Posts from the ‘discovery and innovation’ category

A Shared Commitment to Improving Diabetes Care

Hudson and colleages

From left: Lauren Godsoe, Margo Hudson and Maricruz Merino

I have been going annually to New Mexico with the Outreach Program with Indian Health Service since 2009, and each year gets better. I have primarily been involved with the diabetes program at Gallup Indian Medical Center in Gallup, N.M.

A former Brigham internal medicine resident, Maricruz Merino, MD, is now their chief of Medicine, and we have been working together closely over the years developing inpatient and outpatient glucose-management protocols. We are both close friends as well as colleagues, and we have shared the joys of the birth of children and grandchildren with each other in addition to seeing the growth of the diabetes program.

This past March, I had the pleasure of traveling with Brigham Health nurse practitioner Laura Godsoe, NP, for a week of lecturing and consulting on patients. I am so proud of the work we have done and thankful to Outreach Program for continuing to support this opportunity.

Margo Hudson, MD
Division of Endocrinology, Diabetes and Hypertension

Unraveling the Mysteries of Sex Differences and the Brain

Participants speak at the Interdisciplinary Neuroscience Inaugural Symposium: Sex Differences and the Brain - Implications for Research, Health and Disease.

From left: Ursula Kaiser listens as Cynthia Lemere asks a question during the first annual Women’s Brain Initiative Symposium.

In human disease biology, sex differences are as perplexing as they are pervasive. One crucial place where these differences manifest themselves is in the brain and in conditions affecting or affected by this critical organ.

There are more women than men with Alzheimer’s disease, multiple sclerosis, obesity, eating disorders, anxiety and depression, for example, while men have higher rates of Parkinson’s disease and schizophrenia. Yet the reasons for these differences remain understudied and unknown.

“Women’s health is often understood to mean reproductive health, but that’s a narrow definition for the health of half the human race,” said Charles Jennings, PhD, executive director of the Brigham’s Program for Interdisciplinary Neuroscience and Ann Romney Center for Neurologic Diseases. “We’re increasingly recognizing that many and perhaps most diseases show differences between men and women. In many cases, the effects are quite large, and if we want to understand the cause and eventual treatment of these diseases, we can’t ignore the sex differences.”

With the help of a generous philanthropic gift from Rick and Nancy Moskovitz, the Brigham-wide Women’s Brain Initiative (WBI) launched in 2017 to support research over four years into women’s brain health and the science of sex differences.

WBI-funded projects may span a range of questions from basic biology—how male and female brains became wired differently—to practical clinical questions about sex differences in disease risk and treatment responses, as well as how conditions specific to women (such as pregnancy and menopause) influence brain health. The WBI also supports community-building through an annual symposium and an ongoing Seminar Series starting Dec. 18.

“Surprisingly, there is nothing like the WBI anywhere else,” said Patti Stoll, MBA, director of the Women’s Brain Initiative. “Our goal is to attract not only investigators who are currently interested in the subject but also those who might not yet appreciate how this area could be important for their research.”

A Catalyst for Curiosity

Rosalind Lai, MD, WBI research fellow in the Department of Neurosurgery, is examining how hormones affect subarachnoid hemorrhages—which result from the rupture of an intracranial aneurysm, an abnormal dilation in a blood vessel of the brain—and why these events occur more often in women than men.

“We know that hormonal levels are altered after a head bleed, but we want to know if estrogen is a contributing factor to the rupture of an aneurysm,” said Lai. “Being a part of the WBI means being a part of a supportive community that fosters interest and curiosity about sex differences and the brain.”

Lai attended the inaugural WBI Symposium on Sept. 26 and enjoyed talks by visiting researchers. One lecture that stood out to her was given by Arthur Arnold, PhD, from the Brain Research Institute at the University of California, Los Angeles, who spoke about how chromosomal differences could affect disease risks that have previously been attributed to hormones.

“His talk made me think more about the different factors that may affect sex differences,” said Lai.

Meeting of the Minds

Another goal of the WBI is to connect researchers and clinicians at the Brigham and encourage these experts in different disease areas to think about the effects of sex differences.

Ursula Kaiser, MD, WBI-funded researcher and chief of the Division of Endocrinology, Diabetes and Hypertension, studies the effects of endocrine-disrupting chemicals, which can act similarly to estrogens, on increased risk of premature puberty in girls.

Needing guidance about how to examine the role of estrogen in Parkinson’s disease, Silke Nuber, PhD, WBI-funded researcher in the Ann Romney Center, came to Kaiser for her expertise. Kaiser invited Nuber to her lab to learn some of the techniques for examining the effects of ovarian function and estrogen levels in preclinical models.

“I think one of the wonderful things about WBI is that it brings so many multidisciplinary groups together who perhaps haven’t interacted as much in the past,” said Kaiser. “It makes all of us more aware of other research being conducted at the Brigham.”

Building on a Brigham Legacy

The WBI does not exist in isolation—it builds on and unites entities and areas of focus with a long legacy at the Brigham. One of those collaborating entities is the Mary Horrigan Connors Center for Women’s Health and Gender Biology.

Hadine Joffe, MD, MSc, executive director of the Connors Center and vice chair for psychiatry research, has encouraged researchers to join the WBI to increase funding opportunities and further advances pertaining to sex differences and the brain. One of those investigators is Katherine Burdick, PhD, of Psychiatry, whose research on predictors of cognitive impairment in postmenopausal women with major depressive disorder (MDD) has become part of the WBI’s portfolio.

“I became aware of the opportunity to apply for funding via the WBI thanks to Hadine Joffe, with whom I worked to develop the protocol for the funded study,” said Burdick. “With support from the WBI, we are trying to identify clinical and biological explanations for why some postmenopausal women with MDD develop cognitive and functional disability while others do not. This information will hopefully lead to a more personalized-medicine approach in the future.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

AERD Center Aims to Clear the Air on an Underdiagnosed Disease

From left: Alice Maxfield speaks with David Doyle during a recent follow-up appointment.

