Body

Edinburgh has some of the highest known rates of inflammatory bowel disease in the world and the figure is expected to rise in the next 10 years.

Researchers say that one in 125 people in the city have Crohn's disease or ulcerative colitis - collectively known as inflammatory bowel disease (IBD).

They predict this figure will rise to 1 in 98 by 2028, putting further strain on NHS resources.

The University of Edinburgh study shows that Crohn's disease affects 284 people out of every 100,000 in Scotland's capital. The world's highest rate is 322 people out of 100,000 in Hesse, Germany.

Ulcerative colitis, meanwhile, affects 432 people out of every 100,000 in Edinburgh - second in the world only to south-east Norway, where it affects 505 people in every 100,000.

These findings broadly apply to the rest of Scotland, the UK and across the western world, researchers say.

Crohn's disease and ulcerative colitis are lifelong and debilitating conditions with no known cure. They are characterised by highly unpredictable and intrusive symptoms, such as diarrhoea, pain, weight loss and extreme fatigue.

The cause is unknown, but it is thought to be caused by an overactive gut immune response in genetically pre-disposed people. The makeup of normal gut bacteria and diet can also play an important role.

While patients with IBD require regular treatment and monitoring, the condition has a low mortality. Experts say this - combined with an ageing population - means the number of older people with IBD is set to increase in the coming years.

The study was published in the scientific journal Gut.

Dr Gareth-Rhys Jones, clinical lecturer in IBD at the University of Edinburgh's Centre for Inflammation Research, said: "IBD is a condition that disrupts the lives of patients and their families all too frequently. Our findings highlight that more resources are needed to provide patients with the research, treatment and care they deserve."

Dr Charlie Lees, a consultant gastroenterologist in the Edinburgh IBD Unit, added: "There is no doubt that IBD is now becoming a global pandemic. This study provides much-needed data and can act as a launchpad for pivotal new studies to help patients."

Sarah Sleet, CEO of Crohn's and Colitis UK, said: "This important study contributes to the growing evidence that the prevalence of IBD is significantly higher than is currently recognised."

A group of European scientists led by KU Leuven has found a biomarker that can identify patients with symptoms of kidney rejection symptoms after a transplant as a result of antibodies. The identification can be done through a simple blood test and at an early stage. It is the first known biomarker for rejection by antibodies. The researchers hope that the test can be further developed quickly for use in the hospital.

After a kidney transplant, patients have to take medication to suppress their immune system. However, kidney rejections occur frequently. To determine if the body is rejecting the organ, doctors usually take a biopsy: using a needle, they remove a small piece of tissue from the transplanted kidney and examine it under a microscope. This procedure is often uncomfortable. Moreover, rejection symptoms are often discovered too late, so that correct treatment is not always possible anymore.

At the University Hospitals Leuven in Belgium, kidney transplant patients systematically undergo a kidney biopsy three months, one year, and two years after the transplant. However, the biopsy only can detect rejection symptoms that are present at that moment, while rejection can occur at any time. Moreover, about ten to twenty percent of rejections remain undetected with current methods, which leads to graft failure, reinitiation of dialysis and the need for a repeat transplant.

Milestone in kidney transplant research

For several years, kidney transplantation research has focused on finding biomarkers that can detect symptoms of organ rejection in the blood. Such a biomarker has now been discovered in a European study* in four university hospitals (Leuven, Paris, Hannover and Limoges) that was spearheaded by nephrologists from KU Leuven.

It is the first time that researchers have found a biomarker for kidney transplant rejection by antibodies. For T cell-mediated rejection, a common type of rejection, some biomarkers in the blood have recently been found, which are now being further developed for clinical use. Rejection by T cells is treatable, but there are fewer treatment options for rejection with antibodies.

"Rejection by HLA antibodies often has serious consequences," said professor Maarten Naesens, nephrologist at the University Hospitals Leuven and principal investigator of the study. "Traditional tests for assessing the function of transplanted kidneys can often only identify rejection when it is already chronic and irreversible. Thanks to our biomarker, we can detect rejection much earlier and with a simple blood test. Because the test is less invasive, we will be able to test more often than with the current biopsies."

Clinical value

In the first phase, the European researchers* performed a genome-wide study to find out differences in RNA molecules among 117 patients with and without kidney rejection symptoms after a transplant. In the second phase, the different molecules of an independent group of 183 patients were processed into a mathematical model. The final biomarker consists of eight RNA molecules that are measured with an RT-PCR technique. In the third phase, the biomarker was validated in 387 patients in four European academic hospitals.

