Many U.S. Travelers Don’t Get Measles Shot

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A study led by Massachusetts General Hospital investigators found that many U.S adults travel abroad without first getting the full recommended course of measles vaccines. Researchers are now looking to find ways to increase the vaccination rate in order to protect travelers and the people they come in contact with back home.

The measles virus is a highly contagious disease that spreads through the air via coughing and sneezing. Even though a case of measles can be limited to fever, rash and cough, many cases can be severe and require hospitalization. The virus has been contained in the United States thanks to the introduction of the measles vaccination in the 1960s, but it remains a common disease in many parts of the world. Right now there are outbreaks in Germany, Italy and Romania.

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Emily Hyle, MD, MSc

“Measles has been eliminated in the U.S. since 2000, which means that all measles cases in the country can be traced back to an imported case,” says Emily Hyle, MD, MSc, of the MGH Division of Infectious Diseases, lead and corresponding author of the report in Annals of Internal Medicine. “Since more than 60 percent of the measles importations into the country are due to returning U.S. travelers, increasing the number of travelers who are immune to measles will reduce the number of measles cases.”

The Advisory Committee on Immunization Practices recommends two documented doses of the measles, mumps, rubella (MMR) vaccine for adults traveling outside the U.S. who were born after 1956 and don’t have documented evidence of either two prior vaccinations, a previous measles infection or protective anti-measles antibodies in their blood.

Researchers gathered data from questionnaires filled out by 40,810 patients at 24 clinics nationwide that provide pre-travel health advice and vaccinations. Of the 6,612 respondents who were vaccine-eligible, approximately 1,730 refused a vaccination when offered one during the pre-travel clinical visit. The top reason for refusal was a lack of concern about measles; other reasons included concerns about vaccine safety and concerns about costs.

“Our results also suggest ways to improve the rate of MMR immunization among eligible travelers,” says Hyle. “We can definitely improve how often providers specializing in pre-travel medical advice offer MMR vaccine to eligible travelers and encourage clear discussions with patients about the risks of contracting measles and of spreading the disease after their return to the U.S.”

Hyle is as an infectious disease clinician investigator at Mass General exploring ways to improve outcomes for patients with HIV and to measure the effectiveness of medical interventions to prevent disease transmission during international travel. Read more about her work in a recent interview with the Research Institute.

Regina C. LaRocque, MD, MPH, of the MGH Division of Infectious Diseases, is senior author of the paper. Drs. Edward Ryan, MD, and Rochelle Walensky, MD, MPH, both of the MGH Division of Infectious Diseases, are co-authors.

Mass General Researchers Investigate the ‘Big Eaters’ of the Immune System: #MacrophageMonday

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Macrophage in the body. Credit: Cell Press

Macrophages serve a vital function in the body’s immune system— these white blood cells are in charge of engulfing pathogens, foreign materials and dead cells.

Two new studies from Massachusetts General Hospital researchers have identified two unexpected roles that macrophages play in the body. In the heart, macrophages play a beneficial role, helping heart muscle cells maintain a steady heartbeat. When it comes to fighting cancer, however, macrophages appear to play a detrimental role by interfering with immunotherapy treatments.

Macrophages prove helpful in maintaining a steady heart beat

Researchers have known for decades that macrophages can be found in high numbers around inflamed or diseased hearts to help heal damaged tissue. However, macrophages’ function in healthy hearts has remained a mystery. A new study from Matthias Nahrendorf, MD, PhD, Director of the Mouse Imaging Program at the Center for Systems Biology at Mass General, suggests that macrophages help the heart function properly and keep its rhythm.

The research began when an MRI and an electrocardiogram of a mouse heart that was genetically engineered to lack macrophages revealed that it was beating too slowly. Comparative tests of a healthy mouse heart revealed that large quantities of macrophages could be found at the atrioventricular node, which passes electricity from the atria to the ventricles of the heart.

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Heart cells (red) and macrophages (green) in a human atrioventricular node.
Credit: Maarten Hulsmans & Matthias Nahrendorf

Nahrendorf and his team found that these congregated macrophages lend a helping hand by facilitating the conduction process — they prepare heart cells for continuous bursts of electricity by creating gap junctions to connect the cells to each other so the electrical current that regulates heartbeat can flow through smoothly.

This study is a giant step forward in understanding how the heart works and communicates with the body’s cells. Nahrendorf plans to continue investigating the relationship between macrophages and conduction in the heart to answer more unresolved questions.

When macrophages rebel

Another recent study from Mikael Pittet, PhD, of the Center for Systems Biology at Mass General, suggests that macrophages aren’t always the good guys.

Using advanced imaging techniques, Pittet and colleagues were able to see how macrophages can render cancer immunotherapy drugs inactive in the body within moments of the drugs being administered.

