Body

A new study by Althea Campuzano, Ph.D. a student at The University of Texas at San Antonio, and Floyd Wormley, Jr., Professor of Biology and Senior Associate Dean for Research and Graduate Studies, sheds light on little-known fungal infections caused by the fungus Cryptococcus. There are currently no vaccines available for any fungal infection, which can be extremely deadly to patients under treatment for diseases like HIV, AIDS and cancer. Campuzano and Wormley suggest that more research is needed to develop an effective solution to these infections.

"Cryptococcus is a type of fungus that all humans are frequently exposed to without much effect," Campuzano said. "People with healthy immune systems might be infected but may feel no symptoms. It is often cleared or kept in check without people even knowing they've encountered it."

However, a person whose immune system is weakened by illness could face serious complications from being infected by Cryptococcus because the immune system is less able to respond appropriately to the infection when it's weakened. As a result, the body's innate cells, which normally destroy pathogens, allow the fungal infection to spread to the brain, which can lead to meningitis.

"Most people who are infected with fungal meningitis find they have a stiff neck or a headache. The danger is that if it's left untreated, they could be dead within weeks," Wormley said.

People undergoing treatments that could weaken their immune systems are most susceptible to fungal infections. Patients about to undergo organ transplants, for example, take medication to suppress their immune systems to keep their bodies from rejecting the new organ. AIDS, HIV and cancer patients also experience weakened immunity as a result of the illness or their treatments.

"People who have HIV or AIDS often have to be on anti-fungal treatments for the rest of their lives," Wormley said. "That long treatment can lead to the development of fungi that are resistant to the anti-fungal therapy. Also, it's a very trying thing to treat for a long period of time."

In their study, Wormley and Campuzano highlight all current knowledge of the receptors on innate cells, which are responsible for recognizing fungal pathogens and present an argument for more research in the effort of a vaccine or immunotherapy treatment for Cryptococcus.

"One of the biggest challenges we're facing is that no vaccine currently exists for any fungal infection," Campuzano said. "It's not for lack of trying, but part of the problem is that the immune system has such a hard time distinguishing between a human cell and a fungal cell."

Campuzano is working toward that goal by taking a closer look at CARD9, a protein that regulates receptors on innate cells. She and Wormley are interested in how CARD9 regulates the ability of the body to recognize fungi and whether they could manipulate it to trigger an immune response.

"We need more research involved with fungal pathogens in general," she said. "We're advocating for it so that we can work on a vaccine. A lot of people know about the dangers in bacteria and viruses, but this just isn't on their radar at all. We're going to change that."

(PHILADELPHIA) -- The most common type of lung cancer, non-small cell lung cancer (NSCLC), continues to be difficult to treat, with five year survival rates of about 36 percent for stage 3A tumors. Jefferson College of Pharmacy researchers are developing a new treatment approach based on nanotechnology that was recently shown to be effective in mouse models of the disease. The research was published in the journal Molecular Pharmaceutics.

The nanoparticles were designed to deliver a molecule that's been shown to stall tumor growth and may make tumors more susceptible to chemotherapy. The molecule, called microRNA 29b, would be ineffective if delivered by injection alone, as it quickly becomes degraded in the bloodstream or picked up and removed by immune cells.

To bypass these limitations, Sunday Shoyele, PhD, Associate Professor in the Department of Pharmaceutical Sciences at Jefferson (Philadelphia University + Thomas Jefferson University) and colleagues, developed a nanoparticle comprised of four parts. First, Dr. Shoyele included part of a human antibody, immunoglobulin G (IgG), to cloak the particle from the immune system. Second, the research team added the MUC1 antigen, which acts like a navigation system guiding the nanoparticles to the MUC1-covered lung tumors. Finally, the therapeutic payload, microRNA-29b, along with the other two components are glued together using a sticky polymer called poloxamer-188.

Dr. Shoyele and colleagues showed that these components formed a spherical nanoparticle capable of properly finding the lung tumors and shrinking the tumors in mouse models of the disease. "This work extends our previous work demonstrating that these particles were effective in shrinking tumor tissue in a petri dish. Here we show that they are also effective in a more complex living system," said Dr. Shoyele.

Additional tests are needed before the technology is ready for testing in human clinical trials. Dr. Shoyele plans to continue the research with comprehensive toxicity tests and scaling the nanoparticle manufacturing process for clinical trials.