"In addition to developing the biomarker, that third phase was very important," said Dr Elisabet Van Loon from the Nephrology and Kidney Transplantation research group at KU Leuven. "Researchers are often satisfied with a new discovery, even though they are unable to test it in independent clinical studies. Thanks to international cooperation, we could validate our biomarker in a large group of patients. That gives us a lot of confidence in the clinical value of the new biomarker. "

The researchers now want to consult with medical diagnostic companies to further develop and standardise the test. "In principle, our antibody rejection test has been sufficiently validated for commercialisation," said Professor Naesens. "This is the next and necessary step to be able to offer the test to patients. With the test, patients who have no rejection of antibodies will no longer have to undergo a biopsy. The biomarker will also help to detect rejection sooner and will support the search for better medicines against rejection by antibodies."

The real burden of tuberculosis is probably higher than estimated, according to a study on samples from autopsies performed in a Mozambican hospital. The study, led by the Barcelona Institute of Global Health (ISGlobal), an institution supported by "la Caixa", shows that highly sensible molecular techniques can detect cases that escape clinical diagnosis and even traditional post-mortem examination of organs and tissues.

Tuberculosis (TB) is the leading infectious cause of disease globally and the most frequent cause of HIV-related deaths. In 2017, there were 10 million cases and 1 million TB deaths, according to WHO figures. But estimating the real burden of TB mortality is not easy, since clinical diagnosis or verbal autopsies are often unreliable.

Under the framework of CaDMIA, a project that seeks to validate the use of minimally invasive autopsies to determine causes of death and that is directed by Dr Jaume Ordi, Dr Clara Menéndez and Dr Quique Bassat, a team led by ISGlobal researcher Miguel Martinez performed a post-mortem study to evaluate the real TB burden in a hospital in Southern Mozambique, a region where the HIV and TB epidemics have devastating consequences. The research team analysed clinical data and samples from 223 complete autopsies performed on children, mothers and other adults. "The detailed histopathological and microbiological analysis we performed during the autopsies represents the most reliable way of identifying the cause of death and generating reliable information on the burden of TB," says Miguel J. Martínez.

The results indicate that TB was the cause of death in 31 of the 223 cases; in 31 other cases disease signs were detected although it was not the cause of death. Most of these cases were incorrectly diagnosed by the clinician. In 18 additional cases, genetic material of the M. tuberculosis bacterium was detected, without any clinical or histological sign, which could reflect very early stages of the disease.

"This investigation is part of one of the largest autopsy studies conducted to date in sub-Saharan Africa," says Alberto García-Basteiro, ISGlobal researcher and first author of the study, "and reveals the enormous burden of tuberculosis among population that dies in a reference hospital in Mozambique. Overall, 28% of patients had the disease at the time of death. The TB burden was even higher in HIV-positive adults (M. tuberculosis was detected in up to 51% of cases).

The results of the study, published in the European Respiratory Journal, also reveals the high number of cases that are missed by clinicians. "The routine use of these molecular techniques among patients in severe condition in high-burden TB countries could result in earlier detection of the disease and a better clinical management and prognosis of tuberculosis patients," adds García-Basteiro.

A new study, led by Professor Elina Hyppönen from UniSA's Australian Centre for Precision Health, presents the strongest evidence yet of a causal relationship between obesity and a wide range of serious conditions, including cardiovascular disease, diabetes, cancer, and neurological, musculoskeletal and respiratory afflictions.

The study, published in Lancet Digital Health, draws data from the UK Biobank - a research database holding health and genetic information from half a million volunteers - to analyse associations between body mass index (BMI) and a range of disease outcomes in 337,536 people.

"In this study we used a genetic approach to seek evidence for true health effects associated with higher body mass index, which assesses our weight against our height and is commonly used to measure obesity," Prof Hyppönen says.

Previous research has suggested that high BMI is associated with increased risk of chronic diseases such as type 2 diabetes, cardiovascular disease and cancer, but due to the difficulty of conducting clinical trials related to obesity, it has been hard to prove causation.

Prof Hyppönen and her team developed a multi-dimensional analysis in which genetic data was subjected to a suite of stringent examinations in order to deliver high confidence of causality.

"We compared evidence from five different statistical approaches to establish how strong the evidence for causal effect actually is," she says.

"Fully consistent evidence across all approaches was seen for 14 different diseases, and for 26 different diseases evidence was obtained by at least for four of the five methods used.

"What increases the confidence that these associations are largely reflective of real effects is the fact that those effects which came across with consistent evidence are also ones for which we have previous clinical evidence."

One key finding from the study was the extent to which it confirms existing concerns over the link between obesity and diabetes, with many of the diseases identified as related to high BMI known to be commonly associated with poorly controlled diabetes.

"For example, we saw evidence for effects on peripheral nerve disorders, chronic leg and foot ulcers, and even gangrene and kidney failure, which are all known to be diabetic complications. This suggests a key aspect to reduce comorbidity risk in obesity is careful monitoring of blood sugar and effective control of diabetes and its complications," Prof Hyppönen says.

