Body

Philadelphia, September 25, 2018 - Patients with venous thromboembolism (VTE) carry a high risk of recurrence. Accordingly, a 16-year Danish prospective cohort study of nearly 74,000 patients with incident VTE concluded that the risk of recurrence is substantial. Furthermore, the scientists found that the recurrence risk is similar for patients with cancer and patients with unprovoked VTE, reports The American Journal of Medicine.

VTE, comprising deep vein thrombosis and pulmonary embolism, is the third most common cardiovascular disease after myocardial infarction and stroke. Historical trials have reported a cumulative recurrence risk of nearly 40 percent after 10 years with associated high mortality. Recurrent VTE is largely preventable if patients receive extended duration anticoagulation therapy, but the protective effect must be carefully weighed against the risk of anticoagulant-related bleeding.

"Optimal duration of anticoagulation is a pivotal and an ongoing scientific and clinical concern," explained lead investigator Ida Ehlers Albertsen, MD, of the Department of Cardiology, Aalborg University Hospital, and Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark. "The emergence of the non-vitamin K antagonist oral anticoagulants has changed the landscape for prevention of thrombosis, and contemporary risk stratification approaches may need to be adjusted according to these effective and safer agents."

The study investigated the risk of recurrence after incident VTE stratified according to provoked (i.e., following surgery or trauma), unprovoked (without well-known provoking risk factors), and cancer-related VTE in a group of close to 74,000 routine care Danish in- and outpatients. Researchers linked nationwide Danish health registries to identify all patients with incident VTE from January 2000 through December 2015. The study revealed a ten-year cumulative incidence of more than 15 percent for all groups, indicating a substantial risk of recurrence for all patients with VTE, even in a contemporary clinical setting.

At 10-year follow-up, patients with unprovoked VTE (without cancer or any provoking factor) and cancer patients had the highest risk of recurrence compared with patients with provoked VTE.

"Our concept of VTE is undergoing a major transition as we increasingly consider it as a chronic illness," commented co-investigator Professor Samuel Zachary Goldhaber, MD, of the Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. "Ideally, stratification based upon well-defined risk factors should consistently identify patients needing continued treatment and, conversely, patients who can be safely managed with shorter time-limited treatment."

"Given the high risk of recurrence among all the types of incident VTE, it is worth discussing if the current recommended treatment duration after VTE according to clinical guidelines is optimal," noted Dr. Albertsen. "To optimize duration of anticoagulation, we may need to rethink the arbitrary categorization of provoked/unprovoked when risk stratifying patients with incident VTE and aim for more nuanced risk stratification."

LOS ANGELES (Sept. 25, 2018) -- A newly developed drug can prevent the most common type of pancreatic cancer from growing and spreading in laboratory mice, according to a study led by Cedars-Sinai.

The study, published recently in the journal Gastroenterology, also demonstrated in mice that the drug, called Metavert, may prevent patients from developing a resistance to currently used pancreatic cancer chemotherapies.

"This is an exciting step toward improving survival rates in pancreatic cancer patients," said study lead author Mouad Edderkaoui, PhD, assistant professor of Medicine and Biomedical Sciences at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai. "If the results are confirmed in humans, we could have a drug with the potential to significantly extend the lives of patients with pancreatic ductal adenocarcinoma (PDAC), which is very difficult to treat."

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, according to the American Cancer Society. This year, about 55,000 people in the U.S. will be diagnosed with the disease and more than 44,000 will die, making it one of the deadliest cancers. The pancreatic cancer five-year survival rate is 7 percent.

Ninety-five percent of pancreatic cancer patients are diagnosed with PDAC, which develops from cells lining small tubes in the pancreas. PDAC can be difficult to treat because the cancer cells prompt normal cells that reside in the pancreas--called stellate cells--to produce pancreatic scar tissue. Scar tissue makes it difficult for chemotherapy agents and blood to enter the pancreas, said study senior author Stephen J. Pandol M.D., director of Basic and Translational Pancreas Research at Cedars-Sinai.

The cancer and stellate cell interaction also creates an environment that stimulates local tumor growth and cancer spread to distant sites in the body, said Pandol, a professor of Medicine at Cedars-Sinai. Additionally, the activity levels of certain enzymes rev up, fueling resistance to cancer treatments.

"I've seen patients who respond to therapy for a while, and then the disease takes off because the cancer becomes smart--it blocks chemotherapy from working," Pandol said. "Metavert targets that action."

Over a four-year period, the investigators designed and synthesized new chemicals that
inhibit cancer cell activity. They discovered that Metavert blocked drug resistance and also significantly boosted the positive effects of radiation and two chemotherapy agents commonly used in humans. In one of the mouse studies, Metavert increased the survival rate by about 50 percent.

The investigators currently are developing a version of the drug to test in humans, Pandol said.

Black women are more likely to be diagnosed at later stages of breast cancer partly due to barriers to timely screening mammography. Programs that use patient navigators--individuals who provide guidance to patients to help overcome various barriers to care--may reduce breast cancer disparities, but a study published early online in CANCER, a peer-reviewed journal of the American Cancer Society, indicates that such programs must consider how minority women's views on gender and race/ethnicity may affect how they seek help and support for their health needs.

Sage Kim, PhD, of the University of Illinois at Chicago's School of Public Health and UI Cancer Center, and her colleagues examined the rates at which women in a randomized clinical trial reported barriers to obtaining a screening mammogram. The trial, called the Patient Navigation in Medically Underserved Areas (PNMUA) study, randomly assigned patients to one of two groups; one group received a patient navigation support intervention and the other group served as a control.

Of the 3,754 women who received the patient navigation intervention, only a small proportion of women (14 percent) identified one or more barriers, which led to additional interactions with navigators who helped overcome barriers. Dr. Kim and her colleagues found that black women, women living in poverty, and women who reported high levels of distrust of the health care system were the least likely to report barriers, and therefore were less likely to receive additional support. Comparatively, women who reported barriers were more likely to have additional contact with navigators and obtain a subsequent screening mammogram.

