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Newswise — Princeton, NJ— Value in Health, the official journal of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), announced today the publication of new research indicating that testing for variants in 7 cancer-associated genes (versus the usual process of testing in just 2 genes) followed by risk-reduction management could cost-effectively improve life expectancy for women at risk of hereditary breast cancer. The report of these findings, A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at Risk of Hereditary Breast Cancer, was published in the April 2017 issue.   Using hypothetical cohorts of women at risk of hereditary breast cancer, the authors used a decision-analytic model to compare the relative cost and effectiveness of two test strategies for detecting pathogenic genetic variants: 1) the usual BRCA1/2 test strategy, and 2) a next-generation 7-gene strategy that tests for variants not only in BRCA1 and BRCA2, but also in TP53, PTEN, CDH1, STK11, and PALB2. The authors then used these test results to select appropriate breast cancer risk reduction treatments / therapies. In the base-case scenario for 50- and 40-year-old women undergoing genetic testing, the incremental cost-effectiveness ratio (ICER) for the 7-gene test strategy compared with the BRCA1/2 test strategy was $42,067 and $23,734 per life-year gained, or $69,920 and $48,328 per quality-adjusted life-year gained, respectively. At these ICER levels, the 7-gene test strategy would be considered cost effective according to the World Health Organization guidelines. “Pathogenic variants in the BRCA1 and BRCA2 genes explain only about 15% of the breast cancer familial relative risk,” said lead author Yonghong Li, PhD, Quest Diagnostics, USA, “while pathogenic variants in other genes, including TP53, PTEN, CDH1, and PALB2 contribute further to the familial relative risk. The results of this study,” Dr. Li added, “demonstrate the potential value of newer testing options that allow for the simultaneous analysis of expanded panels of additional genes whose pathogenic variants confer moderate to high risk for breast cancer.”  ###

Newswise — Many people might not have heard of theAedes aegypti mosquito until this past year, when the mosquito, and the disease it can carry – Zika – began to make headlines. But more than 220 years ago, this same breed of mosquito was spreading a different and deadly epidemic right here in Philadelphia and just like Zika, this epidemic is seeing a modern resurgence, with Brazil at its epicenter.     It was August of 1793 and Philadelphia – the nation’s capital and the busiest port in the United States – was experiencing a remarkably hot and dry summer. Water levels in streams and wells were low, creating an excellent breeding ground for mosquitos, which seemed to overtake the city. Along with the mosquitos also came an influx of thousands of refugees from the Caribbean seeking to escape political turmoil. But the refugees also brought something else: yellow fever.  The conditions in Philadelphia created the perfect storm for an outbreak. Symptoms start with head, back, and limb pain and a high fever. Sometimes after a few days, the initial symptoms would subside, giving its victims a false hope of recovery. But within a few days, the disease would return with a vengeance, bringing with it an even higher fever, bleeding, vomiting and eventually turning a person’s skin a ghastly shade of yellow – hence the disease’s name – and ultimately leading to death.  Philadelphia's medical community was mystified. Benjamin Rush, MD, the city’s leading physician advised citizens to flee. A large portion of Philadelphia’s citizens, along with members of Congress, President Washington, and his Cabinet, all abandoned the city. By the time the epidemic finally ended in November of that same year, more than 10 percent of the city’s population, approximately 5,000 people, had perished. Rush, and his protégé, Philip Syng Physick, MD, worked with the few other doctors who stayed behind to try and root out the cause of the outbreak. At that time, little was understood about infectious diseases, especially those that are transmitted via a vector, like a mosquito. Rush and his colleagues tried many unsuccessful techniques that were common at the time, including bloodletting, “purifying” the city’s air with smoke, and finally quarantining the sick. None of it worked. It took more than a century for physicians and public health experts to discover the true culprit behind yellow fever:  the mosquito. Yellow fever is not transmitted by contact with another sick person, but instead by contact with the mosquitoes itself. The mosquito serves as a vector transmitting disease when it bites a person who is infected with yellow fever and then bites a healthy person. With this discovery, public officials also worked to improve water and sanitation efforts, create drainage systems in densely populated areas, and educate the general public about how the disease is transmitted. The last reported yellow fever outbreak in North America was in New Orleans in 1905. “Actually, the initial steps to stop yellow fever are not so very different than the recommendations we made locally last summer to combat Zika,” said Pablo Tebas, MD, a professor of Infectious Diseases in the Perelman School of Medicine. “We told residents here in Philadelphia to avoid standing water and places where there are a lot of mosquitos—the same advice we were giving people 100 years ago.” But with climate change, deforestation, and other environmental challenges, there is concern that yellow fever could again be on the rise. Brazil has been battling an unusually high number of yellow fever cases since December 2016, with at least 326 confirmed cases, including 220 deaths, and