.

"When we transmit virus particles from the faeces of lean mice to obese ones, the obese mice put on significantly less weight compared to those that do not receive transplanted faeces," says Professor with Special Responsibilities (MSO) and senior author of the study, Dennis Sandris Nielsen of the University of Copenhagen's Department of Food Science.

Also works against type 2 diabetes

The method also seems to protect the mice against developing glucose intolerance (a hall mark of type 2 diabetes), a disease that inhibits the body from properly absorbing sugar. The experiments demonstrated that the obese mice that received an intestinal virus transplant from lean mice reacted to a shot of glucose no differently than the lean ones.

"In the obese mice on high fat diet, that didn't receive the virus transplant, we observed decreased glucose tolerance, which is a precursor of diabetes. Thus, we have influenced the gut microbiome in such a way that the mice with unhealthy lifestyles do not develop some of the common diseases triggered by poor diet," explains PhD student Torben Sølbeck Rasmussen, first author of the study.

He emphasizes that the method is not a stand-alone solution and that it must be complemented with a change in diet. Furthermore, the treatment will probably not be targeted at general obesity, but more towards the most serious cases.

It is understood that obesity and type 2 diabetes are linked to imbalances in the gastrointestinal microbiome, also known as gut flora. In recent years, it has been discovered that the composition of viruses in the gut plays a crucial role in the balance of this microbiome.

"If one eats poorly for long enough, they risk creating an imbalance in their intestinal tract. Here, we have a means of recuperating balance by shooting missing virus particles back into the system," says Dennis Sandris Nielsen.

The researchers extracted faeces from mice fed a standard low-fat diet over a period of time. The stool was then filtered so that all live bacteria were sorted out, while the virus particles -- mainly bacteriophages -- were concentrated. The viruses were transplanted via a tube into the mice that had been on high-fat diets for 6 weeks. The mice continued the fatty diet for another six weeks. Thereafter, the mice were examined after a glucose test and measured for weight gain.

Virus only - no bacteria

The study addresses one of the current problems with faecal transplants. Today, stool is transplanted in an unfiltered form, in the belief that it is the gut bacteria which are most effective. However, in rare cases, the method produces side effects when diseases are inadvertently transmitted via the transplanted stool bacteria. Indeed, a patient in the United States died from just such an occurrence last year.

"Our study demonstrates that there is an effect after the live bacteria have been filtered from stool. Therefore, primarily virus particles are transmitted. This makes the method safer," says Dennis Sandris Nielsen.

He expects that it will be a number of years before the method can be broadly deployed. More experiments are needed, and obviously, human trials as well.

"Mice are the first step. But because the findings suggest that it will work in humans, that is the next. Our hope is that, in the long term, a well-defined cocktail of bacteriophages can be developed that has a minimal risk of side effects," concludes Dennis Sandris Nielsen.

FACTS:

The results demonstrated significantly decreased weight gain in mice on a high-fat diet with transplanted intestinal viruses, compared against non-transplanted mice on the high-fat diet. At the same time, the blood glucose tolerance of transplanted mice was normalised, whereas it was reduced in the other obese mice.

Faecal transplantation, also known as faecal microbiota transplant, is the transfer of gut bacteria from a healthy donor to a sick recipient. The method used in this study is known as Faecal Virome Transplantation. The method filters stool of live bacteria so that primarily virus particles are transmitted.

Researchers do not yet know how long the effect of each transplant is. The study demonstrates an effect of at least 6 weeks.

Prof. Viktor Seledtsov, a senior researcher at the IKBFU Center of Medical Biotechnologies and Alexei von Delwig, a researcher at Innovita Res (Vilnius, Lithuania) have published an article in Expert Review of Vaccines scientific journal. A new way to prevent autoimmune diseases associated with aging like atherosclerosis, Alzheimer's disease, and Parkinson's disease was described in the article.

Prof. Viktor Seledtsov said:

"There are several biological mechanisms that limit a human being's life span. And the most important of them all is the immunological one. After time immune cells known as T-lymphocytes become more and more autoreactive. To put it simply, they become less aggressive towards foreign pathogens attacking instead of the body's own tissues. And those attacks are the main cause for autoimmune diseases, usually associated with aging".

According to prof. Seledtsov, a person's immune system becomes hostile to the one it ought to protect, because of the logic shift, as it is now not aimed at keeping the "owner" alive but becomes aimed at the species survival, which means constant renewing, with the young replacing the old. Because renewing means adapting to changeable conditions. Thus these aging mechanisms keeps the human population safe by constantly stimulating adaptation. Can we lower the pathologic autoreactivity of the immune cells?