For David Doyle, 54, taking in the flavors and aromas of food is more than his passion – as co-owner of several restaurants in Jamaica Plain, it’s also his livelihood. So when what seemed like unusually intense seasonal allergies caused his senses of smell and taste to diminish three years ago, Doyle grew concerned.

First experiencing severe nasal and chest congestion, he tried several over-the-counter allergy medications. Nothing worked – in fact, his symptoms worsened. Within a few months, Doyle not only felt miserable physically, but he was also devastated to find he could no longer smell or taste anything.

“I didn’t really want to eat because there was no joy in it,” Doyle said. “On a professional level, it was also really hard to work with these great chefs who would ask, ‘David, can you taste this?’ and all I could comment on was the texture.”

Hoping his symptoms would eventually subside, he continued taking allergy medications and pain relievers, even though their effects were minimal. It wasn’t until after suffering a frightening medical event that Doyle would learn the very medications he was taking to feel better were actually making him sick.

Doyle was on vacation with his family in Spain when he realized something was gravely wrong with his health. Suffering from a bad headache and congestion, he took some ibuprofen, a treatment he had used before without incident. This time, however, he began experiencing serious respiratory distress within a few hours and was rushed to a local hospital.

“My lungs were filled with fluid. I felt like I was suffocating,” Doyle said. “I had no idea what had prompted that reaction, but I was starting to suspect something had changed inside me.”

After returning home, he was referred by his primary care provider to Tanya Laidlaw, MD, director of Translational Research in Allergy in the Division of Rheumatology, Immunology and Allergy, who diagnosed him with aspirin-exacerbated respiratory disease (AERD). Triggered by a sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, AERD is a chronic condition that includes severe asthma and recurrent, fast-growing nasal polyps.

Also known as Samter’s Triad, the disease often strikes otherwise healthy adults and progresses rapidly. Its cause is unknown, and effective treatments are elusive.

“This is a disease that is really not well-known and is underdiagnosed,” said Laidlaw, who also serves as director of the Brigham’s AERD Center. “It requires a multidisciplinary approach, particularly between ear, nose and throat surgeons and allergists – specialists who don’t ordinarily talk to each other about patients with these symptoms. Without that communication, an ENT surgeon is unlikely to ask about an aspirin allergy, and an allergist doesn’t typically look for nasal polyps.”

Founded five years ago, the Brigham’s AERD Center brings together allergists, ENT surgeons and researchers to explore new treatments and improve the lives of patients with AERD. The center’s clinicians diagnose and treat hundreds of patients per year, and its investigators manage an international research registry of more than 1,000 people with AERD. Combined with its robust clinical trials program, these efforts make the Brigham’s AERD Center the largest clinical and research center for the disease worldwide.

“We have an incredibly collaborative relationship between bench scientists and those of us who see this disease in patients,” Laidlaw said. “We are all in constant communication. Every patient with an aspirin allergy seen by an ENT surgeon is likely referred to us. That proves education can solve the diagnosis gap. However, there is still an enormous need for broader awareness and research funding.”

Tasting Success

Upon returning home and beginning treatment at the Brigham, Doyle enrolled in a clinical trial at the AERD Center to initiate high-dose aspirin treatment, which involves administering increasing doses of aspirin to patients and closely monitoring them for the next several hours.

After starting this daily therapy and seeing only marginal improvement, Doyle underwent two surgeries to remove nasal polyps under the care of Alice Maxfield, MD, an ENT surgeon in the Department of Otolaryngology. A third procedure adjusted the blood flow in his nose to reduce inflammation. Within days of the last surgery, Doyle said he felt dramatically better.

Today, Doyle estimates he’s recovered about 90 percent of his senses of taste and smell, and his respiratory symptoms are largely under control. Although it was a long road, Doyle said he is deeply grateful for the expert, compassionate care he has received at the Brigham.

“I feel like my experience mirrors many others with AERD. It’s really frightening to develop symptoms that don’t make sense to you, so it was a huge relief just to know what was happening,” he said. “My hope is more clinical trials will shed light on not only the causes of this disease but also treatments for it.”

Shortly after recovering from his final surgery, Doyle and his family returned to Europe to vacation in Italy. It was on this trip that he realized his senses started to return. The first food he remembers tasting? Truffles.

Brigham Health’s Strategy in Action: Advanced, Expert Care
Learn more about our strategic priorities at BWHPikeNotes.org.

NICU Milk Analyzer Study Aims to Personalize Pre-Term Infant Nutrition

From left: Mandy Brown Belfort and Valencia Koomson, with baby Justin

During a prenatal visit for their second child, Valencia and Jude Koomson were surprised to learn Valencia had pre-eclampsia, a form of high blood pressure that can occur during pregnancy. The diagnosis, just 28 weeks into her pregnancy, led to immediate hospitalization and, within days, the premature birth of their son.

That was the best option for the health of both Valencia and baby Justin, born 12 weeks before his due date and weighing just over 3 pounds. He would require intensive support to continue to grow and develop in the Brigham’s Neonatal Intensive Care Unit (NICU).

With breathing assistance for Justin’s developing lungs and a feeding tube to deliver human breast milk to his belly, he grew and thrived. He soon graduated from the Intensive Support area to the Growth and Development area, no longer needing oxygen support and becoming strong enough to feed on his own.

One novel technology available to him was a breast milk analyzer, a device that assesses nutritional composition of human breast milk. Justin was among the first babies enrolled in a new study at BWH to examine whether knowing the exact nutrition in individual feedings of human milk, and adding the right nutrients (also known as fortification), could aid the smallest babies.

“We know that more optimal nutrition is a predictor of better growth and neurodevelopment,” said Mandy Brown Belfort, MD, MPH, of the Department of Pediatric Newborn Medicine.