hundreds of additional cases under investigation – making it Brazil's worst yellow fever outbreak among humans in decades according to the World Health Organization (WHO). And cases are creeping closer to two of the country’s largest cities — Rio de Janeiro and São Paulo — sparking fears that the disease could spread to other regions in the Americas. “The challenge with diseases like yellow fever and Zika is that the conditions that foster an outbreak are not always avoidable, especially in tropical climates, and therefore a vaccine is needed to prevent infection,” Tebas said. Fortunately, a vaccine for yellow fever is readily available and effective. First issued widely in 1939, WHO recommends the yellow fever vaccine for anyone living in an area where the disease is endemic. Health officials in Brazil have requested millions of doses of the vaccine from an international emergency stockpile in order to be prepared if the virus continues to spread. “The yellow fever vaccine is actually highly successful,” Tebas said. “It’s 99 percent effective and usually only needs to be administered once. Researchers, including our team at Penn, are using it as a foundation for developing vaccines for other mosquito-borne illnesses like Zika and Dengue.” At Penn, two different Zika vaccine candidates are in various stages of development. A phase I clinical trial for a Zika vaccine which began in August 2016 in partnership with the Wistar Institute and Inovio/GeneOne Pharmaceuticals aims to discover the safety and effectiveness of a DNA vaccine for Zika. And an mRNA-based Zika vaccine showed great promise in pre-clinical trials, protecting mice and monkeys against the virus with a single dose. “We are optimistic that we will make progress in creating an effective vaccine to stop Zika from spreading and by using innovative technology like DNA and mRNA, we can hopefully get these vaccines to market faster than traditional vaccines,” Tebas said. Currently, WHO is recommending the yellow fever vaccine to anyone who plans to travel to Brazil or the surrounding areas as a precaution.       

Newswise — (New York –April 17, 2017) –– A new study from the Icahn School of Medicine at Mount Sinai provides important insights into how the body regulates its production of heat, a process known as thermogenesis that is currently intensely studied as a target of diabetes and obesity treatment in humans. While researchers had previously hypothesized that macrophages, a class of white blood cells, played a major role in thermogenesis, the new study suggests that the main driver of thermogenesis is the sympathetic nervous system, which is chiefly controlled by the brain. The results were published online today in Nature Medicine. The Mount Sinai research team led by Christoph Buettner, MD, PhD, senior author of the study and Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at the Icahn School of Medicine at Mount Sinai, focused on catecholamines, hormones released by the sympathetic nervous system to activate brown fat tissue. Brown adipose tissue is a type of fat tissue that burns energy to produce heat and keep us warm. Catecholamines can also convert white fat tissue, the more familiar kind of fat tissue that stores lipids, into a tissue that resembles brown fat. The researchers tested whether macrophages could provide an alternative source of catecholamines, as had been proposed in recent years. “Thermogenesis is a metabolic process that receives a lot of interest as a target of drugs that allow you to burn energy and hence reduce obesity and improve diabetes. It turns out that macrophages are not that important, as they are unable to make catecholamines, but clearly the brain through the sympathetic nervous system is,” says Dr. Buettner. “Therefore, it is very important to study the role of the brain and the sympathetic nervous system when it comes to understanding metabolism.” The ability to generate heat is critical for the survival of warm-blooded animals, including humans, as it prevents death by hypothermia. “This evolutionary pressure shaped the biology of humans and that of other warm-blooded animals, and may in part explain why humans are susceptible to developing diabetes in the environment in which we live,” says Dr. Buettner. According to Dr. Buettner, while a lot of effort has been invested in targeting the immune system to cure diabetes and insulin resistance, as of yet there are no anti-inflammatory drugs that have been shown to work well in humans with metabolic disease. “Our study suggests that perhaps the key to combating the devastating effects of diabetes and obesity in humans is to restore the control of thermogenesis and metabolism by the brain and the autonomic nervous system,” says Dr. Buettner. This study was performed collaboratively between Mount Sinai and eight other institutions from around the world, most prominently with the group of Timo D. Müller, PhD, Institute for Diabetes and Obesity at the Helmholtz Center Munich in Germany. This work was further supported by grant from the German Research Foundation DFG-TS226/1-1, DFG-TS226/3-1,SFB1123, Nutripathos Project ANR-15-CE14-0030, European Research Council ERC AdG HypoFlam no. 695054 (to M.H.T.); DFG He3260/8-1, the EU FP7 Network “DIABAT,” the EU ITN Network “TRAIN” 721531 (to S.H.); NIH R01AA023416, DK082724 and a career-development award from the American Diabetes Association (to C.B.); NIH R01DK099222 (to S.D.); NIH DK17844 (to S.C.W.); the Israeli Science Foundation and European Research Council (AdvERC grant 340345) (to S.J.) and the Swedish Research Council and the Knut and Alice Wallenberg Foundation (to J.N. and B.C.). About the Mount Sinai Health System The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the “Honor Roll” of best hospitals in America, ranked No. 15 nationally in the 2016-2017 “Best Hospitals” issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation’s top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai’s Kravis Children’s Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube. # # #