Viktor Seledtsov and Alexei von Delwig have offered a method of lymphocytic vaccination to counter autoimmune diseases. This technology is aimed at the natural autoimmune mechanism's stimulation. The method proved to be clinically effective in the treatment of multiple sclerosis and rheumatoid arthritis.

Prof. Seledtsov continued:

"There is also an approach to counter the immunology aging, which is to create an immunology cell bank to keep immunocompetent cells extracted during a person's youth. When injected into an aging body, these cells are able to enhance immunological protection against infection, take control of "old" autoimmune cells and thus prolong a person's life. And a person's own cells are the best material for the injection. And to make this procedure possible, we need the immunology bank".

Seledtsov believes that a young person may give his immune cells to the bank and later inject those cells back to him upon reaching the age of 65, for example.

The technologies like this will not solve all human beings' health issues and will not grant immortality, but they may prolong life and improve living standards.

A team of researchers has developed a portable, more environmentally friendly method to produce hydrogen peroxide. It could enable hospitals to make their own supply of the disinfectant on demand and at lower cost.

The work, a collaboration between the University of California San Diego, Columbia University, Brookhaven National Laboratory, the University of Calgary, and the University of California, Irvine, is detailed in a paper published in Nature Communications.

Hydrogen peroxide has recently made headlines as researchers and medical centers around the country have been testing its viability in decontaminating N95 masks to deal with shortages amid the COVID-19 pandemic.

While results so far are promising, some researchers worry that the chemical's poor shelf life could make such decontamination efforts costly.

The main problem is that hydrogen peroxide is not stable; it starts breaking down into water and oxygen even before the bottle has been opened. It breaks down even more rapidly once it is exposed to air or light.

"You maybe only have just a couple of months to use it before it expires, so you would have to order batches more frequently to keep a fresh supply," said UC San Diego nanoengineering professor Zheng Chen. "And because it decomposes so quickly, shipping and storing it become very expensive."

Chen and colleagues developed a quick, simple and inexpensive method to generate hydrogen peroxide in house using just a small flask, air, an off-the-shelf electrolyte, a catalyst and electricity.

"Our goal is to create a portable setup that can be simply plugged in so that hospitals, and even households, have a way to generate hydrogen peroxide on demand," Chen said. "No need to ship it, no need to store it, and no rush to use it all before it expires. This could save up to 50 to 70% in costs."

Another advantage is that the method is less toxic than industrial processes.

The method is based on a chemical reaction in which one molecule of oxygen combines with two electrons and two protons in an acidic electrolyte solution to produce hydrogen peroxide. This type of reaction is known as the two-electron oxygen reduction reaction, and it is user-friendly because it can produce dilute hydrogen peroxide with the desired concentration on demand. "In the next step, we will develop electrocatalysts suitable for other electrolyte solutions to further increase the range of its applications," said UC San Diego chemical engineering graduate student Qiaowan Chang.

The key to making this reaction happen is a special catalyst that the team developed. It is made up of carbon nanotubes that have been partially oxidized, meaning oxygen atoms have been attached to the surface. The oxygen atoms are bound to tiny clusters of three to four palladium atoms. These bonds between the palladium clusters and oxygen atoms are what enable the reaction to occur with a high selectivity and activity due to its optimal binding energy of the key intermediate during the reaction.

Columbia University chemical engineering professor Jingguang Chen said, "The coordination between oxygen-modified Pd cluster and the oxygen-containing functional groups on carbon nanotubes is the key to enhancing its catalytic performance."

The team originally developed this method to make battery recycling processes greener. Hydrogen peroxide is one of the chemicals used to extract and recover metals like copper, nickel, cobalt and magnesium from used lithium-ion batteries. Similarly, it also makes the activation of hydrocarbon molecules more efficient, which is a critical step in many industrial chemical processes.

"We had been working on this project for about one and a half years. As we were wrapping things up, the COVID-19 pandemic hit," Chen said. Seeing news reports about the use of hydrogen peroxide vapor to disinfect N95 masks for reuse motivated the team to pivot directions.

"We saw that there was a more pressing need for efforts to help health care workers who may not have sufficient protection while caring for patients suffering from the new coronavirus," he said.

The work is at the proof-of-concept stage. Moving forward, the team will work on optimizing and scaling up the method for potential use in hospitals. Future studies include modifying the method so that it can be done using a neutral electrolyte (basically a salt solution) instead of an acidic one, which would be better for household and clinical applications, Chen said. Part of this continuing work is currently supported by UC San Diego's Sustainable Power and Energy Center.

Even under normal circumstances, nursing can be a stressful profession. The COVID-19 pandemic only exacerbates it.

