Body

For decades, hospitals have worked to get doctors, nurses and others to wash their hands and prevent the spread of germs.

But a new study suggests they may want to expand those efforts to their patients, too.

Fourteen percent of 399 hospital patients tested in the study had "superbug" antibiotic-resistant bacteria on their hands or nostrils very early in their hospital stay, the research finds. And nearly a third of tests for such bacteria on objects that patients commonly touch in their rooms, such as the nurse call button, came back positive.

Another six percent of the patients who didn't have multi-drug resistant organisms, or MDROs, on their hands at the start of their hospitalization tested positive for them on their hands later in their stay. One-fifth of the objects tested in their rooms had similar superbugs on them too.

The research team cautions that the presence of MDROs on patients or objects in their rooms does not necessarily mean that patients will get sick with antibiotic-resistant bacteria. And they note that healthcare workers' hands are still the primary mode of microbe transmission to patients.

"Hand hygiene narrative has largely focused on physicians, nurses and other frontline staff, and all the policies and performance measurements have centered on them, and rightfully so," says Lona Mody, M.D., M.Sc., the University of Michigan geriatrician, epidemiologist and patient safety researcher who led the research team. "But our findings make an argument for addressing transmission of MDROs in a way that involves patients, too."

Studying the spread

Mody and her colleagues report in the new paper in Clinical Infectious Diseases that of the six patients in their study who developed an infection with a superbug called MRSA while in the hospital, all had positive tests for MRSA on their hands and hospital room surfaces.

In addition to MRSA, short for methicillin-resistant Staphylococcus aureus, the study looked for superbugs called VRE (vancomycin-resistant enterococcus) and a group called RGNB, for resistant Gram-negative bacteria. Because of overuse of antibiotics, these bacteria have evolved the ability to withstand attempts to treat infections with drugs that once killed them.

Mody notes that the study suggests that many of the MDROs seen on patients are also seen in their rooms early in their stay, suggesting that transmission to room surfaces is rapid. She heads the Infection Prevention in Aging research group at the U-M Medical School and VA Ann Arbor Healthcare System.

Additionally, since many patients arrive at the hospital through the emergency room, and may get tests in other areas before reaching their hospital room, it will be important to study the ecology of MDROs in those areas too, she says.

"This study highlights the importance of handwashing and environmental cleaning, especially within a healthcare setting where patients' immune systems are compromised," says infectious disease physician Katherine Reyes, M.D., lead author for Henry Ford Health System researchers involved in the study. "This step is crucial not only for healthcare providers, but also for patients and their families. Germs are on our hands; you do not need to see to believe it. And they travel. When these germs are not washed off, they pass easily from person to person and objects to person and make people sick."

More about the study

The team made more than 700 visits to the rooms of general medicine inpatients at two hospitals, working to enroll them in the study and take samples from their bodies and often-touched surfaces as early as possible in their stay. They were not able to test rooms before the patients arrived, and did not test patients who had had surgery, or were in intensive care or other types of units.

Using genetic fingerprinting techniques, they looked to see if the strains of MRSA bacteria on the patients' hands were the same as the ones in their rooms. They found the two matched in nearly all cases - suggesting that transfer to and from the patient was happening. The technique is not able to distinguish the direction of transfer, whether it's from patient to objects in the room, or from those objects to patients.

Cleaning procedures for hospital rooms between patients, especially when a patient has been diagnosed with an MDRO infection, have improved over the years, says Mody, and research has shown them to be effective when used consistently. So lingering contamination from past patients may not have been a major factor.

But the question of exactly where patients picked up the MDROs that were found on their bodies, and were transmitted to the surfaces in their rooms, is not addressed by the current study and would be an important next step based on these results.

Why MDROs matter

Also important, says Mody, is the fact that hospital patients don't just stay in their rooms - current practice encourages them to get up and walk in the halls as part of their recovery from many illnesses, and they may be transported to other areas of the hospital for tests and procedures.

As they travel, they may pick up MDROs from other patients and staff, and leave them on the surfaces they touch.

So even if a relatively healthy person has an MDRO on their skin, and their immune system can fight it off if it gets into their body, a more vulnerable person in the same hospital can catch it and get sick. The researchers are exploring studying MDROs on patients in other types of hospital units who may be more susceptible to infections.

Patients and staff may also get colonized with MDROs in outpatient care settings that have become the site of so much of American health care, including urgent care centers, freestanding imaging and surgery centers, and others.

Mody and colleagues are presenting new data about MDROs in skilled nursing facilities at an infectious disease conference in Europe in coming days. They showed that privacy curtains - often used to separate patients staying in the same room, or to shield patients from view when dressing or being examined - are also often colonized with superbugs.

"Infection prevention is everybody's business," says Mody, a professor of internal medicine at the U-M Medical School. "We are all in this together. No matter where you are, in a healthcare environment or not, this study is a good reminder to clean your hands often, using good techniques--especially before and after preparing food, before eating food, after using a toilet, and before and after caring for someone who is sick-- to protect yourself and others."

The European Centre for Disease Control and Prevention (ECDC) estimates that 9 million cases of healthcare-associated infections (HAIs) occur across Europe each year--with around one in 15 patients in acute care hospitals and one in 24 residents in long-term care facilities having at least one infection on any given day, according to the most comprehensive assessment of HAIs in Europe to date, being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April).

Importantly, the findings also reveal low microbiological testing rates that vary widely between countries, suggesting that more must be done to protect patients and residents from these preventable complications.

