Body

At the core of the antibiotic-resistance crisis is the lack of a rapid and general antibiotic susceptibility test (AST) that can assess the infecting pathogen's sensitivity to antibiotics and thus inform treatment decisions directly at the point of care. In two new papers publishing March 19 in the open-access journal PLoS Biology, researchers from the lab of Rustem Ismagilov at the California Institute of Technology have developed two distinct, highly innovative AST methods for directly measuring a pathogen's susceptibility to beta-lactams (a class of antibiotics that includes penicillin) on extremely short time scales (about 30 minutes).

Rapid "genotypic" tests detect the presence of antibiotic-resistance genes in a pathogen, but these tests can detect only a small handful of the myriad potential antibiotic-resistance mechanisms. By contrast, "phenotypic" tests directly measure a pathogen's response to an antibiotic and thus are the gold standard. However, most phenotypic tests require the pathogen to be cultured and are thus too slow (taking hours to days).

New phenotypic tests quantify small changes in the concentration of the pathogen's nucleic acids after antibiotic exposure, and are promising for fast-growing pathogens and antibiotics that affect DNA replication. However, there has not been a path for developing these rapid ASTs for slow-growing pathogens or antibiotics that do not immediately impact DNA replication, such as beta-lactams (one of the most important classes).

This breakthrough in AST development was made possible by measuring the accessibility of a bacterium's DNA after exposure to antibiotics. Beta-lactam antibiotics work by inhibiting a bacterium's ability to make and repair its cell wall. The researchers therefore reasoned that the bacterium's resistance or susceptibility to beta-lactams can be assessed by measuring how much of the DNA is no longer protected by an intact cell wall thus directly linking--for the first time ever--cell wall damage to a rapid DNA readout.

"One of the most exciting parts of this project was realizing that we could use a DNA readout to measure antibiotic susceptibility even if the antibiotic being tested did not directly impact the bacterium's DNA replication" says Nathan Schoepp, a former PhD student in the Ismagilov Lab and a co-author on both studies.

Each AST method represents an innovative approach needed to overcome the inherent challenges of rapidly determining a pathogen's susceptibility to beta-lactams. Each paper includes pilot experiments with patient samples, demonstrating the relevance and potential of these tests to eventually be translated to clinical settings.

Importantly, the two methods target two of the three top priorities on the CDC's list of greatest antimicrobial resistance threats: carbapenem-resistant Enterobacteriaceae (CRE) and Neisseria gonorrhoeae.

"At the end of the day we aspire to design diagnostic tests that are useful in a clinical context," says Emily Savela, a Caltech PhD student and a co-author on both studies. "There is a lot of complexity added when working directly with patient samples and point-of-care timescales. Our research team works to identify and incorporate these added variables in the early stages of development."

The clinical work in these two papers was made possible through the Caltech team's collaborations with co-authors Dr. Jeffrey Klausner (AIDS Healthcare Foundation and UCLA), Dr. Olusegun O. Soge (Global Health STI Laboratory, University of Washington), and Dr. Omai Garner (UCLA).

Getting these new AST methods into the clinic will still require a huge amount of work; however, the research team is optimistic that these new capabilities finally lay the pathway toward a general, rapid test of antibiotic susceptibility.

A study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, offers new insight into genetic alterations associated with osteosarcoma, the most common cancerous bone tumor of children and adolescents. The researchers found that more people with osteosarcoma carry harmful, or likely harmful, variants in known cancer-susceptibility genes than people without osteosarcoma. This finding has implications for genetic testing of children with osteosarcoma, as well as their families.

The study was published March 19, 2020, in JAMA Oncology.

"With this study, we wanted to find out how many people with osteosarcoma may have been at high risk for it because of their genetics," said Lisa Mirabello, Ph.D., of NCI's Division of Cancer Epidemiology and Genetics (DCEG), who led the research. "We not only learned that at least a quarter of the people in the study with osteosarcoma had a variant in a gene known to predispose someone to cancer, we also uncovered variants that had never before been associated with this cancer."

In the study, the researchers looked for harmful (or likely harmful) variants in 238 known cancer-susceptibility genes in DNA samples from 1,244 people with osteosarcoma and compared the frequency of such variants with that in people in a cancer-free control group. They identified a harmful or likely harmful variant in a known cancer-susceptibility gene in 28% of the people with osteosarcoma. By contrast, only 12% of people in the cancer-free control group had such a variant.

When the authors looked at a subset of 166 genes that are known to be inherited in an autosomal dominant fashion--that is, where inheriting one alteration from one parent is sufficient to increase cancer risk--they saw harmful or likely harmful variants in about 18% of the patients but only 5% of controls. And another 25% of the patients had a rare variant of uncertain significance that was predicted to be harmful.

Patients who had harmful variants were younger at age of osteosarcoma diagnosis, on average, than patients who did not (15.3 years versus 16.9 years). In addition, the youngest children in the study (ages 0?10 years) had the highest prevalence of harmful variants.

If a child is found to have a gene variant associated with osteosarcoma, the authors say that genetic testing may be warranted for the child's family members, who may also carry the variant. Family members who have the variant could undergo screening for the cancers associated with that variant, potentially leading to earlier detection.

"The idea is, if you have a new patient with osteosarcoma, we found that a quarter of them have a [harmful] variant in a gene associated with increased risk of other cancers," said Sharon Savage, M.D., senior author of the study, also of DCEG. "Genetic testing of the patient likely makes sense, because they could be at risk of other cancers, and they might have family members who carry the variant who might be at risk of other cancers."

Because osteosarcoma is a rare cancer, the researchers assembled case samples from 10 international research centers, making this the largest collection to date of a pediatric solid cancer evaluated for cancer-susceptibility gene variants.

The researchers found harmful or likely harmful variants in several cancer-susceptibility genes that hadn't been associated with osteosarcoma--or, indeed, pediatric cancers--before. Because the biological function for the variants newly found to be associated with osteosarcoma remain unknown, this could open new areas of research related to cancer susceptibility.