New research led by Marian Reven, a Ph.D. student in the West Virginia University School of Nursing, suggests that aromatherapy may reduce nurses' on-the-job feelings of stress, anxiety, exhaustion and being overwhelmed. Her pilot study results appear in the International Journal of Professional Holistic Aromatherapy.

"If we can improve our nurses' emotional reserves and give them more resiliency by using aromatherapy--give them a place to step back, to do some mindfulness--we're doing a good thing at the other end of it by improving patient care," she said.

In an eight-week study, she and her colleagues--WVU researchers Janelle Humphrey-Rowan and Nina Moore--provided aromatherapy patches to 19 nurses who worked at the Infusion Center at the WVU Cancer Institute. The nurses affixed the patches to the badges they wore on lanyards around their necks. The patches were infused with a citrusy blend of essential oils: lemon, orange, mandarin, pink grapefruit, lemongrass, lime and peppermint.

"I sat down with people from the WVU Cancer Institute's Mary Babb Randolph Cancer Center, and we smelled three different oil blends," said Reven, a registered nurse with WVU Medicine and certified, registered aromatherapist. "When they smelled this blend, everybody's face lit up, and they were immediately happy."

Cutting stress levels in half

The nurse participants wore aromatherapy patches on their ID badges for four-to-eight-hour stretches, on eight separate occasions, while working at the infusion center.

Before and after wearing the patch each time, study participants completed a survey about their moods. They reported how strong certain emotions were, on a scale of one to 10.

The researchers found that participants felt significantly less stressed, anxious, fatigued and overwhelmed after wearing the aromatherapy patches. The levels of anxiety and fatigue they reported fell by 40 percent, and their stress levels and feelings of being overwhelmed decreased by half.

"Oncology nurses face a type of stress that is unique," Reven said. "There are so many cancers that are considered chronic illnesses that oncology infusion center nurses probably see these people for years instead of months. They know them. They get very invested in their lives."

"It's a stressful job," said Laurie Theeke, professor and director of the Ph.D. Program at the School of Nursing and nurse practitioner in the Department of Family Medicine. "You're dealing with life or death or chronic illness every day. And people in all of the health professions are stressed. This doesn't just have application to nursing. It's about workplace stress."

Stressful times, lonely patients

Aromatherapy might improve patients' moods, too, particularly during the COVID-19 pandemic, when hospital patients can't receive visitors.

"I work nightshift weekends," Reven said. "Last weekend, several of the patients tugged on my heart strings. They missed their family and friends so much during this time of 'no visitors.' I just wanted to be able to do something more for them. An aromatherapy patch with lavender or citrus might have helped.

"As a nurse, I spend a lot of time at the bedside of very ill people," she added. "I often think, 'How would I feel if it was me?' I get very sad sometimes watching the suffering, and yes, I personally use aromatherapy to help with my resiliency."

Loneliness isn't just unpleasant. It's also a predictor of depression, functional decline and mortality.

"People do die of loneliness," Theeke said.

The research results also suggest that aromatherapy might make people outside of healthcare settings feel better as they shelter in place to prevent the spread of SARS-CoV-2, the virus that causes COVID-19. After all, a patch on an employment badge isn't the only way to use essential oils. Someone can plug in an essential oil diffuser or simply add a drop of pure lavender essential oil to a teaspoon of lotion.

Reven emphasized the importance of buying essential oils only from reputable sources.

"There are two professional organizations that can give the layperson credible information about where to find essential oils and how to use them safely: the Alliance of International Aromatherapists and the National Association of Holistic Aromatherapy," she said.

But you don't have to buy anything special to enjoy the benefits of aromatherapy. Common household items, used during common household tasks, can be enough.

"Baking is aromatherapy," Reven said. "Cutting up an orange is aromatherapy. We need some aromatherapy all the time."

Cytokine storms may affect the severity of COVID-19 cases by lowering T cell counts, according to a new study published in Frontiers in Immunology. Researchers studying coronavirus cases in China found that sick patients had a significantly low number of T cells, a type of white blood cell that plays a crucial role in immune response, and that T cell counts were negatively correlated with case severity.

Interestingly, they also found a high concentration of cytokines, a protein that normally helps fight off infection. Too many cytokines can trigger an excessive inflammatory response known as a cytokine storm, which causes the proteins to attack healthy cells. The study suggests that coronavirus does not attack T cells directly, but rather triggers the cytokine release, which then drives the depletion and exhaustion of T cells.

The findings offer clues on how to target treatment for COVID-19, which has become a worldwide pandemic and a widespread threat to human health in the past few months. "We should pay more attention to T cell counts and their function, rather than respiratory function of patients," says author Dr. Yongwen Chen of Third Military Medical University in China, adding that "more urgent, early intervention may be required in patients with low T lymphocyte counts."