Special Nutritional Needs

Human breast milk is uniquely equipped to meet nutritional needs of full-term infants. But pre-term babies – especially those born before 35 to 36 weeks’ gestation – generally require that a fortifier containing calories, protein, calcium and micronutrients such as zinc and Vitamin A be added to a breast milk diet. This aims to replicate the nutrition the baby would receive from the mother’s placenta if still in the womb.

Typically, a premature infant’s growth is followed carefully, but the fortifier is only adjusted if the baby’s weight gain slows over several days. Belfort and her team are using the milk analyzer to avoid this lag, with the goal of delivering accurate, customized fortification with each feeding.

The milk analyzer was initially developed and used in the dairy industry. Recently adapted for human breast milk, it is approved for use in Europe and Canada. In the United States, it is currently available only for research purposes. BWH is one of a few NICUs engaged in that research.

Prior research by Belfort and others has shown surprising variations in the nutritional composition of a mother’s milk throughout a given day. Nutritional makeup also varies from one mother to the next, and it is not necessarily related to the mother’s diet. It’s also known that nutritional quality can degrade as expressed milk is handled and stored.

In Belfort’s current study, each feeding of milk is sampled and analyzed using the countertop device that sits in the NICU’s milk storage room. A tiny syringe, containing less than a teaspoon of milk, is inserted into the analyzer. A readout shows within seconds the milk’s nutritional elements. The results determine how much fortifier should be added on top of the standard fortifier to ensure that nutrient targets are met.

Study results won’t be known immediately as to whether this nutritional fine-tuning will improve growth and development in pre-term babies. The first patients began in the study in spring 2018. Belfort’s team is continuing to offer NICU families the opportunity to volunteer.

Valencia, a scientist herself, was glad to know that she was giving her baby every opportunity to grow, while contributing to newborn science.

“We are thrilled and blessed that he could participate to customize his feedings to his specific nutritional needs,” Valencia said. “Particularly for NICU mothers, there is so much anxiety and uncertainty about what your baby needs. It’s a great comfort to know he’s being fed well here. A baby needs to eat to grow.”

She also expressed her gratitude for the high-quality, compassionate care that she and her family received.

“All the people here are so consistently amazing,” Valencia said. “I want to say a big thank you to the staff at Brigham and Women’s Hospital and the NICU. At all levels of staff, there are such wonderful, caring and loving people here.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

iHub Celebrates 5 Years of Innovation at the Brigham

Interactive demonstrations at the ‘iHub Turns 5’ celebration showcase digital health innovation at the Brigham.

On Sept. 12, more than 200 clinicians, scientists, staff and entrepreneurs commemorated the fifth anniversary of the Brigham Digital Innovation Hub (iHub) during a celebration of innovation and digital advancement at BWH and beyond.

The half-day event, “iHub Turns 5,” featured panel discussions with BWH innovators, iHub alumni and senior leaders from the Brigham and Partners HealthCare in the Hale Building for Transformative Medicine.

Since 2013, iHub has helped innovators launch and advance projects focused on using technology to streamline hospital operations, improve care delivery and enhance the patient and employee experience. One example is the Brigham’s online wayfinding tool, which provides step-by-step directions for navigating the hospital. iHub members have also worked with Medumo, a startup co-founded by Internal Medicine and Dermatology resident Omar Badri, MD. The company’s flagship application – in use at the Brigham’s Endoscopy Center – delivers precisely timed reminders via email and text message to patients for various purposes, such as preparations for procedures.

“We are aspiring to drive the safest, most patient-centered and efficient care through the use, development, evaluation and commercialization of digital health solutions,” said Adam Landman, MD, chief information officer of Brigham Health.

Improving Lifesaving Care Through Innovation

During a panel highlighting current and former BWHers’ journeys from ideation to innovation, YiDing Yu, MD, shared her experience of working with iHub to grow a startup company from a single idea.

When she was a second-year Internal Medicine resident, Yu attended iHub’s inaugural hackathon five years ago wanting to solve a problem she had encountered firsthand, specifically the communication challenges care teams encounter when a patient is arriving via ambulance.

Due to privacy concerns, emergency medical service (EMS) responders can only transmit limited information about an incoming patient to hospital care teams over public radio channels. Yu wanted to develop a tool to bridge this gap – a technology that would provide emergency departments with timely information while protecting patient privacy.

Yu was determined to solve this problem, despite the fact that she had no experience starting a tech company. “All of us were first-time entrepreneurs. We had no idea what we were doing,” said Yu.

Yu’s application, Twiage, is now used by over 50 hospitals in 12 states. Its secure digital platform enables first responders and emergency departments to accelerate lifesaving care by sending real-time clinical data and location updates directly to hospital care teams. Yu said that while it was daunting to pivot her career path to focus on Twiage – she also practices medicine at Atrius Health a few hours a week – she believes in her startup.

Yu attributes part of her success to the support she has received from iHub and the larger Brigham community. “I came to the Brigham to train because of the culture here,” said Yu. “I think you have to be surrounded by people who support your passion – I have bosses and mentors who do that. They help ignite that fire in your belly.”

Yu was joined on the panel by Karen Fasciano, PsyD, a psychologist at BWH and Dana-Farber Cancer Institute, who discussed her work on banYAn, an app that helps young adults coping with cancer; Alexander Lin, PhD, director of the Center for Clinical Spectroscopy in the Department of Radiology, who launched a company called BrainSpec to make virtual biopsies a reality; and Scott Weiner, MD, MPH, of the Department of Emergency Medicine, who is working on several digital health projects related to the opioid crisis.

In addition to the speaking program, the celebration was a homecoming for many iHub alumni, including Lesley Solomon, MBA, who helped create iHub and was honored that evening with the inaugural Disrupting Medicine Award for her contributions and leadership.

Reflecting on iHub’s early days, Solomon said the Brigham had to chart new territory to get iHub off the ground: “You just have to go for it. You just have to start doing things.”