The investigators noted that the ability to recognize barriers may determine women's likelihood of reporting barriers and consequently receiving additional support. For example, medical distrust due to past and current experiences of blacks, as well as social norms and images of women, may influence how black women deal with their own needs and interact with healthcare providers.

"Our findings suggest that black women and women living in poverty, who need patient navigation interventions the most, are in fact less likely to report their barriers to optimal care," said Dr. Kim. "Perhaps women who do not trust the health care system may not feel comfortable telling care providers about their barriers that could potentially affect the ways in which they engage in healthcare."

Dr. Kim noted that although patient navigation is known to be effective, it is important to understand how minority women and women living in difficult life circumstances interact with this intervention and improve services accordingly. She said, "If we don't, providers may have a false sense of security," she said. "They might incorrectly assume that women who do not report barriers are not in need of patient navigator support and are all doing well."

Dr. Kim stressed the need to enhance training of patient navigators and pay close attention to how patient navigator interventions are implemented, so that women are better able to seek out needed assistance. "It is not enough to implement a well-tested intervention, because it might not be equally effective for all groups across race/ethnicity and economic conditions," she said.

PITTSBURGH, September 24, 2018 - Organs affected by autoimmune disease could be fighting back by "exhausting" immune cells that cause damage using methods similar to those used by cancer cells to escape detection, according to a study by researchers at the University of Pittsburgh School of Medicine published today in the Journal of Clinical Investigation.

The conclusions, based on studies in mouse models of systemic lupus erythematous (SLE) - referred to as lupus - could explain why autoimmune diseases may take a long time to cause significant organ damage. They could also explain how widely used cancer immunotherapy drugs can have deleterious autoimmune side effects on normal organs.

"These findings really turn our current understanding of autoimmune tissue damage on its head and suggest that we could more effectively treat these diseases if we can develop targeted methods to enhance the body's natural ability to tune down the immune system," said senior author Mark Shlomchik, M.D., Ph.D., UPMC endowed professor and chair, Department of Immunology, Pitt School of Medicine, and an investigator at the UPMC Immune Transplant and Therapy Center.

In autoimmune diseases like lupus, immune cells that normally protect against invaders, such as bacteria or cancer cells, instead begin to recognize the body's own cells as foreign and attack them. In lupus nephritis, a kidney disease associated with SLE, a large number of these autoreactive cells - called kidney infiltrating T cells (KITs) - were thought to be activated, causing damage over time.

Wondering how exactly these cells cause kidney damage, Jeremy Tilstra, M.D., Ph.D., an assistant professor of medicine at Pitt and a researcher in Shlomchik's lab, began to study them in three different mouse models of lupus nephritis.

As the researchers expected, there were millions of KITs in the kidney, but surprisingly, they were not highly active as had previously been thought.

"The T cells were there, but they weren't aggressively active, in fact, it was the exact opposite," said Tilstra. "They were sluggish, ineffective killers and didn't divide very well, which was completely unexpected."

Experiments showed that these KITs did not respond to stimulation like normal T cells - they neither released characteristic inflammatory proteins, nor did they reproduce very well. The cells also took up and used much less energy, displaying signs of metabolic exhaustion.

Interestingly, the exhausted KITs were quite similar to T cells found inside tumors. The affected kidney cells also resembled tumor cells in certain ways, as they expressed higher levels of a protein called PD-L1, which cancer cells use to suppress T cells that enter the tumor.

"Our findings suggest that the body is capable of actively fighting back against autoimmune diseases, not sitting idly by. The similarity between T cells in lupus-affected kidneys and in tumors has important implications," noted Shlomchik. "It suggests that the ability to suppress T cells is not an abnormal mechanism that cancer cells have somehow developed to defeat the immune system, rather it's an existing natural mechanism against autoimmune disease that tumors have adopted to their advantage."

In the future, the researchers plan to expand the study to patients with lupus to see if they can find similar exhausted T cells in urine or tissue samples.

CHICAGO --- Being obese or overweight during pregnancy can result in serious health problems for the mother and child. Obstetricians are often reluctant to recommend restricted weight gain for pregnant women due to safety concerns for the baby and lack of time and tools to safely guide women in their weight control efforts.

A new Northwestern Medicine study shows with proper nutrition guidance it is safe and feasible to restrict weight gain in obese and overweight pregnant women. The obese and overweight women in the study gained five pounds less during their pregnancy than those in the control group. Their babies were born in the normal weight range.

The approach included nutritional counseling on a healthy diet and lifestyle as supported by a commercially available smartphone diet app, with ongoing coaching via the phone and online.

"We need to help these women, who make up the majority of pregnancies in the U.S, leverage this unique opportunity during their pregnancy to adopt a healthier diet and lifestyle plan that they can follow throughout pregnancy and, hopefully, post-partum," said lead study author Linda Van Horn, professor of preventive medicine at Northwestern University Feinberg School of Medicine. "These results show promise in harnessing modern technology to help a mom achieve those goals."

The majority of U.S. women of reproductive age are overweight or obese, and the risk of excess gestational weight gain is higher for them than women of healthy weight. Among the risks for women and their babies: diabetes, preeclampsia, hypertension and birth defects.

Van Horn, along with obstetrician colleague Dr. Alan Peaceman, developed and led the study, called MOMFIT (Maternal Offspring Metabolics: Family Intervention Trial). It was part of the Lifestyle Interventions for Expectant Moms (LIFE-Moms) Consortium, a National Institutes of Health (NIH)-supported research project, with each study implementing separate interventions.

The Northwestern study was novel because it concentrated on improving diet quality and healthy lifestyle in the moms using modern tools and focused on potential maternal fetal nutrition advantages that could have lifelong benefits, Van Horn said.

The study will be published Sept. 24 in the American Journal of Preventive Medicine.

This is believed to be the first study of obese and overweight pregnant women using a technologically advanced, commercially available weight-loss smartphone app to test the effects of a specially tailored diet combined with modest physical activity.

Existing commercial weight control technologies target non-pregnant women and don't address prenatal energy and nutrient needs, the authors said. Most commercial apps are designed to support weight loss. During pregnancy, weight gain is anticipated and appropriate, but it should be curtailed in overweight and obese women.