A microorganism was reported for just over half (53%) of the HAIs in acute care hospitals. For 11% of the microorganisms reported, antimicrobial susceptibility testing results were not available on the day of the survey. In long-term care facilities, over three quarters of infections had no documented microbiological results. In long-term care facilities overall, only 19% HAIs had a microbiological test result available in the facility to guide treatment and control. In acute care hospitals, the figure was 53%.

"Our analysis shows that healthcare-associated infections still pose a major public health threat in European countries and healthcare institutions", says Pete Kinross from the European Centre for Disease Prevention and Control. "Culture-directed antibiotic treatment is an important aspect of the treatment and control of these kinds of infections. The variability of microbiological testing suggests poor availability of information for effective treatment, as well as alertness to potential outbreaks."

This study is based on data from two ECDC point prevalence surveys of HAIs and antimicrobial use in both acute care hospitals and long-term care facilities in European Union (EU) and European Economic Area (EEA) countries between 2016 and 2017.

In 2016, the European Centre for Disease Prevention and Control (ECDC) estimated that the
burden of HAIs (eg, pneumonia, urinary tract infection, Clostridium difficile infection) in European acute care hospitals exceeded the combined burden of all other infectious diseases under surveillance by ECDC such as influenza, HIV/AIDS, and tuberculosis combined [1]. However, these estimates did not take into account infections in other healthcare facilities.

In these latest ECDC surveys, trained staff used standardised questionnaires to collect data from voluntarily participating acute care hospitals and long-term care facilities (eg, general nursing homes, residential homes) on every patient/resident who was present on the day of the survey.

In total, 310,755 patients from 1,209 acute care hospital in 28 EU/EEA countries and 117,138 residents from 1,798 long-term care facilities in 24 EU/EEA countries were included in the analyses.

The findings show that on any given day in 2016-2017, 98 166 (6.5%) patients in acute care hospitals and 129 940 (3.9%) residents in long-term care facilities had at least one HAI.

However, much of the difference in national HAI rates in acute care hospitals is explained by their different rates of testing blood samples. Essentially, countries with lower test rates (e.g. Hungary, Lithuania, Romania) detect fewer HAIs compared to those with higher testing rates (e.g. Belgium, Finland, United Kingdom).

Respiratory tract infections (particularly pneumonia) were the most common, accounting for a quarter of all HAIs in hospitals and a third in long-term care facilities, followed by urinary tract infections (almost a fifth and a third, respectively).

Pete Kinross says: "Healthcare-associated infections in acute care hospitals are responsible alone for more deaths in the EU/EEA than all other infectious diseases under surveillance. It is crucial to apply recommendations and guidelines available in both acute care hospitals and long-term care facilities, since our study showed that there are as many healthcare-associated infections in long-term care facilities as there are in acute care hospitals."

Lisbon, Portugal - 12 April 2019: Kicking the habit works best in pairs. That's the main message of a study presented today at EuroPrevent 2019, a scientific congress of the European Society of Cardiology (ESC).1

"Quitting smoking can be a lonely endeavour," said study author Magda Lampridou, of Imperial College London, UK. "People feel left out when they skip the smoke break at work or avoid social occasions. On top of that, there are nicotine withdrawal symptoms. Partners can distract each other from the cravings by going for a walk or to the cinema and encouraging replacement activities like eating healthy food or meditating when alone. Active support works best, rather than nagging."

Half of coronary patients smoke and 90% of people at high risk of cardiovascular disease are smokers. ESC cardiovascular prevention guidelines advise against tobacco in any form, and people who stop smoking generally halve their risk of cardiovascular disease.2 "Smoking cessation interventions should incorporate couples where possible to achieve a smoke-free household," said Ms Lampridou.

This study evaluated the supporting role married or cohabiting partners might have in smoking cessation. The study enrolled 222 current smokers who were at high risk of cardiovascular disease or had suffered a heart attack. Partners were also recruited: 99 were current smokers (45%), 40 ex-smokers, and 83 never-smokers.

Couples attended one of four preventive cardiology programmes: EUROACTION, EUROACTION plus, MyAction Galway, and MyAction Westminster. At the start they were asked about current smoking status, history of smoking, and previous quit attempts. Smoking status was validated with a carbon monoxide breath test. During the 16-week programme, couples were offered nicotine replacement therapy with patches and gum. In one programme, participants could choose the prescription drug varenicline instead.

At the end of the programme, 64% of patients and 75% of partners were abstinent - compared to none and 55% at the start, respectively. The odds of quitting smoking at 16 weeks were significantly higher (5.83-fold) in couples who tried to quit together compared to patients who attempted it alone.

"Previous research has shown that ex-smokers can also positively influence their spouse's attempts to quit, but in this study the effect was not statistically significant," said Ms Lampridou. "As for non-smoking partners, there is a strong risk that they will adopt their spouse's habit." Ms Lampridou noted that research is needed to confirm the findings in smokers who are otherwise healthy.

Lisbon, Portugal - 12 April 2019: Prolong your life by increasing your muscle power. That's the main message of a study presented today at EuroPrevent 2019, a congress of the European Society of Cardiology.1

"Rising from a chair in old age and kicking a ball depend more on muscle power than muscle strength, yet most weight bearing exercise focuses on the latter," said study author Professor Claudio Gil Araújo, director of research and education, Exercise Medicine Clinic - CLINIMEX, Rio de Janeiro, Brazil. "Our study shows for the first time that people with more muscle power tend to live longer."