Study: Plastic Surgery Done Abroad Linked to Medical Complications

With the promise of inexpensive procedures luring patients to travel abroad for plastic surgery, medical tourism has become an expanding, multi-billion dollar industry. While the price tag for cosmetic procedures may be lower in developing countries, they can place a significant burden on U.S. public health systems when patients return with medical complications. A new study by investigators at BWH describes the magnitude of complications that can result from plastic surgery performed in destination countries.

“Many think of medical tourism as wealthy patients traveling to receive care at high-quality medical institutions abroad, but that doesn’t fully reflect what we see. We’re reporting on repercussions that can result when patients who are originally from less-developed parts of the world return to their home countries to undergo elective plastic surgery procedures at a lower cost,” said senior author Dennis Orgill, MD, PhD, medical director of the Wound Care Center. “Patients need to be very cautious when they go outside of the U.S. for elective plastic surgery. The safety and regulatory systems that protect patients in the U.S. are often not in place in a patient’s country of origin.”

In a retrospective analysis published in Plastic and Reconstructive Surgery, Orgill, along with his practice assistant, Kimberly Ross, MPH, and other colleagues evaluated patients who had been treated at BWH over the last seven years for complications or complaints associated with plastic surgery performed in a developing country.

Of the 78 patients evaluated as part of this study, the most common complications – including infections, pain and wound-healing issues – were seen following abdominoplasty (tummy tuck) or breast augmentation.  None of the patients came to their Brigham appointments with their foreign medical records.

The most common destination for these surgeries was the Dominican Republic – 75 percent of the patients in the study traveled there for elective procedures. The second most common destination for medical tourism among patients studied was Colombia.

Fourteen patients arrived at BWH with infections at their surgical site, including cases of infection resulting from multi-drug resistant bacteria. Eight patients required the removal of damaged tissue or foreign objects from the wound site over a series of office visits.

The researchers found that some patients may not have received appropriate preoperative counseling and did not stay in the foreign country long enough to treat early complications. Other patients reported unwanted breast implants, showing communication issues in the consent process.

In some cases, Orgill and his colleagues attempted to contact the surgeons from outside the country, but either never received a response or were told the surgeon had never heard of any complications reported from their surgeries.

The Centers for Disease Control and Prevention and the U.S. State Department have issued numerous alerts advising U.S. citizens not to travel to the Dominican Republic, specifically, to undergo plastic surgery, as there is a high incidence of complications, rare types of infections and high rates of death associated with the procedures.

In the BWH study, researchers noted how complications can occur even when highly trained surgeons practice at the best institutions, regardless of geography, and added that there are dangers even within the U.S. from surgeons not trained or properly credentialed to perform plastic surgery procedures. They said raising patient awareness of resources available to them regarding surgeon selection and the dangers of medical tourism is necessary. Because of the continued expansion of medical tourism, the Joint Commission in the U.S. formed the Joint Commission International to accredit institutions that meet their qualifications abroad.

“We hope this study will bring attention to this emerging issue and encourage others to report any results related to medical tourism treatment and patterns,” the authors wrote.

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

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New Cardiac Pump Improves Long-Term Outcomes for Heart Failure Patients

Mandeep Mehra

BWH investigators have found that heart failure patients who received a novel circulatory heart pump had lower rates of pump-related blood clots and stroke after two years compared to patients who had received a commercially available model. Mandeep R. Mehra, MD, executive director of the Center for Advanced Heart Disease and medical director of the Heart & Vascular Center, presented findings from the clinical trial known as MOMENTUM 3 at this year’s American College of Cardiology meeting in Orlando, Fla. Results were simultaneously published in The New England Journal of Medicine.

“This is a pivotal study in the field of advanced heart failure,” said Mehra. “Left ventricular assist devices have been in development for 40 years, and while there have been improvements in their technology, several challenges exist, including problems of blood clots forming in these devices, requiring device replacement. The field has been trying to engineer devices that could make these devices more compatible with blood, and we’re reporting on some important advances.”

The trial, sponsored by the HeartMate’s manufacturer, Abbott Inc., evaluated the performance of the HeartMate 3 left ventricular assist system versus its predecessor, the HeartMate II. The HeartMate 3, which includes several technological adaptations intended to reduce risk of complications, consists of a fully magnetically levitated, continuous centrifugal-flow circulatory pump. This means the device runs like a bullet train – its rotor contains no mechanical bearings, pushes blood using only magnetism and is thus frictionless. It is designed to reduce a form of mechanical strain on blood elements known as shear stress, which is thought to cause blood clots to form in pumps.

By comparison, the HeartMate II uses an axial-flow pump, which uses a rotor that spins on a central ruby bearing to pump blood from the heart throughout the body.

The trial evaluated how many participants had not suffered a disabling stroke or had an operation to replace or remove a malfunctioning device after two years. Researchers reported that about 78 percent of patients who received the HeartMate 3 did not experience a disabling stroke or need a reoperation compared to approximately 56 percent of those on the HeartMate II.

Only three people who received the newer pump needed a reoperation – and none of those due to blood clots – compared to 30 with the commercially available implant.

Improving Access to Novel Therapies

MOMENTUM 3 launched in 2014 and was designed to dramatically reduce the overall timeline for clinical trials. All patients with refractory heart failure who needed a cardiac pump were eligible for the trial, regardless of whether the pump was intended as bridge to transplantation or the primary therapy.

“Traditional trials must first complete safety testing, followed by testing in populations of healthier transplant eligible patients, and it can be more than a decade before the broader advanced heart failure population has access to such therapies,” said Mehra. “Removing restrictions based on transplant status resulted in a unique study that has been extremely successful in its enrollment and highly expeditious in delivering results.”

In its next phase, MOMENTUM 3 will evaluate 1,028 patients at the two-year mark to further validate the current findings. Results of the full cohort are expected in 2019.