"MOMFIT demonstrates the feasibility of counseling pregnant women in healthy diet and lifestyle behaviors through nutrition coaching using modern technology," Van Horn said. "Applying this approach in a clinical setting could help women achieve recommended weight-gain goals during pregnancy and improve postpartum lifestyle behaviors for the whole family."

One unusual outcome of the trial was a higher rate of cesarean sections for the women in the intervention group. Researchers are investigating possible contributors to this finding.

Will MOMFIT kids have less risk of developing obesity?

"The next big question is whether the children born to moms who restricted their weight gain will have a reduced risk of becoming obese themselves compared to children whose moms were in the control group," Van Horn said.

Children born to overweight and obese moms have more than a 50 percent chance of becoming overweight themselves. If both parents are overweight or obese, this risk can increase to more than 70 percent, according to epidemiological data.

The difference in the children's obesity risk won't be evident until they are three, four and five years old, which is when weight trajectories start to separate. Van Horn and colleagues have recently launched a new study - KIDFIT - to monitor the children of the women in her MOMFIT study and determine whether prenatal and/or postpartum diet and lifestyle counseling can help these children lower their risk of obesity.

Rebooting the whole family's diet

The study's goal was not weight loss. "Weight loss during pregnancy is not encouraged. Rather, we aimed for controlled weight gain by developing healthy diet habits and increasing physical activity that could be sustained long term.

"The overarching goal of MOMFIT was to help the mom make these changes while she was still pregnant, a time when many women are more motivated to do what is right for their babies, and then maintain these new behaviors and become a role model for the family and better informed about how to feed them," Van Horn said.

"The perpetuation of obesity is a never-ending cycle. We're attempting to interrupt that cycle and successfully influence the risk for developing pediatric obesity starting in utero and -- with additional follow up -- protect that child from adopting that parental heritage in the family home."

Fewer participants in the intervention group, 68.6 percent versus 85 percent, exceeded the National Academy of Medicine recommendations for pregnancy weight gain for obese and overweight women, which is limited to 11 to 25 pounds compared to 25 to 35 pounds for women of healthy weight. This is important evidence demonstrating the challenges of encouraging pregnant women to adhere to recommended diet and activity levels at a time when emotional-eating and reluctance to exercise tend to increase.

How the study worked

MOMFIT studied 281 ethnically diverse overweight or obese women ages 18 to 45, who were divided into the intervention or control group. Women in the intervention group met with a nutritionist who calculated the appropriate amount of calories for each participant and counseled her on a DASH-type diet -- higher in fruits, vegetables, whole grains, nuts, fish and lean protein. It was modified to the restricted weight gain recommendations for each participant.

The DASH (Diet Approach to Stopping Hypertension) eating pattern is ideally suited to pregnancy, providing a pregnant woman with the calcium, potassium and protein she needs without the salt, sugar and saturated fat that she does not need, Van Horn said.

The women were also encouraged to walk at least 30 minutes or take 10,000 steps per day. The nutrition coach tracked each woman's weight gain, food intake and exercise. Telephone, text message prompts and e-mail reminders encouraged women to adhere to the program.

"It was technologically convenient yet strategic and nutritionally individualized," Van Horn said. "MOMFIT took a precision medicine approach to healthy eating utilizing a commercially available product."

Women tracked their food intake with the Lose It! app. Participants were also encouraged to sleep seven to nine hours daily, because sleep deprivation hampers metabolism and contributes to weight gain.

Arnhem (The Netherlands), 24 September 2018 - Public awareness of urological conditions is alarmingly low throughout Europe. Results of a new international survey1 of more than 2,500 responders from 5 countries show that women know more about men's health issues than men do, men have poor knowledge of key urological symptoms and don't take early signs of potentially life-threatening urological conditions seriously.

The low level of awareness indicated by the survey is of particular concern as urological conditions are on a rise due to the ageing European population. Prevention and early diagnosis are crucial to save lives and to control increasing costs.

Fundamental Lack of Knowledge of Urology

Responses showed that urology as a medical speciality still has a long way to go to reach general awareness: 40% of respondents were unable to identify what a urologist does, 10% stated that they had never even heard of a urologist and almost 15% believe that a urologist treats disorders of the skeletal, nervous or circulatory systems.

"The results of our latest survey clearly demonstrate that people are ill-informed when it comes to urological conditions. Men in particular have less knowledge than women and turn a blind eye to symptoms and early diagnosis" comments Prof. Hein Van Poppel, urologist and Adjunct Secretary General of the EAU. "Persuading men to take their health seriously presents a serious challenge. They need to have a better understanding of the risk and symptoms of their conditions. They should be encouraged to seek support from a medical professional if they suspect anything unusual."

The Prostate Remains a Mystery to Many Men

Every year, almost 450,000 men across the continent will be diagnosed with prostate cancer, leading to 92,000 deaths in Europe2. Despite prostate cancer being the most common cancer in males throughout Europe, three quarters of men admitted that they have limited knowledge of its symptoms. Men are, in fact, more confident in recognising the symptoms of breast cancer (31%) than they are of prostate cancer (27%).

In addition to the low awareness of prostate cancer symptoms, just 1 in 4 respondents could correctly identify the location of the prostate and surprisingly, a higher proportion of women (28%) were able to identify the location of the prostate than males (22%). Worryingly, 54% of men believe that women have prostates.

Erectile Dysfunction and Incontinence Still Taboos

Erectile dysfunction (ED) prevalence in Europe is estimated at 50%3 of the sexually active men of 50 years and older. However, the topic remains a taboo leading to misunderstanding and ignorance. 75% of the respondents were not aware of the numbers of men that suffer from erectile dysfunction in their country. Similarly, 85% were unaware of the amount of people in their country that suffer from urinary tract issues.

"Men's health issues involve partners too", says Prof. Van Poppel. "Women are more used to checking their bodies. They should encourage men to do the same and discuss their health more in detail. Women should actively participate in conversations with their male partners and doctors."

