Posts from the ‘scalable innovation’ category

Morteza Mahmoudi

Morteza Mahmoudi displays the latest prototype of a novel skin patch designed to heal chronic wounds.

Morteza Mahmoudi, PhD, vividly remembers the fear and heartache he felt as a child growing up in Iran during the Iran-Iraq War in the 1980s. The armed conflict played out in the streets of his hometown of Tehran, where he says it wasn’t unusual to encounter a friend, neighbor or loved one suffering from traumatic injuries following a missile attack.

But just as clearly, Mahmoudi recalls what the voice inside him often said those days: Help people. Help heal their pain.

Now a biomedical investigator at the Center for Nanomedicine and the Department of Anesthesiology, Perioperative and Pain Medicine, Mahmoudi has spent the last three decades following that calling. It has propelled him to fulfill his life mission to ease suffering, no matter the obstacle.

“The war was a very hard period, but when I think about those days, I realize that kind of experience puts fuel in your motivational tank for the rest of your life,” he said. “From the time I entered university, I made the decision to use my past as a driving force for the future.”

As the winner of the seventh annual BRIght Futures Prize, Mahmoudi is especially hopeful about what tomorrow holds for patients around the world. The competition’s $100,000 award will support his project, “Time to Heal Chronic Wounds.”

Sponsored by the Brigham Research Institute, the BRIght Futures competition invites the Brigham community and the public to vote for one of three finalists whose innovative research is poised to transform medicine. This year’s competition garnered its largest-ever number of votes: 16,530. Mahmoudi was announced as this year’s winner during an awards ceremony at Discover Brigham on Nov. 7.

For the past 10 years, Mahmoudi has been working to develop a skin patch to heal chronic wounds that the body is unable to repair on its own, such as bedsores and diabetic wounds. There is no effective treatment for these types of wounds, which can easily become infected and sometimes lead to amputation or even death.

Mahmoudi’s patch is made from multifunctional nanofibers – fibers that are 1,000th the diameter of a single human hair – that mimic most of the skin’s characteristics. They are engineered to deliver a cocktail of healing biomolecules and immunotherapeutic nanoparticles to a wound site. These unique properties can help cells reach the site of a wound and create new blood vessels. Meanwhile, the nanoparticles detect and help fight infections while also lessening inflammation. The BRIght Futures Prize funding will help advance the project from the lab bench to clinical trials so that it can be rigorously tested in humans.

A Long Road

Once he got the idea for the patch, Mahmoudi soon realized how ambitious an endeavor creating it would be. It demanded expertise in four highly complex, distinct scientific fields: materials science and engineering, biomedical engineering, nanomedicine and cell biology. Undeterred, Mahmoudi earned a degree in each one (a bachelor’s, master’s, doctorate and post-doctorate, respectively).

“The time in which I was working on bachelor’s and master’s was extremely hard, as in addition to my university courses and research, I had to work over 70 hours per week as a high school teacher to support my family at the time,” Mahmoudi recalled. “The motivational fuel and my old friend – my internal monologue – gave me the stamina to make it through those days and continue my scientific activities while also taking care of my immediate family.”

He kicked off his research career at universities in Ireland, Switzerland and the U.S., advancing his understanding of science and medicine as he chipped away at the project’s protocols and prototypes.

“I was like a scientific nomad,” he said. “Ten years ago, the crosstalk between different experts was not great – not like today – so that’s why I had to train in different medical and engineering fields.”

Each part of the patch – its precise structure and physical, chemical and mechanical properties – took years to perfect.

“I would say that this was one of the hardest projects I’ve ever done because it took a lot of time, and I could have easily given up many times, but I kept going,” he said. “My long-term collaborators and I made a huge number of prototypes. We haven’t yet published anything on this topic, as I believe that the scientific community and patients would benefit from the A-to-Z story, rather than progressive reports. We needed to make sure our final prototype was error-free, and we are now at that stage.”

Being part of the Brigham’s highly collaborative clinical and research community has been a tremendous gift in advancing this work, Mahmoudi said.

Today, he is excited to see the project move one step closer to changing outcomes for patients with chronic wounds, thanks to the BRIght Futures Prize.

“If I can reduce the pain of one patient, even for one minute, I have done my share. But if these patches can help many lives, that would be my ultimate dream,” Mahmoudi said. “This prize opens the way to that.”

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Waldor Lab members, from left: Brandon Sit, Alyson Warr, Gabriel Billings, Matthew Waldor and Troy Hubbard (not pictured: Carole Kuehl)

When an outbreak of cholera unfolds, a vaccine that offers rapid protection could mean the difference between life and death for tens of thousands of people.

In a preclinical study, investigators at the Brigham are developing a new class of vaccine that can combat cholera, a highly contagious, quickly fatal diarrheal disease with a long history of causing epidemics. The vaccine is designed to act in two ways – training the immune system to detect and destroy the bacteria in the long term and protecting a person immediately from cholera’s effects. Using mathematical modeling, the research team predicts that, if successful in humans, their highly innovative approach could change the trajectory of a cholera epidemic.

This novel therapeutic, which has been tested in a preclinical model, is made from a live strain of the disease and protects against cholera-like illness less than a day after it is administered. Traditional, oral cholera vaccines are made from strains that have been killed and take effect after about 10 days.

“Our work represents a whole new concept in vaccinology – this dual-acting agent elicits a long-term immune response and confers protection almost immediately,” said Matthew Waldor, MD, PhD, of the Division of Infectious Diseases and the study’s corresponding author. “What we’ve done is something very different than what others have done before.”