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

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Study: Surgery May Offer Better Outcomes for Obesity, Diabetes Control

Donald Simonson

Patients with worrisome levels of obesity and poor control of their Type 2 diabetes face two dramatically different options to improve their health: surgery or significant lifestyle changes. In a randomized controlled clinical trial, scientists from BWH and Joslin Diabetes Center found that patients who underwent a form of weight-loss surgery known as Roux-en-Y gastric bypass did significantly better after three years than those who followed an intensive diabetes- and weight-management program.

“Our study demonstrates that in patients with mild-moderate obesity and Type 2 diabetes, gastric bypass surgery leads to a sustained reduction in weight, improvement in glycemic control and decrease in cardiovascular risk, compared to a medical diabetes- and weight-management program,” said lead author Donald Simonson, MD, ScD, MPH, of the Division of Endocrinology, Diabetes and Hypertension.

Other BWH contributors to the research include Florencia Halperin, MD, medical director of the Program for Weight Management, and Ashley Vernon, MD, a member of the Center for Metabolic and Bariatric Surgery.

The paper, which will be published the April issue of Diabetes Care, provided the results from the SLIMM-T2D (Surgery or Lifestyle with Intensive Medical Management in the Treatment of Type 2 Diabetes) study, which randomly assigned 38 obese patients with Type 2 diabetes to Roux-en-Y gastric bypass surgery at BWH or an intensive lifestyle management program at Joslin. Initially, participants had an average weight of 230 pounds and body mass index (BMI) of 36.3.

After three years, patients who underwent surgery experienced far more weight loss, dropping 55 pounds on average. Those in the lifestyle-management intervention lost an average of 11 pounds over the same period.

Additionally, patients in the surgery group lowered their blood sugar to a greater degree, seeing hemoglobin A1c levels drop 1.79 percentage points. In comparison, patients in the lifestyle-management program experienced a 0.39 percentage point decrease. Those who received surgery also showed significantly lower risk of coronary heart disease and stroke.

‘A Viable Option’

Although patients given the lifestyle-management program made encouraging initial progress in both weight loss and diabetes control, investigators noted that those improvements dropped noticeably over time.

“Patients who had the gastric bypass procedure had superior ability to sustain changes both in weight and blood sugar, and they did so requiring less medication for their diabetes, their blood pressure and their lipids,” said Allison Goldfine, MD, head of clinical research at Joslin during the trial and senior author on the paper.

Participants from both groups reported improvements in overall quality of life. Those who were assigned the surgical intervention experienced greater improvement in physical functioning, self-esteem and work performance, and weight loss had a significantly higher effect on their quality of life compared to the other group.

“As a result of these findings, we expect that more physicians will consider gastric bypass surgery as a viable option for patients with Type 2 diabetes and mild to moderate obesity when previous attempts to lose weight and improve glycemic control have not been successful,” said Simonson.

The Roux-en-Y gastric bypass procedure is done laparoscopically through small cuts in the abdomen. Surgeons form a small pouch at the top of the stomach and connect the pouch to the middle of the small intestine.

Joslin’s 12-week intensive lifestyle-management program included a change in diabetes medications to enhance weight reduction, structured dietary intervention with lower carbohydrates and higher protein and meal replacement, an exercise program with emphasis on strength training, and weekly educational and support sessions.

Goldfine emphasized that treatment must be personalized for all patients with obesity and diabetes, as gastric bypass surgery may not always be the best option. She noted that today’s surgical procedures and intensive lifestyle-management techniques both take advantage of major medical advances achieved in the past decade or two.

“Older surgical procedures were much more invasive, with much higher surgical risk and complication rates, and older types of procedures had higher failure rates over time,” she said. “Laparoscopic surgery made the biggest impact on the surgical experience and recovery, but we have improved surgical techniques all the way from preoperative evaluations to better postoperative care.”

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

Study: Stroke Risk Factors Unique to Women Identified

Kathryn Rexrode

Stroke disproportionately affects more women than men. It’s the fourth leading cause of death in women in the U.S., a prominent cause of disability and affects 55,000 more women than men each year. But what causes the disparity?

Investigators from BWH are looking to answer this question by exploring the effects of risk factors that are unique to women, including hormone levels, hormone therapy, hormonal birth control, pregnancy, first menstrual period and menopause.

In a paper published in Stroke earlier this week as part of a special issue focused on women’s health in honor of American Heart Month, investigators highlight these risk factors as well as areas where future research is needed, including the effects of hormone therapies for transgender people.

Corresponding author of the paper Kathryn Rexrode, MD, MPH, chief of the Division of Women’s Health, said that many people don’t realize that women experience a stroke more frequently than men and that mortality is much higher among women.

“As women age, they are much more likely to have a stroke as a first manifestation of cardiovascular disease rather than heart attack,” said Rexrode, who led a team that delved into the scientific literature to investigate evidence behind this finding. “We want to better understand susceptibility: Why are women more susceptible to strokes than men? What factors are contributing and disproportionately increasing a woman’s risk?”

Considerations for Clinicians

In this review, researchers reported on several hormonal factors that elevate the risk of stroke among women, including experiencing first menstruation and menopause at an early age, having low levels of the hormone dehydroepiandrosterone (DHEA) and taking oral hormones, whether as estrogen oral contraceptives or postmenopausal hormone therapy.

The team noted that while many of these factors are extremely common, the absolute risk in younger women is relatively small. However, Rexrode emphasizes it’s important for clinicians to consider these factors when evaluating a female patient’s risk of stroke. Additional factors unique to women include a history of pregnancy complications, such as gestational diabetes, pre-eclampsia or hypertension during or immediately following pregnancy.

“These women should be monitored carefully, and they should be aware that they are at a higher risk, and motivated to adhere to the healthiest lifestyle to decrease the risk of hypertension and subsequent stroke,” Rexrode said.