The study also highlights the importance of genetic research to further our understanding of the role genes play in obesity, and the insights it can provide for the future management and treatment of obesity.

"There is an urgent need to find new approaches to manage and prevent obesity," Prof Hyppönen says.

"We know that obesity has a strong genetic basis, which can make weight management very difficult to some of us and the same strategies for prevention may also not work for all. Genetic studies are giving us deeper insights into the biological pathways which drive obesity, and hopefully these types of studies will also provide us with new strategies for prevention."

WASHINGTON--(July 2019)--A novel palliative care intervention developed at Children's National Health System for caregivers of children and adolescents with rare diseases has shown preliminary success at helping families talk about potentially challenging medical decisions before a crisis occurs.

"Our goal was to find out if it the tools we've developed are feasible and not too burdensome for the caregivers of children and adolescents with rare diseases," says Maureen Lyon, Ph.D., a clinical psychologist at Children's National who leads the Family Centered Advance Care Planning Team (FACE) within the Center for Translational Research at Children's National. "Developing the tool with their needs in mind was crucial because these families are already doing so much--including many tasks that used to be only done in a hospital-inpatient setting."

The approach was tested in a small sample of families whose children receive medical care through the Complex Care Program at Children's National. The findings from this preliminary study were recently published in the journal BMJ: Supportive and Palliative Care.

The intervention, which was guided by family feedback including review by the Patient and Family Advisory Council as well as families from the Leukodystrophy and Myelin Disorders Programat Children's National, includes two evidence-based modules:

A caregiver needs assessment, based on the validated Carer Support Needs Assessment Tool (CSNAT) Approach

An advanced care planning discussion, adapted specifically for families of children with rare diseases based on the validated Next Steps: Respecting Choices curriculum.

The two modules were delivered through four sessions led by two seasoned registered nurses who are familiar with the population. All families rated the sessions as useful and helpful, and while emotionally intense, not harmful in any way. In addition, feedback indicated that the last two sessions would be best served if they were combined into one longer session that coincided with an existing medical visit.

The adapted CSNAT needs assessment allowed the research team to collect some additional important information about the pressing needs and top priorities of the caregivers, which included:

Knowing what to expect in the future

Having personal time to recharge

Financial challenges

"It's important to strike the right balance of relatability and knowledge so families know they aren't alone in this journey," says Jessica Thompkins, BSN, RN, CPN, research nurse coordinator for the FACE program, who facilitated the CSNAT sessions with families. "Families and their care providers both want to have these conversations ahead of time to avoid having to make important medical decisions in a crisis situation. But we have to first help them address their immediate needs, which will open the door to the right environment for these conversations."

This is the first time these two separate tools have been combined into a single comprehensive program. It is also the first time that the CSNAT, originally designed for caregivers of adults in hospice care, has been adapted for use in a pediatric population. The team also had to tailor the Next Steps: Respecting Choices curriculum, which was first applied at Children's National to give adolescents with HIV a voice in their own advanced care planning decisions, for use in this context, to make sure the tools speak to these caregivers, who are often the only voice for the needs of nonverbal or noncommunicative children.

"There are few tools developed to tackle these challenging topics for pediatric populations in general. Even fewer look at the serious needs of the people who care for them and how we can deliver important information to help them make the best decisions possible for their families and themselves," says Dr. Lyon. "This preliminary study gives us a good idea of where we need to go next to scale up these tools and give more families and care providers the confidence to have these conversations."

New Rochelle, NY, July 31, 2019--The Canadian Society of Palliative Care Physicians has developed a new staffing model for specialist palliative care teams that can deliver an optimal, integrated palliative care program. The model, based on three key interdependent roles--palliative care physician, palliative care resource nurse, and social workers -- is described in detail in a Special Article published in Journal of Palliative Medicine, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Journal of Palliative Medicine website through August 31, 2019.

The Special Article led by the Canadian Society of Palliative Care Physicians is entitled "Staffing a Specialist Palliative Care Service, a Team-Based Approach: Expert Consensus White Paper." The article was coauthored by Dr. J. David Henderson and Stephanie Connidis, MD, Dalhousie University (Halifax), Anne Boyle, MD and David Lysecki, MD, McMaster University (Hamilton), Leonie Herx, MD, PhD (Queen's University (Kingston), Aleco Alexiadis, MD and Doris Barwich, MD, University of British Columbia (Vancouver), and Aynharan Sinnarajah, MD, MPH, University of Calgary, Canada.

