Body

NEW YORK, NY (May 16, 2021)--Brief pulses of ultrasound delivered to nerves near the kidney produced a clinically meaningful drop in blood pressure in people whose hypertension did not respond to a triple cocktail of medications, reports a new study led by researchers at Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian.

In a clinical trial of the procedure, called renal denervation, daytime blood pressure after two months had dropped 8 points compared to a 3-point drop in patients who were treated with a sham procedure. Nighttime blood pressure decreased by an average of 8.3 points in the treatment group versus 1.8 points in the sham group.

"For patients with drug-resistant hypertension, a drop in blood pressure of 8 points--if maintained over longer-term follow-up--is almost certainly going to help reduce the risk of heart attack, stroke, and other adverse cardiac events," says Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, an interventional cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center, and co-principal investigator of the trial.

"These results suggest that renal denervation has potential to become an important add-on to medication therapy--including for those who have difficulty managing several medications to control their hypertension."

Data from the trial, called RADIANCE-HTN TRIO, were presented May 16 at the American College of Cardiology conference and simultaneously published in The Lancet.

The treatment is still experimental, has not been approved for use by the FDA, and is only available through clinical trials. The trial will follow patients for five years to determine if the drop in blood pressure is maintained over time.

Need for Additional Blood Pressure-Lowering Therapies

About two-thirds of people who take medications to lower blood pressure are able to control their condition. But in others, the drugs do not work or people do not take them as directed.

"There are a variety of effective medications for lowering blood pressure, but many people need to take several drugs to control their hypertension, which can have side effects. In addition, many people simply don't want to take additional medications and are poorly adherent to them," says Kirtane. "It's clear that we need additional therapeutic approaches to help patients get their blood pressure under control."

Why Renal Denervation?

The kidney plays a role in blood pressure by controlling how much water is in the bloodstream (more water = more pressure) and acting as a central signaling center for other systems that regulate blood pressure. Renal denervation, a minimally invasive procedure, uses ultrasound energy to disrupt signals from overactive nerves in the renal arteries. The therapy is delivered via a catheter that is threaded through an artery in the leg.

Targeting these nerves is not a new idea in hypertension treatment; several existing medications reduce renal nerve activity to reduce blood pressure.

"But unlike medications, which are only effective when you take them, renal denervation is a therapy that's always 'on,'" Kirtane says.

Initial studies of renal denervation had several flaws--including the lack of an adequate control group, variable measurement of participants' blood pressure, and frequent changes in background medications--that made the results challenging to interpret.

How the Study Worked

In this study, the researchers tested the effectiveness and safety of a device that delivers two to three short blasts of ultrasound to nerve fibers that travel close to the renal artery.

The study included adults with moderate to severe hypertension despite taking three or more antihypertensive drugs. All of the patients were switched to the same medication regimen for their hypertension. (To help with patient adherence, participants took a single pill that combined three commonly used antihypertensive drugs.)

"In our study, 80% of patients continued to take their medication as directed, and while that's a good adherence rate, it still means that one in five patients weren't adherent to the medication regimen," Kirtane adds.

Of 136 patients whose blood pressure remained high after four weeks on the new regimen, 69 were treated with renal denervation and 67 had the sham procedure.

Previous studies in patients with less severe hypertension who were not taking any antihypertensive medications showed that renal denervation was more effective than a sham procedure in lowering blood pressure.

"Additional studies will be needed to determine if this therapy may be effective for other groups, including older patients with hypertension and those with chronic kidney disease," says Kirtane.

An innovative cardiac rehabilitation intervention started earlier and more custom-tailored to the individual improved physical function, frailty, quality-of-life, and depression in hospitalized heart failure patients, compared to traditional rehabilitation programs. Supported by the National Institute on Aging (NIA), part of the National institutes of Health, these new study results were published May 16 in the New England Journal of Medicine and also presented at the American College of Cardiology's 70th Annual Scientific Session.

"Designing earlier and more personalized individual-specific approaches to heart failure rehab shows great promise for improving outcomes for this common but complex condition that is one of the leading causes of hospitalization for older adults," said NIA Director Richard J. Hodes, M.D. "These results mark encouraging progress on a path to better overall quality of life and physical function for the millions of older Americans who develop heart failure each year."

For this new study, a research team led by Dalane W. Kitzman, M.D., professor of cardiovascular medicine and geriatrics/gerontology at Wake Forest School of Medicine, Winston-Salem, North Carolina, followed 349 clinical trial participants with heart failure enrolled in "A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients" (REHAB-HF). Participants had an average of five comorbidities -- diabetes, obesity, high blood pressure, lung disease or kidney disease -- that also contributed to loss of physical function.