This study is part of a larger pediatric cancer susceptibility research program at NCI through which researchers are studying common and rare causes of osteosarcoma and other pediatric cancers. In earlier research, Dr. Mirabello found that TP53 gene variants, which are associated with the cancer predisposition disease Li-Fraumeni Syndrome, were more common than previously thought in children and adolescents with osteosarcoma. In the current study, TP53 gene variants had the highest frequency of the harmful or likely harmful cancer-susceptibility gene variants in children with osteosarcoma, another finding that Dr. Mirabello said warrants additional research.

Diabetes is a disease that affects people's lives more in the long term and requires emotional support and information. It is increasingly common for people with diabetes to participate in digital communities and seek help in so-called OSGs (online support groups) to share experiences and glean information. This social phenomenon has been little studied.

A group of researchers from the Department of Communication at UPF consisting of Noelia Herrero, Frederic Guerrero-Solé and Lluís-Mas Manchón has attempted to ascertain whether there is a relationship between participation in specific forums and support groups for people with diabetes and the self-management of the disease and its impact on their health.

"We asked ourselves about the correlation between the participation of people with diabetes in OSGs (Facebook in particular) and other aspects of their life, such as their emotional well-being or their health", says Noelia Herrero, first author of the work.

To conduct the study, the researchers contacted participants through the website "Dulces Diabéticos", and online publications in forums on diabetes: "Diabetes Foro" and also Facebook groups related to the disease. Between 19 May and 6 September 2018, they conducted an online survey and collected data for evaluation from 307 Spanish participants, most of whom, 210, diagnosed with type 2 diabetes, the most active in these digital environments; 82 diagnosed with type 1 diabetes and the remainder reported having other types of diabetes. In their analysis, the researchers took into account sex, age, education and type of diabetes.

Highly significant results in type 2 diabetes

Analysis of the study data has shown that "people with diabetes who participate in these groups generally have worse health than those who do not and, in addition, they also have more disease-related complications (neuropathy, nephropathy, etc.)", says Herrero, who plans to continue in the course of her doctoral studies at the Department of Communication at UPF with this line of research taking the role of health personnel and technologies available to patients into account.

The results indicate that participants in these forums present lower levels of disease management, and more disease-related health complications. So far, this connection is not statistically significant for users with type 1 diabetes, but is strong for users with type 2 diabetes, the authors suggest in their article.

The findings of this research are very important because people with diabetes, as occurs with other diseases, look to the Internet and social networks for information and support, and it may be that, contrary to what they might believe, the information they find there may not be sufficiently reliable and their consultation could be counterproductive for their health.

Russian researchers from the Moscow Institute of Physics and Technology, Kurnakov Institute of General and Inorganic Chemistry of RAS, and Russia's famed Tretyakov Gallery have conducted a comprehensive preconservation study of "The Portrait of F.P. Makerovsky in a Masquerade Costume" (1789) by the Russian painter Dmitry Levitsky. The paper was published in the journal Heritage Science.

The portrait analyzed in the study is one of the masterpieces of the renowned painter's mature period and a rare example of a children's dress-up portrait in Russian art. However, rough restoration interventions of a century ago, thick layers of old yellowed varnish, and damage to the paint layer of unknown origin distorted the aesthetic perception of the image. The conservator, Tatiana Seregina, faced the difficult task of bringing the portrait as close to its original state as possible today, without affecting the painter's work.

"Our laboratory and the gallery's research team maintain a long-standing methodological collaboration, which manifested itself in a 2017 agreement between MIPT and the Tretyakov Gallery, with the support of its chief curator Tatiana Gorodkova," said Viktor Ivanov, the head of the Center for Functional Materials Testing at MIPT. "Under that agreement, we jointly develop approaches for comprehensive studies of artworks using modern methods for local analysis of materials and nanomaterials. The methodological expertise that we accumulated enabled us to participate in a preconservation study of the painting by Dmitry Levitsky and establish the unity of the paint layers across the entire canvas."

The research team comprised numerous physicists, chemists, art specialists, and conservators from MIPT, IGIC RAS, and the State Tretyakov Gallery.

Besides enabling more grounded decisions regarding the conservation techniques to be used, the analysis of the art materials also resolved a long-standing mystery. Levitsky's painting consists of three fragments, and while there were never any doubts concerning the authorship of the main part, it remained unknown when the two horizontal extension pieces with the figure from the knees down had been sewn to the canvas. While the extension pieces are visible in early-20th-century photographs, there were reservations about the earlier period in the painting's history, because of a distinct structure of the seams connecting the three fragments: While the upper seam is very neat, the lower one is much coarser.

"The last time the portrait underwent conservation was in 1914," study co-author Nikolay Simonenko from IGIC RAS and MIPT said. "We conducted a comprehensive preconservation analysis of art materials composition. This allowed us to establish that the extension pieces were indeed painted by Levitsky."

Painter in a hurry?

By analyzing the ground layers, the team first revealed a distinction between the main canvas and the extension pieces. The two layers of ground, customarily used by the painter, were only found in the main canvas. However, a closer look revealed the structure and composition of the ground in the two extensions to be alike. It also proved similar to the lower of the two ground layers of the main canvas.

The authors of the paper suggest that the painter might have had more time at the outset to thoroughly prepare the canvas. It is likely, the researchers hypothesize, that Levitsky's concept of the painting evolved as the work progressed, necessitating a bigger canvas. To accommodate his new vision, the painter first added one extension piece and then another.

Malachite pigment

By examining the paint layers, the team could show their similar composition across the entire painting, including the two extension pieces. Specifically, the green pigment is present in each of the three fragments and has a common nature: Infrared spectroscopy revealed it was malachite.

Interestingly, none of the other 10 or so analytic techniques used in the study could identify malachite, although elemental analysis did provide an indirect confirmation by detecting copper in the green paint. This is why the researchers had to employ such a wide range of tools in their study.

The common origin of the two extension pieces was also confirmed by the analysis of the brown pigment, which involved infrared and Raman spectroscopy, and scanning electron microscopy combined with energy dispersive X-ray spectroscopy.