Chen says he and his co-authors became interested in examining T cells when they noticed that many of the patients they treated for COVID-19 had abnormally low numbers of lymphocytes, a type of white blood cell that includes T cells. "Considering T cells' central role of response against viral infections, especially in the early stage when antibodies are not boosted yet, we took the T cells as our focal point," says Chen.

Authors examined 522 patients with coronavirus along with 40 healthy controls. All patients studied were admitted to two hospitals in Wuhan, China between December 2019 and January 2020, and ages ranged between 5 days and 97 years old. Of the 499 patients who had their lymphocytes recorded, 76% had significantly low total T cell counts. ICU patients had significantly lower T cell counts compared with non-ICU cases, and patients over the age of 60 had the lowest number of T cells.

Importantly, the T cells that did survive were exhausted and could not function at full capacity. Not only does this have implications for COVID-19 patient outcomes, but T cell exhaustion leaves patients more vulnerable to secondary infection and calls for scrupulous care.

Chen says that future research should focus on finding finer subpopulations of T cells in order to discover their vulnerability and effect in disease, along with identifying drugs that recover T cell numbers and boost function.

Authors say that Tocilizumab is an existing drug that may be effective, but that it needs to be investigated in the context of coronavirus. Antiviral treatments, such as Remdesivir, may also prevent the progression of T cell exhaustion, but all future treatments will require further study.

In the meantime, this new research deepens our understanding of how the novel coronavirus affects the body and it indicates ways to lessen its impact.

Boston, Mass. -- Since the World Health Organization declared COVID-19 a Public Health Concern of Global Interest on January 30, more than one million have tested positive for the illness in the United States, and more than 62,000 have died. With no FDA-approved treatments available to date, the anti-malarial drug, hydroxychloroquine, has emerged as a potential therapy for the pneumonia associated with COVID-19, with or without the antibiotic azithromycin.

In a brief report published today in JAMA Cardiology, a team of pharmacists and clinicians at Beth Israel Deaconess Medical Center (BIDMC), part of Beth Israel Lahey Health, found evidence suggesting that patients who received hydroxychloroquine for COVID-19 were at increased risk of electrical changes to the heart and cardiac arrhythmias. The combination of hydroxychloroquine with azithromycin was linked to even greater changes compared to hydroxychloroquine alone.

"While hydroxychloroquine and azithromycin are generally well-tolerated medications, increased usage in the context of COVID-19 will likely increase the frequency of adverse drug events (ADEs)," said co-first author Nicholas J. Mercuro, PharmD, a pharmacy specialist in infectious diseases at BIDMC. "This is especially concerning given that that patients with underlying cardiac co-morbidities appear to be disproportionately affected by COVID-19 and that the virus itself may damage the heart."

Hydroxychloroquine and azithromycin each can cause an electrical disturbance in the heart known as a QTc prolongation, indicated by a longer space between specific peaks on an electrocardiogram. QTc prolongation denotes that the heart muscle is taking milliseconds longer than normal to recharge between beats. The delay can cause cardiac arrhythmias, which in turn increases the likelihood of cardiac arrest, stroke or death.

In this single-center, retrospective, observational study, Mercuro and colleagues evaluated 90 adults with COVID-19 who were hospitalized at BIDMC between March 1 and April 7, 2020, and received at least one day of hydroxychloroquine. More than half of these patients also had high blood pressure, and more than 30 percent had diabetes.

Seven patients (19 percent) who received hydroxychloroquine alone developed prolonged QTc of 500 milliseconds or more, and three patients had a change in QTc of 60 milliseconds or more. Of the 53 patients who also received azithromycin, 21 percent had prolonged QTc of 500 milliseconds or more, and 13 percent experienced a change in QTc of 60 milliseconds or more.

"In our study, patients who were hospitalized and receiving hydroxychloroquine for COVID-19 frequently experienced QTc prolongation and adverse drug events," said co-first author Christina F. Yen, MD, of BIDMC's Department of Medicine. "One participant taking the drug combination experienced a potentially lethal tachycardia called torsades de pointes, which to our knowledge has yet to be reported elsewhere in the peer-reviewed COVID-19 literature."

In 2003, preliminary data suggested hydroxychloroquine may be effective against SARS-CoV-1, a fatal but hard-to-transmit respiratory virus related to the coronavirus that causes COVID-19. More recently, a small study of patients with COVID-19 appeared to benefit from the anti-malarial drug. Subsequent research, however, has failed to confirm either finding. In light of their data, Gold and colleagues urge caution and careful consideration before administering hydroxychloroquine as treatment for COVID-19.