Waldor and colleagues engineered the live vaccine based on the strain of cholera that caused a large epidemic in Haiti beginning in 2010. The research team engineered the strain by removing the genetic code that gives cholera its deadly properties. They also encoded within it a system that keeps out any toxin-producing genes, preventing the strain from ever regaining toxin production abilities. The team performed additional engineering to prevent other side effects, including mild diarrhea.

Researchers tested the vaccine in a preclinical model of cholera.

The vaccine, known as HaitiV, did not elicit cholera-like symptoms and caused minimal or no fluid accumulation in the intestines after being administered, even though the vaccine colonized the small intestine. When the team exposed the preclinical experimental group to cholera 24 hours later, no signs of disease were present.

The team also performed mathematical modeling to predict the public health impact the vaccine might have compared to traditional vaccines. The researchers’ simulations showed that in a population of 100,000 people, a fast-acting vaccine could prevent 20,000 infections compared to vaccines that can take the typical 10 days to build up a host’s immunity.

“The speed with which you respond to an outbreak significantly helps your ability to control it and prevent people from getting cholera,” said lead author Troy Hubbard, PhD, a graduate student in the Waldor Laboratory at the Brigham. “We are very focused on feasibility – the idea of being able to come in with a single-dose intervention that works rapidly but confers immunity over a long period.”

The team notes that evaluating the immune response that HaitiV elicits in human volunteer studies is a critical next step.

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Training class for staff at Gillette Stadium

This tourniquet training class for staff at Gillette Stadium was one of many conducted by BWH researchers last year.

In the immediate aftermath of an accident or attack, can bystanders help save the life of someone who has experienced a traumatic injury? Brigham researchers recently sought to answer this question by studying how well different training methods prepared laypeople to apply tourniquets to stop uncontrolled bleeding, finding that those who underwent in-person training were most likely to successfully perform and retain this skill.

Traumatic injuries are the leading cause of death for Americans under 46, and uncontrolled bleeding is the most common cause of preventable death following a traumatic injury. Since the Boston Marathon bombings in 2013, several national initiatives, including the White House’s “Stop the Bleed” program, have emerged to empower laypeople to act as immediate responders until emergency personnel arrive on scene. These efforts have led to the development of different training methods, but it was previously unknown which type, frequency and format of training would competently prepare nonmedical personnel to conduct hemorrhage control.

To determine the best training method for tourniquet education, BWH researchers completed the PATTS Trial (Public Access and Tourniquet Training Study). The study was funded by The Gillian Reny Stepping Strong Center for Trauma Innovation and conducted in partnership with Gillette Stadium and the New England Patriots.

In total, 465 Gillette employees, who had no prior training in this area, participated in the study. The trial was designed to not only train staff in responding to uncontrolled bleeding, but also to test whether, and under what conditions, such training was effective. The results were published in JAMA Surgery this month.

Participants were randomly assigned to one of four groups. The first was provided instructional flashcards to learn about proper tourniquet application. The second group used flashcards and audio kits. The third received in-person training through the Bleeding Control Basic (B-Con) course, led by BWH instructors. The final cohort was asked to apply tourniquets with no training or instructions. Participants in the first, second and fourth groups later received in-person training.

Researchers found that in-person training, via the B-Con course, was the most effective instructional method and resulted in 88 percent of participants correctly applying a tourniquet. By comparison, participants who received no training applied a tourniquet correctly only 16 percent of the time, and participants who had access to instructional flashcards or an audio kit with flashcards experienced only small gains in effectiveness.

Looking at skill retention, researchers discovered that only about half of the participants could correctly apply a tourniquet three to nine months later, emphasizing the need for refresher training.

“Before the PATTS Trial, we didn’t know what was the best way to train the public in bleeding control,” said Adil Haider, MD, MPH, a trauma surgeon and Kessler director of the Center for Surgery and Public Health. “Now that we know, we can be more effective in creating training programs, public awareness campaigns and tools to empower people.”

Researchers stress that most external hemorrhages, or bleeds, can and should be controlled by direct pressure. While bystanders were critical first responders following the Boston Marathon bombings, subsequent research indicated that all 27 improvised tourniquets administered at the scene were applied incorrectly.

Looking ahead, Eric Goralnick, MD, MS, medical director of Emergency Preparedness and lead author of this study, said clinicians and public health investigators will convene to define a common research agenda for laypeople and bleeding control.

Meghan McDonald, MSN, RN, nurse director of the Trauma Program in the Division of Trauma, Burn and Surgical Critical Care and co-author of the study, said intervention from bystanders in any situation, not just mass-casualty events, can help save lives.

“Some people hesitate, especially when it comes to tourniquets, because they are afraid of causing more harm,” McDonald said. “Educating laypeople on hemorrhage control, be it direct pressure or tourniquet application, is not only the responsible thing to do as a trauma center – it is also the right thing to do.”

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BWH and Dana-Farber Cancer Institute (DFCI) researchers are using artificial intelligence to detect ovarian cancer early and accurately with a simple blood test.

The team looked at a set of molecules called microRNAs, which help control where and when genes are activated. With the aid of an advanced computer algorithm, researchers identified a network of microRNAs that are associated with risk of ovarian cancer and can be detected from a blood sample.

Artificial intelligence, also known as AI, is a branch of computer science in which machines are trained to identify patterns and make predictions after analyzing large amounts of data.

“When we train a computer to find the best microRNA model, it’s a bit like identifying constellations in the night sky. At first, there are just lots of bright dots, but once you find a pattern, wherever you are in the world, you can pick it out,” said Kevin Elias, MD, of BWH’s Department of Obstetrics and Gynecology, and lead author of the study, published in eLife.

Unlike other parts of the genetic code, microRNAs circulate in the blood, making it possible to measure their levels from a sample.