The broader interprofessional team, in which primary care physicians, nurses, and social workers play a central role, will also include therapists, pharmacists, home healthcare workers, and others. All members of the team are interdependent and need to work collaboratively for this approach to be successful. The article presents a detailed description of the model, the assumptions underlying the model, staffing requirements, and the clinical and non-clinical responsibilities of the team.

Charles F. von Gunten, MD, PhD, Editor-in-Chief of Journal of Palliative Medicine and Vice President, Medical Affairs, Hospice and Palliative Medicine for the OhioHealth system, states: "Palliative care is a team sport. It's important to develop standards so palliative care isn't watered down and the impact diminished."

Having bad breath can mean someone ate a smelly lunch, but it could indicate that the person is sick. Various scent compounds have been linked to illnesses such as diabetes, lung cancer and Parkinson's disease, leading scientists to develop technology that measures these substances. However, the challenge is creating instrumentation that can detect low, diagnostic levels of these disease biomarkers. Now, scientists report in ACS' Analytical Chemistry a highly sensitive "sniff-cam" that fits the bill.

Before the advent of modern technology, ancient medical practitioners used breath and body odor to diagnose disease. But healthy people also emit smelly volatile organic compounds (VOCs), and the levels of these substances can vary depending on other factors, such as sex and body mass, so analysis can be complicated. Over the years, researchers have developed several different types of instruments to detect VOCs, such as ethanol (EtOH), a metabolite of the microbiome in humans that can provide an indication of glucose levels. But current systems to detect VOCs typically require large, expensive equipment and trained professionals. Previously, Kohji Mitsubayashi and colleagues developed a "bio-sniffer" that measured VOCs, such as acetone, a product of lipid metabolism. More recently, they reported the first generation sniff-cam, which could visualize EtOH emissions from the skin of someone who had consumed alcohol. However, the researchers wanted to refine the device so it could detect diagnostic levels of biomarkers.

The researchers constructed a new version of the sniff-cam, which now consists of an ultraviolet ring light, filters and a camera. An enzyme mesh, already used in the previous device, reacts EtOH with oxidized nicotinamide adenine dinucleotide (NAD), producing the fluorescent reduced form of NAD, which the camera records. A new imaging analysis method improved the sensitivity of the system so that low amounts of EtOH could be measured. The updated sniff-cam was then tested on a group of male subjects who had not consumed food or drink, and the device detected miniscule levels of EtOH in their breath. These results show that the sniff-cam can visualize a broader range of VOC levels than previous devices, and its versatility may aid in the further study of the relationship between scent and disease. 

Mothers of young children with autism who focus on improving the quality of their own relationship skills--as opposed to teaching developmental skills to their children--experience dramatic improvements in their level of parenting stress and depression.

That's according to a new research study involving Case Western Reserve University.

The study, co-authored by Gerald Mahoney, the Verna Houck Motto Professor of Families and Communities and associate dean for research and training at the Jack, Joseph and Morton Mandel School of Applied Social Sciences, examined the effects of this technique in a small experimental research study involving 28 preschool-aged children with autism and their parents in Saudi Arabia.

One focus of the study was to examine whether mothers' high stress and depression levels might improve based on their level of responsiveness in daily interactions with their children.

"Saudi Arabia is a country where there are not a lot of services for young children with disabilities," Mahoney said. "We wanted to examine the effects of this low-cost intervention strategy that focused on improving the quality of parents' involvement with their children and evaluate the effects of this intervention on both children and their parents."

Mahoney was joined in this study by a team of researchers from King Saud University and King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia.

Autism is a disability not only affecting child development, but also interfering with children's ability to engage in social interaction with their parents and others. Parents of children with autism commonly report extremely high levels of parenting stress and depression not only when their children are young but continuing throughout childhood.

Mahoney said that "parents of autistic children in Saudi Arabia are generally not involved with intervention services there, while parent involvement is a major focus of early intervention services in the United States and elsewhere."

So, focusing on improving mother/child relationships made sense, he said.

Mahoney said the strategy worked.

At the beginning of this four-month study, all parents reported clinical levels of stress, and 70% reported clinical levels of depression. By the end of the research, the percentage of parents who received responsive teaching experiencing clinical levels of stress dropped to 30%; and the percentage of parents experiencing clinical levels of depression dropped to 15%. In comparison, there were no improvements reported for parents in the control group receiving no treatment.

In addition, children of parents receiving responsive teaching made significant developmental improvements as well: 44% attained better social skills; 37% improved language development; and 24% enhanced fine motor skills compared to children in the control group.

These findings were recently published in the International Journal of Disability, Development and Education.

"Although this was a small sample, we can say that this research was quite successful," said Mahoney, who has spent decades researching interventions for children with disabilities. "By changing the intervention to a relationship focused approach, we found that mothers' depression and stress dropped dramatically."