Certain risk factors, such as taking transdermal estrogen or progestogen-only contraception, need further research, according to the authors. The team also conducted a search of the literature for studies on the impact of hormones on stroke risk in transgender individuals, but reported there is scant evidence on the effects of  medical treatment with estrogens, anti-androgens or a combination of both.

Brigham Health’s Strategy in Action: Discovery & Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

Ground Control to STRATUS: Simulating Medical Emergencies in Space

From left: Gregory Porretto, Abdulrahman Sabbagh and Kara Brown simulate a scenario in STRATUS’ mock spacecraft medical bay.

With funding and support from NASA, the Neil and Elise Wallace STRATUS Center for Medical Simulation recently collaborated with experts from McMaster University and Northern Ontario School of Medicine (NOSM) in Canada to design and construct a simulated spacecraft medical bay – a first-of-its-kind facility researchers will use to study how astronauts can best manage medical emergencies in space.

That’s one small step for man, one giant leap for health care simulation at the Brigham.

Based on the International Space Station’s (ISS) medical bay, the simulator will serve as a testbed where BWH researchers can implement a nontechnical skills training program they’ve developed for astronauts on human-exploration missions to Mars, near-Earth asteroids or the moon. The simulator was designed by Thomas Doyle, PhD, MESc, an associate professor of Electrical Engineering at McMaster.

“The most exciting part of this project is that we’ve been successful in creating an environment that mimics the medical facilities that might be available to astronauts on a long-duration mission. This allows us to create scenarios where crew members face a variety of medical emergencies,” said Jamie Robertson, PhD, MPH, assistant director of Simulation-Based Learning at STRATUS. “By studying the behavior of the team in these situations, we can identify the behaviors that might increase survival and mission success. Hopefully, this research will lay the groundwork for the training programs that will train the first Mars astronauts.”

A mission to Mars, which NASA hopes to launch in the 2030s, would take several years. That creates a very different dynamic than a five-day trip to the ISS, explained Steven Yule, PhD, director of Education and Research at STRATUS and principal investigator (PI) of the project. The longer trip makes it far more likely the crew will experience a medical emergency. In addition, there will be relatively limited supplies on board, and there may only be one or two astronauts with medical training among a crew of scientists, engineers and military service members.

Communication with Mission Control also becomes more difficult. Whereas ISS crews experience a one-second delay, the time delay between Earth and Mars can reach 20 minutes – each way.

These conditions are similar to those faced in remote areas during medical emergencies, which led Yule to team up with a longtime collaborator, David Musson, MD, of NOSM, who specializes in simulating medical event management in rural and remote locations and serves as co-PI of the NASA project.

“The first few minutes of a medical event can be really critical. If something occurs, the crew has to be able to deal with some of that themselves,” Yule said. “They can ask for assistance from the ground, but they’re not going to be available to immediately help.”

Developing Nontechnical Skills Training

While BWH researchers also hope to help NASA determine the medical capabilities needed for these missions, their immediate focus will be on skills such as situation awareness, decision-making, communication, leadership and teamwork.

The interdisciplinary team at STRATUS – which also includes postdoctorate fellow Roger Dias, MD, MBA, PhD – and the Center for Surgery and Public Health, as well as experts from McMaster and NOSM, has worked with NASA for the past year. Together, they are developing a behavior observation system, training programs and checklists to teach astronauts these skills. The simulator itself allows researchers to test and document the program’s effectiveness in various scenarios. From there, BWH will help develop the nontechnical skills training programs for eventual integration with NASA’s astronaut training in Houston.

“The work that Steve, Jamie and the rest of the team have done on this important project with NASA is another indication of how much STRATUS and BWH have contributed to the growth of medical simulation and highlights the importance of nontechnical skills in the practice of medicine – even on a mission to Mars,” said Charles Pozner, MD, executive director of the STRATUS Center.

‘More Than Just a Prop’

Although it looks like a movie set, the simulator offers the most realistic environment possible for research and training, Yule said. In addition to its authentic appearance, the simulator mimics many other characteristics of a spacecraft medical bay – minus, of course, zero gravity. Alarms, lights, smoke machines and vibrations provide a greater sense of immersion for simulation participants.

“It’s more than just a prop,” Yule said. “The psychological fidelity is really important for simulation training.”

Researchers themselves also look the part. Next to the simulator is a rack of NASA astronaut flight suits. Though amid all the realism, STRATUS added one fictional, but fun, detail: The name badges on the flight suits include Ash, Ripley and Brett – characters from the 1979 film Alien.

Become an ‘Astronaut’ During HUBweek

BWH is participating in HUBweek, a weeklong festival celebrating innovation in Boston. On Wednesday, Oct. 11, 3-5 p.m., all staff are invited to explore innovation at Brigham Health through an interactive scavenger hunt, which includes a stop at STRATUS’ state-of-the-art spacecraft medical bay.

Step into a flight suit and experience “blast-off.” A fellow “astronaut” will complain of chest pain and difficulty breathing. Under the guidance of a physician, you’ll respond as a team to the mock medical emergency.

The event is free to attend and open to all staff. Register and learn more here.

Learn About Simulation at Pop-up STRATUS

Celebrate Healthcare Simulation Week with the STRATUS team on Tuesday, Sept. 12, 9 a.m.-1 p.m., at an information table on the Tower 2 mezzanine and learn about medical simulation, explore skills training equipment and simulation gadgets, and get an up-close look at the manikins (patient simulators) used at STRATUS.

Brigham Health’s Strategy in Action: Discovery & Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

BWHers Uncover Compound That Corrects Iron-Delivery Defects

Physician-scientist Barry Paw (second from left) with members of his lab.

Iron is an essential element for life. Red blood cells rely on it to create the protein required to transport oxygen in our body. Iron is shuttled to the right places in the body through an elaborate series of reactions and processes, but when that system fails, it can cause diseases.

Drawing from a natural substance found in the wood of certain species of trees, BWH researchers recently identified a compound that can correct iron-delivery defects in preclinical models. The compound, known as hinokitiol, is described in a paper published this month in Science.