In an earlier pilot study, Kitzman and his colleagues at Duke University, Durham, North Carolina, and the Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, found striking deficits in strength, mobility and balance, along with the expected loss of endurance in older patients with acute heart failure, the vast majority of whom were categorized as frail or pre-frail. The team decided to focus on improving patients' physical function, which already weakened by chronic heart failure and age, was worsened by the traditional cardiac hospital experience featuring lots of bedrest and resulting in loss of functions that tended to persist after discharge.

The REHAB-HF team designed earlier and more customized exercise programs that emphasized improving balance, strength, mobility and endurance. They also began REHAB-HF during a patient's hospital stay when feasible instead of waiting until the traditional six weeks after discharge. After release from the hospital, the study participants shifted to outpatient sessions three times per week for three months.

Compared to a control group that received usual cardiac rehab care, REHAB-HF participants showed marked gains in measures of physical functioning and overall quality of life, including significant progress in Short Physical Performance Battery, a series of tests to evaluate lower extremity function and mobility, and a six-minute walk test. They also had notable improvements in self-perception of their health status and depression surveys compared to pre-trial baselines. More than 80 percent of REHAB-HF participants reported they were still doing their exercises six months after completing their participation in the study.

"These findings will inform choices of heart failure rehabilitation strategies that could lead to better physical and emotional outcomes," said Evan Hadley, M.D., director of NIA's Division of Geriatrics and Clinical Gerontology. "Tailored interventions like REHAB-HF that target heart failure's related decline in physical abilities can result in real overall benefits for patients."

Research led by scientists at Children's Cancer Institute and published this week in the international journal, Clinical Cancer Research, has found a combination of therapies that appears to be highly effective against high-risk neuroblastoma and other forms of aggressive childhood cancer.

Up to half of all cases of neuroblastoma newly diagnosed in children are 'high-risk', meaning the cancer grows aggressively and is difficult to treat. Despite receiving intensive treatment, most children with high-risk disease die within five years of diagnosis, while those who survive are often left with serious long-term health effects.

Professor Michelle Haber AM, a senior author on the paper and co-head of the Molecular Targets and Cancer Therapeutics theme at Children's Cancer Institute, said children diagnosed with high-risk neuroblastoma have less than a 50-50 chance of survival. "That is a devastating prognosis. We are absolutely determined to find better ways to treat this disease and improve that survival rate."

The research focuses on two different types of therapies, both of which have been found to be effective against high-risk neuroblastoma in the laboratory. The first, CBL0137, is a compound called a curaxin, structurally similar to antimalarial drugs. The second is panobinostat, a new type of compound known as a histone deacetylase inhibitor. In the new research, the scientists tested whether the two therapies could work synergistically when used together, each enhancing the anticancer effect of the other.

The researchers found that the two compounds did indeed work well together, effectively inhibiting the growth of cancer cells in culture, as well as in mice bred to develop human high-risk neuroblastoma. As an added bonus, the therapies also jointly acted to heighten the body's immune response to cancer, which is important since immunotherapy in neuroblastoma is currently challenging.

"In our experiments, we found that the combination of CBL0137 and panobinostat resulted in remarkable growth suppression and an immune response that was tumour-specific," said Professor Haber. "This is very encouraging, because ideally you want a cancer treatment to specifically target cancer cells and leave healthy cells unharmed, reducing the problem of side effects."

Dr Lin Xiao, joint first author and Research Officer in the Experimental Therapeutics Group at the Institute added, "When we used these two compounds together in mice with high-risk neuroblastoma, we saw complete and lasting tumour regression, with minimal ill-effects on the mice. Our results suggest that this combination could work well as a type of immunotherapeutic approach to treating high-risk neuroblastoma."

Further research at Children's Cancer Institute has shown that this type of multimodal therapy is also effective against other high-risk childhood cancers, including some forms of brain cancer. Together, it is hoped these results will lead to a new therapy for aggressive childhood cancer.

Scientists at UCL have identified a new immunotherapy to combat the hepatitis B virus (HBV), the most common cause of liver cancer in the world.

Each year, globally, chronic HBV causes an estimated 880,000 deaths from liver cirrhosis and hepatocellular carcinoma/liver cancer (HCC).

The pioneering study used immune cells isolated directly from patient liver and tumour tissue, to show that targeting acyl-CoA:cholesterol acyltransferase (ACAT), an enzyme that helps to manage cholesterol levels in cells*, was highly effective at boosting immune responses.

Published in Nature Communications, the findings show that blocking the activity of ACAT with ACAT inhibitors boosts the specific immune cells that can fight both the virus and associated cancerous tumours, demonstrating its effectiveness as an immunotherapy. Inhibiting ACAT was also found to impede HBV's own replication, thereby also acting as a direct antiviral. ACAT inhibitors such as avasimibe, taken orally, have previously been shown to be well-tolerated as cholesterol-lowering drugs in humans.

