World AIDS Day 2017

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World AIDS Day takes place on the 1st of December each year. It’s an opportunity to highlight the success of worldwide efforts to combat HIV/AIDS, as well as the importance of continued support for these efforts.

Researchers and clinicians, including those at Massachusetts General Hospital, acknowledge that although great strides have been made in the clinical treatment of HIV over the past three decades, there is still work to do.

In recognition of World AIDS day, we have collected some recent stories about the ways Mass General investigators are working to expand our knowledge of the virus, reduce transmission rates, improve health outcomes for HIV-positive patients and advance treatment.

The Ragon Institute

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The Phillip T. and Susan M. Ragon Institute was established in February 2009 at Mass General, MIT and Harvard with the dual mission of contributing to the accelerated discovery of an HIV/AIDS vaccine and subsequently establishing itself as a world leader in the collaborative study of immunology. Learn more about their exciting research efforts.

Exploring the Risks of Cardiovascular Disease in HIV-positive Women

sara looby.pngSara Looby, PhD, ANP-BC, FAAN, is a Nurse Scientist at the Yvonne L. Munn Center for Nursing Research, an Assistant Professor of Medicine at Harvard Medical School, and a Principal Investigator in the Program of Nutritional Metabolism at Mass General. Through her research efforts, Looby is investigating how HIV might influence the development of conditions such as heart disease and the increased risk for heart attacks that tend to impact HIV-positive populations at an earlier age compared to non-infected populations. Learn how she’s using a patient-centered approach to reduce cardiovascular disease risk for HIV-positive women.

Levison Makes a Dramatic Bid to Improve HIV Care Compliance

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Julie Levison, MD, MPH, MPhil, FACP, is a clinician-investigator in the Division of General Internal Medicine at Mass General, an Assistant Professor of Medicine at Harvard Medical School, and a bi-lingual (Spanish-English) infectious disease physician at MGH Chelsea HealthCare Center. Levison and her team have created a dramatic video illustrating the consequences of letting HIV care lapse. The video is part of a research project designed to improve outcomes in one subset of the HIV patient population—migrants from Puerto Rico and Latin America. Watch the video and learn how it could potentially improve HIV care adherence by Latino immigrants.

The Health Hazards of Smoking in HIV-positive Populations

196368.jpgKrishna Reddy, MD, is a physician in the Division of Pulmonary and Critical Care Medicine and the Medical Practice Evaluation Center at Mass General. His research focuses on comorbidities in people living with HIV, including smoking-related diseases and tuberculosis. He recently led a study that found people with HIV who smoke are more likely to die from lung cancer than from HIV itself. Read more about the study and its implications.

(top photo courtesy of The Ragon Institute)

Celebrity Patients Bring Lupus into The Headlines, But Much Remains Unknown

This September, actress and singer Selena Gomez announced on Instagram that she underwent a kidney transplant as part of her treatment for lupus, an autoimmune disease in which a body’s immune system begins to attack its own tissues and organs.

Gomez and other celebrities such as Nick Cannon, Toni Braxton and Seal have publicly spoken out about their struggles with lupus, which affects 1.5 million Americans and over five million people worldwide. Despite these high-profile patients, the disease still remains a mystery to much of the general public and the scientific community.

To shed light on symptoms, causes and treatment options for the disease, April Jorge, MD, a research fellow in the rheumatology unit at Massachusetts General Hospital , recently gave a talk on “Understanding the Mystery of Lupus” at Mass General’s Maxwell and Eleanor Blum Patient and Family Learning Center.

What is Lupus and Who Does it Affect?

The immune system typically protects us against infections by forming antibodies that detect and respond to invading pathogens, such as viruses and harmful bacteria. However, Jorge explained that in patients with lupus, the body forms auto-antibodies that target the own body’s cells as if they were intruders.

Lupus is a non-contagious and non-infectious disease that is caused by a combination of environmental and genetic factors. Jorge said that at least 50 different genes contribute to an increased risk of developing the disease.

Lupus is more common in women, and in African Americans and Hispanic populations. Patients are typically diagnosed between the ages of 15 to 45 years.