By investigating the painted layer, the team established that it belonged to Levitsky in its entirety, confirming the hypothesis that a single artistic process united all three parts of the canvas.

Fine arts and hard sciences

In a research project like this, the chemists and physicists are after great detail in the results, which may in part go against the wish of the museum workers and conservators to preserve the work of art fully intact.

"In my opinion, the presence of art historians, chemists, and physicists in one team was key to the success of this endeavor," said Ivan Volkov, a chief researcher at the MIPT lab involved in the study. "We held regular meetings featuring both the Tretyakov Gallery team and us, materials scientists. We had to slowly work out a common language, but it was worth it. There was also an arrangement for the sampling methods and tools to be approved by the gallery staff."

With no room for error, the team needed to be very careful in taking samples, and extract maximum information from each of them. The researchers sought a middle ground to draw information from the portrait without damaging it. For example, some of the samples were taken from the edges of the painting.

New discoveries

This is the first time such a detailed and comprehensive study of a painting by Levitsky has been carried out. According to art specialists from the Tretyakov Gallery, the study has not only been important for preparing the conservation task, but also expanded the understanding of Levitsky's oeuvre and the late 18th-century art practice in Russia.

Now that the methodology has been developed and successfully tested, it can be applied to other works. Meanwhile, the conservation of Makerovsky's portrait is in its final stages, and it will soon return to the main exhibition. The conservation began long before the publication in Heritage Science and lasted about a year and a half.

University of Massachusetts Amherst researchers have invented a portable surveillance device powered by machine learning - called FluSense - which can detect coughing and crowd size in real time, then analyze the data to directly monitor flu-like illnesses and influenza trends.

The FluSense creators say the new edge-computing platform, envisioned for use in hospitals, healthcare waiting rooms and larger public spaces, may expand the arsenal of health surveillance tools used to forecast seasonal flu and other viral respiratory outbreaks, such as the COVID-19 pandemic or SARS.

Models like these can be lifesavers by directly informing the public health response during a flu epidemic. These data sources can help determine the timing for flu vaccine campaigns, potential travel restrictions, the allocation of medical supplies and more.

"This may allow us to predict flu trends in a much more accurate manner," says co-author Tauhidur Rahman, assistant professor of computer and information sciences, who advises Ph.D. student and lead author Forsad Al Hossain. Results of their FluSense study were published Wednesday in the Proceedings of the Association for Computing Machinery on Interactive, Mobile, Wearable and Ubiquitous Technologies.

To give their invention a real-world tryout, the FluSense inventors partnered with Dr. George Corey, executive director of University Health Services; biostatistician Nicholas Reich, director of the UMass-based CDC Influenza Forecasting Center of Excellence; and epidemiologist Andrew Lover, a vector-borne disease expert and assistant professor in the School of Public Health and Health Sciences.

The FluSense platform processes a low-cost microphone array and thermal imaging data with a Raspberry Pi and neural computing engine. It stores no personally identifiable information, such as speech data or distinguishing images. In Rahman's Mosaic Lab, where computer scientists develop sensors to observe human health and behavior, the researchers first developed a lab-based cough model. Then they trained the deep neural network classifier to draw bounding boxes on thermal images representing people, and then to count them. "Our main goal was to build predictive models at the population level, not the individual level," Rahman says.

They placed the FluSense devices, encased in a rectangular box about the size of a large dictionary, in four healthcare waiting rooms at UMass's University Health Services clinic.

From December 2018 to July 2019, the FluSense platform collected and analyzed more than 350,000 thermal images and 21 million non-speech audio samples from the public waiting areas.

The researchers found that FluSense was able to accurately predict daily illness rates at the university clinic. Multiple and complementary sets of FluSense signals "strongly correlated" with laboratory-based testing for flu-like illnesses and influenza itself.

According to the study, "the early symptom-related information captured by FluSense could provide valuable additional and complementary information to current influenza prediction efforts," such as the FluSight Network, which is a multidisciplinary consortium of flu forecasting teams, including the Reich Lab at UMass Amherst.

"I've been interested in non-speech body sounds for a long time," Rahman says. "I thought if we could capture coughing or sneezing sounds from public spaces where a lot of people naturally congregate, we could utilize this information as a new source of data for predicting epidemiologic trends."

Al Hossain says FluSense is an example of the power of combining artificial intelligence with edge computing, the frontier-pushing trend that enables data to be gathered and analyzed right at the data's source. "We are trying to bring machine-learning systems to the edge," Al Hossain says, pointing to the compact components inside the FluSense device. "All of the processing happens right here. These systems are becoming cheaper and more powerful."

The next step is to test FluSense in other public areas and geographic locations.

"We have the initial validation that the coughing indeed has a correlation with influenza-related illness," Lover says. "Now we want to validate it beyond this specific hospital setting and show that we can generalize across locations."

For decades, public health officials have directed the containment of emerging pandemics - perhaps most notably - the worldwide eradication of smallpox starting in the early to mid-1960s. Since then, surveillance systems have increased in number and sophistication with advances in data collection, analysis, and communication. From influenza to smallpox, the establishment of systematic reporting systems and prompt action based on results have enabled public health officials to lead the charge in containing emerging pandemics.

Researchers from Florida Atlantic University's Schmidt College of Medicine and Christine E. Lynn College of Nursing, in collaboration with the Christine E. Lynn Women's Health & Wellness Center, Boca Raton Regional Hospital/ Baptist Health South Florida and the University of Wisconsin School of Medicine & Public Health, have published a commentary online ahead of print in the American Journal of Medicine about the urgent need for public health leadership in the wake of the emerging coronavirus (COVID-19) pandemic.

Their message? Public health leaders, namely, Anthony S. Fauci, M.D., director of the United States National Institute of Allergy and Infectious Diseases, whom they liken as the "Babe Ruth" of virology, should guide the nation and other comparable world leaders through this pandemic and ensure preparedness for the challenges ahead.