Taking part in a hot chilli pepper eating contest might have some unexpected consequences, highlight doctors in the journal BMJ Case Reports.

Their warning comes after a young man ended up in emergency care with excruciatingly painful episodic headaches after eating a 'Carolina Reaper,' the world's hottest chilli pepper.

His symptoms started immediately after he had eaten the chilli, with dry heaves. But he then developed severe neck pain and crushingly painful headaches, each of which lasted just a few seconds, over the next several days.

His pain was so severe that he sought emergency care, and was tested for various neurological conditions, the results of which all came back negative.

But a CT (computed tomography) scan showed that several arteries in his brain had constricted, prompting doctors to diagnose him with thunderclap headache secondary to reversible cerebral vasoconstriction syndrome (RCVS).

RCVS is characterised by temporary artery narrowing often accompanied by thunderclap headache. It doesn't always have an obvious cause, but can occur as a reaction to certain prescription meds, or after taking illegal drugs.

This is the first case to be associated with eating chilli peppers, explain the authors, although

they point out that eating cayenne pepper has been linked to sudden constriction of the coronary artery and heart attacks.

"Given the development of symptoms immediately after exposure to a known vasoactive substance, it is plausible that our patient had RCVS secondary to the Carolina Reaper, write the authors.

The man's symptoms cleared up by themselves. And a CT scan 5 weeks later showed that his affected arteries had returned to their normal width.

PHILADELPHIA -- A promising class of drugs known as CD40 monoclonal antibodies could be the spark needed to light the fire in the immune system of patients who don't respond to the newer cancer immunotherapies.

Robert H. Vonderheide, MD, DPhil, director of the Abramson Cancer Center at the University of Pennsylvania and an internationally renowned cancer immunotherapy expert, makes the case for the drugs in a new perspective piece published this week in Cancer Cell, as part of a series in the issue focusing on the next phase of the evolving field of cancer immunotherapy.

"The 'immuno revolution' is upon us: We're battling cancers like never before by tapping into the power of the immune system with checkpoint inhibitors and personalized cellular therapies that have elicited stellar responses in patients," Vonderheide said. "But there is a bittersweet quality to these successes: many patients do not respond or quickly relapse after an initial response."

The PD-1 antibody pembrolizumab, for example, is approved for use as a first-line therapy for patients with metastatic non-small cell lung cancer that overexpresses PD-L1, which cancer cells use to hide from the immune system, yet nearly 30 percent of patients don't respond to the therapy and another 25 percent have tumor progression at one year.

"To overcome the resistance in these patients, we need to go back to the beginning and prime the T cells before we jumpstart their immune system with other therapies to attack the cancer," Vonderheide said.

The CD40 antibodies activate antigen-presenting cells, such as dendritic or B cells, to prime tumor-specific T cell responses, effectively "pushing the gas" on the immune system to make it work harder. This "lead-in" therapy, which is being investigated in clinical trials around the world, including at Penn Medicine, has been shown to turn so-called "cold" tumors hiding from the body's defenses into "hot" ones by "priming" the T cells before other treatments.

Think of the body's immune response like an assembly line, with points A, B, C, D, and E, that kill the tumor at the end, Vonderheide said. For example, a T cell starts, it expands, it gets exhausted, and stops because of the PD-1 pathways. Checkpoint inhibitors take that brake off toward the end, so the T cells can then attack the tumor.

"We've been drugging the very last step," said Vonderheide, who serves as a principal investigator on several CD40 combination trials at Penn, including a national trial through the Parker Institute of Cancer Immunotherapy. "In many patients, however, that won't work because points A through E hasn't happened. You can give them a checkpoint inhibitor, but there are no T cells to take the brakes off."

"With the CD40 drugs, we're back at point A to prime the T cells in the body to continue on in the immune response," he added. "Once you get A going, you can potentially treat more patients."

CD40 agonists have moved successfully from preclinical studies, many of which have been conducted by Penn researchers, where they have demonstrated anti-tumor activity, especially in combination with checkpoint inhibitors and chemotherapy, into human trials in recent years.

There are currently four clinical trials being conducted at Penn, including:

A Phase I study, led by Vonderheide, to learn if adding the investigational anti-CD40 drug RO7009789 to nab-paclitaxel and gemcitabine both before surgery and after surgery is safe, feasible, and beneficial to patients with pancreatic cancer.