Power depends on the ability to generate force and velocity, and to coordinate movement.2 In other words, it is the measure of the work performed per unit time (force times distance); more power is produced when the same amount of work is completed in a shorter period or when more work is performed during the same period.3 Climbing stairs requires power - the faster you climb, the more power you need. Holding or pushing a heavy object (for example a car with a dead battery) needs strength.

Professor Araújo said: "Power training is carried out by finding the best combination of speed and weight being lifted or moved. For strength training at the gym most people just think about the amount of weight being lifted and the number of repetitions without paying attention to the speed of execution. But for optimal power training results, you should go beyond typical strength training and add speed to your weight lifts."

Muscle power gradually decreases after 40 years of age. "We now show that power is strongly related to all-cause mortality. But the good news is that you only need to be above the median for your sex to have the best survival, with no further benefit in becoming even more powerful," said Professor Araújo.

The study enrolled 3,878 non-athletes aged 41-85 years who underwent a maximal muscle power test using the upright row exercise between 2001 and 2016 (see photo). The average age of participants was 59 years, 5% were over 80, and 68% were men. The highest value achieved after two or three attempts with increasing loads was considered the maximal muscle power and expressed relative to body weight (i.e. power per kg of body weight). Values were divided into quartiles for survival analysis and analysed separately by sex.

During a median 6.5-year follow-up, 247 men (10%) and 75 women (6%) died. Median power values were 2.5 watts/kg for men and 1.4 watts/kg for women. Participants with a maximal muscle power above the median for their sex (i.e. in quartiles three and four) had the best survival. Those in quartiles two and one had, respectively, a 4-5 and 10-13 times higher risk of dying as compared to those above the median in maximal muscle power.

Professor Araújo noted that this is the first time the prognostic value of muscle power has been assessed. Previous research has focused on muscle strength, primarily using the handgrip exercise. The upright row exercise was chosen for the study because it is a common action in daily life for picking up groceries, grandchildren, and so on. The researchers are currently examining the link between muscle power and specific causes of death including cardiovascular disease and cancer. He added: "Doctors should consider measuring muscle power in their patients and advise more power training."

How to train to increase your muscle power:

Choose multiple exercises for the upper and lower body

Choose a weight with the load to achieve the maximal power (not so easy to lift and not so heavy that you can barely lift it)

Do one to three sets of six to eight repetitions moving the weight as fast as possible while you contract your muscles (slow or natural speed in returning to initial position)

Rest for 20 seconds between each set to sufficiently replenish the energy stores in your muscles to start the new set

Repeat the above for the other exercises (biceps curl, etc.).

How to progress:

Start with six repetitions in each set and when the exercise becomes easy, try to increase to eight

If it becomes easy again, increase the weight and go back to six repetitions

If you unable to complete the repetitions with the proper technique, avoid "cheating" and go back to less repetitions or less weight. This is important to prevent injuries.

Photo: Maximal muscle power test using the upright row exercise. One foot is placed in front of the other to protect the lower back. The bar is pulled up as fast as possible and increased weights are progressively used until a maximal power reading is obtained. Power is measured in watts and expressed in absolute terms as well as relative (per kg of body weight).

Photo credit: Exercise Medicine Clinic - CLINIMEX.

NEW YORK, April 11, 2019 -- A newly published paper in the Lancet journal EBioMedicine identifies a link between high levels of blood lipids and worsening of disease in multiple sclerosis (MS) patients who are overweight or obese.

The longitudinal investigation, conducted by researchers at the Advanced Science Research Center(ASRC) at The Graduate Center of The City University of New York's Neuroscience Initiative in collaboration with clinicians at the Icahn School of Medicine at Mount Sinai, followed recently diagnosed MS patients for two years. The researchers found that individuals who were overweight or obese had higher levels of blood lipids called ceramides, which placed markers on the DNA of monocytes, making them proliferate. Monocytes are blood cells that can travel to the brain and damage nerve fibers, and two years into their diagnosis, study participants with higher levels of ceramides and monocytes also had greater loss of motor skills and more brain injury.

"Our study identifies important correlations between ceramide levels, body mass index, and disease progression in MS patients," said ASRC Neuroscience Initiative Director Patrizia Casaccia, a professor at The Graduate Center. "We found that overweight and obese individuals with MS have higher ceramide levels than people with the disease who are not overweight and also than individuals who are overweight or obese but otherwise in healthy conditions. This is important because we and others had previously identified ceramides in the cerebro-spinal fluid surrounding the brain of MS patients, and we attributed their increased abundance to the body's efforts to recycle the damaged myelin. In this study, however, we also detect higher ceramide levels in the blood of overweight and obese MS patients than we did in patients with normal body mass index, suggesting that overabundant lipids can be derived not only from damaged brain cells, but also from excessive dietary intake of saturated fats."

Methodology

Two cohorts of patients -- a primary one and a validation group -- were recruited from the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai and the National Institutes of Health to participate in the study. For the first group, 54 therapy-naïve MS patients 18 to 60 years old with high or normal body mass indexes (BMIs) were evaluated using brain MRI to identify signs of brain damage; a clinical assessment to ascertain weight, disabilities and other vital information; and blood tests to analyze the types of circulating lipids and white blood cells. An independent validation group of 91 MS patients from the National Institute of Health with the same characteristics and additional control cohorts of healthy individuals within the same BMI range were similarly evaluated.