Over the course of a decade spanning the tenures of U.S. presidents John F. Kennedy, Lyndon B. Johnson, Richard Nixon and Gerald Ford, using evidence-based leadership, public health officials led the U.S. and worldwide efforts that resulted in smallpox becoming the first human disease ever eradicated from the face of the earth. At the helm of this effort were Alexander D. Langmuir, M.D., who created the Epidemic Intelligence Service (EIS) and Epidemiology Program at the U.S. Centers for Disease Control and Prevention (CDC), and Donald A. Henderson, M.D., chief of the Virus Disease Surveillance Program at the CDC in the 1960s.

"Based on the existing totality of evidence, it appears that coronavirus is comparable in communicability to influenza but with perhaps a tenfold higher case fatality rate," said Charles H. Hennekens, M.D., Dr.P.H., first author and first Sir Richard Doll Professor in FAU's Schmidt College of Medicine, who trained under Langmuir when he was a lieutenant commander in the U.S. Public Health Service as an EIS medical epidemiologist with the CDC. "The anticipated number of deaths due to coronavirus may become comparable to the most lethal epidemic of influenza in U.S. history, which occurred in 1918 when approximately 675,000 Americans died."

In contrast, with respect to usual outbreaks of influenza, the 2018-19 flu season affected about 42.9 million Americans, of which 647,000 were hospitalized and about 61,200 died.

Hennekens and co-authors Safiya George, Ph.D., dean of FAU's Christine E. Lynn College of Nursing; Terry A. Adirim, M.D., M.P.H., M.B.A., senior associate dean for clinical affairs, chair of the Department of Integrated Medical Sciences and professor of pediatrics in FAU's Schmidt College of Medicine; Heather Johnson, M.D., preventive cardiologist/cardiologist at the Christine E. Lynn Women's Health & Wellness Center, Boca Raton Regional Hospital/Baptist Health South Florida; and Dennis G. Maki, M.D., professor of medicine, University of Wisconsin School of Medicine & Public Health, and an internationally renowned infectious disease clinician and epidemiologist who was a fellow EIS officer with Hennekens under Langmuir and Henderson.

"U.S. health care workers today are appropriately confused about current and future issues concerning COVID-19, an infectious disease that is caused by the severe acute respiratory syndrome coronavirus known as SARS-coV2, which is now responsible for an emerging pandemic," said Adirim, who recently served as deputy assistant secretary of defense for health affairs at the Department of Defense and a senior medical official at the Department of Homeland Security during the 2009-H1N1 Pandemic. "Appropriate concerns and not fear should play a major role in the emerging pandemic, and public health efforts should focus on public health issues, not political or economic considerations."

More than 80 percent of symptomatic individuals will experience only mild flu-like symptoms. However, more alarmingly, approximately 15 percent of affected patients will become seriously ill and 5 percent will need critical care. Younger and healthier people will represent a larger proportion of the population with mild to moderate symptoms. Those at highest risk - the elderly, those with certain chronic diseases such as cardiovascular disease and lung disease as well as those receiving chemotherapy or who are otherwise immunocompromised through illness or therapies.

"The good news is that the majority of those infected with the virus will recover, however, the most vulnerable are not projected to fare as well. It is therefore, extremely important that we all take an active role in not only protecting ourselves, but also those among us who are the most vulnerable," said George, who specializes in immunology, oncology and HIV/AIDS. "In only eight days, Florida went from 18 cases and two deaths on March 9 to 314 positive cases and seven deaths on March 18. However, these numbers are still less than 10 percent of the rising number of cases in New York and still much less than California and Washington. Therefore, education, social distancing, staying away from others when symptomatic and continued handwashing and vigilance remain key in minimizing transmission."

The authors note that the staggering estimates of the potential numbers of hospitalizations could paralyze the U.S. health care delivery system. Moreover, the overcrowding of hospitals by patients with coronavirus could make it more difficult to provide care to those with life threatening conditions.

"The first case was reported in Wuhan, China on Dec. 31, 2019 and in the U.S. on Jan. 22," said Adirim. "During that interval, containment was potentially achievable in the U.S. but required collaborative efforts such as widespread utilization of rapid testing kits available from the World Health Organization. Now, however, we must employ strategies to flatten the curve to decrease avoidable morbidity and mortality."

By March 8, South Korea, which has a population of about one-sixth that of the U.S., had tested more than 240,000 (1 per 250) compared to the U.S., which had tested about 13,662 (3,903 from the CDC and 9,721 from public health laboratories). In both South Korea and the U.S., only about 3 percent of these cases tested positive for coronavirus.

Health care providers as well as the general public should also be aware that any vaccine is likely to emerge in one to two years. Furthermore, there is a possibility that chloroquine phosphate (a class of drugs still used to prevent and treat malaria and was formerly used to treat inflammatory arthritis) may have apparent efficacy and an acceptable safety profile against COVID-19.

Statins are widely used to lower cholesterol and prevent heart disease and related deaths, but can they also help guard against heart damage caused by certain breast cancer therapies? New research being presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC) suggests the answer may be yes.

Chemotherapies with anthracycline, as well as the targeted cancer medicine trastuzumab, are commonly used to treat breast cancer. Separate research estimates that nearly 1 out of 4 women with early stage breast cancer will receive anthracycline or trastuzumab, but these same lifesaving treatments are also known to be toxic to the heart and, in some cases, can trigger heart failure--a serious condition that affects the heart's ability to pump enough blood to meet the body's needs. In some women, reduced heart function can occur within months of initiating cancer therapy.

"To date, there has been limited evidence supporting the safety and effectiveness of large-scale use of cardioprotective medications for patients with early stage breast cancer. Angiotensin antagonists and beta blockers have only shown modest cardioprotective effects in clinical trials, and these medicines are sometimes poorly tolerated in this population given their side effects of fatigue and dizziness, which many patients already have from their cancer therapies or the cancer itself," said David Bobrowski, medical student at the University of Toronto, Canada and the study's lead author. "Our results suggest that taking statins is associated with a significantly lower risk of developing heart failure requiring hospital-based care among women with early stage breast cancer who received one of these cancer therapies."