International Differences in Testicular Cancer Knowledge

Testicular cancer is the most common type of cancer to affect younger men. However, survey results stated that only 18% of male respondents knew that men aged 16 to 44 years have the highest risk. Whilst knowledge was found to be low throughout Europe, there were stark differences; only 10% of the respondents from Spain know the at-risk age group compared to 27% in the UK.

Symptom awareness was also low with 70% of men lacking confidence in recognising the symptoms of testicular cancer, which may include a swelling or lump in one of the testicles and a dull ache or sharp pain in the testicles or scrotum.

Significant Delays in Visiting the Doctor

Symptom awareness is recognised as a leading factor in the early diagnosis of urological conditions. The majority of deaths in male cancers occur because most men do not address their conditions in time. Despite this, they continue to ignore their symptoms and delay seeing their doctors.

The survey reveals that 43% of people would not go to their doctor straight away if they notice blood in their urine; 23% would wait longer than a month if they suffered a frequent urge to urinate; 28% would wait for more than a week if they suffered burning or pain during urination; and only 17% of people surveyed associate pain in their lower abdomen with a serious problem.

Professor of urology and Executive Member for Communications at the EAU, Manfred Wirth adds "Urological diseases are extremely common; they cause a lot of discomfort and at times, can be life-threatening. It's time for Europe to change its attitude towards urology and invest in educational campaigns to increase urological knowledge and to break taboos."

Long-held assumptions that stepfathers are far more likely to be responsible for child deaths than genetic parents have been challenged by researchers at the University of East Anglia (UEA).

Approximately 20 children in England and Wales are killed by their fathers each year - and stepfathers are recorded as the perpetrators in a quarter of these cases. So while very few stepparents pose a threat to their children, the numbers are still more than would be expected, given the relatively low proportions of children who have stepfathers.

However, findings from a new study led by psychologists at UEA suggest that differences in rates of child homicides by stepfathers and genetic fathers are considerably smaller than previous researchers have claimed, and that these differences are unlikely to be explained by a biological relationship. The results indicate that the relative ages of fathers implicated in these crimes is more significant than whether they are the biological father of the child.

The researchers, from UEA's School of Psychology and Norwich Medical School, and the Department of Sociology, University of Essex, reviewed data from the UK Home Office Homicide Index between 2000 and 2015 and compared it with detailed population data from three large surveys for the same period.

Their findings, published in the Journal of Experimental Psychology: General, cast doubt on the so-called 'Cinderella effect', a theory first proposed by psychologists in the 1970s, which suggests there is a direct link between step-relationships and child abuse or homicide. Those supporting the theory claim stepfathers have no genetic reason to invest parental resources in a child they are not biologically related to and so they are more likely to maltreat, abuse or even kill these children.

But previous studies into child homicide only considered figures from children aged between 0 and 5 years. The UEA and Essex team widened the age range to look at children between birth and 17 years and found only a small difference between stepfathers' and genetic fathers' rates of homicide.

Significantly, the team also looked at the ages of the fathers implicated in child homicides, an aspect also not considered in previous studies. They found that most men convicted of these crimes are relatively young, and this was true of both stepfathers and genetically related fathers.

"In general, the data indicates that younger fathers are more likely to abuse or kill their children than older fathers, regardless of whether they are stepfathers," said Dr Gavin Nobes, who led the study.

"Also, the population surveys show that stepfathers are, on average, much younger than genetic fathers. This means that the Cinderella effect can be at least partly explained by stepfathers' relative youth, rather than not being genetically related to their victims.

"There are many possible reasons for the link between parental age and child maltreatment - young parents are more likely to be on low incomes, perhaps less well-educated and possibly less equipped to cope with the stresses of parenthood."

Another reason the Cinderella effect continues to attract attention is that individuals responsible for violence against children are sometimes recorded as a 'stepfather' for convenience, even when they are not. Many may be short term or casual partners of the mother, with no significant relationship to the child, and not even living with them.

The researchers say a message for policy and practice is to identify and support families when both the father and child are young - particularly in the first year of their relationship - and when the father, or mother's partner, does not live with the child. "Child abuse researchers and social workers already understand that there are many complex causes of child abuse and these can be extremely difficult to predict," said Dr Nobes.

"Our research offers a fresh perspective on the available data which could help practitioners and policy makers decide where to channel resources when supporting families. In particular, rather than assuming that stepfathers are more dangerous than genetic fathers, other factors - such as both father and child being young, and their not living together - are actually better predictors of whether a child is at risk of being abused or killed."

SAN DIEGO--In the largest multi-institutional study to date, led by researchers from Penn Medicine, the team found that among patients who underwent a transcatheter aortic valve replacement (TAVR), a high number experienced severe and moderate cases of prosthesis-patient mismatch (PPM)--meaning the implanted heart valve is too small for the patient which can lead to inadequate blood flow. The team also found that the risk of death and of heart failure readmissions were 19 percent and 12 percent higher, respectively, after one year as compared to patients without severe PPM.

Results of the study were presented today as a late-breaking abstract at the Transcatheter Cardiovascular Therapeutics (TCT) 2018 meeting in San Diego and simultaneously published online in the Journal of the American College of Cardiology.

"This is an important contemporary snapshot of what's happening in the real world with commercial TAVR procedures," said the study's lead author Howard C. Herrmann, MD, FACC, MSCAI, the John W. Bryfogle Professor of Cardiovascular Medicine and Surgery at Penn's Perelman School of Medicine and director of Penn Medicine's Interventional Cardiology Program, who presented the results at TCT. "This is the first study that is large enough to demonstrate meaningful data associated with PPM for a relatively new procedure like TAVR. Based on these findings, PPM is an important problem in this population, one that deserves greater awareness among operators. And being aware of it is the first step in trying to prevent it."

TAVR was approved by the Food and Drug Administration in 2011 for the treatment of aortic stenosis, a narrowing of the heart's aortic valve, and has revolutionized valve replacement options for patients with this disease who are too sick or too high risk for surgical (open-heart) valve replacement (SAVR). This minimally invasive, catheter-based approach allows physicians to replace the aortic valve without need to remove the old, damaged one.