The study, done in collaboration with scientists at University of Illinois Champaign-Urbana, lays the groundwork for investigating hinokitiol’s full potential beyond cellular and model organisms, possibly one day in humans. If successful, these findings may lead to novel therapies for diseases such as iron deficiency anemia (too little iron), hemochromatosis (too much) or sideroblastic anemia (too much in the wrong part of a cell).

“The long-term therapeutic implications of our work with hinokitiol points to potentially using this chemical to correct anemias caused by genetic deficiencies of iron transporters required for normal red cell formation,” said co-corresponding author Barry Paw, MD, PhD, of the Division of Hematology. “More extensive clinical trials are necessary to work out the full potential of hinokitiol and to identify potential toxicities that we have not identified using preclinical models.”

Hinokitiol is a natural product found in the wood of trees. Originally isolated from the Taiwanese hinoki tree, this small molecule is also found in cedar wood.

The research team studied the properties of hinokitiol in yeast, mouse red blood cells and zebrafish models, all of which lacked the ability to transport iron. When the team administered hinokitiol in these preclinical models, they found that it corrected the anemia at the cellular level.

“We found that hinokitiol can restore iron transport within cells, out of cells or both,” said Paw. “It can also promote iron gut absorption and the creation of hemoglobin in some of our models. These findings suggest that small molecules like hinokitiol that can mimic the biological function of a missing protein may have potential for treating human diseases.

Brigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

WMIF 2017 Highlights Innovation in Cardiovascular Medicine

From left: Joseph Loscalzo, chair of the Department of Medicine, moderates a fireside chat with former FDA Commissioner Robert Califf.

More than 1,000 attendees gathered for Partners HealthCare’s World Medical Innovation Forum (WMIF) from May 1 to May 3, featuring senior experts and rising stars from BWH and beyond. This year’s forum focused on advances in cardiovascular medicine, including powerful new technologies and discoveries that are helping to shape the future of cardiovascular care.

“This year’s forum highlights the convergence and cooperation occurring between academia and industry to redesign cardiovascular care and improve the lives of millions of patients around the world,” said Calum MacRae, MD, PhD, chief of the Division of Cardiovascular Medicine and co-chair of this year’s WMIF. “New technologies are emerging – not just traditional medical devices, but also wearables, online apps and more. We need to think through how these advances can work together seamlessly to help change medicine for the better.”

Among this year’s BWH speakers were 10 early-career investigators who presented as part of the First Look session on the forum’s first day. Topics ranged from improving cardiovascular outcomes for cancer survivors (presented by cardiologist John Groarke, MD, MPH) to using zebrafish for modeling cardiovascular disease (presented by research fellow Manu Beerens, PhD).

Benjamin Olenchock, MD, PhD, who presented his work in developing mouse models of remote cardioprotection, won a $10,000 Austen-Braunwald Award to support his research.

Other Brigham highlights of this year’s forum included a panel about global clinical trials, moderated by Marc Sabatine, MD, chair of the Thrombolysis in Myocardial Infarction (TIMI) Study Group. Brigham Health President Betsy Nabel, MD, moderated a fireside chat with National Heart, Lung and Blood Institute Director Gary Gibbons, MD.

Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention, participated in a panel about new targets in coronary artery disease. Ben Scirica, MD, spoke about drug pricing during another panel discussion.

The forum concluded with its annual Disruptive Dozen session, highlighting concepts, advances and technologies anticipated to transform cardiovascular medicine over the next decade. Among the topics selected was “Harnessing Big Data and Deep Learning for Clinical Decision Support,” foreshadowing the theme of next year’s WMIF: artificial intelligence.

“We’ve heard about so many innovative projects and advancements that leverage or generate vast amounts of data. At the end of the day, we are all projecting toward the topic for next year’s forum and how to put all of the data together,” said MacRae.

Read more coverage of this year’s event at ConnectWithPartners.org.

Brigham Health’s Strategy in Action: Discovery & Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

A Breath of Fresh Air for Severe Asthma Research

Melody Duvall

About 10 percent of people with asthma have severe asthma, a form of the disease that is not controlled by current medications. Many of these patients are prescribed increased dosages of corticosteroids – a medication intended to reduce inflammation in the airways – but continue to experience daily symptoms and recurrent infections. New research led by a team of BWH investigators suggests a reason why corticosteroids may actually aggravate severe asthma. Their insights appear online this month in Science Immunology.

“Our findings point to an interesting and pivotal role for a certain type of white blood cells, known as natural killer cells, in the asthmatic airway and suggest that continually giving high doses of corticosteroids may actually be making things worse for patients with severe asthma,” said Bruce Levy, MD, chief of the Division of Pulmonary and Critical Care Medicine at BWH.

Elliot Israel

Asthma affects an average of one out of every eight Americans at some point in their lives, but severe asthma is relatively rare. In order to better understand severe asthma, seven U.S. asthma research centers joined forces to collect and share patient samples as part of the Severe Asthma Research Program-3 (SARP-3) Study funded by the National Heart, Lung and Blood Institute of the National Institutes of Health.

Levy and Elliot Israel, MD, the division’s director of Clinical Research and director of BWH’s Asthma Research Center, are the co-principal investigators of the Boston-based site of the study. Study participants, recruited from the Asthma Research Center, gave blood, sputum and exhaled breath samples as well as tissue samples from deep in the lungs.

By examining specimens that originate in close proximity to the source of severe asthma from a relatively large number of patients, researchers were able to gain insights that had not been possible before.

Bruce Levy

Lead author Melody Duvall, MD, PhD, a postdoctoral research fellow in the Levy lab, joined by Levy, Israel and other colleagues, examined immune cells in samples from patients with severe asthma, patients with nonsevere asthma and healthy control subjects.