In fact, compared with women who were not on a statin before undergoing cancer treatment, women who were taking statins while receiving anthracyclines or trastuzumab had significantly lower risk of developing heart failure, 58% and 66% respectively over the median five-year follow-up period.

"Our research expands on earlier, smaller studies. If these associations are confirmed in a prospective trial, this will represent an important step forward to optimize cancer outcomes by decreasing the trade-off of long-term cardiac disease or related deaths," Bobrowski said, adding that this study is the largest to examine the role that statins might play in protecting against treatment-related heart failure and the first to show risk lowering in women receiving trastuzumab with or without anthracycline at a population level.

This population-based study analyzed the medical records of 2,545 anthracycline-treated women and 1,345 trastuzumab-treated women aged 66 years or older without a history of heart failure who were diagnosed with early stage breast cancer between 2007 and 2017 in Ontario, Canada. Of these, 953 anthracycline-treated women and 568 trastuzumab-treated women were deemed to be taking statins. Statin use was based on whether women were prescribed a statin within a year of starting their cancer treatment, but researchers were not able to validate whether the women actually took the statin. For the analysis, researchers then matched these women in a 1-1 ratio with similar women who were not using a statin, resulting in 723 pairs of anthracycline-treated women and 399 pairs of trastuzumab-treated women (median age 69 and 71 years, respectively). Unlike most previous studies that focused on declines in left ventricle function (the amount of blood pumped out of the heart) as an indicator of heart failure, Bobrowski and his team looked at clinically overt heart failure, defined as a woman presenting to the emergency department or being admitted to the hospital with heart failure. The risk of heart failure-related hospital visits was significantly lower with statin exposure.

"Declines in left ventricle function can be predictive of heart failure, but overt heart failure gives a more clear-cut outcome that carries more relevance to cancer patients and their physicians," Bobrowski said. "The findings provide impetus for future prospective trials to determine whether initiating a statin before receiving anthracycline-based chemotherapy or trastuzumab can effectively prevent cardiotoxic events."

Statins have effects that go beyond lowering cholesterol, including reducing oxidative stress and the production of free radicals in heart cells, which Bobrowski said is compatible with clinicians' understanding of how these cancer therapies induce cardiotoxicity. Moreover, because there is often an overlap of risk factors between cancer and cardiovascular disease, including diabetes and obesity, many of these patients may also benefit from statin therapy based on current guidelines for cardiovascular risk reduction.

Breast cancer is the most common cancer in American women, aside from skin cancers. It's estimated that 1 out of 8 women will develop breast cancer at some point during their lifetime.

"While death rates have been declining, largely due to earlier detection and improving treatments, we now know many women will later develop heart disease," Bobrowski said. "It's a bit of a double-edged sword; cardiovascular disease is the leading and competing cause of death among older early stage breast cancer survivors."

Women who ate slightly more than the recommended daily amount of protein were significantly less likely to develop atrial fibrillation (AFib), a dangerous heart rhythm disorder that can lead to stroke and heart failure, when compared with those who consumed less protein, according to research being presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC). This is the first study to investigate protein as a possible nutritional driver for AFib, which is more common with age.

Protein is an important part of women's diets, especially as they age, because it can help prevent frailty and loss of bone mass and lean muscle mass. This is important, as older women can lose a half-pound of lean body mass per year. Current U.S. guidelines recommend consuming 0.8 grams of protein per kilogram of bodyweight, which for a 140-pound person is about 51 grams per day. In the U.K., the recommendation is even lower at 0.75 grams of protein per kilogram daily.

"Women with the lowest protein intake--which was roughly equivalent to the current recommended daily amount of protein in the U.S.-- had the highest incidence of AFib, and eating a little more was protective, even after taking into account other factors that can predispose someone to develop AFib," said Daniel Gerber, MD, cardiovascular medicine fellow at Stanford University and the study's lead author. "This modifiable risk factor for AFib may be a fairly easy way for women to potentially lower their risk."

The analysis of over 99,000 postmenopausal women (median age of 64 years) from the Women's Health Initiative Randomized Controlled Trials and Observational Study found that those who ate 58-74 grams of protein a day were 5-8% less likely to develop AFib, but there seemed to be a ceiling effect after eating more than 74 grams, at which point the benefit was no longer statistically significant.

So how much more protein does this translate to? Not much, Gerber said.

"It's not a huge amount, we're talking about eating 10-20 more grams of protein per day--that's only four ounces of healthy protein such as chicken breast or salmon, a cup of Greek yogurt or two eggs," he said. "Of course, when we talk about increasing protein intake, it needs to be with heart-healthy foods and lean proteins, not with cheeseburgers and other foods that are high in saturated fat, cholesterol and sugar."

Of the nearly 100,000 women in the study, 21,258 (21.3%) developed new AFib during the average 10-year follow up period. Researchers excluded women with existing heart rhythm issues and had a two-year run-in period to be sure women didn't have any signs of occasional AFib. Researchers assessed protein intake using a food questionnaire, and these reports were adjusted using validated urine tests to confirm how much protein was consumed. The women were then grouped into four quartiles based on protein intake (74 g/day) and then assessed for new cases of AFib.

The average protein intake was 60 grams/day, with women who ate between 58 and 74 grams a day having significantly less risk of AFib. This relationship remained even after adjusting for age, ethnicity, education and other cardiovascular conditions and risk factors such as body mass index, physical activity, tobacco and alcohol use, high blood pressure, high cholesterol, diabetes, coronary and peripheral artery disease and heart failure. Interestingly, women typically underestimated their daily protein intake by about 10 grams and caloric intake by 600-700 calories, which speaks to the need for more nutritional awareness and education, researchers said.

"Based on our findings, it seems that eating more protein may not only help strengthen women physically, but it may also have cardiovascular benefits in terms of reducing AFib and related death, strokes and heart failure," Gerber said. "About 1% of the U.S. population has AFib and, with an aging population, it is projected to increase several-fold by 2050, so doing something as little as eating an extra few grams of protein a day could potentially have a huge impact across the population."