Explaining the study, lead author Professor Mala Maini (UCL Division of Infection & Immunity), said: "Chronic hepatitis B virus infection is a major global health problem and the most common cause of liver cancer in the world.

"The development of novel therapeutic options is crucial to improve patient care. Immune cells such as T cells are indispensable for fighting viruses and tumours but are often highly dysfunctional and fail to control these diseases. Current standard of care treatments are often incapable of eliminating the virus, do not prevent cancer development and do not rescue immune cells.

"In this study we aimed to identify a treatment target to directly inhibit the virus while also boosting the immune cells fighting it."

Cholesterol is a lipid (fat) that we ingest every day in our diets and that can exert multiple functions within different cells of the body. HBV infects the liver, an organ highly enriched in cholesterol and well known for limiting local immune responses.

In this study, using human liver disease tissue samples in vitro, Professor Maini's lab at UCL showed that ACAT inhibitors boosted human antiviral T cells capable of eliminating the virus. This response is in contrast to currently available therapies. The immune-boosting effect was especially striking in T cells found in the HBV-infected liver and within liver cancer, overcoming the local restraints on immune cell function, allowing the T cells to target both the virus and cancerous cells.

The Maini group then collaborated with Professor Jane McKeating's lab at the University of Oxford to show that ACAT inhibitors could also block the HBV life cycle in a way that other antivirals are unable to. These drugs therefore have a unique combination of antiviral and immunotherapeutic effects.

Commenting on the findings, first author Dr Nathalie Schmidt (UCL Division of Infection & Immunity), said: "We have found a highly effective novel target for the treatment of chronic hepatitis B virus infection and liver cancer.

"Modulating cholesterol metabolism with ACAT inhibitors has the unique features of directly targeting the virus and tumours while at the same time boosting the T cells that fight them. This enables us to tackle the disease from multiple directions at the same time."

Dr Schmidt added: "The cholesterol-modifying drug is already known to be safe in humans and we hope that our study now informs the development of clinical trials combining cholesterol modulation with other immunotherapies. In summary, our findings offer exciting new possibilities for the treatment of patients with chronic viral infections and cancer."

This research was carried out by researchers at UCL, supported by the University of Oxford, the Royal Free London NHS Trust, and Leiden University Medical Centre, the Netherlands.

Grant funding came from the Wellcome Trust and Cancer Research UK.

*The enzyme is required for cholesterol esterification, a mechanism which prevents excessive cellular levels of cholesterol, which can be toxic to cells.

A new study led by University of Liverpool researchers has confirmed that children with cystic fibrosis (CF) in the US have better lung function than UK children with the disease.

The study suggests that differences do not appear to be explained by early growth or nutrition, but could be linked to differences in the use of early treatments.

This long-term analysis follows a 2015 study comparing UK and US CF populations in the year 2010, which first highlighted potential differences in lung function.

CF is a serious, multi-organ inherited disease characterised by pulmonary infections and progressively declining lung function. Most people with CF die prematurely from their disease through respiratory failure. In the 1960s, median survival in the UK was estimated to be below 10 years of age. In the decades since, outcomes have improved due to multidisciplinary care, nutritional support and new treatments, such that half of the babies born with CF in the UK and the US today can be expected to live at least in to their late 40s.

The study compared longitudinal trajectories of lung function in children aged 6-18 with CF and homozygous F508del genotype between the US and UK, and explored reasons for differences between them. Data used was captured between 2003-2014.

Corresponding Author Dr Daniela Schlüter said: "It is important to understand the causes of the observed differences and it is really exciting that the CF Registry data are available to help us gain potentially valuable insights into optimal treatment and care. For example, we found that children in the US received more aggressive mucolytic therapy earlier in life than children in the UK. Further research will be needed to unpick the impact of different treatment patterns and study further potential underlying causes.

"Our study was limited to people aged 6-17 who were homozygous for the F508del mutation and used data that pre-ceded the licensing of CFTR modulator therapies. Therefore, the results may not apply to people over the age of 18 or those with a different genotype, and the introduction of modulators may have changed the observed trend."

Researchers used mixed effects regression analysis to model lung function trajectories in the study populations captured in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) and UK Cystic Fibrosis Registry. Using descriptive statistics, they compared early growth and nutrition (height, weight, BMI), infections (P.aeruginosa, S.aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics).

The research team included clinicians from the US and the UK alongside colleagues from the Cystic Fibrosis Trust and Cystic Fibrosis Foundation.

Rebecca Cosgriff, Director of Data and Quality Improvement at the Cystic Fibrosis Trust, said: "This study is an excellent example of the power of cystic fibrosis Registries, made possible through the support of people with cystic fibrosis and their clinical teams. We're grateful for the collaboration of the Cystic Fibrosis Foundation (CFF), which has surfaced invaluable insights. Since this study was undertaken, access to modulator therapies has increased dramatically. Comparative studies will continue to play an important role as we work to ensure people in the UK have the best possible treatment for cystic fibrosis."