Leesburg, VA, July 31, 2019--Aspirin therapy is associated with both improved liver function test results and survival after transarterial embolization (TAE) for hepatocellular carcinoma (HCC), according to an ahead-of-print article published in the September 2019 issue of the American Journal of Roentgenology (AJR).

In a retrospective review of 304 patients led by F. Edward Boas at Memorial Sloan Kettering Cancer Center in New York City, among the 42 patients taking aspirin at the time of initial TAE for HCC, bilirubin level evidenced lower 1 day (0.9 vs 1.3, p

"Although the differences in liver function test results in the groups taking and not taking aspirin were small," wrote Boas, "standard biochemical liver function tests are insensitive to early cirrhotic changes."

Clarifying further, Boas noted, "small changes in biochemical liver function test results might underestimate the degree of liver injury after embolization."

Whereas aspirin use indicated no disparity in initial response rate (88% vs 90% complete response or partial response, p = 0.59), median time to progression (6.2 vs 5.2 months, p = 0.42), initial site of progression (p = 0.77), or fraction of patients dying with disease progression (88% vs 89%, p = 1.00), the median overall survival period after TAE for HCC measured longer for the cohort taking aspirin (57 vs 23 months, p = 0.008).

Despite comparable liver function, American Joint Committee on Cancer stage, comorbidities, and other clinical characteristics before embolization in both groups, because his study was retrospective, Boas acknowledged that a confounding variable may account for the improved survival among patients taking aspirin.

Researchers at the Stanford University School of Medicine have discovered a new signal that cancers seem to use to evade detection and destruction by the immune system.

The scientists have shown that blocking this signal in mice implanted with human cancers allows immune cells to attack the cancers. Blocking other "don't eat me" signals has become the basis for other possible anti-cancer therapies.

Normally, immune cells called macrophages will detect cancer cells, then engulf and devour them. In recent years, researchers have discovered that proteins on the cell surface can tell macrophages not to eat and destroy them. This can be useful to help normal cells keep the immune system from attacking them, but cancer cells use these "don't eat me" signals to hide from the immune system.

The researchers had previously shown that the proteins PD-L1, CD47 and the beta-2-microglobulin subunit of the major histocompatibility class 1 complex are all used by cancer cells to protect themselves from immune cells. Antibodies that block CD47 are in clinical trials. Cancer treatments that target PD-L1 or the PDL1 receptor are being used in the clinic.

The Stanford researchers now report they have found that a protein called CD24 also acts as a "don't eat me" signal and is used by cancer cells to protect themselves. A paper describing the research will be published July 31 in Nature. Amira Barkal, an MD-PhD student, is the lead author. Irving Weissman, MD, professor of pathology and of developmental biology and director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research, is the senior author.

"Finding that not all patients responded to anti-CD47 antibodies helped fuel our research at Stanford to test whether non-responder cells and patients might have alternative 'don't eat me' signals," said Weissman, who holds the Virginia and D.K. Ludwig Professorship for Clinical Investigation in Cancer Research.

Looking for additional signals

The scientists began by looking for proteins that were produced more highly in cancers than in the tissues from which the cancers arose. "You know that if cancers are growing in the presence of macrophages, they must be making some signal that keeps those cells from attacking the cancer," Barkal said. "You want to find those signals so you can disrupt them and unleash the full potential of the immune system to fight the cancer."

The search showed that many cancers produce an abundance of CD24 compared with normal cells and surrounding tissues. In further studies, the scientists showed that the macrophage cells that infiltrate the tumor can sense the CD24 signal through a receptor called SIGLEC-10. They also showed that if they mixed cancer cells from patients with macrophages in a dish, and then blocked the interaction between CD24 and SIGLEC-10, the macrophages would start gorging on cancer cells like they were at an all-you-can-eat buffet. "When we imaged the macrophages after treating the cancers with CD24 blockade, we could see that some of them were just stuffed with cancer cells," Barkal said.

Lastly, they implanted human breast cancer cells in mice. When CD24 signaling was blocked, the mice's scavenger macrophages of the immune system attacked the cancer.

Of particular interest was the discovery that ovarian and triple-negative breast cancer, both of which are very hard to treat, were highly affected by blocking the CD24 signaling. "This may be a vulnerability for those very dangerous cancers," Barkal said.

Complementary to CD47?

The other interesting discovery was that CD24 signaling often seems to operate in a complementary way to CD47 signaling. Some cancers, like blood cancers, seem to be highly susceptible to CD47-signaling blockage, but not to CD24-signaling blockage, whereas in other cancers, like ovarian cancer, the opposite is true. This raises the hope that most cancers will be susceptible to attack by blocking one of these signals, and that cancers may be even more vulnerable when more than one "don't eat me" signal is blocked.