Symptoms of Lupus

Symptoms of lupus include skin rashes, hair loss, sores in the mouth, foggy thinking, seizures, vision problems, joint pain, liver inflammation, inflammation in the lining of the lungs and heart, blood clots, fatigue, and fever, among others.

“People with lupus also have a higher risk of heart attacks and strokes, and can be at a greater risk of getting osteoporosis and depression,” said Jorge. Lupus can also damage internal organs, especially the kidneys. Up to 50 percent of patients with lupus develop lupus nephritis—an inflammation of the kidneys that can prevent them from functioning properly.

Jorge suggested patients look out for several symptoms that may be warning signs of kidney damage.

“There can be some signs like swelling in the legs or belly,” she said. “Sometimes, it’s picked up by doctors if the patient has high blood pressure.” Other lupus patients may not have any outward symptoms of kidney damage, which makes it important for them to undergo regular screenings.

Diagnosis

Jorge explained that the disease is so complex because signs and symptoms differ from person to person. Many times, symptoms of lupus overlap with those of other disorders. Hence, it takes an average of 6 years to obtain a lupus diagnosis.

Diagnosis is typically made by factoring in combination of symptoms, blood tests and other factors, such as impaired liver or kidney function as a result of inflammation.

Treatment

While there is no cure for lupus, it is possible to treat the symptoms with medications and lifestyle changes.

Pharmaceutical Options

Medications prescribed for treating lupus include Prednisone (a corticosteroid that acts as an immune suppressant), Hydroxychloroquine (a drug originally used to treat malaria) and other immunosuppressant medications.

Currently doctors and scientists are trying to identify new and more effective treatments for lupus with fewer side effects. Jorge is optimistic about new drugs on the horizon that could improve treatment options. She said that biologics (products derived from natural—rather than chemical—sources) target certain parts of the immune system and are some of the most effective medications for lupus.

“Belimumab (manufactured under the brand name Benlysta®), which is given either as an injection or through an IV infusion, is the first drug to be approved for lupus in 50 years,” said Jorge. “But in the next five to 10 years, there will be many more.”

Lifestyle Modifications

Lifestyle changes can also help manage the symptoms of lupus, such as:

  • Exercising regularly
  • Getting enough sleep
  • Eating a healthy diet with fruits, vegetables and lean meats
  • Avoiding excess sun exposure
  • Using sunscreen lotions with at least SPF 50 and wearing protective clothing
  • Avoiding tobacco, as studies have indicated that smoking can make the disease more severe and harder to control

Based on recent research findings, the same strict guidelines may not apply to alcohol consumption. Jorge is currently investigating the impact of alcohol use on risk of heart attacks and death in patients with lupus. The research team has found that patients with lupus who consume light to moderate alcohol intake have lower rates of heart attacks and overall mortality than those who do not consume any alcohol.

To learn more about Lupus, please visit the Lupus Foundation of America’s website.

Meet a Mass General Postdoc: Amy Tsurumi

In honor of National Postdoc Appreciation Week, all this week we’ll be sharing profiles of just a few of our amazing Mass General postdocs to highlight their research and what inspires them.

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Our fourth and final featured postdoc this year is Amy Tsurumi, PhD, a research fellow in the Rahme Lab.

Where did you get your PhD from?

University of Rochester School of Medicine and Dentistry

What questions are you asking in your current research? What do you hope to find out?

My research is elucidating epigenetic mechanisms of host susceptibility and response to infections using Drosophila, mice and tissue culture Pseudomonas aeruginosa infection models.  I hope to identify specific histone post-translational modification marks and genomic loci that are relevant and explore the possibility of alleviating the negative impact of pathogenic encounters by reversing these epigenetic marks.  Given the rise of antibiotic resistant bacteria, developing host-targeted methods as an alternative approach may be significant.  I also conduct epidemiological and biomarker studies for prediction of vulnerability to infections and infections-related outcomes in burn and trauma patient cohorts. 

What drew you to this field?