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A macrophage (red) removing immunotheraphy drugs (yellow) from a T-cell (blue).  
Credit: Center for Systems Biology, MGH

Immunotherapy drugs are designed to bind to T-cells in the body, another type of white blood cell that relies on chemical signals to identify and kill harmful cells in the body.

One way that tumor cells avoid detection and destruction by these T-cells is by adopting a chemical signal that tumor cells use to inhibit T cells from attacking them, essentially rendering themselves “invisible” to the immune system. Immunotherapy drugs are designed to override this process by binding to T cells at the receptors that typically receive this “all is well” signal, thus making the tumor cells vulnerable to attack.

However, as Pittet and his colleagues observed, when immunotherapy drugs were administered, macrophages would clear away the drugs from the T-cells within minutes of the treatment, essentially making the treatment ineffective. Pittet’s observation also explains why this type of promising immunotherapy hasn’t been proven widely successful (the treatment can work extremely well, but only in a minority of patients).

The good news is that Pittet also determined the chemical pathway that was driving this macrophage response, and identified potential strategies for blocking that pathway in mouse models. More research is needed to determine whether similar strategies improve the results of immune checkpoint blockade in human patients.

Using Plain Language to Help Patients Cope with Cancer

So many questions run through a patients mind when they’re diagnosed with cancer. Now two Mass General doctors from the Cancer Center and the Division of Palliative Care are hoping to help answer those questions using clear and simple language.

David Ryan, an oncologist, and Vicki Jackson, a palliative care physician, have put together a comprehensive, user-friendly guide to coping and living with cancer, modeled after the iconic pregnancy handbook What to Expect When You’re Expecting. Their finished work, called Living with Cancer, was published earlier this month.

“People needed a guide to how to take care of their cancer that was practical and explained all the doctor speak in lay terms,” Ryan told Boston Magazine. “Vicki and I always had a tendency to tell our patients stories—to say, ‘Well, I had a patient just like you.’ That technique we put into the book, and I think it allows us to explain the difficult medical situations in a much more friendly fashion.”

Avoiding scientific jargon is essential for communicating science and is especially important when it comes to communicating health information to patients. A serious diagnosis, such as cancer, can be traumatic for patients – resources like this book can help guide patients along the path to treatment.

You can read more about the book in this article from Boston Magazine.

Research Teams at Mass General Explore Ways to Limit Alcohol-Induced Damage to the Liver and Better Understand Alcoholism’s Effect on the Brain

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Summer is almost upon us, which for many people means more outdoor time, cookouts, and for some—more drinking. While moderate alcohol consumption may have some health benefits, drinking too much can take a toll on our body. Researchers from Massachusetts General Hospital are investigating the long-term effects of excessive drinking on liver and brain function to find ways to reduce its impact on our health.

Enzyme treatment reduces alcohol-induced liver damage

Excessive drinking of alcohol can damage our liver in various ways. One way is through drinking more alcohol than the liver can process. And another is by making the gut’s intestinal membrane more permeable, which allows toxins to enter the blood stream and damage the liver.

Researchers in the lab of Richard Hodin, MD, in the Mass General Department of Surgery, reported in a new study that supplemental doses of an enzyme called intestinal alkaline phosphatase (IAP), which is known to stop bacterial toxins from entering the bloodstream through the gut, may also reduce liver damage from excess drinking.

In mouse models of binge drinking and chronic alcohol consumption, the research team found that feeding the mice a supplement of IAP reduced the amount of fat accumulation and inflammation in the liver and lessened signs of liver damage.

The enzyme appears to work in two ways. The first is by reducing the toxic effects of the lipopolysaccharide(LPS) molecule, which kills several important bacteria in the microbiome and can damage the liver if it passes through the intestinal membrane. The second is by reducing alcohol-induced membrane permeability in the intestine, which limits the overall amount of LPS that passes through the intestine. To be effective, the enzyme had to be administered before or at the same time as the alcohol. Administration after the fact had no effect. Human research is now being planned to confirm these results, and researchers plan to investigate other molecules that may have a role in liver inflammation.

“Liver damage is one of the most devastating effects of excess alcohol consumption, and so blocking this process could save millions of lives lost to alcohol-related liver diseases such as cirrhosis and liver cancer,” says Hodin, the study’s senior author. Read more here.

Imaging study reveals structural difference in brains of male and female alcoholics

It is known that alcoholic men and women have different psychological and behavioral profiles. Female alcoholics tend to have higher levels of anxiety, while male alcoholics tend to become more antisocial. But how do men and women’s brain structures that comprise the reward system that responds to alcohol compare? A collaborative study by researchers at Mass General and Boston University was the first to take a look.

The brain’s reward system includes the amygdala, which controls the fight or flight instinct, and the hippocampus, which controls long-term memory and emotional response.  The system is known to be involved in the development of substance abuse disorders like alcoholism.