Bethesda, MD (May 14, 2021) -- Combining minimally invasive endoscopic sleeve gastroplasty (ESG) with the diabetes drug semaglutide can provide additional significant weight loss for patients who are not candidates for invasive weight-loss surgery, according to research that was selected for presentation at Digestive Disease Week® (DDW) 2021.

"As the worldwide obesity rate continues to climb, so do the number of people seeking bariatric surgery to treat their condition," said Anna Carolina Hoff, MD, lead researcher on the study and founder and clinical director of Angioskope Brazil, São José dos Campos. "Surgical procedures are some of the most successful ways to help patients lose weight, but they can eventually come with complications. Our study shows that patients may not have to undergo invasive surgery to get similar results."

In a double-blind study, researchers randomized 61 patients undergoing ESG into two groups with one group of 29 patients receiving semaglutide -- an injectable glucagon-like peptide-1 receptor that has been known to stimulate weight loss -- beginning one month after the procedure. Another group of 29 patients received a placebo administered with look-alike injector pens. Three patients were lost to follow-up. Participants were monitored each month for body weight and body composition, and blood panels were taken every three months.

Patients who received semaglutide lost on average 26.7 percent of their total body weight compared to the control group, which on average lost 19.6 percent of total body weight. The semaglutide group lost 86.3 percent of their excess weight -- the amount of weight the patients needed to lose to reach normal BMI -- compared to 60.4 percent for the control group. The semaglutide group also lost 12.7 percent of their body fat by weight compared to 9 percent for the control group. Finally, glycated hemoglobin (Hb1Ac) levels fell 0.95 for the semaglutide group and 0.61 for the controls.

Surgical procedures, such as laparoscopic sleeve gastrectomy, come with increased costs and a higher risk for complications, such as gastroesophageal reflux disease, or GERD. These surgical procedures are typically limited to those with a BMI of at least 35 with comorbidities, or with a BMI above 40. ESG can be performed at an earlier stage of the disease and at a lower BMI, so more patients can get the treatment they need before their disease progresses. Treating patients with obesity earlier can help reduce death and comorbidities as well as reduce costs associated with treatments for these conditions.

"ESG has been available to patients for years, but it has not always been as successful as surgical options in helping patients lose weight," said Dr. Hoff. "We now have a minimally invasive procedure that can be just as successful when combined with semaglutide and can be made available to even more people looking to lose a significant amount of weight."

ESG is performed by guiding a device through the patient's throat and into the stomach, where an endoscopist uses sutures to make the stomach smaller. This helps patients lose weight by limiting the amount they can eat. Patients are candidates for ESG if they have a BMI at or above 30, and diet and exercise have not helped them lose weight, or if they are not a candidate for surgery, or do not wish to pursue surgery.

The researchers caution that long term durability of the treatment still needs to be determined.

DDW Presentation Details

Dr. Hoff will present data from the study, "Semaglutide in association to endoscopic sleeve gastroplasty: Taking endoscopic bariatric procedures outcomes to the next level," abstract Su548, on Sunday, May 23, at 12:15 p.m. EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

Bethesda, MD (May 14, 2021) -- Inpatient consults for alcohol-related gastrointestinal (GI) and liver diseases have surged since the beginning of the COVID-19 pandemic and remained elevated, according to research selected for presentation at Digestive Disease Week® (DDW) 2021. The proportion of patients that required inpatient endoscopic interventions for their alcohol-related GI and liver diseases has also increased, highlighting an apparent worsening trend in the severity of disease.

"When we went into lockdown, many people experienced significant negative impacts, such as social isolation, job loss and an increase in anxiety and depression," said Waihong Chung, MD, PhD, lead researcher of the study and a research fellow for the Division of Gastroenterology at the Warren Alpert Medical School of Brown University, Providence, Rhode Island. "These experiences may have led people to increase their alcohol consumption, which could explain why we are seeing a surge in the volume of consultations for alcohol-related diseases."

Researchers conducted a hospital system-wide audit of all inpatient GI consults performed during the lockdown and re-opening phases in Rhode Island during the COVID-19 pandemic. The data was compared to the same timeframe in 2019 to determine the degree of changes in disease burden for alcohol-related GI and liver conditions.

While the total number of all GI consults declined by 27 percent during lockdown -- due to restrictions on hospital visits -- the proportion of consults for alcohol-related GI and liver diseases increased sharply by 59.6 percent, including alcohol-related forms of hepatitis, cirrhosis, pancreatitis and gastritis, researchers found. In comparison, there were no significant changes in the proportions of consults for non-alcohol-related liver diseases, biliary obstruction/injury, inflammatory bowel diseases or gastrointestinal bleeding.