Of the 62,125 patients who received TAVRs in the United States between 2014 and 2017 and who were evaluated, researchers found 12 percent experienced severe PPM, while 25 percent had moderate PPM. Researchers collected and analyzed patient data from the U.S. STS/ACC Transcatheter Valve Therapy (TVT) Registry, which tracks all commercial procedures performed in the United States. To further study patient outcomes, the authors linked patients in the U.S. STS/ACC TVT registry to Centers for Medicare & Medicaid Services' administrative claims data for 37,470 of their patients. After 30 days, patients with severe PPM had higher rates of heart failure hospitalization, stroke, and death.

Historically, PPM has been associated with worse outcomes after SAVR, however, less has been known about the incidence, outcomes, and predictors of PPM in TAVR patients. Past studies have been small, with limited follow up, and some from single centers--combined, they only represent 4,000 patients--and measurement techniques for the valve opening have been inconsistent.

PPM is a mismatch of the blood flow dynamics of the prosthetic valve and the amount of blood the heart needs to pump to the rest of the patient's body. For example, having too small of a valve in a person with a large body surface area (height and weight) affects their ability to get enough blood flow when they exercise. In previous studies, severe PPM in both SAVR and TAVR patients have been associated with higher risk of death and hospital readmission, decreased exercise abilities, and a higher rate of valve deterioration over time.

The authors identified several predictors of PPM, including patients with a smaller valve prosthesis, those who had a larger body surface area, or patients who are female or younger.

"Severe PPM occurs frequently after TAVR procedures, and it results in worse outcomes, even after a short period of one year," Herrmann said. "Now that we're more aware of this, we need to look at strategies and compare devices and techniques in future studies to determine what will help us best limit this risk or avoid it in the future."

A multicenter clinical trial has found that a minimally invasive procedure called transcatheter mitral valve repair significantly reduced hospitalizations and mortality for heart failure patients with moderate-to-severe or severe functional mitral regurgitation.

Findings from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial were published today in the New England Journal of Medicine. Gregg W. Stone, M.D., co-principal investigator of the trial and director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian/Columbia University Irving Medical Center, will present the study this morning at the annual Transcatheter Cardiovascular Therapeutics in San Diego.

"Although some drugs can help alleviate symptoms of functional mitral regurgitation due to heart failure, those therapies are of limited benefit," said Dr. Stone, who is also a professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. "To be able to reduce hospitalizations and improve survival is a breakthrough for patients who previously had few treatment options."

Mitral regurgitation (MR) occurs when the valve that connects the left ventricle and left atrium in the heart doesn't close completely, allowing blood to flow backward into the heart and forcing the heart to work harder to pump blood. Primary MR occurs when the valve leaflets or surrounding tissue become damaged. Functional MR, also known as secondary MR, the focus of this study, occurs when the left ventricle enlarges after heart damage from any cause, such as a heart attack. Primary MR can be treated effectively with surgical valve replacement or repair. However, there is little evidence that surgical procedures improve outcomes for patients with secondary MR, who tend to have a worse prognosis and are thus typically managed medically with drugs such as beta blockers or with pacemakers to regulate heart rhythm. Nearly one in 10 adults age 75 or older in the U.S., or four million Americans, suffer from primary MR. The prevalence for secondary MR is uncertain as it is frequently undiagnosed, but is believed to be substantially higher than that of primary MR.

The trial enrolled 614 heart failure patients with moderate-to-severe or severe secondary MR at 78 sites in the U.S. and Canada who remained symptomatic despite treatment with recommended medical therapies.

Participants were randomized to treatment with MitraClip - a minimally invasive treatment that fastens the mitral valve leaflets together - and medical therapy or medical therapy alone. The researchers then compared the number of heart failure-related hospitalizations and deaths over 24 months in both groups.

Patients who had the minimally invasive procedure had 47 percent fewer heart failure-related hospitalizations and 38 percent fewer deaths than those who were managed medically.

"The improvement in symptoms and reduction in need for hospitalization due to heart failure was almost immediate after the MitraClip. In contrast, the improvement in survival emerged about a year after the procedure, a delayed response consistent with the long-term benefits of reducing volume overload on the heart," said Dr. Stone.

The procedure was also associated with significant improvements in quality of life and functional capacity. The treatment was determined to be safe, with low 30-day rates of death or stroke, and the reduction in MR was durable through the 2-year follow-up of the study.

"Patients with heart failure and severe secondary or functional MR who remain symptomatic despite all the best medical therapies now have substantially more hope because we can improve their quality of life and survival by reducing their MR with a safe, low-risk procedure," said Dr. Stone.

DETROIT - A research team led by Arun Iyer, Ph.D., assistant professor of pharmaceutical sciences in the Eugene Applebaum College of Pharmacy and Health Sciences at Wayne State University, has developed a nanoplatform technology that works in combination with existing chemotherapeutic drugs that may reverse drug-resistance in renal cell carcinoma.

Drug resistance to chemotherapy is a significant clinical and financial burden in renal cell carcinoma and other types of cancers. The resistance can be caused by hypoxia, a decreased level of oxygen in the tumor cells and infiltration of tumor-promoting immune cells aiding the tumor growth in contrast to fighting against it.

To alleviate the drug resistance, Iyer, principal investigator on the project, and co-investigator and lead author of the work, Samaresh Sau, Ph.D., research associate in the Department of Pharmaceutical Sciences in the Eugene Applebaum College of Pharmacy and Health Sciences, set out to find a way to use tumor hypoxia-directed nanoparticles to attack the root cause of the problem.

"Our tumor hypoxia directed nanoparticle used in conjunction with the FDA-approved renal cell carcinoma treatment, Sorafenib, has had positive outcomes in our animal trials," said Iyer. "The nanoparticles can deliver the payload selectively to tumor tissue and penetrate deep into the tumor core and provoke significant tumor inhibition with marked safety."

According to the duo, the results have shown that this targeted approach has great benefits.