“MicroRNAs are the copyeditors of the genome: Before a gene gets transcribed into a protein, they modify the message, adding proofreading notes to the genome,” said Elias, who collaborated with Dipanjan Chowdhury, PhD, chief of the Division of Radiation and Genomic Stability at DFCI.

Need for Early Detection

Most women are diagnosed with ovarian cancer when the disease is at an advanced stage, at which point only about a quarter of patients will survive for at least five years. But for women whose cancer is unexpectedly found at an early stage, survival rates are much higher.

Existing early-detection blood tests frequently report false positives and have shown no meaningful effect on survival rates. With this in mind, BWH and DFCI researchers sought to develop a tool that would be more sensitive and specific in detecting cases of early-stage ovarian cancer.

To do this, the team investigated the microRNAs in blood samples from 135 women before they underwent surgery or chemotherapy. These samples were used to train a computer program to look for differences in microRNA that indicated the presence of ovarian cancer and to accurately distinguish samples from harmless non-cancerous masses.

When the computer program predicted cancer, it was right more than 90 percent of the time. Similarly, a negative test reflected absence of cancer about 80 percent of the time, which is comparable to the accuracy of a Pap smear test.

“The key is that this test is very unlikely to misdiagnose ovarian cancer and give a positive signal when there is no malignant tumor. This is the hallmark of an effective diagnostic test,” said Chowdhury.

To move the diagnostic tool out of the lab and into the clinic, the research team will need to monitor patient samples further. They are particularly interested in determining if the tool will be useful for women at high risk of ovarian cancer as well as the general population.

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Pablo Uribe Lietz (center) demonstrates for Harvard Medical School students how to properly apply a tourniquet.

Even if you have no medical training, you might be able to save the life of someone experiencing a heart attack if there’s an automated external defibrillator (AED) nearby. Designed to be used by those with minimal or even no training, these devices automatically detect an abnormal heart rhythm and administer an electrical shock after sensors are applied.

Now, a group of BWHers plans to develop a similar kit for treating uncontrolled bleeding that anyone can use during an emergency before medical personnel arrive. The project is part of Stop the Bleed, a national awareness campaign about how to stop life-threatening bleeding.

In this Q&A, Eric Goralnick, MD, medical director of Emergency Preparedness, discusses the innovative ways BWH is contributing to Stop the Bleed in partnership with The Gillian Reny Stepping Strong Center for Trauma Innovation, Gillette Stadium and several local partners.

What gave rise to this initiative?

EG: Stop the Bleed was started in the wake of the Sandy Hook shootings by a group of clinicians, the Hartford Consensus, whose goal was to find what we can do as a society to minimize preventable deaths after mass shootings or other mass-casualty events.

To do that, they looked at the success the military has had in preventing deaths from extremity injuries by training many ground forces in trauma combat casualty care. The focus is on teaching lay individuals to recognize life-threatening bleeding and intervene – either applying pressure to a wound, packing a wound and then applying pressure or, if it’s an extremity, applying tourniquets. From this, the Hartford Consensus recognized the need to empower laypersons to intervene.

How is the Brigham contributing to the campaign?

EG: Where we think Brigham can particularly add value is in innovation, education and operationalizing the concepts of Stop the Bleed.

We’re working to identify the equivalent of the defibrillator for hemorrhage control, starting with trials of a few commercial “just-in-time training” kits for bleeding control. Potentially, we may design our own.

We’re also developing training programs. When we look at these horrible events, they have traditionally occurred in places like stadiums, public transportation hubs, schools and shopping malls. We want to work with these organizations to train their staff in bleeding control.

This program’s success is possible thanks to our collaboration with the Department of Emergency Medicine and Trauma Service at BWH and Massachusetts General Hospital, the Center for Surgery and Public Health, Fallon Ambulance, South Shore Hospital and Boston MedFlight.

Tell us more about the research and training.

EG: At our first event, we trained more than 50 health care professionals, followed by a series of similar events in the community.

We also launched a randomized study at Gillette Stadium, where we’ve enrolled more than 560 staff, including security officers, vending station operators, parking attendants and others. Each staff member was randomly assigned to one of four groups comparing the effectiveness of tourniquet application after receiving traditional training, “just-in-time training” kits with audio or diagrams or no advance training.

Through focus groups, we’re learning how to design a more intuitive kit. Roughly 90 percent of the people got it right after in-person training, and we think we can develop a kit that’s equivalent.

In addition, Stepping Strong and Gillette purchased 525 first-aid kits that will be worn by personnel who have been trained. They’ve also purchased public-access tourniquet kits that are hung next to AEDs.

Next, we will retest and reevaluate these individuals to gauge how often they should be retrained. Finally, we’ll describe best practices for training a stadium’s workforce, as this is the first Stop the Bleed program in a professional sports stadium that we’re aware of.

This is an opportunity for science to guide us, and the science we have is from the battlefield – and the many soldiers, sailors, airmen and Marines whose lives have been saved because of tourniquets.

‘Stop the Bleed’ at HUBweek

BWH is participating in HUBweek, a weeklong festival celebrating innovation in Boston. On Wednesday, Oct. 11, 3-5 p.m., explore innovation at Brigham Health through an interactive scavenger hunt, which includes a training session with BWH’s Stop the Bleed project. The event is free to attend and open to all staff. Register and learn more here.

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After playing an online game about diabetes self-management, patients in the study had lower blood glucose levels.

Researchers from BWH and the Veterans Affairs (VA) Boston Healthcare System have discovered that an online, team-based game designed to teach patients about diabetes self-management had a sustained and meaningful effect on a key measure of diabetes control.

Published in Diabetes Care last month, the study found that patients – in this case, veterans – who were randomly assigned to play the game had significantly greater reductions in hemoglobin A1c (HbA1c), a common measure of long-term blood glucose control, than their counterparts in the control group. Researchers saw the largest reduction in HbA1c among patients with severe diabetes.