"In further analysis, we noted that during the lockdown phase, the majority of admission for alcohol-related GI and liver diseases clustered around weeks five, six and seven of lockdown," Dr. Chung said. "This timeframe mirrors the length of time it takes for symptoms to appear for these diseases, suggesting the start of the pandemic may have had an impact on patients' alcohol consumption."

In the reopening phase, the total volume of all GI consults was restored to full pre-pandemic levels and the proportion of consults for alcohol-related GI and liver diseases remained highly elevated by 78.7 percent. Furthermore, patients presenting with alcoholic hepatitis more than doubled (127.2 percent) compared to 2019 and those requiring inpatient endoscopic procedures were considerably higher (34 percent vs. 12.8 percent).

Because many people who have alcohol-related diseases are not admitted to a hospital right away, researchers believe health problems related to increased alcohol consumption could be even higher in the community. They encourage primary care physicians and gastroenterologists to double-down on questioning patients about their alcohol consumption to identify anyone who might need help sooner rather than later.

"Validated screening tools, such as the CAGE questionnaire [for alcohol use], only take a minute to administer and offer reasonable sensitivity and specificity for alcohol use disorders," Dr. Chung suggested.

The National Institute on Alcohol Abuse and Alcoholism defines heavy drinking as consuming more than four drinks on any day or more than 14 drinks per week for men; and consuming more than three drinks on any day or more than seven drinks per week for women.

"Alcohol-related GI or liver diseases may cause sudden weight gain, yellowing of the skin, confusion, fatigue, decreased appetite, black stool and/or severe abdominal pain," said Dr. Chung. "I encourage anyone who is experiencing these symptoms as well as anyone who is concerned about his or her own drinking to see a physician as soon as possible."

DDW Presentation Details

Dr. Chung will present data from the study, "Increased burden of alcohol-related gastrointestinal and liver diseases during the COVID-19 pandemic: A hospital system-wide audit," abstract 436, on Saturday, May 21, at 1:50 p.m. EDT. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit http://www.ddw.org/press.

What The Study Did: Researchers analyzed changes in filled prescriptions for naloxone (medication to reverse opioid overdoses) during the COVID-19 pandemic in the United States and compared them with changes in opioid prescriptions and overall prescriptions.

Authors: Ashley L. O'Donoghue, Ph.D., of the Beth Israel Deaconess Medical Center in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamahealthforum.2021.0393)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

What The Study Did: Associations of staffing and testing interventions with COVID-19 transmission in nursing homes are examined in this decision analytical modeling study.

Authors: Rebecca Kahn, Ph.D., of the Harvard T.H. Chan School of Public Health in Boston, is the  corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.10071)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

People with a high polygenic risk score for colorectal cancer could benefit more at preventing the disease by leading healthy lifestyles than those at lower genetic risk, according to a study by Vanderbilt researchers published in the April issue of The American Journal of Clinical Nutrition.

Analyzing data from participants in the UK Biobank, the researchers estimated that maintaining a healthy lifestyle was associated with a nearly 40% reduction in colorectal cancer risk among those with a high genetic risk of developing the disease. The percentage dropped to only about 25% among people at a low genetic risk for this cancer. People with a high genetic risk and an unhealthy lifestyle were more than three times as likely to be diagnosed with colorectal cancer than those with a low genetic risk and a healthy lifestyle.

"Results from this study could be useful to design personalized prevention strategies for colorectal cancer prevention," said Wei Zheng, MD, PhD, MPH, Anne Potter Wilson Professor of Medicine and associate director for Population Sciences Research at Vanderbilt-Ingram Cancer Center (VICC).

In the analysis, lifestyle scores of unhealthy, intermediate and healthy were determined according to waist-to-hip ratio, physical activity, sedentary time, processed and red meat intake, vegetable and fruit intake, alcohol consumption and tobacco use. Polygenic risk scores are used to measure genetic susceptibility to colorectal cancer. Vanderbilt researchers constructed polygenic risk scores using genetic variants associated with colorectal cancer risk identified in recent large genetic studies including more than 120,000 study participants. They also constructed polygenetic risk scores for several other common cancers in research that was published last year in JNCI Cancer Spectrum.

The recently published study in The American Journal of Clinical Nutrition is one of the few that quantifies potential interactions of overall lifestyle with genetic susceptibility to colorectal cancer.

Epidemic. Pandemic. These terms have become second nature to us, popping up in everyday conversation, and for good reason -- COVID-19 is the latest pandemic to pose a threat to humanity.

But in recent months, far less attention has been paid to another widely spread problem that has been proliferating since the late 1970s: Lyme disease.

Lyme disease is the most reported vector-borne disease in the country. Over the past 20 years, the United States has experienced a dramatic increase in both the number of reported cases and the geographic distribution of the disease. In Virginia, the disease is transmitted by blacklegged ticks, which are infected with the Lyme disease-causing bacterium Borrelia burgdorferi.