In a study of 60 men and women with a history of alcoholism, along with a control group of non-alcoholics, researchers from the BU School of Medicine and the 3D Imaging Service and the Center for Morphometric Analysis in the Martinos Center for Biomedical Imaging at Mass General found that women with alcoholism tend to have a larger reward system than women without alcoholism—4.4 percent larger. It also confirmed previous studies that showed men with alcoholism tend to have smaller reward structures than those without—4.1 percent smaller.

It is not yet known if the differences in reward system size preceded the development of alcoholism or were a result of the disease. The results also suggest that alcohol works in different ways on the male and female brain, and that gender-specific approaches to treatment for alcoholism may be more effective than a one-size-fits-all approach. Learn more here.

Researchers Detect “Silent” Seizures in Alzheimer’s Patients

First let’s define a key word:
Hippocampus: The brain structure responsible for memory development. The hippocampus is a key part of the brain affected by Alzheimer’s disease, and also a common source of seizures in people with epilepsy.

New research from Massachusetts General Hospital suggests a potential new connection between the devastating memory loss associated with Alzheimer’s disease (AD) and “silent” seizures in the memory center of the brain.

The small study enrolled two female patients in their 60s with early AD and no known history of seizures. Because electrodes placed on the scalp are often unable to detect seizure activity deep in the brain, researchers surgically implanted electrodes on both sides of the brain through the foramen ovale (FO), a narrow opening at the base of the skull, in addition to scalp EEG. Each patient’s brain activity was monitored for 24 to 72 hours.

The FO electrodes recorded evidence of seizures in the hippocampuses of both patients, while the scalp EEG readings did not detect any abnormal electrical activity. Most notably, these seizures primarily occurred when patients were asleep, a critical time for memory consolidation.

“While it is not surprising to find dysfunction in brain networks in Alzheimer’s disease, our novel finding that networks involved in memory function can become silently epileptic could lead to opportunities to target that dysfunction with new or existing drugs to reduce symptoms or potentially alter the course of the disease,” says Andrew Cole, MD, Director of the Mass General Epilepsy Service and senior author of the Nature Medicine paper.

One patient received anti-seizure medicine as a treatment following the scan, which seemed to cut down on AD-linked symptoms such as confusion and repeating the same question. The other patient started on the medication but it had to be discontinued due to adverse effects on her mood.

A recent study led by Alice Lam, MD, PhD, also of the MGH Epilepsy Service and lead author of the current study, demonstrated a novel tool for detecting hippocampal seizures not detectible by scalp EEGs in patients with epilepsy. Cole and his team are working to refine this tool and apply it to AD.

Due to the small size of the study, further research is also needed to validate the results with a broader population.

Celebrating the Important Role of Nurse Researchers at Mass General

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From left: Gaurdia Banister, director of the Munn Center for Nursing Research, Sara Looby, a nurse scientist at the Munn Center and the keynote speaker at Nursing Research Day, and Jeanette Ives Erickson, Chief Nurse and Senior Vice President for Nursing and Patient Care Services

Attendees of the 2017 Nursing Research Day celebration at Massachusetts General Hospital on May 9 certainly had a lot to be inspired by.

The event began with a poster session featuring 45 posters submitted by nurse researchers at Mass General, and concluded with a series of engaging presentations highlighting the important role that nursing research plays in improving patient care.

“As providers, we have patient experiences that influence our careers and are truly impactful,” said keynote speaker Sara Looby, PhD, ANP-BC, FAAN.

Looby, a Nurse Scientist at the Yvonne L. Munn Center for Nursing Research at Mass General, described several such formative experiences in her own nursing career, including an interaction with a young mother who was suffering from a terminal illness. Witnessing that mother’s experience firsthand gave Looby a better understanding of the human response to illness—and the despair, grief and suffering that comes with it.

Looby said her career as a nurse researcher has been guided by the desire to find ways to help patients cope with these feelings, by providing information, support and connections to clinical trials. Many of her research projects started by understanding the needs and concerns of her patients, she explained.

“Our patients are talking. We are asking them on a daily basis how they are feeling, and they are sharing their concerns, thoughts and opinions. In doing so, they are identifying gaps in knowledge that can be solved by asking research questions.”

Looby acknowledged that nurses already have a full plate of responsibilities taking care of patients, but she encouraged them to go the extra mile to pursue research questions as well. “What more can be done? What questions are not answered?”

“Each of you makes a difference every day, small or large, independently or as a team to help patients. So don’t be afraid to share your ideas with others, and don’t be intimidated by the research process.”

Gaurdia E. Banister, RN, PhD, NEA-BC, FAAN, Director of the Munn Institute and Executive Director of the Institute for Patient Care at Mass General, spoke about the center’s 25-year effort to establish a structure for nursing research at the hospital and credited Jeanette Ives Erickson, RN, DNP, NEA-BC, FAAN, the hospital’s Chief Nurse and Senior Vice President for Patient Care, for her unwavering support.