This study builds on earlier research by the same research team, which unexpectedly found that lean body mass was a much stronger driver for new AFib than obesity. Gerber said high protein diets have been closely correlated with lean body mass, so the hope with this study was to explore the effect of protein intake on developing AFib.

This study is limited in that it is retrospective and observational. Future research should address whether modifying protein intake can prospectively reduce AFib incidence and uncover what factors are driving this relationship.

While it typically has no symptoms, high blood pressure--or hypertension--has serious health consequences. Rates of deaths related to hypertension have risen by 72% and 20% in rural and urban areas of the U.S., respectively, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

Hypertension is defined by the ACC/AHA High Blood Pressure in Adults guideline as blood pressure consistently above 130 mm Hg systolic pressure or 80 mm Hg diastolic pressure and is a leading risk factor for heart disease. Over time, high blood pressure causes damage to arteries and restricts blood flow, which can weaken the heart muscle or lead to events such as a heart attack or stroke. The study reveals a dramatic uptick in hypertension-related deaths nationwide between 2007 and 2017.

"This is a public health emergency that has not been fully recognized," said Lakshmi Nambiar, MD, cardiovascular disease fellow at the University of Vermont Larner College of Medicine and the study's lead author. "Hypertension-related cardiovascular deaths are rising in the U.S. across all age groups, all regions and in both urban and rural populations. These findings are alarming and warrant further investigation, as well as preventative efforts."

The research is based on over 10 million death records extracted from the Centers for Disease Control and Prevention database. Researchers included in their assessment all individuals whose death certificates listed cardiovascular disease as a cause of death and hypertension as a contributing factor. They analyzed trends in hypertension-related deaths over time in various age groups and geographic regions.

After adjusting for age, the results revealed an increase in hypertension-related deaths across all categories. The increase was most pronounced in the rural South, where individuals showed a 2.5-fold higher hypertension-related death rate compared to the other regions. Age-adjusted death rates increased in the rural South from 23.9 deaths per 100,000 people in 2007 to 39.5 deaths per 100,000 people in 2017.

Nambiar said that a combination of poor diet, a high prevalence of obesity and diabetes and a lack of access to health care could contribute to the regional differences. She added that targeted public health measures could help close the gap by addressing some of those factors.

The findings contrast with other studies that have pointed to a recent decline in death rates from coronary heart disease, which is caused by hardened or narrowed arteries and is the most common form of heart disease. The reduction in coronary heart disease deaths has been attributed to improvements in treatment approaches, in particular the widespread use of statins to control cholesterol.

"We didn't expect to see such a dramatic increase," Nambiar said. "Since hypertension is a leading risk factor for coronary heart disease--for which death rates have improved--I thought we'd see an improvement in hypertension in conjunction with that overall trend. But we're just seeing it get worse and worse."

Since the increase in hypertension-related deaths does not align with trends in coronary heart disease deaths, Nambiar said the data could suggest an increased prevalence of heart failure, a form of heart disease in which the heart becomes too weak to adequately pump blood through the body.

Though more research is needed, the findings underscore the importance of taking hypertension seriously, Nambiar said. Individuals can benefit from more frequent blood pressure screenings at their doctor's office, in the community and at home, as well as nonpharmacologic interventions like changes to diet and exercise. Health care providers should closely follow 2017 ACC/AHA High Blood Pressure in Adults guideline for hypertension diagnosis and treatment and discuss options with patients, she said. Public health measures could also help to reduce the upstream factors that lead to hypertension.

Today, the first investigation of its kind, published in Open Heart, has identified the hidden costs of heart failure (HF) due to under-managed but treatable iron deficiency (ID) and iron deficiency anaemia (IDA). Leading UK clinicians assessed the one-year data of around 80,000 people with HF as part of the analysis.1 Nearly one million people in the UK live with HF, of whom around 50% may also suffer from ID.3,4 However, the investigation revealed that potentially a third of people with HF are not being screened for ID/IDA, with potentially debilitating effects on their quality of life.1,4

ID is simple to identify and treat, but widely ignored. It can lead to avoidable cases of patients arriving as emergencies at A&E departments throughout the country and adds to existing hospital bed pressures.1 This analysis has found that HF patients found to have ID/IDA are more likely to be re-admitted to hospital within 30 days than those without ID, 95% of whom present as emergency admissions.1 With an NHS deficit of £960 million reported for 2017/2018, hospital bed occupancy hitting an eight-year high in 2018, and a near 7% rise in emergency admissions to hospitals reported for 2018/19, correct management of these patients presents an opportunity for cost-savings for an over-stretched healthcare system.5-7

Dr Rani Khatib, Consultant Pharmacist in Cardiology and Cardiovascular Research, Leeds Teaching Hospitals and co-author of the analysis published in Open Heart added, "Some evidence suggests that iron studies are conducted in less than 20% of heart failure patients admitted to NHS Trusts, which is not enough when you consider that 50% of these patients are likely to be iron deficient. The published data estimate an additional £21.5 million a year is being spent on managing co-morbid patients with heart failure and iron deficiency or iron deficiency anaemia, and this is based on the small proportion of those who were found from testing, so the true cost is likely to be much higher. There is a clear need to raise awareness about the growing evidence in this area and translate into practice accordingly."

IDA is one of 19 ambulatory care sensitive conditions (ACSCs), where effective community care and case management can help prevent the need for hospital admissions.8 It is estimated that emergency admissions for ACSCs could be reduced by up to 18%, and this study highlights that consistent management of ID/IDA, treatable co-morbidities in HF, could help relieve some of the current burden on the NHS and improve the quality of life of patients.1,8

Across the NHS, there is a clear disparity in the care that patients with HF receive.2 In patients who were screened and treated for ID, data show that the amount of time they spent in hospital varied widely, with a difference of up to 18 bed days.2 Patients across the lowest and highest tier Clinical Commissioning Groups (CCGs) across England spent eight and 26 days in hospital respectively, with each day costing the NHS around £400 per patient.2 This disparity suggests that international guidance is not being consistently followed. European, Scottish and American guidance highlight the importance of managing ID/IDA in HF in order to improve patients' quality of life and exercise capacity and reducing hospitalisations, recommending that clinicians consider available intravenous iron therapy in appropriate patients.9-11

"Current clinical opinion widely acknowledges that the treatment of iron deficiency in heart failure not only improves patients' functional capacity and symptoms, but most importantly, their quality of life. Treatment can also reduce time-consuming hospital visits for patients and costly readmissions for the wider healthcare economy" says Dr Simon Williams, Consultant Cardiologist, Wythenshawe Hospital, Manchester and fellow co-author of the analysis published in Open Heart. "Our colleagues in Scotland, America and Europe have guidance that provides them with recommendations for treatment of these co-morbid patients, it is disappointing that we are lagging behind and do not have such standardised recommendations to refer to here in England and Wales."