"There are probably many major and minor 'don't eat me' signals, and CD24 seems to be one of the major ones," Barkal said.

The researchers now hope that therapies to block CD24 signaling will follow in the footsteps of anti-CD47 therapies, being tested first for safety in preclinical trials, followed by safety and efficacy clinical trials in humans.

For Weissman, the discovery of a second major "don't eat me" signal validates a scientific approach that combines basic and clinical research. "CD47 and CD24 were both discovered by graduate students in MD-PhD programs at Stanford along with other fellows," Weissman said. "These started as fundamental basic discoveries, but the connection to cancers and their escape from scavenger macrophages led the team to pursue preclinical tests of their potential. This shows that combining investigation and medical training can accelerate potential lifesaving discoveries."

Scientists have created a microneedle patch based on the fangs of a snake that can deliver therapeutic liquids and a vaccine through the skin of rodents in under 15 seconds. Their device circumvents the pumping systems and extra drug preparation steps associated with previous microneedle patches, indicating it could serve as a flexible and easy-to-use drug delivery platform. Medicinal liquids and vaccines are usually delivered with hypodermic needles, but needles carry a risk of infection and are frequently painful. Devices that use patches of microneedles are an attractive alternative for simple and pain-free drug delivery, but existing approaches require taking additional steps to prepare medications and cannot yet effectively deliver liquid formulations of drugs. Here, Won-Gyu Bae and colleagues took inspiration from rear-fanged venomous snakes, which are equipped with a special grooved fang that can quickly inject venom into their prey. They created a patch of microneedles that contain up to six similar grooves and can deliver a variety of liquids by being applied to the skin with gentle pressure from the thumb. Importantly, their patch takes advantage of a form of liquid flow called capillary action, foregoing the need for a complicated pumping system. The team found their device could quickly deliver doses of lidocaine or an inactivated influenza virus through the skin of mice and guinea pigs, resulting in measurable immune responses that protected the animals from subsequent lethal doses of influenza virus. Bae et al. say further studies in large animal models and human volunteers testing a wider variety of liquids are needed before clinical trials can take place.

Roughly 8.5 million people in the United States suffer from peripheral artery disease (PAD), a narrowing of the arteries in the legs or arms (frequently due to the buildup of fatty plaque) that can cut off blood flow to the limbs, causing tissue death, gangrene, and even amputation. Strategies to combat PAD by delivering compounds that promote angiogenesis (the growth of new blood vessels) to bypass the blocked arteries have been investigated, but have largely failed to improve outcomes. More recently, there has been increasing interest in using the body's immune system to treat ischemia as some immune cells are known to secrete blood-vessel-promoting compounds. However, getting therapeutic immune cells to concentrate and secrete a sufficient amount of the desired compounds where new vessels are needed remains a challenge.

A new approach from researchers at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) takes advantage of the surprising combination of implantable biomaterial scaffolds and childhood vaccines to solve this problem. In models of mice with hindlimb ischemia (a severe form of PAD), their technique increased the concentration of T cells at the ischemic site and stimulated angiogenesis, blood flow, and muscle fiber regeneration for up to two weeks. The study is reported in Science Advances.

"One of the most exciting aspects of this work is that it provides a new method of enhancing blood vessel formation that does not rely on traditional biologics, such as cells, growth factors, and cytokines, that are typically used to promote vascularization," said first author Brian Kwee, Ph.D., a former graduate student at the Wyss Institute and SEAS who is now a postdoctoral research fellow at the FDA. "Also, it more broadly suggests that advances in bioengineered T-cell therapies, which have traditionally been used to treat cancers, may be utilized to promote wound healing and regeneration."

The biomaterial scaffold Kwee and the rest of the team used has been in development at the Wyss Institute for several years, and has been used to successfully modulate the immune system for a variety of purposes, including treating cancer and trapping T cells that have gone rogue and are attacking the body. For treating ischemia, they focused on a specific type of immune cell called T helper 2 (TH2) cells, which have been found to secrete molecules that promote blood vessel growth in addition to producing cytokines that initiate immune responses.

TH2 cells are also the crucial "memory" element of vaccinations against pathogens, as they recognize the microbe that is introduced by the vaccine and help the body mount an immune response against it in the future. For reasons that are not yet fully understood, delivering a small amount of aluminum in a vaccine greatly enhances TH2 cell formation, and nearly all Americans receive aluminum-containing childhood vaccines that protect them from a variety of diseases. The Wyss team had a hunch that vaccinated people could potentially mount a stronger TH2 cell response if the right triggering antigen was introduced; and, if that antigen was incorporated into a biomaterial scaffold located near a blocked artery, TH2 cells could be recruited to the scaffold and release their angiogenesis-promoting compounds where they are needed to help treat ischemia.