Diabetes is a growing public health issue among veterans – about one in four have the disease, according to the VA – as well as within the general population.

The online game requires a relatively minor time commitment for patients, and it potentially yields a big benefit for their health, noted corresponding author B. Price Kerfoot, MD, EdM, of the Department of Surgery at BWH and a faculty member at the VA Boston Healthcare System.

“We’ve developed an easily scalable intervention that was well-accepted among patients and led to sustained improvements in their diabetes control,” Kerfoot said.

A Winning Strategy

In total, 456 VA patients from the eastern U.S. were enrolled in the six-month study. Researchers recruited participants with diabetes who had inadequate glucose control while taking oral diabetes medications. Half the patients were randomly assigned to the diabetes education game. The other half – the control group – were assigned to a civics education game.

The diabetes self-management education (DSME) game presented players with multiple-choice questions related to glucose management, exercise, long-term diabetes complications, medication adherence and nutrition. Participants were sent two questions twice a week by email or a mobile app. After answering the question, they were immediately presented with the correct answer and an explanation. The same question would be sent again around four weeks later to reinforce the concept.

Participants earned “points” for correctly answering questions and were assigned to teams based on their geographic location.

HbA1c levels were tested at enrollment, at the six-month mark and 12 months after the launch of the game. Overall, diabetes game participants had significant reductions in HbA1c levels (a drop of 0.74 percent compared to 0.44 percent for the control group). Patients who had the highest HbA1c levels before playing the game experienced the most dramatic drops in HbA1c over 12 months.

Among a subgroup of patients with uncontrolled diabetes, Kerfoot said researchers saw a reduction in HbA1c levels that you would expect to see when a patient starts a new diabetes medication.

“Although their blood glucose levels were still above the target range, this was a strong step in the right direction, and resulted in a sustained and meaningful improvement in blood glucose control,” he said.

Senior author and endocrinologist Paul Conlin, MD, vice chair of the Department of Medicine at BWH and chief of the Medical Service at VA Boston Healthcare System, said about 90 percent of participants requested to participate in future programs using this game. He added this approach could be an effective and scalable method to improving health outcomes for other chronic conditions as well.

Researchers noted that the study was not designed to assess which aspect of the educational game led to improved outcomes. The content of the game focused on exercise, nutrition and glucose management, but the community- or competition-based nature of the game may have also played a role. Kerfoot and his colleagues hope to investigate this further.

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From left: Karen Fasciano, David Ahern and Ash Nadkarni participate in a panel discussion about innovation in behavioral health.

Apple famously coined a phrase that has come to define our relationship with technology: “There’s an app for that.” The sentiment behind the 2009 slogan continues to resonate today in health care, as seen in the cutting-edge apps and gadgets showcased at a recent symposium hosted by the Brigham Digital Innovation Hub (iHub).

More than 250 clinicians, scientists, entrepreneurs and other digital health enthusiasts learned about the latest advancements in technology during the “Digital Health and the Transformation of Care” event on May 17. The half-day symposium, held in the Building for Transformative Medicine, was filled with standing-room-only speaking events and a bustling expo.

“I look out at all of you here today and know that you are our opportunity,” said Brigham Health President Betsy Nabel, MD, speaking to a packed room during the event’s keynote address. “It’s our investment in you, your talents, your skills and your ideas that is going to take us forward. At the end of the day, our greatest resource is all of you.”

Meeting Patients Where They Are

Kicking off the half-day symposium was a panel about digital innovation in behavioral health. Ash Nadkarni, MD, of the Department of Psychiatry, shared her efforts to develop a cognitive behavioral therapy app for Amazon’s Echo – a small speaker embedded with a digital assistant, “Alexa,” that responds to voice commands to play music, make calls, provide information and more.

Nadkarni works closely with BWH’s Crohn’s and Colitis Center to care for patients who cope with depression, anxiety and other mood disorders in addition to – or as a result of – the challenges of their gastrointestinal disease. Their condition makes it difficult to come into Boston for frequent therapy appointments, Nadkarni said. The Echo app, on the other hand, can bring treatment to them.

Karen Fasciano, PsyD, also of Psychiatry, helps young cancer patients navigate the emotional challenges of their illness. She is in the process of working with iHub to develop a mobile app, with input from patients, that will provide resources on coping skills, ways for patients to share their narrative via social networking and a place for peer support.

“Technology not only can be used by patients independently but also in the context of clinical care,” Fasciano said. “For example, we facilitate Twitter chats to help young patients tweet about emotional coping, and I review these in my clinical sessions to stimulate conversation and reinforce skills that peers find helpful – thus integrating peer connection and skill-based learning.”

Looking Ahead

To fulfill the promise of digital health, it is essential to ensure it is used in the right ways, explained iHub Executive Director Lesley Solomon, MBA.

“In addition to us working with the community, both internally and externally, we are working closely with leadership to understand the challenges of the hospital so that we can find the solutions that make the most sense for us,” she said.

During a session called “The Future Is Now,” BWH innovators discussed novel projects they’re working on to improve care both in and out of the hospital.

When patients don’t take medication correctly, an issue known as non-adherence, the results are poorer health outcomes and increased health care costs. To help solve the problem, Giovanni Traverso, MD, BChir, PhD, of the Division of Gastroenterology, is developing a capsule that can stay in a person’s stomach for several weeks and be programmed to release the medication at the correct dosage and intervals.