Virginia Tech Assistant Professor Brandon Jutras and his lab have continued to tackle the Lyme disease epidemic over the past year, and they have recently identified another missing piece of the Lyme disease puzzle.

"This discovery furthers our understanding of how Borrelia burgdorferi causes inflammation and disease," said Mari Davis, who is the lead author on the paper, a former master's graduate of the Jutras lab in the Department of Biochemistry in the College of Agriculture and Life Sciences. "It is a testament to how unique that this bacterium is -- and how we need to keep working to understand more about what is going on behind the scenes in order to develop future diagnostics and treatments."

Their findings were recently published in PLOS Pathogens, a peer-reviewed open-access medical journal.

Almost all bacteria, including the Lyme disease-causing bacterium, make a mesh-like bag to protect the inside of their cells. This bag is known as peptidoglycan. In 2019, Jutras identified peptidoglycan, a lingering cell wall component of the bacterium Borrelia burgdorferi, as a likely culprit of the inflammation and Lyme arthritis, the most common late-stage symptom of Lyme disease.

Jutras' previous research has shown that peptidoglycan in Borrelia burgdorferi lingers in the bodies of Lyme arthritis patients after the bacteria has entered the body. Weeks to months after the initial infection, the peptidoglycan remains, inciting inflammation and pain.

In this newest development, the lab discovered a protein associated with the peptidoglycan of Borrelia burgdorferi that plays an amplifying role in causing inflammation in Lyme arthritis patients by acting as a molecular beacon that antagonizes the patients' immune system.

Using an unbiased proteomics approach and The Mass Spectrometry Research Incubator (VT-MSI) from the Fralin Life Sciences Institute's Core Services, the team identified the protein to be NapA. NapA, which stands for Neutrophil Attracting Protein A, is a remarkable immunomodulatory molecule that is able to recruit immune cells, called neutrophils, toward the inflammatory peptidoglycan.

"We are thrilled about Dr. Jutras' NapA discovery, publication, and the implications for Lyme disease diagnostics and treatment. His research perfectly aligns with our institute's vision to impact society by taking a problem-centric approach to tackling environmental and life sciences-related global challenges," said Matt Hulver, executive director of the Fralin Life Sciences Institute.

"NapA is another piece to an ever-evolving puzzle; it seems to play a basic role in everyday bacterial life by helping the overall protective properties of peptidoglycan, but it moonlights as a devious protein capable of tricking our immune system," said Jutras, an affiliated faculty of the Fralin Life Sciences Institute and the Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens.

"We believe NapA's devious side has two modes: Early in infection, when bacteria are dying and releasing NapA and peptidoglycan, it acts as a decoy to attract immune cells, which allows the viable bacteria to escape and cause disease. In later stages of disease, it may act to attract immune cells to peptidoglycan, a molecule capable of causing inflammation and arthritis," Jutras said.

To determine how NapA attracted neutrophils, Davis sought out Caroline Jones, who was an assistant professor in the Department of Biological Sciences in the Virginia Tech College of Science at the time of the discovery. Her lab specializes in the study of neutrophil chemoattraction. Jones placed neutrophils in the middle of a microfluidic chip, which acts as a maze that cells can wander through. On one side of the chip, there was pure peptidoglycan, on the other was peptidoglycan with NapA.

The Jones and Jutras labs showed that neutrophils rapidly migrate toward the side with NapA, proving that the protein is able to give off chemical signals that attract neutrophils in the direction of it, and peptidoglycan.

With this new piece to the puzzle in hand, Jutras plans to add to the lab's current efforts to improve the diagnostic testing and treatment of Lyme disease.

"From a prevention and diagnostic perspective, it's possible that the combination of peptidoglycan and NapA could be a novel target for diagnostics," Jutras said. "It could, in theory, be a possible avenue of vaccine development as well. These are big picture possibilities that we are actively pursuing. One thing that we know for sure is that this finding furthers our understanding of how peptidoglycan can drive Lyme arthritis patient symptology."

CHICAGO --- For men physicians, the professional perks of networking on social media, like being asked to give a talk, are abundant, a new Northwestern Medicine study reports.

For women physicians, the benefits are far less plentiful, the study found.

What's more, women physicians are more than twice as likely to be sexually harassed on social media than men physicians, according to an earlier study, published in January, of this same group of study participants.

The findings mirror the struggles women physicians face in person when trying to advance their careers, said first author Nicole Woitowich, research assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine.

"There's been this line of thinking that social media can be used to level the playing field and give women equal opportunities, but it turns out the same biases that promote men are occurring online as well," Woitowich said. "Women are not reaping the benefits of social media, and they're doing so in the face of more online harassment."

The study will be published May 13 in the journal JAMA Network Open.