My father was a physician-scientist with a microbiology research background and fascination in human genetics, so I grew up being curious about the field of biomedical sciences.  As a graduate student, I learned about epigenetics for the first time and studied histone lysine demethylases, a relatively novel class of epigenetic regulators back then, which I found to be absolutely exciting.  I was thrilled to join the Rahme lab where I was lucky to have been given the opportunity to continue to conduct epigenetics research that I am interested in, but shift from the context of Drosophila development to host-microbe interactions using a variety of model organisms and also incorporate patient cohort clinical research.

What is a typical day like for you?

It is difficult to define a “typical” day, which I actually enjoy. Most days, I spend the majority of the time running experiments on the bench or conducting patient data analyses.  When there are grant/fellowship deadlines, I spend the day focusing on writing.  I find myself to be extremely lucky that there are many different types of experimental methods I get to do and various model organisms available in the Rahme lab.  The variety of techniques offered has given me an incredible learning experience thus far.

What do you like most about being a postdoc at MGH?

I am awed by the highly collaborative environment at MGH.  The Rahme lab is diverse in terms of scientific background (and home countries!) and I am very thankful to my mentor for the excellent mentorship and also to other postdocs around me, especially labmates and floormates for the invaluable input and help I receive daily.  I also feel fortunate to be part of collaborative projects with various PIs within MGH and around the globe, as well as the vast amount of resources offered by neighboring labs, MGH core facilities and other Harvard campuses.  All the research that goes on every day at MGH is stimulating and my mentor and colleagues I have the opportunity to work with are inspiring.

Meet a Mass General Postdoc: Robert Lochhead

This week is National Postdoc Appreciation Week, a time to recognize the significant contributions that postdoctoral scholars make to the research community.

In celebration, all this week we’ll be sharing profiles of just a few of the amazing postdocs here at Mass General to highlight their research and what inspires them.

First, we’d like to introduce Robert Lochhead, a clinical research fellow for the Center for Immunology and Inflammatory Diseases in the Division of Rheumatology, Allergy & Immunology:

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Where did you get your PhD from?

I got my PhD in microbiology and immunology from the University of Utah School of Medicine.

What questions are you asking in your current research?

I am studying the immunopathology of Lyme arthritis, and the relationship between infection and autoimmunity.

What do you hope to find out?

From a microbial and immunological perspective, Lyme disease is a fascinating human infectious disease model. The pathogen, Borrelia burgdorferi, is highly adapted to hiding from the immune system within connective tissue, resulting in infections that can go undetected for many months. What’s more, there is a wide range of disease manifestations and severity, depending on both host and pathogen factors. Lyme arthritis, the most common late-disease manifestation, may persist or worsen even after the bacteria have been cleared by antibiotic therapy, called post-infectious Lyme arthritis. My research is focusing on how B. burgdorferi infection and subsequent tissue damage may trigger chronic autoimmune arthritis, with the hope of determining mechanisms of how infection may induce autoimmunity.

What drew you to this field?

As a young graduate student interested in host-pathogen interactions, I was attracted to the immunology of Lyme arthritis as a model of studying infection-induced autoimmunity. I’ve stuck with Lyme disease ever since, first in mouse models as a graduate student, now in humans as a postdoc.

What is a typical day like for you?

I spend most of my time analyzing big RNA sequencing datasets, in the microscope room, collecting and processing clinical samples, and writing grant applications and manuscripts. Right now my typical day is mostly writing.

What do you like most about being a postdoc at MGH?

Without a doubt, the best thing about being a postdoc here at MGH is the opportunity to collaborate with wonderful clinicians and patients who are so invested in the research side of human disease. Seeing the impact of these diseases on patients brings an urgency and focus to my research that will certainly shape the rest of my scientific career.

Evaluating the Impact of Cutbacks to HIV Programs in Resource-Limited Nations

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Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, an international team of investigators reports. In their paper published online in Annals of Internal Medicine, the team led by researchers at Massachusetts General Hospital and the Yale School of Public Health describes how a 33 percent cutback in funds earmarked for HIV/AIDS prevention, treatment and research in recent budget proposals would only save $900 per year of life lost in the countries of South Africa and Côte d’Ivoire.