"If considering the use of hydroxychloroquine, particularly combined with azithromycin, clinicians should carefully weigh the risks and benefits, and closely monitor QTc -- particularly considering patients' co-morbidities and concomitant medication use," said senior author Howard S. Gold, MD, an infectious disease specialist at BIDMC and an assistant professor of medicine at Harvard Medical School. "Based on our current knowledge, hydroxychloroquine for the treatment of COVID-19 should probably be limited to clinical trials."

Bethesda, MD (April 30, 2020) -- Toxin exposure appears to have contributed to dramatically higher rates of fatty liver disease among first responders to the attack on the World Trade Center on Sept. 11, 2001, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2020. DDW® data will be published in the May online supplements to Gastroenterology and GIE: Gastrointestinal Endoscopy.

"Non-alcoholic fatty liver disease (NAFLD), one of the most serious diseases of the digestive system, is generally thought to be caused by obesity, metabolic syndrome and poor lifestyle choices," said Mishal Reja, MD, resident physician in internal medicine at Robert Wood Johnson University Hospital, Newark, New Jersey, and a lead researcher of the study. "However, recent research shows a higher burden of this disease among workers exposed to environmental toxins in coal mining, demolition and factories. This exposure is similar to the toxins faced by 9/11 responders."

Reja and his team reviewed medical records of 243 first responders with gastrointestinal symptoms who were referred to the World Trade Center Health Program between January 2014 and August 2019. Testing for signs of fatty liver disease and comorbidities, researchers found nearly 83 percent had fatty liver disease compared to 24 to 45 percent in the general population.

"This research shows that 9/11 first responders need to be particularly concerned about fatty liver disease, and they must be examined more closely for it. Additionally, they should be especially careful in managing their diet and any related comorbidities because their risk for fatty liver disease is compounded by toxin exposure," said Dr. Reja.

Toxin-associated fatty liver disease (TAFLD) was recently identified as a form of NAFLD among people exposed to chemicals and toxins. Researchers believe occupational and industrial toxins disrupt endocrine signaling, causing weight gain associated with type 2 diabetes and fatty liver, which can lead to a host of life-threatening conditions, including liver cancer and cirrhosis.

Previous studies have confirmed that workers involved in the cleanup and recovery efforts at the World Trade Center have suffered a variety of health conditions, including digestive disorders, such as acid reflux, and respiratory disorders, such as lung disease, COPD and asthma. However, the effect on the liver has not been closely studied.

In addition to providing a warning to first responders and their families, this research adds to the literature linking environmental chemicals and TAFLD. To build on this research, Dr. Reja and his team hope to compare liver ultrasounds of first responders to a control group of the general population to gather more detailed information on the rate of TAFLD.

There was no outside funding provided for the study (abstract Mo1507).

Men might not be more reluctant to see a doctor than women are, as is popularly believed, but may simply have different trigger points for seeking healthcare, suggests research published online in the Journal of Epidemiology & Community Health.

The threshold for making an appointment with a family doctor seems to be lower among women, while older women also tend to live longer with disabling conditions than men do, so more of them will be accessing primary care, the findings indicate.

Women tend to live longer than men after a serious illness, with their greater use of primary healthcare, and therefore greater likelihood of timely diagnosis, often suggested as the explanation for this particular advantage.

To explore this further, the researchers looked at the patterns of primary healthcare use among 65, 622 Danish men and women aged 60 and above, before and after admission to hospital for serious illness between 1999 and 2011.

Serious illness included: stroke; heart attack; chronic obstructive pulmonary disease (COPD); and cancers of the digestive tract, which are among the leading causes of admission to hospital in Denmark.

Every primary care consultation was recorded for each person in five 6-month periods in the 30 months before and the 30 months after first admission to hospital for one of the four conditions.

The average age at which women were admitted to hospital was significantly older than that of men: 77 vs 75.

Once engaged with primary healthcare, patterns of use didn't differ significantly between men and women.

But before hospital admission, while a substantial proportion of women didn't access primary healthcare, men were still significantly less likely than women to do so for all four conditions.

And after hospital admission, with the exception of stroke, the gap had narrowed considerably as both sexes were more likely to access primary healthcare.

For example, before hospital admission, one in four (25%) of all men in their 60s admitted with a heart attack hadn't used primary healthcare services compared with around one in seven (15%) of all women of the same age.

But afterwards, only 2% of all men and only 1% of all women who had been admitted for a heart attack didn't visit their family doctor.

Absolute gender differences in primary healthcare use were greatest for stroke and heart attack, the symptoms of which often come on suddenly or if already present, might be overlooked, say the researchers.

At the other end of the spectrum, the gender gap in primary healthcare use was generally smallest for COPD, the symptoms of which tend to be present long before admission.