Newswise — MINNEAPOLIS – Both obesity and being underweight are associated with an increased risk for migraine, according to a meta-analysis published in the April 12, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. The researchers looked at all available studies on body mass index (BMI) and migraine. “As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said study author B. Lee Peterlin, DO, of Johns Hopkins University School of Medicine and a member of the American Academy of Neurology. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.” A total of 12 studies with 288,981 participants were included in the meta-analysis. When the researchers compiled all of the results and adjusted for age and sex, they found that obese people were 27 percent more likely to have migraine than people of normal weight. People who were underweight were 13 percent more likely to have migraine than people of normal weight. Obesity was defined as a BMI of 30 or higher. Underweight was defined as a BMI of less than 18.5. Peterlin said the risk between obesity and migraine was moderate and similar in size to the link between migraine and bipolar disorders and ischemic heart disease, a condition of recurring chest pain or discomfort when part of the heart does not receive enough blood. According to Peterlin, age and sex were important variables in the relationship between body mass index and migraine. “This makes sense, as the risk entailed by obesity and the risk of migraine is different in women and men and in younger and older people,” she said. “Both obesity disease risk and the occurrence of migraine is more common in women and in younger people.” She continued, “It’s not clear how body composition could affect migraine. Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It’s also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.” Limitations of the meta-analysis include that for half of the studies people self-reported that they had migraine and for more than half of the studies people self-reported their body mass index.   The study was supported by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. To learn more about migraine, visit www.aan.com/patients. The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with 32,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy. For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+, LinkedIn and YouTube.

Newswise — WINSTON-SALEM, N.C. –  It doesn’t matter if it’s Bach, the Beatles, Brad Paisley or Bruno Mars. Your favorite music likely triggers a similar type of activity in your brain as other people’s favorites do in theirs. That’s one of the things Jonathan Burdette, M.D., has found in researching music’s effects on the brain. “Music is primal. It affects all of us, but in very personal, unique ways,” said Burdette, a neuroradiologist at Wake Forest Baptist Medical Center. “Your interaction with music is different than mine, but it’s still powerful. “Your brain has a reaction when you like or don’t like something, including music. We’ve been able to take some baby steps into seeing that, and ‘dislike’ looks different than ‘like’ and much different than ‘favorite.’” To study how music preferences might affect functional brain connectivity – the interactions among separate areas of the brain – Burdette and his fellow investigators used functional magnetic resonance imaging (fMRI), which depicts brain activity by detecting changes in blood flow. Scans were made of 21 people while they listened to music they said they most liked and disliked from among five genres (classical, country, rap, rock and Chinese opera) and to a song or piece of music they had previously named as their personal favorite. Those fMRI scans showed a consistent pattern: The listeners’ preferences, not the type of music they were listening to, had the greatest impact on brain connectivity – especially on a brain circuit known to be involved in internally focused thought, empathy and self-awareness. This circuit, called the default mode network, was poorly connected when the participants were listening to the music they disliked, better connected when listening to the music they liked and the most connected when listening to their favorites. The researchers also found that listening to favorite songs altered the connectivity between auditory brain areas and a region responsible for memory and social emotion consolidation. “Given that music preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of our results was unexpected,” the researchers wrote in the journal Nature Scientific Reports (Aug. 28, 2014). “These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem.” Not surprising to Burdette was the extent of the connectivity seen in the participants’ brains when they were listening to their favorite tunes. “There are probably some features in music that make you feel a certain way, but it’s your experience with it that is even more important,” said Burdette, who also is professor of radiology and vice chairman of research at Wake Forest School of Medicine. “Your associations with certain music involve many different parts of the brain, and they’re very strong. “In some cases, you might not even like the particular song, but you like the memories or feelings that you associate with it.” In other research projects, Burdette and colleagues at the School of Medicine and the University of North Carolina-Greensboro have found that trained music conductors are likely to be better at combining and using auditory and visual clues than people without musical training; that activity in brain areas associated with vision