A Phase 1b/2 study to evaluate the efficacy of the combinations of APX005M, Nivolumab, Gemcitabine, and nab-Paclitaxel or APX005M, Gemcitabine, nab-Paclitaxel in treating patients with metastatic pancreatic adenocarcinoma. The principal investigator is Mark O'Hara, MD, an assistant professor of Hematology Oncology.

Using the immuno-activating monoclonal antibody called APX005M, administered in combination with nivolumab to adults with metastatic melanoma. The Phase 1/2 trial is led by Gerald P. Linette, MD, PhD, the chief medical officer for Cancer Immunotherapy and clinical director of the Sean Parker Institute.

A study of the anti-CD40 drug APX005M in adults with solid tumors. The principal investigator is Dr. Ronac Mamtani, MD, MSCE, an assistant professor of Hematology Oncology.

Additionally, Abramson Cancer Center researchers are planning trials using this approach in patients with advanced and metastatic solid tumors.

In a recently published study in the Annals of Family Medicine, Aimee English, MD, et al, describe a cluster-randomized trial evaluating the differential impact on cardiovascular disease care of engaging patients and communities in practice transformation in addition to standard practice facilitation support. The article, entitled “A Community Engagement Method to Design Patient Engagement Materials for Cardiovascular Health,” details the development of locally tailored cardiovascular disease patient engagement materials through Boot Camp Translation, a community engagement process that occurred before practice recruitment but after cluster randomization.

Cluster-randomized trials with community-based interventions present study design and implementation challenges. The BCTs elicited unique contextual messages and materials, suggesting that interventions designed to help primary care practices decrease CVD risk may not be one-size-fits-all.

Chronic obstructive pulmonary disease (COPD) is widespread in China with 8.6 percent of the country's adult population - almost 100 million people -suffering from the chronic lung disease, according to a new Tulane University study published in The Lancet.

The study, which provided lung-function screenings for more than 50,990 participants, is the largest survey of COPD across age groups ever conducted in China, researchers say.

COPD, an inflammatory lung disease that causes obstructed airflow into the lungs, is the third leading cause of death in China. It is caused by long-term exposure to irritants in the air, including cigarette smoke. During the past decade, ambient air pollution has become a major public-health crisis in the country while cigarette smoking remains high, especially among men, says senior author Dr. Jiang He, Joseph S. Copes Chair of Epidemiology at Tulane University School of Public Health & Tropical Medicine.

"Our research shows that COPD is highly prevalent in the Chinese adult population. The biggest preventable risk factors for the disease are cigarette smoking and air pollution," He says. "Prevention programs and increased efforts to catch COPD early should be public-health priorities in China to reduce COPD-related diseases and deaths."

The study found that men had a higher prevalence (11.9 percent) of COPD than women (5.4 percent). The sex difference was noted among all age groups in the general population and even among those who never smoked.

Based on the lung-function screenings, researchers estimated the total number of individuals aged 20 years or older with COPD in China was 99.9 million in 2015. Of these, 68.4 million were men and 31.5 million were women.

Researchers found that most people with COPD were unaware of their condition, and few had received a pulmonary function test prior to the study. Only 2.6 percent of participants were aware of their condition, and only 12 percent of those found to have COPD reported getting a previous pulmonary function test.

Researchers found COPD prevalence increased with age. It was 2.1 percent for individuals aged 20-39 years old compared to 13.7 percent for those aged 40 years or older. The disease was more common for rural residents (9.6 percent) than for those in urban areas (7.4 percent). The same trend was noted among non-smokers.

Researchers suspect that those who didn't smoke developed COPD due to other risk factors or environmental exposures such as air pollution, chronic cough during childhood, parental history of respiratory diseases, low bodyweight and low education.

The study calls for new national public health strategies to prevent COPD that include smoking cessation programs, stricter control of ambient air pollution and biomass use, and COPD screenings for high-risk individuals using pulmonary function tests.