Jayender Jagadeesan, PhD, of the Department of Radiology, sees opportunity for innovation inside the operating room. During the event, he showcased his efforts to develop surgical navigation systems that use mixed and augmented reality, technologies that merge real-world objects with a virtual world. Using head-mounted displays, Jagadeesan is working on ways to display diagnostic and intraprocedural images in a surgeon’s field of vision – with virtual images of a tumor, for example, overlaid on the patient while they are on the operating table.

The Path to Success

Brigham entrepreneurs also shared their thoughts on launching a digital health startup company.

Omar Badri, MD, a resident in Internal Medicine and the Harvard Combined Dermatology Residency Program, Brad Diephuis, MD, MBA, of the Internal Medicine Residency Program, and Peter Najjar, MD, MBA, a resident in Surgery, discussed the process of establishing a startup while balancing the demands of residency.

Although they cautioned that starting a company can be time-consuming and expensive, especially during residency, they highlighted several benefits. Forming a relationship with a hospital has allowed their startups to perform pilots and long-term studies. In certain circumstances, hospitals can also provide resources for product development.

Panelists also talked about the challenges associated with selling a new technology to a hospital and the benefits of knowing the right people to work with to push an implementation forward.

“You want to find an internal champion,” Badri said. “That’s really critical when you’re an early startup that doesn’t have a lot of validated data or big reputation.”

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Researcher Pamela Ghosh, first author of the paper, with physician-scientist Jose Halperin

A single blood test developed by BWH researchers may be able to identify, with a high level of precision, gestational diabetes in pregnant women nearing the end of their second trimester. If proven as a reliable diagnostic tool, it would reduce the need for many women to undergo the multiple, time-consuming tests that are the current standard of care.

Investigators found that a single measurement of a novel biomarker for diabetes known as plasma glycated CD59 (GCD59), performed at weeks 24-28 of gestation, was able to identify women who had failed the standard of care screening test as well as women with confirmed gestational diabetes. The findings were published in a recent issue of Diabetes Care.

Gestational diabetes is a type of diabetes that occurs during a woman’s pregnancy. It increases the mother’s risk of delivering an infant whose birth weight is greater than the 90th percentile for their gestational age, which can lead to preterm birth, fetal injury, stillbirth, early neonatal death and cesarean delivery. Gestational diabetes is also a risk factor for two complications in pregnancy related to blood pressure: preeclampsia and gestational hypertension. Since treatment of gestational diabetes can lessen the risk of adverse pregnancy outcomes, practice guidelines recommend screening all non-diabetic pregnant women for the disease.

The current standard of care to both screen and diagnose gestational diabetes involves a two-step approach that can be time-consuming, cumbersome and uncomfortable for patients – driving the need for a more patient-friendly alternative, say BWH researchers.

In the standard approach, called the glucose challenge test, a patient consumes a sugary drink and undergoes blood sugar measurement in the lab one hour later. Women who fail this screening must take a longer test that requires fasting overnight, drinking a more concentrated sugar solution and undergoing baseline and hourly blood draws for three hours. Glucose tests like these are currently the only methods used to diagnose gestational diabetes.

“Ours is the first study to demonstrate that a single measurement of plasma GCD59 can be used as a simplified method to identify women who are at risk for failing the glucose challenge test and are at higher risk for developing gestational diabetes,” says Jose Halperin, MD, director of the Hematology Laboratory for Translational Research and senior author of the publication.

Findings at a Glance

The team studied 1,000 pregnant women who were receiving standard prenatal care at BWH. Half had normal results in the glucose challenge test; half had failed the first screening and required the follow-up test. Researchers found that the median amount of GCD59 in the second group’s blood was 8.5 times higher than that of  women with a normal glucose challenge test result.

The researchers also found that higher plasma GCD59 levels at gestational weeks 24-28 were associated with a greater prevalence of babies whose birth weight was high for their gestational age. Increased levels of the biomarkers indicated a higher risk.

“Our studies opened an avenue for larger multicenter studies to further assess the clinical utility of plasma GCD59 for screening and diagnosis of gestational diabetes among the general population of the United States,” Halperin said. “If our results are confirmed, we’re hopeful that the GCD59 test could be available in clinical practices within the next few years.”

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The Brigham and Massachusetts General Hospital have teamed up to form the MGH & BWH Center for Clinical Data Sciences (CCDS) to create, promote and commercialize artificial intelligence in health care.

If you’re not sure what artificial intelligence is, you’re not alone. For many outside the tech world, it brings to mind science-fiction movies with sentient cyborgs or IBM’s Watson, the supercomputer that competed in Jeopardy! and beat two prior champions in 2011. The term, also known as AI, refers to a branch of computer science in which machines are trained to perform or simulate human tasks and behaviors.

In health care, this technology is being used for everything from improving the accuracy of diagnostic readings to recognizing patterns of diseases to identifying new candidates for clinical trials. At the CCDS, scientists from BWH and MGH are working on more than 20 projects, including ways to use artificial intelligence to identify cancer cells in pathology images, classify bone age based on X-rays and recognize brain tumor mutations from MRI scans. These projects require providing powerful computers with massive amounts of data that can be organized and analyzed.

The more data available, the more likely computers will be able to, for example, identify patterns and make predictions. This is a type of artificial intelligence known as machine learning, an area where the CCDS is currently focusing its efforts. These applications are overseen and validated by a human expert.

“The combined power of both the Brigham and Mass General will allow the CCDS unprecedented access to the data and clinical expertise required to create real-world applications that empower clinicians and enhance outcomes,” said Giles Boland, MD, chair of the Department of Radiology. “We’re harnessing the power of data so we can put it to work to develop smarter, more efficient ways to care for patients and run our systems.”

The CCDS was founded at MGH last year, but it soon became apparent that making the Brigham an equal partner would benefit all involved, said Mark Michalski, MD, the CCDS’ director. As a result of the collaboration, BWH clinicians and researchers will have greater access to the CCDS’ resources when needed.