decreases during tasks that involve listening; and that different levels of complexity in music can have different effects on functional brain connectivity. “I find this type of work fascinating, because I think music is so important,” Burdette said. “If science can help get more people to recognize what music does to and for us, great.” Music is just a small part of Burdette’s research activities – his most recently published study, for example, showed that brain volume could be an accurate predictor of success in weight-loss attempts by the elderly – but it has long been a big of part his life. Burdette grew up playing viola, piano and guitar. He has been singing since childhood and continues to do so, including in the chorus in productions staged by the Piedmont Opera, of which he has been a board member for more than 10 years. He’s also done some conducting. His wife, Shona Simpson, plays piano. Their three teenage daughters – Fiona, Ellie and Jessie – perform professionally as the Dan River Girls. His brother, Kevin, is a singer who has appeared as a soloist with the Metropolitan Opera, Los Angeles Philharmonic and other top-tier opera companies and symphony orchestras. “Music is my avocation,” the physician in the family said. “Radiology is my vocation.” Burdette additionally has deep interest, if not direct involvement, in music’s clinical applications. “Music isn’t going to cure anything, but it definitely can play a therapeutic role,” he said. In countries such as Germany, Burdette noted, music therapy is commonly an integral part of the rehabilitation process for people who have had strokes, brain surgery or traumatic brain injuries. “If you’re trying to restore neuroplasticity in the brain, to re-establish some of the connections that were there before the injury, music can be a big help, and I’d like to see it used more widely in this country,” he said. Burdette also is a proponent of programs that help people with Alzheimer’s, dementia and other cognitive and physical problems re-connect with the world through music. One such program is Music & Memory, which employs iPods with customized playlists featuring songs popular when the participating individual was under 30 years old. “You can actually see the power of music,” Burdette said. “People who were just sitting there, not engaged in anything, light up when they start hearing music from when they were 25. “It’s fantastic. What else can do that? I can’t think of anything other than music.”

People who suffer heart attacks or cardiac arrests in the vicinity of an ongoing major marathon are more likely to die within a month due to delays in transportation to nearby hospitals, according to newly published research from Harvard Medical School. The delays, the researchers say, likely stem from widespread street closures during major races that can hamper transportation in an emergency. Writing in the April 13 issue of the New England Journal of Medicine, the study authors call for citywide strategies that ensure unhampered access for medical crews in a certain radius of major races and other large public gatherings, such as sporting events or parades.  Previous studies have examined death rates among marathon runners to assess the cardiac risks of endurance training, but this is believed to be the first study to analyze the impact of such races on those living nearby due to causes that have nothing to do with the physical exertion of running a marathon. “We have traditionally focused medical preparedness and emergency care availability to address the needs of race runners, but our study suggests that effects of a marathon may spread well beyond the course of the event and affect those who live or happen to be nearby,” said the study’s senior author, Anupam Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy at Harvard Medical School. The investigators examined 10 years’ worth of patient records analyzing death rates among older Americans, 65 years of age and over, within 30 days of having a heart attack or a cardiac arrest near a major marathon across 11 U.S. cities. Researchers compared death rates among patients hospitalized on the day of the race with those hospitalized five weeks prior or five weeks after the race. Additionally, the researchers divided patients by zip code, comparing death rates among those living near the marathon and those living in zip codes well outside of the event’s radius and unaffected by street closures. Patients admitted to a hospital on race day were nearly 15 percent more likely to die within a month of suffering a heart attack or cardiac arrest compared with those admitted on a non-marathon day or in a hospital outside of the marathon’s zip code(s). That spike translated into a nearly 4 percent difference in the number of deaths. In other words, the researchers say, for every 100 patients with heart attack or cardiac arrest, three to four more people died within a month in the group admitted to a hospital on race day if they happened to go to a hospital near the race course. The research also showed that ambulance transport was delayed by an average of 4.4 minutes on marathon days, 32 percent longer travel time compared with transports not delayed by marathons. Additionally, nearly a quarter of patients in the study got themselves to the hospital without an ambulance. While there is no record of the amount of time private transportation took, the authors suspect that many such trips would have been slow on marathon days. While the findings do not establish cause and effect between street closures and greater mortality, the researchers point out that many studies have shown that even very small delays in getting care could make the difference between life and death.  “When it comes to treating people in the throes of a heart attack, minutes do matter. Heart muscle dies quickly during a heart attack, so current guidelines call for rapid intervention, preferably within an hour or so of diagnosing a heart attack, to salvage cardiac muscle function,” said Jena, who is also a physician at Massachusetts General Hospital. As runners speed through the streets of the nation’s most popular marathons, traffic around race routes slows to a crawl. Marathon organizers make every effort to ensure safe and smooth passage for runners, but large public gatherings—such as major sporting events, parades or Independence Day fireworks—can cause major traffic snags. So, the HMS researchers wondered what kind of unintended consequences these sprawling, 26.2-mile events might have on the health of people who live near the race course. The findings suggest that between three and four preventable deaths likely occur each year among older residents who suffer heart attacks and cardiac arrests during marathons across the eleven cities studied. “Marathons and other large, popular civic events are an important part of the fabric of life in our big cities, and they bring people a lot of pride and joy,” Jena said. “But the organizers of these events need to take these risks to heart when they are planning their events, and find better ways to make sure that the race’s neighbors are able to receive the lifesaving care that they need quickly.” The races included in the analysis took place between 2002 and 2012 in Boston, Chicago, Honolulu, Houston, Los Angeles, Minneapolis, New York City, Orlando, Philadelphia, Seattle and Washington, D.C. To rule out other possible explanations for the spike in mortality, the researchers checked to see whether patients were sent to different hospitals, whether they traveled longer distances, whether out of town spectators or race participants skewed the mix of patients, whether people waited until their conditions were more severe before calling for an ambulance, or whether staffing levels or the type of treatment used on marathon days were different from usual, and they found no evidence to support any of these possibilities. The researchers say that their findings suggest that citywide strategies for emergency medical preparedness need to do more to account for the risks to nonparticipants whose emergency medical care may be delayed.  “When cities host big marathons, or when people participate in races, they don't think that there might be a chance that a person not taking part in the race could die because of the event,” Jena said. “These findings don’t mean we shouldn't have large public events, but hopefully our research will shine some light on the problem and suggest ways that planners can better provide for the health and safety of the people who live nearby.” N. Clay Mann, professor in the Department of Pediatrics at the University of Utah School of Medicine and director for research at the Intermountain Injury Control Research Center; Leia N. Wedlund, a student at Harvard University; and Andrew Olenski, a research assistant in the HMS Department of Health Care Policy, were co-authors of this study.  This research was supported with funding from the Office of the Director, National Institutes of Health (NIH Early Independence Award, Grant 1DP5OD017897-01).   Release written by Jake Miller

Newswise — DALLAS – April 10, 2017 – UT Southwestern Medical Center pediatric researchers have harnessed an analytical tool used to predict the weather to evaluate the effectiveness of therapies to reduce brain injury in newborns who suffer oxygen deprivation during birth. The analytical tool, called wavelet analysis technology, is best known for predicting long-term weather patterns, such as El Nino. UT Southwestern researchers say this same analytical tool can help improve assessment and treatment of newborns with asphyxia, which is when the baby’s brain is deprived of oxygen due to complications during birth. The non-invasive method produces real-time heat maps of the infant’s brain that doctors can use to determine whether therapies to prevent brain damage are effective. “These are babies to whom something catastrophic happened at birth. What this technology does is measure physiologic parameters of the brain – blood flow and nerve cell activity – to produce a real-time image of what we are calling ‘neurovascular coupling.’ If there is high coherence between these two variables, you know that things are going well,” said Dr. Lina Chalak, Associate Professor of Pediatrics at UT Southwestern and lead author of the study. The wavelet analysis correlates information from two non-invasive technologies that are currently used on a day-to-day basis in neonatal intensive care: amplitude EEG and near infrared spectroscopy. The approach combines the results from these commonly done tests in a sophisticated way and creates a new proxy measure of brain health called neurovascular coupling. When neuronal activity and brain perfusion are synchronized – as indicated by large areas of red on heat maps created by this method – treatment is working well. About 12,000 newborns experience oxygen deprivation (asphyxia) during birth in the U.S. each year, according to a 2010 article in Lancet. This can occur for a number of reasons, such as the cord being wrapped around the baby’s neck, a difficult breech birth, or the separation of the placenta from the uterus too soon, Dr. Chalak explained. These infants are at high risk of developing serious consequences such as cerebral palsy, epilepsy, and cognitive deficits. No treatments were available until about 10 years ago when a national study in which UT Southwestern participated, showed that reducing the baby’s core temperature could counteract the impact of birth asphyxia for some infants. The cooling blankets are now standard treatment, but only about half of babies treated with a cooling