Practice facilitation is a promising approach to helping medical practices implement quality improvements. In a recently published study in the Annals of Family Medicine, Megan McHugh, et al, aimed to describe practice facilitators’ and practice leaders’ perspectives on implementation of a practice facilitator-supported quality improvement program and describe where their perspectives aligned and diverged. The article, entitled “Practice Facilitators’ and Leaders’ Perspectives on a Facilitated Quality Improvement Program,” describes the dual perspectives of practice leaders and practice facilitators and provides a more holistic picture of enablers and barriers to program implementation.

Observations suggest there may be greater opportunities to assist small practices through simple, targeted practice facilitator-supported efforts rather than larger, comprehensive quality improvement projects.

The U.S. population is largely unaware that there are shortages in the availability of cancer drugs, according to a study published early online in CANCER, a peer-reviewed journal of the American Cancer Society. Most people surveyed in the study said if they were patients, they would want to know about a substitute therapy that would be given due to a shortage, and most would transfer care to avoid a substitution with major differences from the preferred therapy.

Drug shortages can impair patient care, raise healthcare costs, and hamper clinical trials. Regarding cancer drug shortages, studies have investigated the experiences and opinions of oncologists or examined the economic impact of shortages, but there are sparse data regarding how patients might approach any drug shortages.

To investigate, a team led by Gregory Abel, MD, MPH, and Zachary Frosch, MD, of Dana-Farber Cancer Institute and Brigham and Women's Hospital, in Boston, administered a 13-item survey to 420 respondents randomly selected from an online sample demographically representative of the adult United States population with respect to gender, age, race-ethnicity, education, geography, and income.

Overall, 16 percent of respondents reported being aware of drug shortages, and respondents with a personal history of cancer were more likely to be aware (31 percent versus 14 percent). Most survey respondents reported that if they were patients, they would want to be informed about a substitution due to a shortage: 87 percent and 82 percent for major or minor differences in efficacy, and 87 percent and 83 percent for major or minor differences in side effects. Most also reported that they would transfer care to avoid a substitution with major differences from the preferred therapy: 72 percent for major differences in efficacy, and 61 percent for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy.

"It can be stressful for patients with cancer to learn that their care may be impacted by drug shortages, but it's important for oncologists to engage patients in these discussions," said Dr. Frosch. "Our data suggest that people expect disclosure of shortages as part of the caregiving process."

Dr. Frosch noted that awareness of shortages--by patients and the public at large--may result in increased pressure to address the system-wide shortcomings that lead to shortages. "It's important that everyone--clinicians, patients, and the public--have a seat at the table as these strategies are developed."

A legacy of social and political factors rather than bad parenting may be influencing people's decisions not to vaccinate their children, according to a study from the University of Waterloo.

The study, which appears in the Canadian Medical Association Journal, shows that a history of drug scandals, medical training practices, and a lack of political priority placed on disease prevention that started in the 1960s could be responsible for the immunization apathy, also known as vaccine hesitancy, we're seeing today.

"It's not all about the parents, said Heather MacDougall, history professor at Waterloo and co-author of the study. "History reveals systemic problems including lack of public education, lack of access, lack of training, and, perhaps most importantly, lack of political will for a national immunization schedule."

MacDougall and co-author Laurence Monnais of Université de Montréal, trace and analyze the contested adoption of the measles vaccine over three decades up to 1998, just before the infamous Andrew Wakefield publication that falsely linked the MMR vaccination to autism.

Their study shows that the vaccine hesitancy phenomenon started well before the 1990s and offers insight on the forces at play behind current instances of vaccine hesitancy.

The historians documented trends since the 1960s, such as the thalidomide disaster of 1962, and the emergence of new styles of parenting, second-wave feminism, and the popularization of alternative medicine.

Measles outbreaks in the 1970s and 1980s corresponded with a shift to individual rather than collective responsibility for personal health and health promotion, according to the study. By the 1990s, the national and international focus on children's rights and child health made young parents more willing to question whether their child would benefit from vaccination.

"Lack of sustained training in the rapidly changing science of immunology left Canadian health care practitioners with limited knowledge to provide guidance when asked to explain the benefits of vaccination to anxious parents," said MacDougall.

The division of federal, provincial, and territorial powers over healthcare have created a systemic disadvantage for the consensus needed to develop a consistent national immunization program.

"By publishing our research, the Canadian Medical Association Journal confirms the relevance of humanities disciplines such as history to help us understand social phenomena such as vaccine hesitancy in the face disease outbreaks," said MacDougall.