CHICAGO (March 19, 2020) -- Frailty measurements have become increasingly important in assessing surgical risk in patients with mitral valve disease, and research published online today in the Annals of Thoracic Surgery shows that frailty plays a significant role in outcomes following mitral valve procedures.

"Frailty correlates with mortality and length of hospital stay, as well as with more readmissions after mitral valve surgery. Underappreciated is the effect that frailty has on readmission burden after surgical interventions," said Amit Iyengar, MD, MSE, from Penn Medicine in Philadelphia.

Dr. Iyengar and colleagues from Penn Medicine, examined data from the National Readmissions Database (NRD)--an archive that includes discharge information from hospitals across more than 20 states and is helpful in estimating immediate outcomes after surgery. The researchers identified 102,114 adult patients who underwent mitral valve replacement surgery between 2010 and 2014. After various exclusion criteria were applied, 50,410 patients composed the final study group. Among these patients, frailty was present in 7.9%.

The researchers found that frail patients were more likely to experience complications after surgery (76.7% vs. 46.6%), be discharged to a destination other than home (49.8% vs. 20.5%), be readmitted to the hospital within 30 days (27% vs. 19.8%), and experience in-hospital mortality (11.6% vs. 3.9%). In addition, the length of initial hospital stay was significantly longer among frail patients, with 23 days for frail patients vs. 9 days for non-frail patients.

Overall, the study showed that readmission was approximately 30% for frail patients (most often for heart failure) and 20% for non-frail patients, and the cost of hospitalization was nearly double for frail patients--$91,081 vs. $47,899.

He said this study suggests that frailty screening may help better risk-stratify patients before mitral valve surgery because frailty compromises the body's ability to cope with stressors such as surgery; yet clear/definitive standards for evaluating and treating frailty before surgery do not exist. Frailty sometimes is measured by a patient's grip strength, weight, activity level, and walking test results.

"Frailty is a hot topic and we feel confident that with further study and discussion among surgeons, we as a community can arrive at a consensus method for assessing frailty that could then be adopted widely," said Dr. Iyengar.

In the meantime, surgeons have done an "excellent job" of incorporating this relatively new concept of frailty into their work-ups and discussions with patients before surgery, noted Dr. Iyengar. "Careful consideration of frailty is an important step in preoperative risk assessment and shared decision-making for patients with mitral valve disease. Frailty should be part of the discussions between patients, cardiologists, and surgeons regarding what to expect from mitral valve surgery, what the risks of surgery might be, and how to counsel patients and families before and after surgery," he said.

Philadelphia, March 19, 2020 - Puerperal sepsis, also known as childbed fever, is the leading cause of maternal deaths. In this novel study in The American Journal of Pathology, published by Elsevier, scientists report on the discovery of group A streptococcus (GAS) surface proteins involved in female reproductive tract infections such as puerperal sepsis that may pave the way to developing vaccines and more effective treatments.

GAS is a major pathogen causing more than 700 million human infections a year worldwide and 15 million cases each year in the United States. Although the main site of infection is in the throat, GAS can also colonize the female genital tract and cause severe neonatal infections and diseases in the mother during and after labor such as puerperal sepsis. Both GAS neonatal infections and puerperal sepsis have high morbidity and mortality rates. However, after more than 100 years of study, there is still no licensed GAS vaccine available.

"We are still way behind the curve of understanding the molecular basis of puerperal sepsis," explained lead investigator James M. Musser, MD, PhD, chair of the Department of Pathology and Genomic Medicine at Houston Methodist Hospital and the Fondren Presidential Distinguished Chair at the Houston Methodist Research Institute, Houston, TX, USA. "Our understanding of GAS genes contributing to interaction with the female genital tract is a knowledge desert, in part because of limited relevant animal models. It is therefore an important area for translational research to develop vaccines or treatments."

Investigators developed two new animal models for the study of GAS infection biology and used transposon mutant library screens to identify pathogen genes contributing to colonization of the vaginal tract mucosa and infection in the uterine wall. They identified 69 GAS genes required for colonization of the vaginal mucosa in animal models and 96 genes required for infection of the uterine wall ex vivo. They discovered a common set of 39 genes important for GAS fitness in both environments. Notably, they found that genes encoding surface protein SpyAD, and immunogenic secreted protein Isp2, are crucial for GAS fitness in the female genital tract. These warrant translational research that may lead to developing effective new treatments and vaccines and perhaps novel diagnostics.

"This research takes us a step closer toward resolving a long-standing gender health disparity," noted Dr. Musser. "It is the first time we have been able to address this neglected area of research into puerperal sepsis occurring before, during, and after labor.

"Such studies could make important contributions to our understanding of the molecular basis of puerperal sepsis, a disease that has an unusually rich history in medicine because of the pioneering studies by the physician and scientist Ignaz Semmelweis," he concluded.

The Hungarian physician and scientist Ignaz Semmelweis (1818-1865) discovered that the incidence of puerperal fever could be drastically reduced by the use of hand disinfection in obstetric clinics. Despite publication of results in which hand-washing reduced mortality to below one percent, his ideas were initially rejected. The practice only earned widespread acceptance after his death.