blanket benefit. Until the adaptation of the wavelet technology, doctors couldn’t determine which infants were benefitting from cooling treatment and which babies may need additional therapies, which are being developed. Wavelet analysis information also can help in evaluation of new therapies. Dr. Chalak plans to use wavelet analysis as part of the HEAL study, a large clinical trial to determine the effectiveness of erythropoietin, a hormone that promotes the formation of red blood cells, to treat newborns with asphyxia. Wavelet analysis will be used to evaluate infants who are part of the HEAL study at the Neonatal Intensive Care Unit at William P. Clements Jr. University Hospital, Parkland Hospital, and Children’s Medical Center. Wavelet technology also may help determine which children should be treated. “Of the babies who are oxygen-deprived, some don’t qualify for cooling because their brain damage or encephalopathy is judged to be mild. Yet some of these children have adverse outcomes. This technology may help us identify who needs cooling,” said Dr. Rashmin Savani, Chief of Neonatal-Perinatal Medicine and Professor of Pediatrics and of Integrative Biology, who holds The William Buchanan Chair in Pediatrics. It could also lead to other discoveries. “Understanding of brain blood flow regulation and its impact on brain function in newborns with asphyxia using this novel technology has great potential for developing new sensitive biomarkers for clinical diagnosis, treatment, and prognosis for these sick babies, which is desperately needed in the field,” said co-author Dr. Rong Zhang, Associate Professor of Neurology and Neurotherapeutics, and of Internal Medicine, and a member of the Peter O’Donnell Jr. Brain Institute at UT Southwestern. The research appears in Nature’s Scientific Reports. Other UT Southwestern researchers who contributed to this paper are Dr. Beverley Adams-Huet, Assistant Professor of Clinical Sciences and of Internal Medicine; Diana Vasil, research nurse; and Dr. Takashi Tarumi, Instructor in Neurology and Neurotherapeutics, along with Dr. Fenghua Tian, Assistant Professor of Biomedical Engineering at UT Arlington. The research was funded by grants from the National Institutes of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. Dr. Chalak said the new tools represent a paradigm shift for physicians who treat oxygen-deprived newborns. “Hopefully, the future will be bright for babies who suffered asphyxia, differing from the bleak prognoses of the past.” About UT Southwestern Medical Center UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year. ###

Newswise — A 5K fun run shouldn’t involve more physical preparation than major surgery, but that’s the disconnect Michael Englesbe, M.D., sees all too often. Just as an athlete might work to build up stamina before a race, a person entering the hospital also can benefit from prepping the mind and body. Even minor adjustments to diet and mental health could help some individuals go home sooner — and, in turn, save hospitals and insurance companies money. But for many health care providers, that concept isn’t always put into practice. “We do a lot in medicine to get people ready for surgery, but they’re primarily administrative tasks — checking off boxes that don’t necessarily make a patient better,” says Englesbe, a Michigan Medicine transplant surgeon who has studied and championed the idea for nearly a decade. “The more you can do to manage your status preoperatively, the quicker you’ll be able to bounce back.” In February, Englesbe, colleague Stewart Wang, M.D., Ph.D., FACS, and several other authors confirmed their longtime hunch: A study published in Surgery found that basic fitness and wellness coaching, administered in advance, could reduce a surgical patient’s average hospital stay two days, from seven down to five, when compared to a control group. And, in a benefit to patients and providers alike, the regimen cut medical costs 30 percent. Moreover, the participation rate among the study’s 641 subjects was high — about 80 percent, far better adherence than what might follow a typical medical appointment. “As a physician, you always tell people to quit smoking and exercise,” says Englesbe, “but the compliance rates are notoriously abysmal.” The prospect of serious surgery, he notes, can be a change agent in itself: “Big health crises can scare people straight, so to speak, and change their lifestyle.” Still, the researchers say, promoting healthful habits in advance of an operation is a measure that should be just as crucial as any other step in the admittance process. Adds Wang: “The condition of the body is so important. It’s so much common sense that people often fail to recognize it.” A virtual coach  The recent study marks the third time Englesbe and Wang have examined the idea of athletic training applied to surgical preparation, which they call “prehab.” Hospitalization times and cost savings were consistent among the analyses. Each review followed the Michigan Surgical and Health Optimization Program (MSHOP), an initiative aimed at helping patients target and strengthen weaknesses before surgery. A web-based risk assessment tool using a person’s existing data enables shared decision-making between patient and physician and helps identify patients who will best benefit from MSHOP. Elements of the program include improving one’s diet, reducing stress, breathing exercises and smoking cessation, and, most crucial, an emphasis on light physical activity — with the latter reinforced via daily notifications. Most MSHOP patients are advised to log 12 miles of walking per week, or about an hour a day. Each participant is given a pedometer to track progress. It sounds simple, but it can pay off: Walking aids blood flow and speeds healing. “The vast majority of the program