“We’re in the golden age of this technology,” Michalski said. “There are great investigators at the Brigham already doing work in this space, and we’re happy to be able to facilitate that so we can start to look at all our data comprehensively. It’s a tremendous opportunity to take two of the best hospitals in the world and make machine learning part of both.”

Before the collaboration was formalized this month, some BWHers were working informally with the CCDS on various projects. Ziad Obermeyer, MD, MPhil, of the BWH Department of Emergency Medicine, has worked with the CCDS on several studies, including one to develop an algorithm to identify signs of a pulmonary embolism too subtle for the human eye to detect.

“Overall, I think we are benefiting enormously from their expertise as well as the data and computing resources, and it’s a real privilege to be working with them,” Obermeyer said.

Learn more about the CCDS.

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Xiaolei Yin

The cells in our ears that enable us to hear are delicate, easily destroyed by exposure to loud sounds and some medications. The body is unable to regenerate them, so when these cells die, our hearing is permanently damaged.

BWH researchers recently developed a new technique for growing large amounts of these specialized cells in a lab, pioneering the way toward a possible treatment for hearing loss.

Inner ear sensory cells, also known as hair cells, are responsible for detecting sound and helping to signal it to the brain. They can be produced artificially, but scientists have struggled historically to produce them in quantities large enough to recover a person’s hearing. Humans are born with 15,000 sensory hair cells in each cochlea, a region of the inner ear.

To figure out how to grow these cells en masse, researchers looked to the animal kingdom for answers.

“Amazingly, birds and amphibians are capable of regenerating hair cells throughout their life, suggesting that the biology exists and should be possible for humans. Intrigued, we decided to explore whether these hair cells could be regenerated,” said Jeff Karp, PhD, biomedical engineer at BWH and co-corresponding author of a recent paper in Cell Reports about the findings.

Jeff Karp

In their paper, scientists from the Brigham, Massachusetts Institute of Technology and Massachusetts Eye & Ear describe a technique to grow large quantities of inner ear progenitor cells, which can be programmed to turn into specific types of cells. In this case, researchers converted them into hair cells. The same techniques show the ability to regenerate hair cells in the cochlea.

To accomplish this, researchers took cells expressing a particular biomarker, known as Lgr5, and treated them with a drug cocktail that stimulated critical pathways, says Xiaolei Yin, PhD, co-lead author on the paper, of the Department of Medicine.

This technique produced more than 2,000 times the number of progenitor cells than what had been achieved in prior studies. The next step was to turn them into hair cells. Large quantities of those progenitor cells were successfully converted, resulting in approximately 60 times more hair cells from a single isolated cochlea than previously reported. The team also demonstrated this approach could work with cells from preclinical models and human tissue.

The drug cocktail “generates new sensory hair cells in intact cochlear tissue, which shows promise for a therapy to treat patients with hearing loss,” Karp said.

Frequency Therapeutics, a bioengineering company based in Woburn, is advancing this work from the lab to patient care settings. The company, for which Karp and Yin are scientific advisory board members, is using these new techniques to develop a therapy to treat chronic hearing loss. The treatment is expected to be in clinical settings within the next 18 months.

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Michael Cho (foreground) and Brian Hobbs examine their data on COPD.

Michael Cho (foreground) and Brian Hobbs examine their data on COPD.

BWH researchers have identified new genetic markers associated with chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States. The discovery sheds new light on the genetic basis for this deadly lung disease – along with hope that the finding may one day lead to new therapies.

Among individuals with COPD, symptoms develop slowly and worsen over time. There is no known cure, and no medications are available to reduce mortality in COPD. Existing treatments focus on easing the disease’s symptoms, which include difficulty breathing and frequent coughing.

Smoking remains the most important risk factor for COPD, but genetics also play a role. With this in mind, a consortium of researchers led by investigators at the Brigham examined the DNA of more than 60,000 people.

Their research uncovered 13 new genetic regions associated with COPD, including four that have not previously been associated with any type of lung function. The findings were released on Nature Genetics’ website last month and will be published in a forthcoming print edition of the journal.

“This is the first step in a process in which we hope to better understand the genetic basis for COPD or what may be several different diseases that present as COPD,” said lead author Brian Hobbs, MD, MMSc, a physician-scientist in the Channing Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine. “Now that we know there are new regions of the genome associated with COPD, we can build on this research by probing new biological pathways, with the ultimate goal of improving therapies for patients with this disease.”

Some of the genetic regions associated with COPD have also been noted in the results of studies of other lung diseases, such as asthma and pulmonary fibrosis. All analyses accounted for the effects of age, gender and cigarette smoking on disease risk.

“While it is extremely important that patients not smoke for many health reasons – including the prevention of COPD – we know that smoking cessation may not be enough to stave off the disease,” said Michael Cho, MD, MPH, one of the senior authors and also a physician-scientist in the Channing Division of Network Medicine and Pulmonary and Critical Care Medicine. “Many patients with COPD experience self-blame, but they may be comforted to know that genetics does play a role in who ultimately develops the disease.”

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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

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Giovanni Traverso

Giovanni Traverso

Imagine swallowing a pill today that continues releasing the daily dose of a medicine you need for the next week, month or even longer. Researchers from the Brigham, in collaboration with investigators at the Massachusetts Institute of Technology, have developed a long-acting drug delivery capsule that may help to do just that in the future.

Upon testing the capsule in preclinical models, researchers discovered it safely stayed in the stomach and slowly released a medication for up to 14 days. The results were published in Science Translational Medicine last month.