"This method essentially takes advantage of the fact that standard vaccines 'prime' the immune system to recognize specific antigens. By reintroducing an antigen via a scaffold in a very localized place, we're able to attract and retain enough TH2 cells that they can effectively treat ischemic tissue and promote the growth of new blood vessels," said senior author David Mooney, Ph.D., who is a Founding Core Faculty member at the Wyss Institute as well as the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Mooney's team injected mice with ovalbumin, the primary protein found in egg whites, to create a mild immune reaction, along with aluminum hydroxide to mimic a human childhood immunization vaccine. Two weeks later the mice got a "booster" of the same vaccine, and four weeks later were implanted with an ovalbumin-containing scaffold in their ischemic hindlimbs. These mice displayed higher numbers of ovalbumin-specific TH2 cells and eosinophils (angiogenesis-promoting cells that are activated by TH2 cells) in their ischemic muscles than mice that received the implant without the priming vaccine.

Vaccinated mice also displayed a lower level of tissue death, higher blood vessel density, greater blood perfusion, and more regenerating muscle fibers in their ischemic hindlimbs after two weeks than unvaccinated mice that received the implant. To confirm that the primed TH2 cells were indeed responsible for this improvement, the researchers introduced antibodies against the TH2 cells into vaccinated mice that received the implant, and observed that neutralizing TH2 cells reversed the benefits observed.

Further work will investigate how changes in the timing between vaccination and implantation affect the TH2 cell response, as humans are often vaccinated when they are very young but develop PAD and ischemia later in life.

"We are very excited about this proof-of-concept study because it demonstrates the novel idea that memory T cells can be used to promote the growth of blood vessels, and it supports the premise that biomaterials can manipulate T cells to enhance regeneration of damaged tissues," said Mooney.

"We are at the dawn of a new age of beginning to understand the extent to which the immune system impacts human health and disease. This work from our Immuno-Materials Platform here at the Wyss Institute provides yet another example of how a bioinspired materials approach to reengineer the immune system can potentially lead to disruptive medical breakthroughs," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.

WASHINGTON--Measuring waistline, blood pressure, cholesterol, blood fats, and blood sugar during doctor visits can detect heart disease and diabetes earlier, according to a Clinical Practice Guideline issued today by the Endocrine Society.

The guideline, titled "Primary Prevention of ASCVD and T2DM in Patients at Metabolic Risk: An Endocrine Society Clinical Practice Guideline," was published online and will appear in the September 2019 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.

The five risk factors for heart disease and diabetes are - large amount of abdominal body fat, low HDL ("good") cholesterol, high levels of fat in the blood known as triglycerides, high blood pressure, and high blood sugar. Patients with at least three of these factors are at metabolic risk (higher risk for heart disease and diabetes). The guideline recommends screening patients with three or more risk factors regularly and screening patients with one or two risk factors every three years. This is in addition to assessing risk factors for cardiovascular disease like "bad" cholesterol, smoking and family history.

The original Endocrine Society guideline on this topic was published in 2008. This revision takes a fresh look at metabolic risk and presents recommendations which reflect more recent trial data on blood pressure and lipids. The guideline prioritizes lifestyle and behavioral interventions and discusses new medical treatment options. The guideline focuses on adults aged 40 to 75 but can be used to guide patients outside of this age range as well.

"Doctors haven't been doing enough to measure waist circumference, but it's essential to identifying patients at metabolic risk earlier and preventing more cases of heart disease and diabetes," said James L. Rosenzweig, M.D., of Hebrew Rehabilitation Hospital in Boston, Mass. Rosenzweig chaired the writing committee that developed the guideline. "We emphasize the importance of lifestyle, dietary and behavioral changes as the first line treatment. However, treatment with medication is appropriate if goals are not met with lifestyle changes alone."

Recommendations from the guideline include:

Measuring waist circumference as a routine part of the clinical examination.

Checking blood pressure annually, and, if elevated, at each subsequent visit.

Prioritizing lifestyle modification as the first-line therapy.

Aiming to lose five percent or more of initial body weight over the first year for individuals at metabolic risk with excess weight.

Undergoing a 10-year global risk assessment for either coronary heart disease or atherosclerotic cardiovascular disease to guide the use of medical or pharmacological therapy.

Prescribing lifestyle modification before drug therapy in patients with prediabetes to reduce blood sugar levels.

OAK BROOK, Ill. - Artificial intelligence (AI) helps improve the efficiency and accuracy of an advanced imaging technology used to screen for breast cancer, according to a new study published in the journal Radiology: Artificial Intelligence.

Digital breast tomosynthesis (DBT) is an advanced method for cancer detection in which an X-ray arm sweeps over the breast, taking multiple images in a matter of seconds.