This suggests that men and women may be just as likely to put off seeing a doctor when they don't consider symptoms to require urgent attention or when they ignore them, say the researchers.

Similarly, fear of the implications of a diagnosis of a serious illness may also deter both sexes from seeking medical help.

This is an observational study, and as such, can't establish cause, added to which the researchers weren't able to assess whether a visit to a doctor was directly related to the reason for hospital admission, or whether it concerned prevention or ongoing treatment.

And the findings may not be more widely applicable to healthcare systems beyond Denmark, where primary healthcare services are free for all citizens, they point out.

Nevertheless, they suggest: "The stronger post-hospitalisation changes among men may indicate that men might have been more reluctant to engage with primary healthcare before experiencing a health shock."

And they conclude: "Our findings indicate a lower threshold for treatment-seeking among women. In addition, higher levels of primary healthcare use among women may be underpinned by the fact that women are more likely to survive with disabling conditions following hospitalisation."

Both men and women should be encouraged to see their family doctor to ensure that health issues get picked up early before they become more serious, they suggest.

Despite overall increases in insurance coverage for low-income individuals in Medicaid expansion states, some gaps remain for individuals who are obese.

That's according to a recent study by a team of researchers at the University of Georgia.

The findings, published in the journal Obesity, show a slower uptake of Medicaid enrollment among low-income obese individuals compared to low-income, non-obese individuals - 5.6% increase in coverage versus 7.4%, respectively.

Though obesity is an issue that impacts individuals of all income levels, evidence points to a higher risk among low-income groups.

The prevention and treatment of obesity requires regular access to health care, said lead author Janani Thapa, an assistant professor of health policy and management at UGA's College of Public Health, and that often requires having health insurance.

"We want more people with obesity to have access to insurance so that they can have their annual checkup, and know their risks of other conditions associated with higher weight on the prevention side," said Thapa, "but also, on the treatment side, if these individuals do not have insurance, they cannot access any health care intervention because of cost."

Since the rollout of the Affordable Care Act in 2010, changes in the uninsured rate have been tracked and reported by government agencies, health advocacy groups and many academic researchers.

Yet, little work has been done to understand whether equal improvement in access to insurance has been achieved among key subgroups, such as low-income groups who were obese and who were not obese, through Medicaid expansion.

Thapa said the uneven rollout of Medicaid expansion among states provided a natural experiment for her team. States that expanded Medicaid served as a treatment group. States that did not expand were the control.

The results of their experiment confirmed that Medicaid expansion provided more coverage to low-income Americans, both obese and non-obese. The observed gaps, said the researchers, should not diminish the positive impact of Medicaid expansion.

But their findings should prompt more action to help more individuals in need, said co-author Donglan Zhang, also an assistant professor of health policy and management in UGA's College of Public Health.

"Our findings reconfirmed the critical importance of Medicaid expansion and that states should do more to help obese individuals get insurance coverage, with community outreach programs and public education to help more qualified individuals sign up for Medicaid coverage, and with legislative efforts or an expansion of existing safety net programs for those non-expanded states," she said.

The standard treatment for men with advanced prostate cancer is androgen-deprivation therapy. Androgens are hormones that fuel prostate cell growth; removing them with either drugs or surgery causes the prostate gland to shrink by 90%.

Nevertheless, the cells that remain can eventually regrow a tumor, and when they do, the tumor is usually resistant to further hormone therapy. It is also more likely to spread to other organs (metastasize).

A new study from researchers at Memorial Sloan Kettering provides insight into how the prostate is able to regrow so swiftly. And it is not what the scientists initially expected.

"Most people, including me, expected to find a rare population of stem cells that is responsible for regenerating the gland," says Charles Sawyers, Chair of the Human Oncology and Pathogenesis Program at MSK and the corresponding author on the paper, published May 1 in the journal Science. "But this is not the case."

Instead, he says, nearly all of the cells that persisted after hormone-deprivation therapy contributed to the regeneration of the prostate gland. Most of these were luminal cells, which form the inside of the hollow organ. The findings have implications for how doctors think about prostate cancer treatment.

A Cellular Atlas of the Prostate

The investigators made their discovery with the help of a powerful technique called single-cell RNA sequencing (scRNA seq). This method of analysis allows scientists to identify which genes are turned on in many individual cells in a tissue at once. Collaborating with scientists from the Dana Pe'er lab in the Sloan Kettering Institute and Aviv Regev's lab at the Broad Institute, the team performed scRNA seq on nearly 14,000 cells in the mouse prostate gland. From these data, they were able to completely map out the cell types found in a normal mouse prostate.

With the information, they could then determine which cell types remained in the prostate after the mice received androgen-deprivation therapy, and which divided to regrow the gland when androgen was restored.