Read the full press release here.

Cuts to NIH Program Could Disrupt Infectious Disease Research at Mass General and Around the World

Mass General researchers working to stop the spread of infectious disease are worried that proposed cuts to the NIH budget would eliminate a key resource for global health efforts.

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Drs. Stephen Calderwood, Ed Ryan, Regina LaRocque, Ana Weil, and researchers at the International Centre for Diarrheal Disease Research in Dhaka, Bangladesh

Back in the 1950s, there was a global effort to control mosquito populations with the hope of eradicating mosquito-borne diseases such as malaria and yellow fever. Unfortunately, the program was stopped before its goals could be met. Fast forward to the present where the issue of mosquito-borne diseases in some countries is much bigger than it was 50 years ago.

Investigators working to stop the spread of infectious disease around the world, including those at Massachusetts General Hospital, are worried that this same cycle could repeat itself if President Trump’s proposed cuts to the National Institutes of Health (NIH) budget are approved, which would eliminate the Fogarty International Center, a key resource for global health efforts.

“To avoid repeating the same mistake with infectious diseases, we must look ahead and provide the resources necessary now to find an answer to Ebola, HIV, cholera and many other diseases internationally,” explains Stephen Calderwood, MD, former Chief of the Division of Infectious Disease at Mass General.

“People are often unaware of what has been prevented, since by definition what has been prevented has not occurred,” adds Edward Ryan, MD, Director of Global Infectious Disease at Mass General. “The U.S. has and will continue to dodge bullets because of the Fogarty. We would be short-sighted to let this defensive wall fall.”

Closing the Fogarty could put an end to decades of progress into international infectious disease research, say advocates at Mass General. Moreover, doctors and scientists from at-risk countries could face even more barriers to conducting their own research and finding solutions that could directly benefit their communities and curb the spread of infectious diseases around the world. Continue reading “Cuts to NIH Program Could Disrupt Infectious Disease Research at Mass General and Around the World”

Adhering to Treatment During Adolescence Keeps HIV-Positive Youth on Healthier Track

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As HIV therapies have improved in recent decades, we are now seeing the first generation of youth who were born with the disease, or acquired it shortly after birth, live to adulthood. As this population matures, researchers are looking to learn more about how these individuals have fared in managing their condition in order to improve long-term treatment and care.

A recent Massachusetts General Hospital study of 1,400 individuals between the ages of 7 and 30 born with HIV found that teens and young adults are more likely to have a difficult time managing their condition than they did as younger children. Those in the study group who had good HIV control generally experienced good overall health outcomes, while those who had poor HIV control – meaning higher levels of HIV virus and lower levels of CD4 immune cells had more physical and mental health conditions, a higher incidence of health complications, and a greater risk of death.

“Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect”, says Anne Neilan, MD, MPH, of the Division of Infectious Diseases and the Medical Practice Evaluation Center, who led the study. “We need to act to strengthen these services for youth, taking into account their developmentally specific needs. That might include youth-friendly services that consider the substantial stigma many of these patients face, novel approaches to antiretroviral therapy delivery, and improving support for youth transitioning from pediatric to adult health care providers.”

Andrea Ciaranello, MD, MPH, of the Massachusetts General Hospital Division of Infectious Diseases and the Medical Practice Evaluation Center, is senior author of the study. Anne Neilan, MD, MPH, of the Division of Infectious Diseases and the Medical Practice Evaluation Center, led the study. Read more about this study here.

Are You Actually Allergic to Penicillin? Researchers Find New Methods to Confirm Antibiotic Allergies

First let’s define a few key words:

  • Penicillin: Penicillin is an antibiotic treatment that is effective at getting rid of common bacterial infections and treat skin, ear, sinus and upper respiratory tract infections.
  • Cephalosporin and Amoxicillin: Antibiotics similar to penicillin.