“We want to make it as easy as possible for people to take their medications over a sustained period of time. When patients have to remember to take a drug every day or multiple times a day, we start to see less and less adherence to the regimen,” said co-corresponding author C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and biomedical engineer in BWH’s Division of Gastroenterology. “Being able to swallow a capsule once a week or once a month could change the way we think about delivering medications.”

Traverso and his colleagues developed a capsule that is about the size of a fish oil capsule when swallowed. Once inside the stomach, the capsule unfolds into a star-shaped structure too large to exit the stomach immediately, but designed to allow food to continue passing through the digestive system.

“The gastrointestinal tract is a strong, durable passageway through the body. We designed the capsule to pause its transit in the stomach to allow for more controlled drug delivery and absorption, before passing through the GI tract without any harm,” said Traverso.

If successful in humans, the benefits of the capsule extend far beyond convenience. Early findings suggest it may also provide a new way to combat malaria and other infectious diseases.

As part of the study, the multidisciplinary research team – which included experts in biomechanical engineering, pharmaceutical sciences, infectious disease modeling, polymer chemistry and health care innovation – tested the capsule’s efficacy in diffusing a medication called ivermectin. The drug is used to combat several kinds of parasites, including the parasitic worms that cause river blindness, an eye and skin disease found mostly in Africa and transmitted by a fly that breeds near fast-flowing rivers and streams.

Ivermectin has also been shown to reduce malaria transmission, as the drug is toxic to the mosquito species that spread malaria. The concentrations of ivermectin in the blood of humans taking the drug are high enough to kill mosquitoes that bite them. Being able to keep the drug in the body for longer periods – something the capsule aims to enable – could offer greater protection, researchers found.

Traverso and his colleagues envision potential applications for the capsule beyond infectious disease, including chronic diseases such as psychiatric disease, heart disease, renal disease and more. The team is also interested in continuing to develop the system so that it can provide the drug for one month or longer.

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Calum MacRae

Calum MacRae

Is it possible to predict whether a teenager will develop heart disease several decades from now – based on data from their smartphone? One BWH researcher has been awarded a $75 million grant to find out.

Calum MacRae, MD, PhD, chief of BWH’s Division of Cardiovascular Medicine, and an international team of collaborators have been selected from among hundreds of applicants to receive the One Brave Idea research award. The five-year, $75 million award from the American Heart Association, Verily Life Sciences (formerly Google Life Sciences) and AstraZeneca will support joint initiatives that seek to cure coronary heart disease.

Under MacRae’s leadership, the team will work to determine the earliest signs of heart disease or new risk factors for developing it later in life, such as someone’s genetic makeup or whether they live somewhere with a higher incidence of coronary disease. The team’s ultimate goal is to prevent onset of the disease.

“We want to look where people haven’t looked before,” said MacRae, speaking at a press conference live streamed on YouTube earlier this month. “The tendency in heart disease is to look at the heart. But we know – and have known for decades – that people with heart disease have abnormalities in their skin. Why can’t we measure that when they’re 5 or 6 years old?”

Tracking trends like that has been difficult to do at a large scale, MacRae said. But technology is helping lower some of those hurdles – a shift MacRae and his team want to tap into. Wearable technologies, such as fitness trackers and smart watches, track biometrics like heart rate and sleep quality, while smartphones also collect other data that may provide additional clues about someone’s risk of heart disease. The team will not only use existing technologies; it also plans to develop new ones.

“Our goal is to leverage all of the tools of modern technology, build on existing science and engage patients and their families in much more holistic ways to build a picture of coronary disease in its earliest stages,” MacRae said.

MacRae will work with investigators from Massachusetts Institute of Technology, Stanford University, Northeastern University, the Million Veteran Program, University of Toronto and Boston University School of Medicine.

“Alone, each of our organizations has helped to transform our understanding of coronary artery disease. Yet, for all the success we have had, there is still a need for resources upon which to continue building,” said MacRae. “Our project will create a global consortium to support programs from idea conception to clinical realization and establish a lasting resource for future research endeavors.”

The work extends the Brigham’s legacy as a leader in cardiology, innovative research and patient care, says BWHC President Betsy Nabel, MD.

“Calum’s vision of how we approach coronary heart disease from both a research perspective and diagnostic perspective is inspiring,” she said. “It embodies our commitment to scalable innovation and to discoveries that can transform patient care.”

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This year’s Stepping Strong Innovator Awards finalists are addressing complex challenges related to trauma research. Each of the three finalists hopes to receive the $100,000 Stepping Strong Innovator Awards, which will be announced online on Monday, Oct. 17. Read about their work below, and vote for your choice.

Jay Zampini, MD

Jay Zampini, MD

Detecting Early Neurological Decline to Prevent Paralysis – Jay Zampini, MD

What challenge does your project address?

Spinal cord injury represents one of the most devastating and long-reaching effects of trauma. Injuries can range from a subtle loss of sensation and muscle function to complete paralysis. More than 273,000 people in the U.S. are living with spinal cord injury, the ranks of which grow by over new 12,000 cases each year.

Typically, patients sustain a spinal cord injury due to a car accident, fall, sports injury or violence. They are transported to a trauma center, where spine surgeons provide treatment designed to optimize the restoration of neurologic function. In other instances, a hospital patient with normal neurologic function may experience a loss of sensation or muscle function for various reasons. Ideally, caregivers can identify these changes rapidly enough to initiate treatment to reverse the symptoms or prevent their progression. Today, a neurologic exam is the only method of detecting changes.

The most challenging group of patients to treat for neurologic decline are those whose mental status and ability to cooperate are compromised. They may be unconscious, confused, agitated or delirious. For these patients, a neurologic exam alone cannot rapidly detect a potentially devastating change in neurologic function.