benefits come from the walking,” says Wang, endowed professor of burn surgery and director of the Morphomic Analysis Group at Michigan Medicine. Early MSHOP efforts encouraging patients to boost their steps involved personal phone calls, a method ultimately revised due to staffing requirements and, given the demands of patients’ work and personal lives, subpar reach. The system now relies on automated daily text messages or automated phone calls to deliver a reminder. Program facilitators worked to craft notes with positive, natural-sounding language to make the exchanges personal and more effective. That way, “the patient feels like someone is actually paying attention to them,” says June Sullivan, the technology director for MSHOP, noting that any replies are monitored and logged. “And, they respond with things like ‘This is a great program’ or ‘Sorry I didn’t do well today — I’ll try harder.’” Training to win  If surgeries were races, the procedures MSHOP patients received — liver, gastrointestinal, pancreas and thoracic surgery; organ transplant; and esophageal resection, among other operations — might be likened more to triathlons than turkey trots. “They were pretty big operations,” Englesbe says. Because the analyzed cases were elective, as about 90 percent of all surgeries in the United States are, the notion of prehab based on the study’s findings could spur some doctors to more carefully evaluate a patient’s readiness (and perhaps delay plans if warranted).   “Surgery is basically controlled injury,” says Wang, whose background is in trauma medicine. “You’re ‘whacking’ patients and hoping that in the end they do better overall because you’ve interrupted the disease process.” No matter the circumstance, be it a car crash or a kidney transplant, a patient’s strength can dictate their path going forward. People with weak psoas muscles, for instance, “did terribly after surgery,” Wang says of the findings that led to the creation of MSHOP. And MSHOP components can not only boost physical healing, but also provide emotional benefits in the days before the procedure — and, ideally, beyond. “Patients don’t care about costs or how long they’re going to be in the hospital; they just want to get through the experience,” Englesbe says. “This is an empowering tool that helps them do something positive in the face of a very negative event.” Growing the franchise  Since its establishment five years ago, the MSHOP curriculum is now offered in more than 20 hospitals and 30 practices across Michigan. Despite plenty of positive feedback and proof of prehab’s benefits, the practice encompasses just a sliver — about 1,250 patients — of the 65,000 surgeries performed annually at Michigan Medicine. Debate about logistics and wider implementation also remain among medical professionals. “First, we hear that everyone thinks it makes sense for their patients,” says Englesbe. “Second, it’s really hard to change clinical practice, especially among busy surgeons. It’s essentially adding work to the busiest people.” Although the cost benefits are notable, that factor doesn’t necessarily register with clinicians, the researchers note. And, says Sullivan, the technology director, surgeons must be the ones to start the dialogue: “They have to deliver the message; that’s who the patient believes.” Still, the MSHOP movement has caught the attention of insurance payers that might be able to help facilitate a wider reach. “Once it’s a billable service, it will really take off,” Englesbe says. Because current prehab guidelines are somewhat general, there also is room to grow. They could one day be tailored to address more specific scenarios, such as prescribing certain exercises prior to a joint replacement surgery. “The technology is scalable,” Wang says. “Expected complications or recovery difficulties could be addressed in advance with targeted training. This is just the beginning.”   SEE ORIGINAL STUDY

Newswise — Researchers in Germany have developed a transgenic mouse that could help scientists identify new influenza virus strains with the potential to cause a global pandemic. The mouse is described in a study, “In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein,” that will be published April 10 in The Journal of Experimental Medicine. Influenza A viruses can cause devastating pandemics when they are transmitted to humans from pigs, birds, or other animal species. To cross the species barrier and establish themselves in the human population, influenza strains must acquire mutations that allow them to evade components of the human immune system, including, perhaps, the innate immune protein MxA. This protein can protect cultured human cells from avian influenza viruses but is ineffective against strains that have acquired the ability to infect humans. To investigate whether MxA provides a similar barrier to cross-species infection in vivo, Peter Staeheli and colleagues at the Institute of Virology, Medical Center University of Freiburg, created transgenic mice that express human, rather than mouse, MxA. Similar to the results obtained with cultured human cells, the transgenic mice were resistant to avian influenza viruses but susceptible to flu viruses of human origin. MxA is thought to target influenza A by binding to the nucleoprotein that encapsulates the virus’ genome, and mutations in this nucleoprotein have been linked to the virus’ ability to infect human cells. Staeheli and colleagues found that an avian influenza virus engineered to contain these mutations was able to infect and cause disease in the transgenic mice expressing human MxA. MxA is therefore a barrier against cross-species influenza A infection, but one that the virus can evade through a few mutations in its nucleoprotein. Staeheli and colleagues think that their transgenic mice could help monitor the potential dangers of emerging viral strains. “Our MxA-transgenic mouse can readily distinguish between MxA-sensitive influenza virus strains and virus strains that can evade MxA restriction and, consequently, possess a high pandemic potential in humans,” Staeheli says. “Such analyses could complement current risk assessment strategies of emerging influenza viruses, including viral genome sequencing and screening for alterations in known viral virulence genes.” Deeg et al., 2017. J. Exp. Med. http://jem.rupress.org.cgi/doi/10.1084/jem.20161033?PR # # #