From these analyses, it was clear that nearly all the luminal cells in the prostate were dividing, rather than just a subset -- as would be expected if a stem cell population were mainly responsible for regenerating the gland.

What's more, the luminal cells (whose typical function is to secrete fluids) had clearly acquired abilities they don't usually have in a hormonally intact animal.

"They became much more stemlike," says Wouter Karthaus, a senior postdoctoral fellow in the Sawyers lab and the paper's first author. "Without androgens influencing their gene expression, they were free to turn on other genes and acquire regenerative properties."

In addition to the mouse work, the investigators performed scRNA seq on prostate tissue taken from men who had been treated for prostate cancer. They found a similar pattern of luminal prostate cells that had acquired the attributes of stem cells. This implies that what is true of mice may also be true of men.

Plastic Identities

The study's findings contradict a classic model of how stem cells regenerate and repair tissue. By that way of thinking, stem cells are a rare and special type of cell that can give rise to many cell types yet retain a proliferative capacity. But recent studies -- including, now, this one -- have questioned how broadly this model applies across different organs. At least in the prostate, fully differentiated cells can become stem cells under the right conditions, this study suggests.

Prior work from the Sawyers lab showed that some prostate cancer cells possess an ability to change their identity. This is called lineage plasticity. They can, for example, reprogram themselves to become a type of prostate cell that does not require androgen to survive. Lineage plasticity is an important way that prostate cancer cells eventually develop resistance to hormone-blocking therapies.

What the latest findings mean for treatment is an open question, but there could be significant implications.

"Androgen-deprivation therapy may be a double-edged sword," Dr. Sawyers says. "Lots of cells die, but the ones that persist acquire this stemlike property."

"It is likely that we push prostate cancer to have a more progenitor-like state during therapy," Dr. Karthaus adds.

The team's next effort will be to identify the molecular and cellular cues that control this switch in the hope of developing ways to turn it off.

In its May issue, The FASEB Journal is publishing a comprehensive review on the science and clinical experiences with the drugs chloroquine and hydroxychloroquine, first introduced as effective weapons against malaria, rheumatoid arthritis, and the autoimmune disease lupus. Recent anecdotal reports suggested these drugs might be effective against the SARS-CoV-2 virus, the cause of the COVID-19 pandemic. This new review describes the growing skepticism regarding adoption of chloroquine and hydroxychloroquine for the respiratory infection caused by this virus.

The review's lead author is Mark Poznansky, MD, PhD, a Harvard Medical School associate professor and director of the Vaccine and Immunotherapy Center in the Infectious Disease Division of Massachusetts General Hospital. "When I went on service a few weeks ago in the ICUs of Massachusetts General Hospital as an infectious diseases attending physician, it was evident to me and my colleagues that there were both risks and benefits of the widespread initial use of hydroxychloroquine in the context of COVID-19 infection. This was based on seeing patients who, for whatever reason, appeared to be doing poorly despite the use of this medication," Poznansky said.

"We chose to dive into this important matter in an expedited manner to create a science-based awareness of this subject," said Poznansky. "Beyond the known cardiac side effects of this drug, we aimed to reveal those aspects of the anti-viral and immune modulatory activities of hydroxychloroquine that could potentially help or, as importantly, impair a patient's response to the virus. The goal was to help physicians make data-informed decisions about how to use this drug for patients with COVID-19 infection within carefully designed clinical trials," he said.

The authors reviewed earlier anecdotal reports and poorly controlled clinical trials that raised considerable optimism about the widespread adoption of this therapy. However, the authors present mechanistic reasons why these drugs may fail for COVID-19. They point to fast-moving data - accumulated through April 22 - that creates significant skepticism for therapy with either chloroquine or hydroxychloroquine for which there was early optimism; namely, that these drugs reduced viral uptake by cells cultured in the laboratory, rather than in patients.

This ray of optimism overlooked something far more worrisome: the powerful immunosuppressive action of these drugs, which is the basis of their potency in rheumatoid arthritis and lupus. But these drugs have failed in previous respiratory virus outbreaks, including influenza. The authors surmise that the drugs inhibit innate immune reactions critical to viral defense, as well as the generation of adaptive, cell-mediated immunity that is also necessary to control a virus like SARS-CoV-2.

The authors emphasize the need for all due caution in utilizing therapies involving these two drugs based solely on data from studies with lab-cultured cells - as opposed to studies in patients. They report that current clinical trial results are leading to a rapidly diminishing view of their utility for COVID-19.

A rapid increase in "virtual" visits during the COVID-19 pandemic could transform the way physicians provide care in the United States going forward, according to a new study led by researchers from NYU Grossman School of Medicine.