Research has shown that DBT improves cancer detection and reduces false-positive recalls compared to screening with digital mammography (DM) alone. However, the DBT exam can take almost twice as long to interpret as DM due to the time it takes for the radiologist to scroll through all the images. This increased time is likely to be more consequential as DBT increasingly becomes the standard-of-care for mammographic imaging.

For the study, researchers developed a deep learning system, a type of AI that can mine vast amounts of data to find subtle patterns beyond human recognition. They trained the AI system on large DBT data sets to identify suspicious findings in the DBT images.

After developing and training the system, the researchers tested its performance by having 24 radiologists, including 13 breast subspecialists, each read 260 DBT examinations with and without AI assistance. The examinations included 65 cancer cases.

Use of AI was associated with improved accuracy and shorter reading times. Sensitivity increased from 77 percent without AI to 85 percent with it. Specificity increased from 62.7 percent without AI to 69.6 percent with it. The recall rate for non-cancers, or the rate at which women were called back for follow-up examinations based on benign findings, decreased from 38 percent without AI to just 30.9 percent with it. On average, reading time decreased from just over 64 seconds without AI to only 30.4 seconds with it.

"Overall, readers were able to increase their sensitivity by 8 percent, lower their recall rate by 7 percent and cut their reading time in half when using AI concurrently while reading DBT cases compared to reading without using AI," said study lead author Emily F. Conant, M.D., professor and chief of breast imaging from the Department of Radiology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

Also showing improvement was the area under the receiver operating characteristic curve (AUC), a graphing variable that combines sensitivity and specificity into a single measure for a better representation of overall radiologist performance. Radiologist performance, measured by mean AUC, increased from 0.795 without AI to 0.852 with AI.

"We know that DBT imaging increases cancer detection and lowers recall rate when added to 2-D mammography and even further improvement in these key metrics is clinically very important," Dr. Conant said. "And, since adding DBT to the 2-D mammogram approximately doubles radiologist reading time, the concurrent use of AI with DBT increases cancer detection and may bring reading times back to about the time it takes to read DM-alone exams."

The researchers expect the deep learning approach to improve as it is exposed to larger and larger data sets, making its potential impact on patient care even more significant.

"The results of this study suggest that both improved efficiency and accuracy could be achieved in clinical practice using an effective AI system," Dr. Conant said.

A single test for women has been shown to aid in predicting which cases of precancerous cervical disease will become more serious, helping with decisions on whether or not surgery is needed, according to a study led by Queen Mary University of London.

For thousands of young women who receive a diagnosis of cervical dysplasia, the decision on how to proceed can be uncertain, confusing, and difficult. In the majority of cases, moderate cervical dysplasia (also called cervical intraepithelial neoplasia 2, CIN2) will resolve itself, but some of these women will go on to develop cervical cancer. Women with moderate dysplasia may face a choice between undergoing prompt treatment, or short-term surveillance.

In the UK most women with moderate dysplasia are advised to undergo surgery without delay, but this has a risk for the outcome of future pregnancies, including miscarriages and premature deliveries. Until now there has been no test to show whether or not their cervical disease will progress.

The study, published in the journal of Clinical Infectious Diseases, looked at different options for these young women and found a test that was able to identify which women with moderate dysplasia are actually at high risk of their disease going on to severe dysplasia (CIN3).

The clinical study involved 149 women in Finland aged around 26 with identified CIN2. It showed that the S5 DNA methylation test is the best predictor of whether moderate cervical disease will progress to CIN3. The single test performed much better than the methods currently used to monitor existing disease.

The study shows that most women with moderate dysplasia can be followed without treatment until their disease resolves. This finding has important global implications for the treatment of millions of young women with cervical disease.

The researchers hope that this discovery will lead to a major change in medical practice, with more active surveillance and fewer surgical interventions. This could also bring cost savings, both for the treatment itself, and the possible costs of caring for premature infants.

Author and Emeritus Professor Attila Lorincz from Queen Mary University of London explained: "It is scary for young women with a potentially serious dysplasia to be told that they may get cancer if they do not undergo surgery. Unfortunately, surgery can lead to a painful and distressing recovery period. In future pregnancies there are substantially higher rates of miscarriage, infection, or premature delivery for mothers as well as many risks for the foetus. Our study shows that most women with moderate dysplasia can be followed without treatment until their disease regresses. This gives the women a better chance for easy and safe pregnancies in the future."

The DNA methylation test is currently under development and more studies in different countries will need to take place as the test moves into routine use. If successful, the researchers say that the test is expected to be available next year in Asia. A CE-marked test, indicating conformity with health and safety standards for sale within Europe, could be available in the UK in the next 2 to 3 years at which point it will be eligible for consideration by the NHS.