Banister noted that the nursing research posters on display during the event represented a broad cross section of interests, including non-pharmacological approaches to pain management, population-based care and strategies to manage care transitions from the hospital to the community.

She also encouraged nurses to continue their advocacy for science and medicine at a challenging time for both disciplines.

“Staying silent is no longer a luxury we can afford. We all must stand together and support science. At its core, science is a tool for seeking answers, and we must aggressively advocate for the right to do so.”

Research Awards and Honors: May 2017

Massachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

weinMarc Wein, MD, PhD,of the Endocrine Unit, has received a Young Physician-Scientist Award from the American Society for Clinical Investigation. These recognize young physician-scientists who are supported by the National Institutes of Health or similar significant career-development awards, are early in their first faculty appointment and have made notable achievements in their research.

“As an endocrinologist, the problem of osteoporosis is extremely important to me. My laboratory studies how bone cells respond to external signals like hormones and mechanical cues. Ultimately, this knowledge will lead to new and improved drugs for our patients with osteoporosis. It was truly an honor to receive this award. Attending the ASCI meeting as a recipient of the Young Physician-Scientist Award was both exciting and inspiring. Four different Nobel laureates gave lectures about their career paths, and provided excellent advice about picking the right research questions that will ultimately help our patients.”

 

hawryluckElena B. Hawryluk, MD, PhD, of the Department of Dermatology, has received Weston Award from the Society for Pediatric Dermatology for her work “Melanoma and Dysplastic Nevi in Children”. This award is given to one pediatric dermatologist every two years and supports career development of future leaders, educators, clinical scholars and/or translational investigators in pediatric dermatology. Awardees must demonstrate a strong commitment to skin research that can advance the field of pediatric dermatology.

“My research investigates moles in children as well as pediatric melanoma, which is quite rare.  Patients with dysplastic (abnormal) moles have an increased risk of melanoma, however, studies of children and adolescents with these moles have not been performed.  I am collaborating with pediatric dermatologists across the country to identify features that might help us better understand which melanomas are most aggressive.  With an increased public awareness of sun protection and melanoma, it is important for pediatric dermatologists to be able to identify skin lesions of concern, and discuss risks that are relevant to children and adolescents.

This is an incredible honor coming from the Society for Pediatric Dermatology: just one pediatric dermatologist every two years is selected for the award.  It means so much to have the support of both the research I’m so passionate about and the investment in my development as a researcher.”

 

tingDavid T. Ting, MD, of the MGH Cancer Center, has received a Phillip A. Sharp Award through Stand Up To Cancer (SU2C), to advance “innovation in collaboration” among SU2C-affiliated scientists. The award program was established in 2014 by SU2C to honor Sharp’s keen interest in team research, and are intended to reward distinctive collaborations that propose to accelerate current research and development models, bringing therapeutic benefits for cancer patients. Ting’s research will focus on “Dissecting the Epigenetic Mechanisms of Repeat RNA Regulation in Cancer.”

“Our research focuses on identify novel methods to engage the immune system against cancer cells. We are working on a set of molecules called satellite RNAs, which we have found to be specifically expressed in cancers compared to normal tissues. These satellites are generated from areas of our genome thought to be silent and were considered “junk” DNA, but cancers have found a way to reactivate these regions through a mechanism called epigenetic regulation. Interestingly, these satellite RNAs appear to have behavior that is shared with viruses, and their presence in cancer cells are thought to alter the immune response to cancer. I am truly honored to receive this collaborative award with Dr. Shelley Berger who is an international leader in epigenetics. Together, we hope to understand how cancers turn on this primordial viral program and identify novel therapies that can enhance our ability to drive the immune system to attack cancer.”

 

demehriShawn Demehri, MD, PhD, has been awarded a grant from the Sidney Kimmel Foundation as part of its Kimmel Scholars Program for “Mechanism of CD4+ T-cell immunity against skin cancer precursors.” Begun in 1997, the program was designed to jumpstart the careers of the most promising and creative researchers and physician-scientists seeking solutions to the riddle of cancer. To qualify, grantees must demonstrate great promise and innovation in their work, and be in the early stages of their research careers.

“Skin cancer is the most common type of cancer and we often see patients in our clinics who are affected by multiple skin cancers. To prevent these cancers, our laboratory has recently developed a topical immune activating treatment, which showed high efficacy in activating T cells leading to the clearance of skin cancer precursors in a randomized clinical trial. We now aim to explore the exact mechanism underlying the potent anti-tumor immune response we observed with our immunotherapy. The Kimmel Scholar Award will enable us to expand this research effort and establish a fundamental role for immunoprevention in cancers of skin and other organs.”