The findings, published online this week in the Journal of the American Informatics Association, captures the largest experience to date of the speed, scale and rapid expansion of video-enabled visits by patients and providers in varied and diverse settings. Specifically, between March 2 and April 14, 2020, virtual urgent care visits at NYU Langone Health grew by 683 percent and non-urgent virtual care visits grew by an unprecedented 4,345 percent in response to COVID-19, in daily averages.

Also participating in the study were researchers from NYU Tandon School of Engineering and NYU School of Global Public Health.

"The pandemic created an urgent need to divert patients from in-patient care and prevent the flooding of our emergency rooms beyond capacity," said Devin Mann, MD, associate professor in the Departments of Population Health and Medicine and senior director for Informatics Innovation and Medical Center Information Technology at NYU Langone Health, and the study's lead author. "Through telemedicine, we pushed the frontlines to locations far from our hospitals and doctor's offices. And because NYU Langone invested early in this technology, we quickly leveraged digital health to help hundreds of thousands of patients."

In recent years, telemedicine's growth has been incremental, utilized by only eight percent of Americans in 2019, according to the researchers. Outside of rural medicine and prior to COVID-19, there were few compelling reasons to replace in-person care. In order to facilitate the rapid expansion in telemedicine captured in this study, U.S. insurers expanded coverage to include all telemedicine visit types, including from home, and states relaxed licensing requirements so that care can be delivered across state lines. Additionally, the U.S. Department of Health and Human Services allowed the use of consumer audio and video communication for telemedicine visits.

Responding to a Pandemic: Study Findings

Using NYU Langone's enterprise electronic health record system Epic, the researchers captured COVID-related visits using diagnostic codes containing relevant respiratory issues and matched them with keywords describing symptoms including fever, shortness of breath, cough, and more.

Over a six-week period, the investigators found:

There were 144,940 video visits conducted involving 115,789 unique patients and 2,656 unique providers.

Of all virtual visits, 56.2 percent of urgent care and 17.6 percent of non-urgent visits were COVID-19-related.

The increase in telemedicine urgent care was enabled by a rapid increase in urgent care providers. A pool of 40 emergency medicine providers, managing less than 100 visits on a typical day, grew to 289 "surge" providers from multiple specialties.

On March 19, NYU Langone Health expanded video visits to all of its ambulatory care settings, reaching more than 7,000 visits within 10 days and representing more than 70 percent of total ambulatory care volume during this time.

Telemedicine usage was highest by patients aged 20 to 44 years, particularly for urgent care. However, patients of all ages were able to use the technology across NYU Langone's telemedicine platform.

Patients' satisfaction ratings with telemedicine visits remained positive, despite the rapid expansion of the program to thousands of new providers.

"Through this massive expansion, the numbers of providers and patients who experienced telemedicine for the first time increased dramatically, facilitating transformation of technologies and work practices across multiple medical specialties," said Oded Nov, PhD, professor and chair of the Department of Technology Management and Innovation at the NYU Tandon School of Engineering, and the study's senior author. "An important question going forward is how much this will continue beyond the COVID pandemic. While we expect patients and providers who got a crash course in telemedicine to continue using it long term, regulators and insurers' decisions will have a major impact."

Virtual Healthcare at NYU Langone

Anticipating that the future of medicine would include virtual delivery of care, NYU Langone was uniquely positioned to expand services with tools that had already been successfully integrated across the health system. As a centralized virtual health ecosystem, all technology is built into NYU Langone's website and the NYU Langone Health MyChart app, where patients have a central point of access for all their healthcare needs.

At the forefront of this strategy is ensuring a seamless and positive patient experience, whether an appointment is in-person or via video visit. Through the MyChart app, patients are easily able to make appointments for Virtual Urgent Care (now operating 24 hours a day, seven days per week) as well as other types of doctor appointment either through video visits or in person.

In addition, providers can see COVID patients remotely at the hospital in ICUs through tablets, which helps save on PPE and exposure to patients. The use of clinical mobile companions also allows providers to communicate with each other using digital health tools.

"Our ability to scale and expand telehealth quickly has allowed us to battle overcrowding and human spread of the disease," said Paul A. Testa, MD, assistant professor, the Ronald O. Perelman Department of Emergency Medicine and Chief Medical Information Officer at NYU Langone Health, and a study co-author. "It also pushes our ability to care for patients beyond any physical boundary, which you can only do digitally."

To further expand the reach of telemedicine services both inside of our hospitals as well as patient homes via remote patient monitoring and other technologies, NYU Langone Health as well as NYU Grossman School of Medicine were each recently awarded grants from the Federal Communications Commission's COVID-19 Telehealth Program.