ARLINGTON, Virginia, April 7, 2018 -- Medical advice about implanted cardiac defibrillators obtained via an online message board appears to be accurate only half of the time, according to preliminary research presented at the American Heart Association's Quality of Care and Outcomes Research Scientific Sessions 2018, a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

The study, based on analysis of two years of messages on an anonymous online board about implanted cardiac defibrillators (ICDs), showed that about 25 percent of the messages contained inappropriate advice, and six percent of advice shared was controversial. Researchers analyzed 127 discussions, 82 of which pertained to medical advice in several topical areas, including cardiovascular disease, device programming and maintenance, physical activity restrictions and management of other health conditions.

The research team said the findings underscore the need to ensure that clinicians follow up with patients about their information sources to ensure they are receiving accurate advice outside of the doctor's offices. Ensuring appropriate advice is particularly important when it comes to complex decisions about advanced procedures, tests and interventions such as the decision to have an ICD, the study authors added.

"The internet is a critical piece of the vast network of information available to patients, as Americans use the internet to understand their health all the time," said Christopher Knoepke, Ph.D., study lead investigator and an instructor of cardiology at the University of Colorado Denver. "Our findings indicate that patients should be advised that discussions on these online message boards can provide some good, basic information, but more complicated and in-depth advice may be problematic."

ICDs are miniature devices surgically implanted in the heart to fire off electric shocks that interrupt potentially lethal arrhythmias and restore normal heart rhythm. Between one and two million people live with ICDs in the United States, the study authors said, and some 130,000 new devices are implanted in patients each year.

Given how common patient use of online medical information is, clinicians must be aware of the potential their patients will be exposed to inaccurate or dangerous information, the research team said.

"Clinicians should caution patients it's impossible for anyone not familiar with his or her case and full medical history to help put information into context for their individual patient needs," Knoepke said.

ARLINGTON, Virginia, April 7, 2018 -- In a survey to assess treatment preferences for high blood pressure, respondents were more likely to choose a daily cup of tea or a pill over exercise, according to preliminary research presented at the American Heart Association's Quality of Care and Outcomes Research Scientific Sessions 2018, a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

Researchers wanted to find out how people weigh the benefits of high blood pressure treatment options against its inconvenience. They asked survey respondents to imagine that they had high blood pressure and then asked about their willingness to adopt any of four "treatments" to gain an extra month, year or five years of life. In this survey, the "treatments" proposed were: a daily cup of tea, exercise, pills or monthly or semi-annual injections.

Results showed that taking a pill or drinking a daily up of tea were the preferred treatments, though some were unwilling to adopt any intervention even if it meant gaining an additional year or five years of life. For each treatment, participants were more likely to say they would adopt it if the benefit were greater:

79 percent of respondents said they would be willing to take a pill for an extra month of life, 90 percent would for an extra year of life and 96 percent would for an extra five years of life;

78 percent said they would drink a daily cup of tea for one extra month of life, 91 percent would for one extra year of life and 96 percent would drink it for an extra five years of life;

63 percent would be willing to exercise for an extra month of life, 84 percent would for an extra year of life and 93 percent would exercise if it meant an extra five years of life;

A shot was the least preferred of the options - 68 percent would take a shot every six months if it would give them an extra month of life, 85 percent would do it for an extra year of life and 93 percent would be willing if it gave them another five years, but only about half (51 percent) would take a monthly shot for an extra month of life, 74 percent would for an extra year and 88 percent would opt for an injection every month if it gave them five extra years of life.

In addition, at least 20 percent of respondents wanted to achieve gains in life expectancy beyond what any of the individual interventions could provide.

"Our findings demonstrate that people naturally assign different weights to the pluses and minuses of interventions to improve cardiovascular health," said Erica Spatz, M.D., M.H.S., the study lead author and an assistant professor of cardiovascular medicine in the Center for Outcomes Research and Evaluation at Yale School of Medicine in New Haven, CT. "I believe we need to tap into this framework when we are talking with patients about options to manage their blood pressure. We are good about discussing side effects, but rarely do we find out if other inconveniences or burdens may be impacting a person's willingness to take a lifelong medication or to exercise regularly."