Researchers found that MS patients with high BMIs had higher ceramide levels and more circulating monocytes than were evident in healthy individuals with the same BMIs. High-BMI MS patients showed worsening disability and more brain lesions at the MRI compared to their normal BMI counterparts. The researchers went on to find that ceramides can enter inside immune cells called monocytes and change the way these cells read the genetic information encoded in the DNA. These epigenetic changes were also found in monocytes circulating in the blood of MS patients with high BMI.

Significance

The detection of ceramides inside the nucleus of blood cells and the ability of these lipids to induce epigenetic changes suggests that saturated fatty acids may have long-lasting functional effects, which over time steer the MS disease course towards worsening disability. In short, bad dietary habits may have negative consequences in healthy subjects, but they have an even more pronounced deleterious effect on patients with MS because the degrading myelin can accumulate and further increase ceramide levels.

"This study gives us a much-needed view into the environmental influences that can affect and change the behavior of cells in an individual's body," said Kamilah Castro, the paper's first author and a graduate student in professor Casaccia's lab. "Our findings suggest that increased levels of saturated fat as a result of dietary habits are one likely cause of the epigenetic changes that advance MS, which gives us a starting point for a potential intervention."

The researchers' findings support the concept of nutri-epigenomics (the ability of food to modify the way genomic information is interpreted by each cell) and the idea that lifestyle factors such as diet and weight can function as disease modifiers. Additional studies on larger cohorts are needed to validate the current findings. Further investigation is also needed to determine whether specific dietary interventions and weight management could be useful in helping MS patients manage and slow the progression of their disease and better respond to disease-modifying treatments.

"This translational study is exciting from a clinical perspective as it sheds light on a potentially important mechanism that can help explain our clinical observations regarding obesity and MS prognosis," said Ilana Katz Sand, associate medical director of the Corinne Goldsmith Dickinson Center for MS at Mount Sinai. "We look forward to continuing to work on this important topic through future clinical studies to evaluate the impact of weight management and dietary intervention in MS."

Researchers at the University of York have shown that costly external NHS hospital inspections are not associated with improvements in quality of care.

The results have prompted researchers to call for less resource-intensive inspections, allowing trusts to continue with their own internal assessments and focus on making impactful improvements in a realistic timeframe.

The team found that rates of falls resulting in harm to patients, and rates of pressure ulcers following treatment, were improving prior to external inspection by the Care Quality Commission (CQC), which exists to monitor and regulate services, and encourage improvement in quality of care. After inspection, however, rates of improvement were slower.

Dr Ana Cristina Castro, from the University of York's Department of Health Sciences, and lead author of the study, said: "Since 2013, CQC inspection teams regularly visit NHS Trusts over several days, with more than 150 inspection measures, and rate them against legally enforceable standards of care.

"This creates a significant pressure on staff before and during the inspection period, and also significant costs, not just of the CQC inspectors but also the NHS staff who are diverted from other activities.

"We calculated that one CQC inspection costs a hospital between £169,000 and £420,000 depending on its size and the preparatory activities performed.

"We suggest that a less resource-intensive approach should be considered so that all staff can focus appropriately on longer-term improvements."

The CQC regulate NHS and independent hospitals, conducting regular comprehensive inspections to observe care and examine records. Researchers at York investigated the impact of these inspections in 150 NHS Trusts in England.

The team looked at monthly data over four years on falls with harm and pressure ulcers and how they changed in relation to two regimes of inspection - one that relied on a significant input from NHS staff and lengthy visits and a second which was less resource intensive.

Researchers compared both inspection regimes with trusts that were not inspected at all during this period. Neither inspection system was associated with improvements in rates of falls, nor cases of pressure ulcers. In fact, the rate of improvement was worse compared to those trusts that did not get inspected.

Karen Bloor, Professor of Health Economics and Policy at the University of York's Department of Health Sciences, said: "CQC provides a broad system of regulation, monitoring quality of care and hopefully incentivising improvements. But inspection and regulation is costly, and cannot substitute for professionalism and health care teams working together to monitor their own performance."

Researchers argue that given that several methods of inspection have been implemented and then replaced over a 20-year period - each with an increasingly complex and burdensome process - that reducing the administrative burden should be tried and tested instead.

Trevor Sheldon, Professor of Health Services Research and Policy also at the University of York's Department of Health Sciences, is author of an editorial published alongside the research paper. He said: "Research shows us that questionable effectiveness and high burden of health service inspection is not only true of the NHS, but also of health care systems internationally.

"The research shows that inspection regimes, like CQC, need to rethink their approach; health service and government leaders need to focus less on the methods of monitoring and more on promoting and supporting the many efforts that already exist nationally and within trusts to improve quality.

"The question that remains is, what is the right dose of oversight that will help improve quality of care, without adding to an already overburdened staff workload?"

The research is published in the Journal of Health Services Research and Policy.

Stepping up efforts to prevent transmission of hepatitis C among people who inject drugs, could reduce future infections by 43 per cent globally, according to a study by researchers at the University of Bristol published in the Lancet Gastroenterology and Hepatology today [Tuesday 9 April 2019].

Hepatitis C is a virus that is passed on through blood exposure and results in liver disease. It is estimated that over 70 million people are infected with the hepatitis C virus worldwide and that around 400,00 people with hepatitis C die each year due to related conditions such as cirrhosis of the liver and liver cancer.

People who inject drugs are at high risk of becoming infected with the virus through the sharing of needles, syringes and other injecting drug equipment. While the percentage of people with hepatitis C is estimated to be less than one per cent in most countries, the percentage of people who inject drugs with hepatitis C tends to be over 30 per cent.