"This hypoxia targeting nanoparticles is not only effective in inhibiting tumor-promoting immune cells but also enhancing function of tumor-killing immune cells," said Sau. "Another important aspect of the nanoparticle is that it can precisely diagnose renal tumors non-invasively that can be utilized for tumor detection, staging and surgery in the clinical setting."

Iyer and Sau stated that along with reversing drug-resistance and helping the immune system work properly, their technology will also save money by repurposing existing drugs to function better with reduced side effects of chemotherapy treatment because of its targeted approach. It also has potential to treat other cancers that have been difficult to treat or have become drug-resistant to current therapies.

"This new approach of using our nanoplatform will reopen doors that were once closed because drugs that had become ineffective to cancer treatment are now once again usable and effective," said Iyer. "It is our hope that this research will one day soon be used in clinics for treating patients."

(PHOENIX - Sept. 21, 2018) Combating glioblastoma remains a major challenge due the complex nature of these tumors, the inability of drugs to penetrate the brain tissue, and lack of correlation between animal models and the human condition.

In a novel first-in-human phase 0 clinical trial study led by Dr. Nader Sanai at Barrow Neurological Institute, in collaboration with Karmanos Cancer Institute and Translational Genomics Institute, a drug called AZD1775 was shown to penetrate the brain tumor providing first evidence of clinically-relevant activity of this drug in human glioblastoma.

This study was published in August 2018 issue of the Clinical Cancer Research journal. The study not only highlights differences between preclinical animal models and human studies but also confirms the utility of phase 0 trials as a part of an accelerated paradigm for evaluating drugs for glioblastoma patients.

Dr. Sanai is the director of the Ivy Brain Tumor Center, which was founded to provide new treatment avenues and hope for glioblastoma patients. The Ivy Brain Tumor Center, which is located at Barrow, is home to the largest phase 0 clinical trials program in the world for brain tumor patients. The phase 0 trial design keeps in mind the importance of time for brain tumor patient and spares them from investing precious time, effort and energy in therapies that do not work.

"Within days of surgery, we identify which investigational therapies have successfully penetrated the patient's tumor and whether these agents have also effectively modulated the tumor's biology. Once the experimental regimen proves its ability to reach its target and undermine the tumor's core programming, then the patient is 'graduated' to this chosen regimen at maximum therapeutic doses" says Dr. Sanai.

A series of internal GlaxoSmithKline reports suggest possibility that serious safety signal had emerged for Pandemrix during 2009 H1N1 vaccine campaigns

Data indicated large discrepancies in rate of adverse event reporting for Pandemrix as compared to other GSK pandemic influenza vaccines

Manufacturer and some public health bodies received reports but did not make them public

Why did questions around the vaccine's safety not emerge earlier?

Is the vaccine safety monitoring system fit for purpose?

An investigation published by The BMJ today raises fundamental questions about the transparency of information surrounding the safety of GlaxoSmithKline's Pandemrix vaccine used in 2009-2010.

Eight years after the 2009 H1N1 "swine flu" outbreak, new information is emerging of a striking difference in the number and frequency of adverse events reported for three GSK pandemic vaccines approved and used across the world.

Internal safety reports from 2009 - unearthed as part of a lawsuit - suggest that GSK and public health officials were aware of a variety of serious adverse events logged in relation to Pandemrix, explains The BMJ's Associate Editor Peter Doshi.

But it would seem neither GSK nor health authorities made the information public, either during the H1N1 outbreak nor in the eight years since.

Doshi learned of the reports from a colleague, Tom Jefferson, who was hired as an expert witness in a lawsuit alleging that Pandemrix caused the sleep disorder narcolepsy.

Jefferson used the information to calculate adverse event rates per vaccine, which showed large differences between Pandemrix and other GSK pandemic vaccines.

The BMJ conducted its own analysis and found that Pandemrix had, proportionally, five times more adverse events reported than Arepanrix and another H1N1 vaccine manufactured by GSK.

The data are insufficient to draw cause-and-effect conclusions, but for Gillian O'Connor, the solicitor involved in the narcolepsy lawsuit, the disparity was "of such striking difference that any person contemplating taking the Pandemrix vaccine would be likely, if in receipt of this information, not to choose to have the Pandemrix vaccination."

In many of the GSK reports, the company refers to having conducted "safety reviews." The BMJ asked GSK for a copy of those reviews, but GSK did not provide them.

Instead, the company said it "continuously evaluated all available safety data and shared the data with the European Medicines Association (EMA) and other regulatory authorities where the vaccine was licensed so that the authorities could conduct their own independent assessments."

The BMJ also asked GSK whether it ever notified healthcare providers about the discrepancies in rate of adverse events between its products, whether it considered pulling Pandemrix from the market, or considered recommending Arepanrix or another company's vaccine. But GSK declined to answer these and all of The BMJ's questions, citing ongoing litigation.

The UK Department of Health also declined to comment on why it recommended Pandemrix over another company's vaccine.

What the EMA knew - or could have known - about the comparative safety of GSK's pandemic vaccines is hard to discern, writes Doshi. The EMA told The BMJ that it "does not perform comparative benefit and risk evaluations between products approved in the EU, or between EU products and products approved or used outside the EU."

These events raise fundamental questions about the transparency of information, and question whether drug and vaccine safety monitoring (known as pharmacovigilance) is fit for purpose, writes Doshi.

For example, when do public health officials have a duty to warn the public over possible harms of vaccines detected through pharmacovigilance? How much detail should the public be provided with, who should provide it, and should the provision of such information be proactive or passive?

"If history were to repeat itself, does the public have a right to know?"

A new study in the Journal of the National Cancer Institute finds that black women are more likely to skip hormone therapy treatments, also known as endocrine therapy, for breast cancer.

Endocrine therapy is used to add, block, or remove naturally occurring chemicals like estrogen and progesterone that stimulate some types of breast cancer. Evidence suggests that taking endocrine therapy for up to 10 years reduces the risk of breast cancer recurrence. However, between 15% and 49% of women with the disease never initiate endocrine therapy, and more than half do not take endocrine therapy drugs as recommended.