Impact of Postdilation on Intervention Success and Long-Term Major Adverse Cardiovascular Events (MACE) among Patients with Acute Coronary Syndromes

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0564, Turan Erdo?an, Hakan Duman, Mustafa Çetin, Sava? Özer, Göksel Çinier, Ece Usta, Mustafa Usta and Tuncay K?r?? from the Department of Cardiology, Faculty of Medicine, Recep Tayyip Erdo?an University, Rize, Turkey, Department of Cardiology, Recep Tayyip Erdo?an Education and Research Hospital, Rize, Turkey, Department of Cardiology, Kaçkar State Hospital, Rize, Turkey and the Department of Cardiology, Atatürk Education and Research Hospital, ?zmir Katip Çelebi University, ?zmir, Turkey consider the impact of postdilation on intervention success and long-term major adverse cardiovascular events (MACE) among patients with acute coronary syndromes.

Postdilation is frequently used during coronary interventions to prevent stent malapposition. Currently there are contradictory findings regarding the benefits of postdilation for both intraprocedural and long-term outcomes. We evaluated the impact of postdilation among patients who presented with acute coronary syndromes (ACS) and underwent percutaneous coronary interventions (PCI). A total of 258 consecutive patients who presented with ACS and underwent PCI were included in the study. The patients were followed up for 25±1.7 months for the occurrence of major adverse cardiovascular events (MACE). During follow-up, 65 patients (25.2%) had MACE. Among patients without MACE, intracoronary nitrate infusion was less frequently used (P=0.005), myocardial blush grade was higher (P

CVIA is available on the IngentaConnect platform and at Cardiovascular Innovations and Applications. Submissions may be made using ScholarOne Manuscripts. There are no author submission or article processing fees. CVIA is indexed in the EMBASE, ESCI, OCLC, Primo Central (Ex Libris), Sherpa Romeo, NISC (National Information Services Corporation), DOAJ and Index Copernicus Databases. Follow CVIA on Twitter @CVIA_Journal; or Facebook.

Associations between Vaspin Levels and Coronary Artery Disease

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0565, Lutfu Askin, Okan Tanriverdi, Hakan Tibilli and Serdar Turkmen from the Department of Cardiology, Adiyaman Education and Research Hospital, Adiyaman, Turkey consider associations between vaspin levels and coronary artery disease.

Vaspin is a new biological marker of CAD. Low serum vaspin levels are associated with coronary artery stenosis. Plasma vaspin concentration reflects possible endothelial dysfunction in CAD patients and correlates with CAD severity. Plasma vaspin concentration is associated with metabolic syndrome and obesity parameters. The ultimate goal regarding vaspin is to detect and prevent diseases caused by atherosclerosis, as well as to preserve vascular health and contribute to public health.

CVIA is available on the IngentaConnect platform and at Cardiovascular Innovations and Applications. Submissions may be made using ScholarOne Manuscripts. There are no author submission or article processing fees. CVIA is indexed in the EMBASE, ESCI, OCLC, Primo Central (Ex Libris), Sherpa Romeo, NISC (National Information Services Corporation), DOAJ and Index Copernicus Databases. Follow CVIA on Twitter @CVIA_Journal; or Facebook.

Advances in treatment have led to the largest yearly declines in deaths due to melanoma ever recorded for this skin cancer, results of a new study suggest.

Led by researchers at NYU Grossman School of Medicine, its Perlmutter Cancer Center, and Harvard University, the study showed that death rates among white Americans - the group that accounts for almost all cases - climbed 7.5 percent between 1986 and 2013, but then dropped by nearly 18 percent over the next three years. The death rates were for metastatic melanoma, the aggressive form that spreads from the skin to other organs, such as the lung, liver, or brain.

The authors say the size of the declines outstrip comparable decreases in cancers of the prostate, breast, and lung, three other common forms of cancer. They also note that the unrivaled drop in melanoma deaths coincided with the introduction of 10 new therapies for the skin cancer. These treatments either harness the body's immune system to fight the disease or directly target melanoma cells that have a specific gene mutation.

"Our findings show how quickly patients and physicians accepted these new drugs because they profoundly reduce deaths from melanoma," says co-senior study author David Polsky, MD, PhD. "These therapies are now considered the backbone of how we treat this cancer," says Polsky, the Alfred W. Kopf, M.D. Professor of Dermatologic Oncology at NYU Langone Health and its Perlmutter Cancer Center.

The report, publishing online March 19 in the American Journal of Public Health, is the first to highlight the role of these new drugs in helping Americans survive melanoma, says Polsky, who is also a professor in the Department of Pathology at NYU Langone.

According to some estimates, melanoma is among the most common forms of cancer in the United States, with about 100,000 new cases occurring every year. Once tumors spread throughout the body, melanoma had been notoriously difficult to treat, and conventional treatment methods like chemotherapy have limited effect against the disease. While the specific causes of melanoma are unclear, genetics and exposure to UV radiation in sunlight and tanning beds are known to increase risk, particularly among fairer-skinned people.

The newer therapies, which came into use in the last decade, are far more effective and less toxic than standard chemotherapy, but are much more expensive, the investigators say. The drugs fall into two broad categories: those that target the BRAF gene, which is mutated in a little less than half of melanoma patients; and immune checkpoint inhibitors, which prevent melanoma tumors from tricking the immune system into ignoring the cancer.

For the study, researchers analyzed new cases and deaths from melanoma collected by the National Cancer Institute and the Centers for Disease Control and Prevention. These numbers spanned from 1986 to 2016 and involved nearly a million Americans. Polsky notes that the steep drop in deaths cannot be readily explained by better detection methods because death rates did not drop steadily over time, but sharply. In addition, many health care groups have been pushing for early detection exams since the 1980s, so the timing of these declines matches up better with the introduction of the new therapies.

Nevertheless, the researchers caution that early detection is still important, allowing for less toxic forms of treatment and lowered health care costs. They emphasized that prevention, avoiding excessive UV light exposure, and promptly seeking medical care when there is a change in the skin's appearance, are crucial to reducing the risk of developing metastatic melanoma.

Polsky says future studies should investigate socioeconomic factors that may affect access to the newer therapies, as well as the effect of these treatments on other ethnic groups.