The researchers used mathematical modelling to estimate how much the sharing of equipment for injecting drug use contributes to the hepatitis C epidemics for 88 countries, which account for 85 per cent of the world's population.

They estimated that, if hepatitis C transmission due to the risk associated with injecting drug use was removed, around 43 per cent of all infections up to 2030 would be prevented globally.

Seventy-nine per cent of hepatitis C infections could be prevented in high-income countries and 38 per cent of infections in low- and middle-income countries. These estimates range from two per cent in Nigeria to 100 per cent in several countries, including Iceland and Finland, with estimates of 98 per cent for the UK and 77 per cent for the USA - rising to 85 per cent when assuming an increasing epidemic of injecting.

Before blood screening was introduced in the early 1990s, contaminated blood transfusions were thought to be the main route of hepatitis C transmission. However, this is no longer the case in many countries, particularly high-income settings such as the UK and the USA. Hepatitis C is also transmitted through the re-use of unsterilised medical equipment, which is much more common in many low- and middle-income countries.

In the last decade new direct acting antiviral treatments for hepatitis C have become available, which cure nearly all individuals with hepatitis C infections. Subsequently, the World Health Organization has set targets to eliminate hepatitis as a public health problem by 2030.

Adam Trickey, from the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol and lead author of the study, said: "As blood screening has improved, and there is less use of unsterilised medical equipment, a higher proportion of hepatitis C infections occur among people who inject drugs through the sharing of drug injecting equipment. This research highlights the importance of combating the hepatitis C epidemic among people who inject drugs, especially for meeting the World Health Organization's 2030 elimination targets."

Professor Peter Vickerman, from the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, who co-led the study, said: "Interventions already exist to reduce the transmission of hepatitis C among people who inject drugs, including methadone maintenance treatment, the provision of clean needles and syringes, and treating hepatitis C infections with direct acting antivirals. However, in most countries, these interventions are not widely used. Without significantly reducing hepatitis C virus transmission among people who inject drugs the World Health Organization's elimination targets cannot be met."

The first comprehensive study of immune cell types in pre- and post-chemotherapy cancer tissues points up a host of targets for new or existing cancer drugs that could improve patients' sensitivity to both chemotherapy and immunotherapy.

Results from the SWOG Cancer Research Network study appear in the latest issue of the Journal for ImmunoTherapy of Cancer. The results provide a detailed look at the immune cells found in breast cancer tumors before and after chemotherapy - providing scientists a rare window into the immune microenviroment and how it's affected by cancer drugs.

"When we better understand the types and functions of immune cells found in cancer tissue, and the effects of drugs on those cells, the closer we get to finding effective treatments," said Lajos Pusztai, MD, chair of SWOG's breast cancer committee and senior author of the journal article. "With this study, we get a unique look at the tumor immune microenvironment - and identify potential therapeutic targets that can be tested in the clinic."

SWOG is a publicly funded cancer research network that has run over 1,400 National Cancer Institute funded trials since 1956. A major benefit of that longevity: the accumulation of over 800,000 blood, tissue, and other specimens in SWOG's biobank. Pusztai, of Yale Cancer Center, and his SWOG team located 60 paired tissue samples in the bank that were taken for S0800, a randomized trial that compared two pre-surgical chemotherapy treatments for patients with HER2-negative, locally advanced, or inflammatory breast cancers.

The team used this subset of paired pre- and post-treatment tissues to accomplish three goals: determine the presence of the cancer-attacking immune cells known as tumor infiltrating lymphocytes (TILs); measure the expression of the immune-suppressing protein PD-L1, and the expression of 750 other immune-related genes that can show immune cell activity in pre- and post-treatment tissues.

To do this work, Pusztai and his team used three methods. These included a pathologist counting TILs under a microscope, and laboratory scientists using an assay to determine PD-L1 expression. In addition, article lead author Xiaotong Li, a computational biologist at Yale, used another assay, the NanoString PanCancer IO 360 Gene Expression Panel, to measure the expression of 750 immune-related genes with the help of a team of from NanoString.

Here are the results:

The team found higher counts of cancer-fighting TILs in the pre-treatment tissue samples of breast cancer patients who saw their cancer disappear after chemotherapy, a phenomenon known as pathologic complete response, or pCR. The TIL counts in post-treatment tissues were significantly lower when compared with pre-treatment tissues, suggesting that immune cells are killed by chemotherapy agents.

Researchers did not find any significant changes to PD-L1 protein expression in any of the comparison groups - between patients whose tumors disappeared to those whose tumors merely shrunk, or between pre- and post-treatment tissue samples.

The team found 24 immune genes more highly expressed in patients who saw a complete response to chemotherapy, including genes that control the cell-killing enzymes granzyme and granulysin and the cytokines CCL21 and CCL19, proteins that activate cancer-fighting T cells. The IL7R gene that controls the production of T calls is also more active in patients who saw their cancer disappear after chemotherapy. This suggests that these molecules play an important role in activating and attracting immune cells - and any drugs that increase their expression or activity could improve treatment response.

The team found that the proteins CXCL1, CXCL2, CXCL3, and CCL20, and the IL6 gene, were more highly expressed in patients who did not get a complete response to chemotherapy. This suggests that drugs that decrease the presence of these proteins and the activity of this gene could improve treatment response.

"Our findings revealed several highly actionable immune targets that can get tested in the clinic," Pusztai said. And, in fact, he is already doing so. Pusztai is leading S1418, a SWOG breast cancer trial testing the immunotherapy drug pembrolizumab, which targets PD-1, to find out if it will improve survival of triple negative breast cancer patients who have PD-L1 expression in their cancer after pre-operative chemotherapy.