Newswise —  ANN ARBOR, Mich. – Researchers at Michigan Medicine have found the livers of patients with a rare disease that affects metabolism have responded positively to leptin therapy. In an open-label study, funded by the National Institutes of Health, the research team predicted the response of 23 patients with partial lipodystrophy-associated nonalcoholic steatohepatitis (fatty liver) to metreleptin, a man-made version of the naturally occurring hormone leptin, which regulates fat and glucose metabolism. The researchers reported patients with a lower baseline leptin level had a higher response rate after one year of treatment with metreleptin, a pharmaceutical produced by Novelion Therapeutics’ subsidiary. They presented their findings today at ENDO 2017, the annual meeting of the Endocrine Society, in Orlando, Florida. Lipodystrophy is a group of rare diseases that share in common the selective loss of fat tissue from the body. Patients affected by the diseases generally have severe insulin resistance, high lipids in their blood and fatty liver. The condition highlights how important fat cells are to regulating a person’s metabolism. Generalized lipodystrophy results in fat loss throughout the entire body. Partial lipodystrophy results in fat loss typically in the arms, legs, head and torso, and fat accumulation in the neck, face and intra-abdominal areas of the body. Metreleptin was approved by the Food and Drug Administration in 2014 to treat generalized lipodystrophy, but has not been approved to treat partial lipodystrophy. “Fatty liver, or excess fat building up in the liver, is a common metabolic disturbance seen in patients with lipodystrophy,” says Elif Oral, M.D., associate professor of endocrinology at Michigan Medicine and principal investigator of the study. “The underlying metabolic disturbances seen in this patient population can be difficult to manage with traditional therapies.” The partial lipodystrophy study participants underwent two liver biopsies, one at the beginning of the trial and after one year of treatment. Investigators observed their NASH score, a numerical score for progression of fatty liver disease in patients, and their NAS score, a numerical score for progression of non-alcoholic fatty liver disease. Of the 23 patients enrolled in the study, 22 were treated with at least one dose of metreleptin at baseline. Of the 18 patients who completed treatment after one year, NASH scores improved from a mean of 6 at baseline (showing moderate to advanced disease) to a mean of 5. NAS scores also improved from a mean of 5 at baseline to a mean of 4 after 12 months of treatment. The researchers noted that these changes were statistically significant in the patient group. “About half of the patients had scores that lowered by two points or more, which is clinically significant in patients with this disease,” says Oral. “Generally, that type of drop is only seen with 10 percent or more sustained weight loss in the common form of fatty liver disease, which usually only occurs with metabolic surgery.” Patients that experienced the two-point or greater reduction improvement in their scores from treatment had a lower baseline leptin level of 14.5 ng/mL versus non-responders whose average leptin level at baseline was 25 ng/mL. In addition, some patients saw reductions in glucose control and lipid levels, but the differences noted in the entire cohort did not attain statistical significance. The most frequently reported adverse events in the study, occurring in more than 20 percent of the patients, were upper respiratory infections, hypoglycemia and diarrhea. “The liver disease at baseline is quite significant among the patients in this study, which showed a significant degree of inflammation and fibrosis, even in the absence of liver test abnormalities,” says Nevin Ajluni, M.D., assistant professor of endocrinology at Michigan Medicine and the presenting author of the study. “This highlights the importance of screening for this complication.” About lipodystrophy research at Michigan Medicine The Michigan Medicine Division of Metabolism, Endocrinology and Diabetes, and the Brehm Center for Diabetes Research collectively host a major referral center for the study of lipodystrophy syndromes. The Division houses a clinical program to deliver state-of-the-art care for atypical forms of diabetes that aims to improve the lives of patients afflicted with these unusual diseases. The program also supports discovery research for uncovering new disease mechanisms and possible new drugs for these disorders. For more information, contact Adam Neidert at (734) 615-0539. About Michigan Medicine At Michigan Medicine, we create the future of healthcare through the discovery of new knowledge for the benefit of patients and society; educate the next generation of physicians, health professionals and scientists; and serve the health needs of our citizens. We pursue excellence every day in our three hospitals, 40 outpatient locations and home care operations that handle more than 2.1 million outpatient visits a year. The U-M Medical School is one of the nation’s biomedical research powerhouses, with total research funding of more than $470 million. For more information, please visit: www.michiganmedicine.org.