What’s the issue researchers wanted to address? “10 to 15 percent of hospitalized patients have penicillin allergy in their medical record, but studies have shown that more than 95 percent are not really allergic,” explains Kimberly Blumenthal, MD, MSc, of the Division of Rheumatology, Allergy and Immunology, the Medical Practice Evaluation Center, and the Lawrence Center for Quality and Safety at Massachusetts General Hospital. Furthermore, alternatives to penicillin (called broad-spectrum antibiotics) are less effective, more toxic, more expensive, increase likelihood of antibiotic resistance and can leave patients vulnerable to certain infections. There is a need to address over-reporting of penicillin allergies.

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The computerized treatment guideline

How did they address the issue? Researchers from Mass General and Brigham and Women’s Hospital developed two approaches – (1) combined use of penicillin allergy skin tests with oral test dose and (2) a computerized guideline – to confirm whether patients previously believed to have a penicillin and cephalosporin allergy were truly allergic to these drugs.

How did they test these approaches? Over a two-year period, researchers compared treatment approaches for inpatients who needed antibiotic treatment and had a recorded penicillin allergy. The first five months served as a comparison period during which time patients received standard treatment (broad spectrum antibiotics) with additional skin testing only if physicians consulted a specialist. For the next seven months, eligible patients received a skin test. Patients whose skin tests were negative and safely tolerated a test dose of amoxicillin were determined not to be allergic. In the final study period, physicians had access to a computerized treatment guideline (see photo) that helped to determine the suitability of penicillin use based on symptoms of the patient’s previous reactions to the treatment. The guideline would recommend either a full dose of broad-spectrum antibiotics, a test dose under observation, or an allergy consultation.

 What were the results? Both tested protocols safely increased the use of penicillin and penicillin-related antibiotics in inpatients. There were barriers that routinely made skin testing impractical. However, of the 43 patients who did receive skin tests, none proved to have a penicillin allergy, and they were 6 times more likely to receive a penicillin or cephalosporin prescription compared to those that received standard treatment. 112 patients completed the computerized guideline protocol and researchers found that the app safely increased the use of penicillins and cephalosporins almost 2-fold compared to the standard treatment.

 What do these results mean? Both approaches help provide safe and effective treatments to improve the care of patients when they are hospitalized and expand antibiotic choices. The computerized guideline tool could be especially useful for hospitals with limited ability to adopt a skin testing protocol or lack of access to staff allergy specialists.  As this tool becomes more widely available, it may have an even greater effect on antibiotic prescriptions.

Kimberly Blumenthal, MD, MSc, is co-lead and corresponding author of the paper. Rochelle Walensky, MD, MGH Division of Infectious Disease, is senior author. You can learn more about this study here.

Five Things To Know: New Therapy for Dangerous Swelling Disorder

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Researchers from the Massachusetts General Hospital Division of Rheumatology, Allergy and Immunology recently came out with a study published in New England Journal of Medicine. Here are five things to know:

  1. Hereditary angioedema (HAE) is a rare but serious condition passed down through families. HAE affects the blood vessels and is caused by a low level or improper function of a protein called the C1 inhibitor.
  2. HAE causes rapid swelling, particularly in tissues in the face, hands, gastrointestinal tract and airway. The uncontrolled swelling not only restricts movement, sometimes for several days, but also can be life-threatening when the airway is involved. While it’s important to treat the swelling during an HAE attack, preventing attacks would be beneficial for many patients. However, current FDA-approved preventive treatments have limitations.
  3. HAE patients participating in this clinical trial (37 total) received either two shots of an antibody called lanadelumab 14 days apart, or a placebo. The strength of the shot varied from 30 to 400 mg and results were analyzed for the 8-50 days following treatment.
  4. Researchers found that from day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer HAE attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group. Reports of pain at the injection site and headache were similar across all groups, and no serious side effects were reported, supporting the safety of the treatment.
  5. “If this kind of efficacy is seen in the larger phase 3 trial, which is now underway here at Mass General and many other sites, this could significantly improve the quality of life for patients with HAE,” says Aleena Banerji, MD, corresponding and a lead author of the NEJM. 

Learn more about this study here.