Researchers from the University of Toronto presented a new study at CHEST Congress 2019 Thailand in Bangkok that aimed to determine the effect of authors' self-promotion on the social media site, Twitter, in regards to the dissemination of their research.

Tweets referencing scientific articles published between June 2011-January 2017 were gathered through Altmetric.com. The study included articles from the top seven respiratory and critical care journals: American Journal of Respiratory and Critical Care Medicine, CHEST®, Critical Care, Critical Care Medicine, Intensive Care Medicine, The Lancet Respiratory Medicine and Thorax. Researchers compared publication and Twitter author names to determine whether authors tweeted their own work. The mean number of tweets at one year after publication were compared between author-tweeted articles versus non-author-tweeted articles, and data were collected on time between publication of the article and the first tweet.

During this period, 5,383 publications were identified and analyzed. Author-tweeted publications had a higher number of tweets at one year post publication than publications not tweeted by authors (21±3.3 vs. 8.2±0.38 tweets). Peak tweeting for publications occurred between 0-2 days post-publication for most journals. Although publications in each of these journals showed an increase in dissemination with author tweeting, publications in Lancet Respiratory Medicine benefited most from author-tweeting, with a 3.5-fold increase in tweets at one year (95% CI, 1.4-6.6) compared with publications whose authors did not tweet their studies.

"Authors may use Twitter strategically to promote their work and thus optimize knowledge translation in the future," said Dr. Keith Gunaratne, lead researcher.

Further results from this study will be shared at CHEST Congress 2019 in Bangkok on Friday, April 12, at 3:00 p.m., in the Exhibition Hall. The study abstract can be viewed on the journal CHEST® website.

People who engage in high-intensity interval training are at greater risk for injury, especially in the knees and shoulders, a Rutgers study found.

These workouts, which combine aerobic exercising, weight lifting and calisthenics at maximum capacity, followed by periods of recovery, have been growing in popularity over the past decade, driven by the efficiency of the exercise to deliver fitness goals in less time.

The study, which appears in the Journal of Sports Medicine and Physical Fitness, acknowledged that while this type of training is effective in improving cardiorespiratory fitness, boosting energy and promoting lean muscle mass and fat loss, it also increases injury risk.

"These workouts are marketed as 'one size fits all.' However, many athletes, especially amateurs, do not have the flexibility, mobility, core strength and muscles to perform these exercises," said Joseph Ippolito, a physician in the department of orthopaedics at Rutgers New Jersey Medical School.

Analyzing records in the National Electronic Injury Surveillance System from 2007 through 2016, the researchers found 3,988,902 injuries resulting from exercise equipment, such as barbells, kettle bells and boxes, or calisthenics, such as burpees, push-ups and lunges, that are common to these programs. Most injuries involved knees, ankles and shoulders. White males aged 20 to 39 were most injured.

The researchers found a steady increase of an average of 50,944 injuries per year, which rose alongside the growth in interest in the workouts as determined by the number of Google searches during the years studied. During this decade, they found a significant increase in nerve damage, internal organ injuries, concussions, puncture wounds, dislocations and strains and sprains.

Athletes who perform these workouts without supervision are at increased risk for injury from poor form and muscle overuse. "There is strong evidence that these types of injuries -- specifically from repetitive overload at the knee -- can lead to osteoarthritis," said Ippolito.

People who are new to these workouts should speak with their physicians first and more experienced athletes should learn how to minimize preventable injuries, the researchers recommended. Athletic trainers, physical therapists and fitness instructors should ensure athletes are conditioned, use proper form and understand the recovery phase.

"We certainly do not want to discourage people from this type of exercise because of its numerous health benefits, but recommend that they understand the pre-existing conditions and physical weaknesses that may predispose them to injury," said co-author Nicole D. Rynecki, a student at the medical school.

Since knee and ankle sprains and strains were the most common injuries from high-intensity interval workouts, people should do neuromuscular training -- especially those that focus on strength, jumping and balance -- and pre-strengthening programs to improve flexibility before starting high-intensity interval exercises, Rynecki said.

"Exercises such as stretches that can increase range of motion and strengthen rotator cuff muscles are important, especially for older people and those who are predisposed to rotator cuff tears," she noted.

Other Rutgers authors include Brianna L. Siracuse and Kathleen S. Beebe.

Fewer than a quarter of breast cancer patients and a third of ovarian cancer patients diagnosed between 2013 and 2014 in two states underwent genetic testing for cancer-associated mutations, according to a study by researchers at the Stanford University School of Medicine and several other organizations.

The findings indicate that substantial gaps exist between national guidelines for testing and actual testing practices. In particular, the findings show that too few women with ovarian cancer are tested for the presence of mutations that could be used to guide health care decisions.

The study looked at about 83,000 women diagnosed with breast or ovarian cancer in California and Georgia in 2013 and 2014.

"We initiated this study -- the largest population-based study of multigene testing in breast and ovarian cancer patients -- because we wanted to see what cancer genetic testing and results looked like in the real world," said Allison Kurian, MD, MSc, associate professor of medicine and of health research and policy at Stanford. "Now we can see that women with ovarian cancer are dramatically undertested. We also learned that between 8 and 15 percent of women with breast or ovarian cancer carry cancer-associated mutations that could be used to drive care decisions and influence family members' health care and screening choices."