They focused on a prominent type of white blood cells: lymphocytes. One important family of innate lymphocytes in the lung are known as natural killer cells, which are pivotal for both mounting an immune response and helping to resolve inflammation. In patients with severe asthma, however, natural killer cells are disabled from resolving inflammation, and become outnumbered by other types of immune cells that provoke it. Treatment with corticosteroids for severe asthma appeared to further suppress the ability of these cells to help clear inflammation.

The team found evidence that molecules called lipoxins may help NK cells resolve inflammation. Further studies of their therapeutic potential are ongoing. On the clinical side, Israel and Christopher Fanta, MD, of Pulmonary and Critical Care Medicine and director of the Partners Asthma Center, will lead a new, multidisciplinary clinical center for patients with severe asthma, opening this May.

StrategyIcon_WordpressBrigham Health’s Strategy in Action: Discovery and Innovation
Learn more about our strategic priorities at BWHPikeNotes.org.

Q&A: Introducing Brigham Health

bh_bwh_pms_293Brigham Health was unveiled earlier this week as the new name for the parent organization that includes Brigham and Women’s Hospital, Brigham and Women’s Faulkner Hospital and the Brigham and Women’s Physicians Organization. All three entities will retain their individual names and identities. Brigham Health replaces Brigham and Women’s Health Care (BWHC). 

Brigham Health President Betsy Nabel, MD, discusses with BWH Bulletin what this change means for us. 

Why did we change from BWHC to Brigham Health?

Nabel: Those who know the Brigham think of it as a top-tier New England hospital – a place to go for care when needed, especially complex procedures. But according to market research, many outside of New England assume we are solely a women’s hospital. And while we are certainly a leader in women’s health care, we want to be sure it’s clear that our excellence and expertise extend to so many other areas. Brigham Health reinforces that we are not just one point on a map, or even a single point of discovery.

The new name eliminates some of the confusion we have found among those outside of New England. Talking about the services of BWH, BWFH and the BWPO as simply Brigham Health will enable us to more effectively reach people who are seeking health information, referrals and care.

How does this change fit into our strategy?

Nabel: This change is a vital component of our institutional strategy. For example, one of our strategic priorities is to improve health. In addition to providing highly specialized care in the hospital and ambulatory settings, we also must engage people around the world as we promote health and wellness and concentrate on preventing disease in populations.

Another example is twofold. By building national and international lines of business, we reinforce our financial strength and advance our work in business development – two areas essential to guaranteeing we continue delivering on our mission.

Why was the name Brigham Health selected?

Nabel: Brigham Health reflects our role as a leader in maintaining and restoring health around the world, encompassing all that we do in delivering care, advancing scientific discovery and educating the next generation of health care professionals. It broadly defines everything we do today and provides a new platform for amplifying our commitment to what everybody desires: health.

For more Brigham Health information and resources – including an FAQ, downloadable logos and presentation templates – visit BWHPikeNotes.org

StrategyIcon_WordpressBrigham Health’s Strategy in Action
Learn more about our strategic priorities at BWHPikeNotes.org.

Elledge Wins Breakthrough Prize for Pioneering Genetics Research

As a young postdoctoral fellow at Stanford University, Stephen J. Elledge, PhD, believed he was close to identifying the genetic component to unlock gene editing. Ultimately, however, the gene he was studying didn’t have the answer. Elledge was heartbroken – until something else about the findings piqued his interest.

“At first, I was really depressed and wanted to throw it all away, but it turned out there was one thing interesting about this gene: It became activated in response to DNA damage,” said Elledge, now of BWH’s Division of Genetics.

That groundbreaking discovery – one that he would spend the next three decades unraveling – was the first of Elledge’s many wide-ranging contributions across multiple fields of biology. His work has since revealed critical mechanisms in cell division, cell aging, cancer growth, and protein breakdown and recycling.

In honor of his many scientific contributions, Elledge was recently named one of five recipients of the 2017 Breakthrough Prize, which recognizes achievements in fundamental physics, life sciences and mathematics. The $3 million prize – said to be the largest in the world for science – was founded by several entrepreneurs and philanthropists, including Google co-founder Sergey Brin and Facebook founder and CEO Mark Zuckerberg.

The awards were presented during a televised gala – attended by celebrities such as Vin Diesel, Morgan Freeman and Jeremy Irons – at the NASA Ames Research Center in Silicon Valley on Dec. 4.

“This magnificent award is a fitting recognition and acknowledgement of Stephen’s outstanding ingenuity, tenacity and vision,” said BWHC President Betsy Nabel, MD. “We are extremely fortunate to count him among our colleagues here at the Brigham, and congratulate him and this year’s other winners on their remarkable achievements.”

Stephen Elledge

Stephen Elledge

One of Elledge’s most pivotal discoveries was unraveling the process by which cells sense DNA damage and initiate self-repair. This critical fail-safe mechanism safeguards both individual cells and the integrity and health of the entire organism.

DNA, which forms the basis of life, fends off constant damage from various sources, including normal metabolic byproducts, environmental toxins, sunlight and normal aging. Such assaults can alter DNA’s chemical structure, leaving behind mutations in the cell’s genetic code. If left unrepaired, these alterations can disrupt key biological processes, leading to serious diseases, including cancer.

Elledge’s work revealed that a protein-enzyme pair sniffs out damaged DNA and notifies the cell’s internal repair machinery to fix the problem. If and when the cell fails to mend broken DNA, it issues a command to self-destroy. This process is the body’s way of stemming the proliferation of abnormal cells and preventing cancer. Elledge’s discoveries explained how and why this mechanism sometimes fails.

“This prize is not just a recognition of my laboratory. It’s also a celebration of science itself,” he said during his acceptance speech. “It’s very important for a society to promote the culture of science.”

Elledge – who won the 2015 Albert Lasker Basic Medical Research Award – plans to apply a significant portion of the Breakthrough Prize toward philanthropic causes, including those promoting secondary and higher education, with an emphasis on science.