Nationally, breast cancer mortality is 41.5% higher among black women compared to white women, despite a historically lower incidence rate. Failure to receive appropriate treatment is an important cause of observed racial disparities in breast cancer mortality. Different use of endocrine therapy by race may contribute to breast cancer outcome disparities, but racial differences in treatment are poorly understood.

In this paper, researchers using data from the Carolina Breast Cancer Study investigated 1,280 women who reported being prescribed endocrine therapy; of these, 43% self-identified as black. For black women, overall, 24% reported underuse of endocrine therapy drugs, compared to 16% of white women. Compared to white women, black women more often reported not taking their pills every day as prescribed (14% versus 5%), whereas about 10% of both white and black women reported discontinuing their medication before the recommended time-period. Younger women were more often underusing endocrine therapy drugs, as were those women insured by Medicaid and those making less than $50,000/year.

A statistically significantly higher proportion of black women also reported: forgetting to take their drugs when traveling away from home (26% for black women versus 19% for white women); that sticking to their treatment plan was hard or very hard (27% versus 14%); trouble remembering to take their pills (27% versus 13%); missing pills due to cost (17% versus 7%); and severe side effects that led to skipping their endocrine therapy pills (25% versus 16%).

"This study provides evidence in a large, racially-diverse cohort study that black women with hormone receptor positive breast cancer experience unique barriers to endocrine therapy adherence which may lead to differential cancer outcomes by race, though we also found burdensome adherence barriers among white women," said lead author Stephanie B Wheeler. "These data are important because they shed light on the modifiable mechanisms through which multifaceted and culturally competent behavioral interventions can help women with breast cancer achieve the best outcomes."

**Country-level data available**

Cancers, cardiovascular diseases, chronic respiratory diseases, and diabetes were responsible for 12.5 million deaths among people aged 30-70 years worldwide in 2016.

Warning as more than half of all countries are not on track to achieve a UN target to reduce by a third the rate of premature deaths from non-communicable diseases (NCDs) by 2030.

One in 10 countries have seen death rates stagnate or worsen - for instance in the USA, NCD rates for women have stagnated, with almost one in eight 30 year old women dying from one of the four NCDS before their 70th birthday, compared with 1 in 20 women in the best performing country (South Korea).

Taking a wider view of chronic diseases in people aged 0-80 years offers a less promising picture, with only 17 countries (9%) for women and five countries (3%) for men on track to meet a third reduction on mortality rates by 2030.

More than half of all countries are predicted to fail to reach the UN target to reduce premature deaths from cancers, cardiovascular disease, chronic respiratory disease, and diabetes by 2030, according to a new analysis published in The Lancet ahead of the third UN High-Level Meeting on NCDs commencing on 27 September 2018.

However, the problem is potentially even more far-reaching and progress is even slower when all non-communicable diseases (NCDs) - including liver and kidney disease [1] - and all ages under 80 years are taken into account.

The authors say that countries must implement policies that reduce premature deaths sooner if they are to meet sustainable development goal (SDG) target 3.4 - to reduce the number of deaths caused by the four major NCDs in people aged between 30 and 70 years by a third by 2030.

"Despite clear commitments, international aid agencies and national governments are doing too little to reduce deaths from cancers, heart and lung diseases and diabetes. Progress is even slower for other diseases that are not a part of SDG target, meaning that the true health of people in most countries is even more dire," says senior author Professor Majid Ezzati, Imperial College London, UK [2].

The report is the first from NCD Countdown 2030 - an independent annual monitor of progress on reducing the worldwide burden of NCDs - a collaboration led by The Lancet, World Health Organisation, Imperial College London and NCD Alliance. It compares the change in death rates for 186 countries from 2010 to 2016 to understand how likely it is for countries to achieve the SDG target for NCDs. In addition, the study includes a more comprehensive measure of all NCDs [1] in people aged between birth and 80 years.

The scale of the NCD problem

In 2016, the likelihood of dying from one of the four major NCDs between the ages of 30 and 70 years was lowest for women in South Korea (less than 5%), and highest for women in Sierra Leone (about 33%) - an almost seven-fold larger risk. For men, the risk was lowest in Iceland (10%) and highest in Mongolia (39%) (full country by country data available in spreadsheet at the end of the press release).

In the UK in 2016, 30-year old women had a 9% chance of dying from one of the four major NCDs before their 70th birthday, and 30-year old men a 13% chance. In the USA, the risks were 12% for 30-year old women and 18% for men, while they were 14% and 20% (respectively) in China, and 20% and 27% in India.

While there were 12.5 million premature deaths from the four major NCDs in people aged 30-70 years in 2016, there were 27.3 million deaths from all NCDs in all people aged less than 80.

The authors also note that the NCD problem in low- and middle-income countries (particularly in sub-Saharan Africa and some countries in the Middle East and north Africa) is much wider than the four major NCDs. As the NCD burden is also biggest in these countries, the SDG target could result in some countries being left behind.

Progress against NCDs

The study found that although NCD mortality is decreasing in most countries, the pace of decline varies substantially, even among countries in the same region.

Of the 186 countries assessed, the majority of countries (86 countries [46%] for women and 97 countries [52%] for men) will not reach the SDG 3.4 target even by 2040 and require policies that substantially improve premature death rates. This includes China and India, the two most populous countries in the world, where premature mortality from the four major NCDs has declined but not sufficiently quickly to meet SDG target 3.4.

In addition, the reduction in NCD deaths has stagnated or increased since 2010 among women in 15 countries (8%) and men in 24 countries (13%) - including the USA for women [3].

The reasons for a lack of progress in most of these countries are not known, but the authors believe that this might be caused by a worsening or lack of improvement in major NCD risk factors (such as blood pressure, diabetes, obesity, alcohol use, and tobacco use), or that these countries' health care systems are not able to adequately prevent, treat, and manage NCDs.

The authors believe that the USA's stagnation is due to failures to reduce premature deaths from NCDs other than in cancer, which has continued to decrease, while the decline from other NCDs has slowed down or reversed. The authors say that this is thought to be particularly common in poorer rural communities.