From March to June 2017, 1,284 U.S. adults recruited through Amazon MTurk and 100 patients attending an outpatient health clinic completed the survey. Most survey respondents were under 45 years old, and half were female. Roughly three-quarters of respondents were non-Hispanic white, 10 percent were African American, 7 percent were Hispanic or Latino, and 8 percent were Asian. Most had high blood pressure.

A study limitation is that most respondents were relatively young. Since cardiovascular disease is more common among older people, they may have different responses than younger people. Another limitation is that survey respondents were not told the true life-extending ability of each intervention.

High blood pressure is a leading risk factor for heart and blood vessel, or cardiovascular, disease. Yet, it is often called the silent killer because it causes no symptoms. To prevent high blood pressure, the American Heart Association recommends getting regular physical activity, in addition to other lifestyle changes. These changes include eating a healthy diet, limiting alcohol, managing stress, maintaining a healthy weight, and quitting smoking. It is also important to work with a healthcare provider and to properly take medications, if prescribed, to reduce blood pressure.

ARLINGTON, Virginia, April 7, 2018 -- Depression, even when undiagnosed, can have many negative effects on cardiovascular patients, including poor healthcare experiences, more use of healthcare resources and higher health costs, according to preliminary research presented at the American Heart Association's Quality of Care and Outcomes Research Scientific Sessions 2018, a premier global exchange of the latest advances in quality of care and outcomes research in cardiovascular disease and stroke for researchers, healthcare professionals and policymakers.

About one-fifth of cardiovascular disease patients suffer from depression.

"While we don't know which comes first--depression or cardiovascular disease--the consensus is that depression is a risk marker for cardiovascular disease, meaning if you have cardiovascular disease, there is a higher likelihood that you could also have depression, when compared with the risk in the general population," said Victor Okunrintemi, M.D., M.P.H., a research fellow at Baptist Health South Florida in Coral Gables, Florida, and lead author of a pair of studies that looked into different aspects of depression and cardiovascular disease.

In one study, Okunrintemi and colleagues evaluated patient experience, healthcare expenditure and resource use in a large population of adult cardiovascular disease patients, dividing them into two groups: those who had been diagnosed with depression and those who had not been diagnosed with depression. Based on responses from a health questionnaire, patients who had not been diagnosed with depression were divided into high- and low-risk groups for depression.

When researchers compared high- and low-risk groups of cardiovascular patients without depression, they found:

Those at high risk for depression spent more on overall and out-of-pocket healthcare expenditures yearly when compared with patients in the low-risk group.

High-risk patients for depression were more than two times more likely to be hospitalized and used the emergency room than those at low risk.

High-risk patients were more than five times more likely to have a poor self-perceived health status, and almost four times more likely to be dissatisfied with their healthcare.

Patients at high risk for depression had notably worse healthcare-related quality of life.

"When we compared non-depressed patients to those who had been diagnosed with depression, we found those who were not depressed and yet had a higher risk for depression had worse healthcare experiences, increased use of the emergency room, poorer perception of their health status and a lower health-related quality of life than those who actually had depression," Okunrintemi said. "That could be because people at high risk for depression simply haven't been diagnosed and treated for depression yet."

In a second study comparing health resource use and expenditures among heart attack patients with and without depression, Okunrintemi and colleagues found that heart attack patients diagnosed with depression were 54 percent more likely to be hospitalized and 43 percent more likely to have emergency room visits, compared to those not diagnosed with depression.

Furthermore, heart attack patients with depression spent an estimated $4,381 more, annually on healthcare expenses, compared with those without depression.

"Depression and heart attack often coexist, which has been associated with worse health experiences for these patients," he said. "As a quality improvement measure to increase healthcare efficiency, we recommend more aggressive depression screening at follow-up visits for heart attack patients."

In a separate study by a different group of researchers, stroke patients diagnosed with depression prior to having a stroke were more likely than those without depression to report functional declines and worse stroke impact on health and quality of life months after their stroke.

Researchers studied more than 1,600 stroke patients with similar stroke severity and functional status when discharged from the hospital. Three and six months after the strokes, they found those diagnosed with depression before having a stroke were 56 percent more likely than those without depression to report functional declines and a greater negative stroke-related impact on health and life.

The researchers call for strategies to more effectively manage existing depression among stroke patients to improve patients' health and quality of life post stroke.