"Our study makes it even more clear that it is necessary to be intentional in how we engage on social media, and the importance of amplifying women, minorities and those with intersectional identities," said senior author Dr. Shikha Jain, a hematologist and oncologist at University of Illinois Chicago. "There are many benefits that can come from engaging online, as has been shown in other studies, but pitfalls that exist in the real world are just as prevalent in the digital space."

The data also suggest these gender biases may be occurring in other, nonmedical, fields that are traditionally dominated by men, which is worrisome, as a majority of interpersonal interactions have shifted online during the pandemic, Woitowich said.

'I use social media to ...'

In the study, "Gender Differences in Physician Use of Social Media for Professional Advancement," 577 participants completed a survey the study authors sent via traceable links on Twitter between Feb. 6 and March 20, 2019.

Participants could choose to identify as "female," "male," "non-binary/third gender" and "prefer to self-describe." No respondents identified as "non-binary/third gender" or "prefer to self-describe." Anyone who identified as "prefer not to say" were excluded from further analysis.

The survey asked respondents to answer if they agreed or disagreed with questions such as "social media has increased my collaborators with individuals at other institutions," "social media has directly led to a speaking opportunity or engagement" and "social media has resulted in a scholarship opportunity."

While both men and women physicians said that they have expanded their professional network through social media, men were more likely to receive requests to give talks (39% of men respondents versus 30% of women respondents) and participate in other scholarly activities (25% of men versus 21% of women) than women.

While men in the study reported being more likely to use social media for research and educational purposes (83% of men versus 68% of women), women in the study said they were motivated to use social media for additional social support (73% of women versus 55% of men). Woitowich said this is likely because men in academic medicine do not face the same levels of sexual and verbal harassment and gender discrimination as women and thus don't need an outlet to seek advice and counsel from their same-gendered peers.

"We did not address this in our survey, but it may be likely that women also use social media to voice and address these gender inequities," Woitowich said. "Simply put, women physicians may not be afforded the luxury of browsing social media solely for scholarly purposes."

"There are strategies and solutions to ensure these inequities do not persist," Jain said. "Groups such as Women of Impact and the Women in Medicine Summit have created strategic social media amplifiers to lift up the voices of those that are often underrepresented. Others, such as IMPACT and Dear Pandemic, have leveraged social media to collaboratively lift up the voices of women experts while also becoming trusted resources during the COVID-19 pandemic."

White evangelicals are best persuaded to mask up through messages that stress the Christian doctrine of "love thy neighbor," according to a UCR-authored study published Tuesday.

The study yielded a second effective way to persuade white evangelicals - but only if they are Republican. That is, messaging from former President Donald Trump that aligns mask-wearing with patriotism.

The lessons learned from the study can be borrowed for pro-vaccine messaging, said study author Jennifer Merolla, a UCR professor of political science.

About 45% of white evangelicals do not plan on getting vaccinated against COVID-19, according to a Pew Research Center poll. Health officials have said persuading the 41 million white evangelical adults in the U.S. to get vaccinated is key to acquiring herd immunity.

"Our research is relevant to vaccines: messages that align with values can change attitudes in ways useful to mitigating the toll of the COVID-19 pandemic," Merolla said.

Since early in the COVID-19 pandemic, the Centers for Disease Control and Prevention and other health officials have advocated for wearing protective face coverings to protect against the airborne particles that can transmit the virus, which has claimed 582,000 lives in the United States.

But, as noted in the new journal article, conservative media and Republicans - most significantly Trump - have been alternately ambiguous and hostile toward the practice.

"Trump sometimes wears a mask and occasionally advocates for masks," the study authors wrote. "But, he often holds events without masks and ridicules opponents for wearing them. Not surprisingly, pandemic- and mask-skepticism has been pervasive among Trump's base."

For the study, the authors targeted 1,500 white evangelicals across the U.S. this past summer via the online surveying platform YouGov to determine which pro-masking messaging would prove most persuasive. The study was engineered to be representative of the white evangelical population: 56% of the study group identified as Republicans, 31% as independent or "other," and 11% as Democrats.

The study's expectation: Messages that align with an individual's values are more likely to move attitudes toward positions an individual would not normally support.

And so the participants were randomly divided into three groups. Group one was offered a religious message, that wearing a mask is a way to love your neighbor. Group two was provided a Twitter message from Trump encouraging mask use as a form of patriotism. The third group, the control group, received no messaging.

The subjects in group one were most likely to be persuaded masks are helpful. The group that received the Trump message also was persuaded - but they were much more likely to be persuaded if they identified as Republicans.

When asked whether it's important for people in their communities to wear masks, there was a significant uptick among those exposed to the religious messaging versus the control group. The Trump messaging did little to incite pro-masking beliefs, with only those identifying as Republicans responding.