The study found that 35 countries (19% of all countries) for women and 30 countries (16%) for men are likely to achieve SDG target 3.4 - these countries range from high-income countries seeing continued reduction (such as Norway, Denmark, South Korea and New Zealand), to middle-income countries starting with high rates and seeing fast declines in NCD mortality (such as Brazil, Iran, Russia and other countries in central and eastern Europe) [4]. In addition, if another 50 countries (27%) for women and 35 countries for men (19%) slightly accelerated the rate of decline of NCD deaths they could achieve the target [5].

When progress was measured on the basis of all NCDs and all ages under 80 years, it was even slower - only 17 countries (9%) for women and five countries (3%) for men would be on track to reduce the probability of premature death by a third [6].

In low- and middle-income countries, reductions in NCD deaths were mainly driven by reductions in cardiovascular diseases. For NCD mortality to decline faster in these countries, the decrease in cardiovascular disease mortality must accelerate, as well as approaches to reduce deaths from cancers, chronic respiratory diseases, diabetes, and other NCDs.

In high-income countries, reductions in NCD deaths are now driven by declines in deaths from cancer, cardiovascular diseases, and diabetes.

Priority policy measures

To accelerate reductions in premature deaths from NCDs, the authors call for policies and interventions that reduce tobacco and alcohol use, including fiscal and regulatory measures, such as taxation, warning labels, restriction of availability and sales, and banning of marketing, advertising, and public smoking.

They also call for early diagnosis and treatment of NCDs, including timely diagnosis and treatment of hypertension, diabetes, treatable cancers, and other acute and chronic NCDs.

"Going forward, the NCD Countdown 2030 is a shot in the arm for the global response to the NCD epidemic which has long needed a stronger accountability process," said Katie Dain, CEO of the NCD Alliance, UK. "The Countdown's inaugural analysis couldn't be more timely with the upcoming UN High-Level Meeting on NCDs on the horizon. The aspirations and promises of commitments from political leaders made at the meeting are now on notice. Even those governments who appear to be on track cannot be complacent - they must remain vigilant and respond with effective policies to emerging threats to health of the next generation, including child obesity, air pollution and the ever evolving tactics of the tobacco and alcohol industries." [2]

The authors note some limitations, including that only around one in four countries (27%, 50 countries) within the study have high quality data on deaths. Expanding and strengthening death registration, including medical certification of cause of death, is a priority area for strengthening accountability towards NCDs.

Writing in an editorial for The Lancet, Editor-in-chief, Dr Richard Horton, says: "Calls for strengthened NCD accountability have been made for at least a decade. Many obstructions have blocked progress. Today is therefore an important inflexion point in the history of attempts to prevent, treat, and control NCDs. The promises made by the international community must be delivered."

SAN FRANCISCO, CA--September 18, 2018-- About one person out of 500 has a heart condition known as hypertrophic cardiomyopathy (HCM). This condition causes thickening of the heart muscle and results in defects in the heart's electrical system. Under conditions of environmental stress such as exercise, HCM can result in sudden death. In other cases, patients may go undiagnosed, with their heart function declining gradually over decades.

3-D Construction Builds a Better Model of the Heart

Although the genetic defects that lead to HCM are known, it has been difficult to understand how those mutations result in disease, in part because cells in a two-dimensional culture dish do not interact the same way cells in a three-dimensional organ do. Now, using the most advanced techniques in gene editing, stem cell generation, and three-dimensional cell culture, researchers from UC Berkeley and the Gladstone Institutes in San Francisco have for the first time developed a "microtissue" model of the heart in which they can study how common environmental stress affects normal and abnormal heart tissue.

The study, published in Nature Biomedical Engineering, was a collaboration between the labs of Kevin Healy, PhD, the Jan Fandrianto and Selfia Halim Distinguished Professor of Engineering in the Departments of Bioengineering and Materials Science & Engineering at UC Berkeley, and Bruce Conklin, MD, a senior investigator at the Gladstone Institutes and professor of medicine at UC San Francisco.

With these new microtissue models, the researchers compared heart tissue grown from normal heart muscle cells to heart tissue in which all the cells had a mutation in the gene encoding myosin binding protein C (MYBPC3), the gene that is most often altered in HCM patients.

For the study, the scientists used laser-guided three-dimensional printing to make a microscopic scaffold on which to grow heart cells. By varying the thickness of the scaffold, the scientists could mimic the stresses that heart cells experience under different conditions. The myocytes were able to contract together to move the scaffolding, similar to the movement of an accordion's bellows under pressure.

When the scientists used normal cells to build microtissues, they found that they were able to adapt well to stress, comparable to the way a normal heart would pump harder to meet an increased oxygen demand during exercise. However, when the microtissues were built from mutant cells, they contracted abnormally and arrhythmically under conditions of elevated mechanical stress, similar to the way HCM patients may experience arrhythmias when heart pressure is elevated due to the demands of exercise.

"With these microtissues we were able to observe how the human heart can develop this syndrome," explained Zhen Ma, one of the lead authors of the study who was a postdoctoral fellow with Healy's laboratory group, and who now is an assistant professor of biomedical and chemical engineering at Syracuse University. "Even though this is a microscopically tiny part of the heart, we could measure its contraction, the mechanical forces generated, and the calcium flow associated with the electrical signaling that triggers contraction of heart muscle."

A Discovery with Broad Applications to Improve Human Health

"This advance gives us an opportunity to study cardiac disease in a much more precise manner," said Healy. "We think it paves the way for new therapies because these precise tissue models will give us a way to better target new therapies to optimize responses in sub-populations of patients."

Conklin, a world leader in using stem cell technologies and gene editing to create cells and living tissues that mimic human heart disease, is also excited about how microtissues might be used to address other scientific problems. "Some of the worst drug safety issues are due to problems with side effects on the heart, so we need better ways to test drugs for potential cardiac effects," Conklin said. "It's possible that in the future microtissues might become the preferred choice for their capability to capture a fuller range of cardiac physiology."