Kurian shares lead authorship of the study, which will be published online April 9 in the Journal of Clinical Oncology, with Kevin Ward, PhD, MPH, assistant professor in epidemiology at Emory University. Lynne Penberthy, MD, MPH, associate director for the National Cancer Institute's Surveillance Research Program, and Steven Katz, MD, MPH, professor of medicine and of health management and policy at the University of Michigan, are co-senior authors.

Changing guidelines

Researchers have known for decades that inherited mutations or variations in certain genes, notably BRCA1 and BRCA2, increase the risk of developing breast and ovarian cancers. Genetic tests for mutations in BRCA1 and BRCA2 have been available for several years. But since 2013, genetic tests have incorporated many more potential cancer-susceptibility genes, and results have become much more complicated.

"Integrating genetic counseling and testing into the management of cancer after diagnosis has become much more challenging for patients and their clinicians," Katz said.

National guidelines recommend that all women with the most common type of ovarian cancer be tested for the presence of cancer-associated mutations; guidelines for testing breast cancer patients have been less expansive. Although the guidelines for genetic testing have expanded to include more patients diagnosed with breast or ovarian cancer and the more extensive multigene panel tests, it's not been clear to what degree these guidelines are followed in real-world clinical settings. Furthermore, the prevalence of known cancer-associated mutations in breast and ovarian cancer patients who are racial or ethnic minorities, as well as in the overall population, is unknown.

For the study, the researchers tapped the National Cancer Institute's Surveillance, Epidemiology and End Results Program, which tracks cancer diagnoses and outcomes in large populations across the United States. They linked data on cancer cases in California and Georgia with data from four laboratories conducting the majority of cancer genetic testing from 2013 to 2014. They found that only 24.1 percent of 77,085 women diagnosed with breast cancer and 30.9 percent of 6,001 diagnosed with ovarian cancer underwent any genetic testing.

Disparities in genetic testing

The researchers also observed disparities in testing, particularly among ovarian cancer patients. Although nearly 34 percent of non-Hispanic white women were tested, only about 22 percent of black women and 24 percent of Hispanic women were tested. Income and insurance status played a role in the prevalence of testing among women with ovarian cancer from all racial and ethnic groups, the researchers found. About 20 percent of patients with Medicare were tested compared with about 34 percent of patients with other forms of health insurance. Testing prevalence decreased to about 20 percent in areas where residential poverty equaled or surpassed 20 percent, and it was about 38 percent in regions where the poverty level was less than 10 percent.

The researchers found that among women with breast cancer in the study who underwent testing for a panel of guideline-designated genes, the prevalence of mutation variants of unknown significance was much higher in minority patients: 28.5 percent, 26.6 percent and 19.3 percent in African-American, Asian and Hispanic patients, respectively, versus 14.5 percent in non-Hispanic whites. The prevalence of pathogenic variants also varied along racial and ethnic lines.

"These differences underscore the need to improve the clarity of genetic test results, especially for racial or ethnic minority patients," Kurian said.

LOS ANGELES (April 8, 2019) -- A recent study found that nearly 18 percent of patients diagnosed with multiple sclerosis before being referred to two major Los Angeles medical centers for treatment actually had been misdiagnosed with the autoimmune disease.

The retrospective study, led by investigator Marwa Kaisey, MD, along with Nancy Sicotte, MD, interim chair of Neurology and director of the Cedars-Sinai Multiple Sclerosis and Neuroimmunology Center, and researchers from UCLA and the University of Vermont, analyzed the cases of 241 patients who had been diagnosed by other physicians and then referred to the Cedars-Sinai or UCLA MS clinics over the course of a year.

Investigators sought to determine how many patients were misdiagnosed with MS, and identify common characteristics among those who had been misdiagnosed.

"The diagnosis of MS is tricky. Both the symptoms and MRI testing results can look like other conditions, such as stroke, migraines and vitamin B12 deficiency," Kaisey said. "You have to rule out any other diagnoses, and it's not a perfect science."

The investigators found that many patients who came to the medical centers with a previous diagnosis of MS did not fulfill the criteria for that diagnosis. The patients spent an average of four years being treated for MS before receiving a correct diagnosis.

"When we see a patient like that, even though they come to us with an established diagnosis, we just start from the beginning," Sicotte said.

The most common correct diagnosis was migrane (16 percent), followed by radiologically isolated syndrome, a condition in which patients do not experience symptoms of MS even though their imaging tests look similar to those of MS patients. Other correct diagnoses included spondylopathy (a disorder of the vertebrae) and neuropathy (nerve damage).

Among those misdiagnosed, 72 percent had been prescribed MS treatments. Forty-eight percent of these patients received therapies that carry a known risk of developing progressive multifocal leukoencephalopathy, a serious disease in the white matter of the brain, caused by viral infection.

"I've seen patients suffering side effects from the medication they were taking for a disease they didn't have," Kaisey said. "Meanwhile, they weren't getting treatment for what they did have. The cost to the patient is huge--medically, psychologically, financially."

Investigators estimated that the unnecessary treatments identified in this study alone cost almost $10 million.

The investigators hope that the results of this study, which will be published in May's issue of the peer-reviewed journal Multiple Sclerosis and Related Disorders, along with recently funded research into new biomarkers and improved imaging techniques, will help improve diagnostic procedures and help prevent future MS misdiagnoses.

Funding for the new research includes $60,000 from Cedars-Sinai Precision Health, a partnership among scientists, clinicians and industry designed to advance personalized medicine. Kaisey said that she hopes these studies will also lead to better availability of treatment for patients who do have the disease.