Asked about mask mandates, control group support was low, at 34%. The religious message boosted support to 43%; the Trump-patriotism message increased support to 41% - with the strongest support again demonstrated by Republicans.

Researchers at Hospital for Special Surgery (HSS) have identified gaps in patient knowledge about pain management and opioid use before total hip replacement, including misconceptions about how much pain relief to expect from opioids after surgery, how to use multiple modes of pain relief (multimodal analgesia) safely and effectively, and proper opioid storage and disposal. These findings were presented at the 2021 Spring American Society of Regional Anesthesia and Pain Medicine (ASRA) Annual Meeting.1

"Patients who are not taught about opioids and pain management may have difficulty with pain control and worse functional outcomes after total joint replacement," explained principal investigator Bradley Lee, MD, an anesthesiologist at HSS.

While research has shown benefits to educating patients about opioids, little is known about what patients understand about pain management prior to surgery.

Dr. Lee and colleagues interviewed patients via a 15-minute phone call to learn about their perceptions of pain management and opioid use. Eligible patients included those between ages 18 and 80 undergoing total hip replacement who are English-speaking with a reading comprehension above the eighth grade level. Survey questions were written by Dr. Lee in collaboration with members of the HSS Controlled Substances Task Force, an interdisciplinary committee focused on evidence-based opioid prescribing. Patients were instructed to answer the questions to the best of their ability, and if unsure to respond "I don't know."

Responses to the interviews revealed that while many patients acknowledge experiencing some pain after surgery is normal and that opioids should be used to reduce pain that limits function, many also believed that the goal of opioid use should be to experience minimal or no pain after surgery, reflecting somewhat inconsistent expectations.

Many patients were aware of the potential risk of addiction from opioid use. However, many did not understand the role of multimodal analgesia--that multiple forms of pain relief should be used in combination to better relieve pain, and that use of non-steroidal anti-inflammatory drugs (NSAIDs) can improve pain after surgery and reduce opioid use.

There were also gaps in patient understanding of opioid use and disposal. While many recognized the importance of keeping opioids away from children, only 15% recognized the importance of locking up these medications. The researchers also found that about half of patients were unsure of how to properly dispose of opioids.

These results show potential areas of patient education that could improve patient expectations and satisfaction, pain relief, and safety. "Patients may benefit from clinicians providing a consistent message on pain expectations and the goal of using opioids after surgery to treat pain. Patients may also benefit from education about the role of multimodal analgesia, as well as proper methods of storage and disposal," Dr. Lee noted.

"Future research should focus on educational interventions that address gaps in patients' understanding of opioids and pain management. Research should seek to identify which interventions are effective and how they affect outcomes," he concluded.

Researchers at Hospital for Special Surgery (HSS) have identified risk factors for persistent opioid use after surgery in pediatric patients.1 Study findings were presented at the 2021 Spring American Society of Regional Anesthesia and Pain Medicine (ASRA) Annual Meeting.

Previous research indicates that prescription patterns for opioids after surgery in children and adolescents may be associated with long-term use and abuse.2

"Pediatric patients have developing brains that are uniquely vulnerable to addiction, and we need to learn to treat their pain safely without putting them at additional risk for opioid misuse," said principal investigator Kathryn (Kate) DelPizzo, MD, an anesthesiologist at HSS.

It is therefore critical for clinicians to understand risk factors for opioid dependence in this vulnerable population, and to develop strategies to prevent long-term opioid use.

Dr. DelPizzo and colleagues examined insurance claims from Truven Health Marketscan data from patients under the age of 21 who underwent inpatient or outpatient surgery from 2013 to 2017. The primary outcome examined was persistent opioid use after surgery, defined as one or more additional filled opioid prescriptions between 90 and 180 days post-surgery.

Out of more than 3.7 million patients, about 9% (N=345,523) filled at least one opioid prescription within six months after surgery, and 0.3% (N=11,334) developed ongoing opioid use.

Several risk factors were identified for persistent opioid use: older age, female sex, earlier year of undergoing surgery (e.g., 2013 versus 2014 through 2017), higher burden of comorbidities, previous use of antidepressants, residence outside of the Northeastern United States, having undergone an inpatient or a musculoskeletal procedure (versus general surgery or other specialties), and previous opioid use.

"This data gives an indication that providers may be able to use a patient's baseline characteristics to predict which children and adolescents are most at risk for trouble with opioids during the postsurgical period," Dr. DelPizzo noted.

HSS is committed to patient safety and being a leader in effective pain management. Its Controlled Substances Task Force continues to make strides in patient education and safe prescribing.

In addition to this study, HSS is ramping up further research on opioids with the help of a $3 million grant from the Starr Foundation. "Future research should explore what practical methods can be put into place to identify these at-risk pediatric patients and how to streamline protocols to help prevent long-term opioid dependence in these patients," Dr. DelPizzo concluded.