WHAT:

Influenza vaccines that better target the influenza surface protein called neuraminidase (NA) could offer broad protection against various influenza virus strains and lessen the severity of illness, according to new research published in Cell. Current seasonal influenza vaccines mainly target a different, more abundant influenza surface protein called hemagglutinin (HA). However, because influenza vaccines offer varying and sometimes limited protection, scientists are exploring ways to improve vaccine effectiveness. The new research builds on previous studies of NA and was conducted by a team of scientists including investigators from the Centers of Excellence for Influenza Research and Surveillance (CEIRS) program, which is organized and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Investigators analyzed blood samples from people vaccinated against influenza and people diagnosed with either the 2009 H1N1 influenza virus or H3N2 influenza viruses. The volunteers were recruited for this study or had taken part in prior influenza research studies. The analyses indicate that influenza vaccines rarely induce NA-reactive antibodies, whereas natural influenza infection induces these types of antibodies at least as often as they induce HA-reactive antibodies. Additional studies in mice reinforced the human data, indicating that current influenza vaccines do not induce NA-reactive antibodies efficiently.

Additional laboratory experiments show that the NA-reactive antibodies induced during natural influenza infection are broadly reactive, meaning they could potentially protect against diverse strains of influenza. To test this theory, scientists isolated NA-reactive monoclonal antibodies from the H3N2 and H1N1 influenza patients (N2-reactive antibodies and N1-reactive antibodies, respectively). They administered 13 N2-reactive antibodies to mice and subsequently infected the mice with a different H3N2 virus strain. Eleven of the 13 N2-reactive antibodies partially or fully protected the mice. They also administered eight N1-reactive antibodies to mice and subsequently infected the mice with a similar H1N1 virus strain or an H5N1-like virus strain. Four of the eight antibodies completely protected the mice against both virus strains.

The authors note that the findings suggest that influenza vaccines should be optimized to better target NA for broad protection against diverse influenza strains. In this regard, NIAID is supporting research to characterize NA responses in infected and vaccinated individuals and to determine the mechanism of action of NA protection. NIAID also supports "NAction!" a CEIRS working group that identifies knowledge gaps in our understanding of NA and sets NA research priorities for improved influenza vaccines. These efforts contribute to NIAID's larger plan to develop a universal influenza vaccine--a vaccine that can durably protect all age groups against multiple influenza virus strains.

April 6, 2018 -- A new blood test has been found to more accurately predict the development of tuberculosis up to two years before its onset in people living with someone with active TB, according to research published online in the American Journal of Respiratory and Critical Care Medicine, an American Thoracic Society journal.

Those living with someone with active TB are at highest risk for developing the disease, yet only about 5-20 percent of people infected with tuberculosis actually develop TB. A blood test that predicts the development of TB without putting large numbers of lower-risk people through unnecessary preventative treatment is not currently available.

In "Four-gene Pan-African Blood Signature Predicts Progression to Tuberculosis," researchers from an international research consortium report that they developed and validated a blood test that measures the expression levels of four genes that can more accurately predict the development of TB in high-risk patients in Sub-Saharan Africa.

"We found that this prediction [up to two years before the onset of the disease] is possible through measurements of a combination of a four-gene signature in the blood," said Professor Gerhard Walzl, MMed, PhD, lead study author and leader of the Stellenbosch University Immunology Research Group, Tygerberg, South Africa.

"This signature, known as 'RISK4,' was found to be present in all cohorts in the study, from South Africa, Gambia and Ethiopia." RISK4 is a combination of four genes associated with inflammatory responses.

For quality control, the scientists used a training-test set approach: they divided the sample data up in a discovery (training) set on which the signature was developed and then tested the signature on the remainder of the samples (test set) in a blinded manner. Although blood samples from individuals in Uganda were initially included in the study design, they were not available in large enough quantities to be properly analyzed.

Focusing on people who lived with someone with active TB, the research team enrolled 4,466 HIV-negative, healthy study participants from the households of 1,098 index cases (people with active TB, who allowed the researchers to enroll members of their household who did not have TB in its active stage). Blood samples were taken from the 4,466 study participants, and stored.

At the end of the initial study period, when it was apparent who had progressed to TB and who hadn't, the blood samples of 79 individuals who progressed to active TB between 3 and 24 months following exposure, and 328 who remained healthy during the 2 years of follow up, were analyzed. (Due to the cost of the tests, the blood samples of the other study participants were not tested.) Various biosignatures - combinations of gene or protein levels that together result in a test readout that relates to current or future risk for developing the condition - were measured.