"The first step, which is what we've done here, is to identify the problem, so now we're working on potential solutions," she said.

Orlando, Fla. (April 7, 2019) - A new study found that offspring born to mice that exercised during pregnancy were less likely to gain weight after consuming a high-fat diet later in life. Although previous studies have shown that exercise by obese females benefits their offspring, this is the first research to demonstrate that the same is true when non-obese females exercise.

"Based on our findings, we recommend that women--whether or not they are obese or have diabetes--exercise regularly during pregnancy because it benefits their children's metabolic health," said Jun Seok Son, a doctoral student at the Washington State University who conducted the study.

Son will present the new findings at the American Physiological Society's annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

The researchers examined the offspring of mice that performed 60 minutes of moderate intensity exercise every morning during pregnancy. Offspring born to mice that didn't exercise were used as a control group.

At weaning, the offspring of the exercising mice showed increased levels of proteins associated with brown adipose tissue compared to the control group. This type of tissue converts fat and sugar into heat. The researchers also observed higher body temperatures in the exercise group, indicating that their brown adipose tissue was more efficient--or had a higher thermogenic function--which has been shown to prevent obesity and metabolic problems.

After weaning, the offspring followed a high-fat diet for eight weeks. The mice in the exercise group not only gained less weight on the high-fat diet but also showed fewer symptoms of metabolic diseases such as diabetes and fatty liver disease.

"Our data suggest that the lack of exercise in healthy women during pregnancy can predispose their children to obesity and associated metabolic diseases partially through impairing thermogenic function," said Son.

The researchers plan to perform additional studies to better understand the biological mechanisms responsible for the improved metabolic health in offspring of mothers who exercised.

Jun Seok Son will present this research on Sunday, April 7, from 10:15 a.m.-12:15 p.m. in Exhibit Hall-West Hall B, Orange County Convention Center and on Monday, April 8 at 4:30 p.m. in room W311B (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

Orlando, Fla. (April 7, 2019) - Research conducted in mice suggests the food additive tert-butylhydroquinone (tBHQ)--found in many common products from frozen meat to crackers and fried foods--suppresses the immune response the body mounts when fighting the flu. In addition to increasing the severity of flu symptoms, the study found evidence that tBHQ exposure could reduce the effectiveness of the flu vaccine through its effects on T cells, a vital component of the immune system.

Researchers say the connection may help explain why seasonal influenza continues to pose a major health threat worldwide. An estimated 290,000-650,000 people globally die from flu-related respiratory problems each year.

"Our studies showed that mice on a tBHQ diet had a weakened immune response to influenza (flu) infection," said Robert Freeborn, a fourth-year PhD candidate at Michigan State University. "In our mouse model, tBHQ suppressed the function of two types of T cells, helper and killer T cells. Ultimately, this led to more severe symptoms during a subsequent influenza infection."

Freeborn will present the research at the American Society for Pharmacology and Experimental Therapeutics annual meeting during the 2019 Experimental Biology meeting, held April 6-9 in Orlando, Fla.

When a person is infected with influenza virus, helper T cells direct other parts of the immune system and help coordinate an appropriate response, while killer T cells hunt down infected cells and clear them from the body. In their experiments, the researchers found mice eating a tBHQ-spiked diet were slower to activate both helper T cells and killer T cells, resulting in slower clearance of the virus.

"Right now, my leading hypothesis is that tBHQ causes these effects by upregulating some proteins which are known to suppress the immune system," said Freeborn. "Expression of these proteins, CTLA-4 and IL-10, was upregulated in two different models we use in the lab. However, more work is necessary to determine if upregulation of these suppressive proteins is indeed causative for the effects of tBHQ during influenza infection."

What's more, when the mice were later re-infected with a different but related strain of influenza, those on the tBHQ diet had a longer illness and lost more weight. This suggests that tBHQ impaired the "memory response" that typically primes the immune system to fight a second infection, Freeborn said. Since the memory response is central to how vaccines work, impairment of this function could potentially reduce the efficacy of the flu vaccine.

T cells are involved in the immune response to a variety of diseases, so tBHQ could also play a role in other types of infectious diseases, Freeborn added.

tBHQ is an additive used to prevent spoilage, with a maximum allowed concentration of 200 parts per million in food products. It is unclear how much tBHQ people are exposed to, though estimates based on model diets have suggested some U.S. consumers eat almost double the maximum allowable amount of tBHQ suggested by the Joint FAO/WHO Expert Committee on Food Additives and that people in other parts of the world may consume up to 11 times the maximum allowable amount. The level of tBHQ exposure in Freeborn's studies falls within estimates of human exposure.

"It can be hard to know if you are consuming tBHQ, as it is not always listed on ingredient labels," said Freeborn, adding that this is often the case when tBHQ is used in food preparation, such as in the oil used to fry a chip. "The best way to limit tBHQ exposure is to be cognizant about food choices. Since tBHQ is largely used to stabilize fats, a low-fat diet and cutting down on processed snacks will help reduce tBHQ consumption."

Freeborn emphasized that getting a yearly flu shot remains the best way to prevent influenza infection. Though it is possible to contract the flu after getting the vaccine, being vaccinated has been shown to significantly reduce the length and severity of the illness.

Building on their studies conducted in mice, the researchers plan to use human blood samples to further investigate how tBHQ affects T cell activity.

Robert Freeborn will present this research on Sunday, April 7, from 9 a.m.-4 p.m. in Exhibit Hall-West Hall B, Orange County Convention Center (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.