"The individual components of this signature may not be sufficient to deliver an accurate diagnosis of prediction, but a combination of these markers improves its accuracy," said Prof. Walzl.

A number of companies have the ability to develop tests that measure the presence of these four genes. "We are hoping that primary health clinics will be able to use such a test and the reagents would then be readily available in that format, similar to the tests that are currently used to diagnose TB," added Prof. Walzl.

While there are currently tests on the market that may predict progression to TB, the test developed by Prof. Walzl and colleagues gives positive results for a smaller percentage of high-risk household contacts than the current tests. This translates to fewer people being treated unnecessarily in order to prevent TB.

"Preventative treatment is several weeks long and has potential side effects," explained Prof. Walzl. "One wants to limit the number of people who have to undergo such treatment to those most likely to be at risk for developing active TB."

Tuberculosis, caused by infection with Myobacterium tuberculosis (M.tb), is the world's leading cause of death brought on by a single pathogen. More than 10 million new cases of TB are diagnosed each year, and almost two million people die from the disease. Globally, 1.7 billion people are estimated to be infected with M.tb.

"This study is the first step, and now the impact of this test on prevention of TB will have to be tested in multicenter clinical trials," Prof. Walzl stated. "In addition, the validity of the prediction in high-risk individuals in Asia, South America and other high-priority areas needs to be assessed."

New research has found treating an infected hip replacement in a single stage procedure may be as effective or better than the widely used two-stage procedure. To date no well-designed study has compared these procedures head-to-head to decide if one is better or if they achieve the same results. Hip replacement is a very common operation that is effective at providing pain relief and improving mobility, however, infection can sometimes occur following joint replacement. The findings have wide implications for orthopaedic surgery, the NHS, and health systems worldwide.

The research team, led by the University of Bristol, conducted a study that reviewed patient data from 44 studies to compare the effectiveness of the two types of surgery currently used to treat infections - one-stage and two-stage revisions.

In the two-stage procedure, the existing artificial joint is removed in one operation and the patient is treated for several months with antibiotics. A new joint is then inserted in a second operation. In the one-stage procedure, the artificial joint is removed along with all infected tissue and a new one inserted in the same operation.

The study found that the one-stage revision strategy is as good, if not better, as the two-stage strategy. The one-stage strategy may also be better suited for patients with certain types of infection or problems that were previously thought not to be appropriate for this type of surgery.

Dr Setor Kunutsor, Research Fellow from the Musculoskeletal Research Unit at the Bristol Medical School: (THS) and lead researcher, said: "For several decades, the two-stage procedure has been presumed to be more effective than the one-stage. However, it has disadvantages for patients such as having two major surgical procedures, significant pain and limited function between stages, long hospital stays, as well as high healthcare costs. The one-stage strategy has potential advantages for patients which include having only one major surgery, shorter time in hospital, reduced functional impairment, and is less expensive.

"When the research team analysed the collected data, the findings confirmed what we had suspected all along - the one-stage strategy may be as effective as, or better than the two-stage strategy.

Speaking about the study, Co-investigator and Senior Author Mr. Andrew Beswick, also a Research Fellow of the Musculoskeletal Research Unit at the Bristol Medical School: (THS), said: "Our research and the subsequent adoption of the one-stage strategy by surgeons and hospitals, could improve lives, prevent unnecessary deaths, and save money."

The researchers suggest a clinical trial should be carried out to compare which of the two strategies is better in treating infection, but it will require several thousands of patients with hip infections.

The research team at Bristol led by Professor Ashley Blom, Head of Translational Health Sciences, Bristol Medical School, University of Bristol, is currently undertaking a trial which is comparing the two surgical strategies using patient reported outcomes such as pain and function. It is hoped that this trial will determine which is the better way to treat infected hip replacements when pain and function are thought to be the most important outcomes.

While the research team await results of this trial and in the absence of any further evidence, surgeons and policy makers are encouraged to consider the current evidence in their practice and guidelines. The Bristol researchers will work with patients, surgeons, nurses and other health professionals, and the NHS to ensure that the results of the study have an appropriate impact on future practice.