We plan to develop a device that automatically detects changes in neurologic function, alerting clinicians to start life- or function-saving treatment.

What is a compelling aspect of your project?

Assessing active muscle function is the most critical aspect of a neurologic exam, requiring patients to move their hands, feet and muscles. Several methods of measuring muscle activity are available. For instance, electromyography uses needles and skin-surface electrodes to stimulate and monitor muscle activity in patients to assess nerve injury. Similar techniques are available for patients under anesthesia, and accelerometers in the iPhone, FitBit and other athletic monitors can differentiate between activities like running, golf, and elliptical training.

The device we propose will adapt available technology for an application that has never been considered before. Our device also takes a time-consuming task of a neurologic examination and automates it, allowing clinicians to better serve their patients.

How will your project benefit future patients who suffer from trauma-related injuries?

Our device has the potential to not only benefit patients who are injured and neurologically intact, but also those whose potential neurologic decline is difficult to detect. We hope it will become the standard of care for neurologic monitoring in hospitalized, at-risk patients.

or read more about the other Stepping Strong Innovator Awards finalists:

mikeweaver_ortho21st Century Tools to Measure
the Progress of Bone Healing
0000016-g-giastadisStimulating Muscles to
Accelerate Rehabilitation

This year’s Stepping Strong Innovator Awards finalists are addressing complex challenges related to trauma research. Each of the three finalists hopes to receive the $100,000 Stepping Strong Innovator Awards, which will be announced online on Monday, Oct. 17. Read about their work below, and vote for your choice.


Michael J. Weaver, MD

21st Century Tools to Measure the Progress of Bone Healing – Michael J. Weaver, MD

What challenge does your project address?

Fractures are an extremely common result of trauma—whether they result from a car accident, an injury on the battlefield or a bad fall. While huge advances have been made in the surgical treatment of fractures, there are currently no medications available to help speed bone healing. The primary reason for this deficit is that, based on current technology, it is challenging to accurately measure bone healing, which makes drug trials exceedingly difficult to perform.

The goal of our project is to develop a reliable method of accurately measuring bone healing. This will enable us to collaborate with pharmaceutical companies to develop medications to improve and accelerate the often lengthy bone healing process.

What is a compelling aspect of your project?

Our project involves combining our understanding of bone healing with advances in CT scan technology that will allow us to measure microscopic changes in bone. We will develop a tool that allows us to measure how much motion occurs between the bone ends at a fracture site, such as a wrist fracture, during the healing process. The device will apply a small load, at a level that produces minimal discomfort, to the broken bone. A high-resolution CT scan will then be used to measure how much motion occurs. Knowing that fractures become stiffer as the healing process progresses, the device will measure the bone knitting together, with less motion over time.

This combination of technologies will allow us to more precisely measure bone healing than previously possible, as well as help to spur the development of medications that can expedite it.

How will your project benefit future patients who suffer from trauma-related injuries?

Over 7 million people break a bone every year. While there are numerous drugs to treat other common medical problems like high blood pressure or asthma, there are no medications to help heal broken bones. The goal of this project is to develop a tool to better measure bone healing, thus spurring drug development companies to discover medications that will both improve the speed of recovery and decrease the challenge of healing problems. Anyone who has had a broken bone, or knows someone who has, knows how difficult the recovery process is. Innovations such as the one we are proposing that speed the healing process will result in less pain, a quicker recovery and the hope that patients can quickly resume their everyday routines.

or read more about the other Stepping Strong Innovator Awards finalists:

jay-zampiniDetecting Early Neurological Decline
to Prevent Paralysis
0000016-g-giastadisStimulating Muscles to
Accelerate Rehabilitation

This year’s Stepping Strong Innovator Awards finalists are addressing complex challenges related to trauma research. Each of the three finalists hopes to receive the $100,000 Stepping Strong Innovator Awards, which will be announced online on Monday, Oct. 17. Read about their work below, and vote for your choice.

Giorgio Giatsidis, MD

Giorgio Giatsidis, MD

Stimulating Muscles to Accelerate Rehabilitation – Giorgio Giatsidis, MD

What challenge does your project address?

Injuries to the legs and arms often destroy muscle, reducing both mass and strength. Today, there are almost no approved therapies or strategies—for use in conjunction with standard physical therapy—to induce muscle regeneration or accelerate recovery following trauma. Unfortunately, current interventions remain rudimentary, and prolonged hospitalization incurs further tissue damage.

Once home, trauma patients face a steep path of rehabilitation. I call this “the trauma iceberg.” That is, what we see—and treat—is only the tip of what our patients actually experience. This project aims to break the trauma iceberg by developing novel therapies to initiate muscle recovery immediately following the trauma, prevent the onset of further inactivity-induced damage and accelerate the rehabilitation path toward a normal life.

What is a compelling aspect of your project?

Our cells regenerate in response to mechanical stimulation. For example, when we go to the gym, we stimulate muscles by stretching and contracting them, and this activity makes them grow. These principles can also be used to design novel, safe, non-invasive and patient-friendly therapies.

This project seeks to address the burden of prolonged trauma rehabilitation by passively stimulating injured muscles to regenerate and accelerate their recovery directly at the bedside. To realize our goals, our team will determine the exact conditions to effectively promote mechanically induced regeneration of injured muscle and, in collaboration with engineers, integrate these findings into the development of a portable device that can be easily applied to trauma patients inside the hospital and at home.

How will your project benefit future patients who suffer from trauma-related injuries?

Traumatic muscle injuries to legs and arms are a very common and dramatic occurrence. Trauma care for these patients does not end with the treatment of acute, life-threatening conditions and wounds. It continues through the long, challenging path of rehabilitation.

Our proposed therapy and device will help to facilitate muscle regeneration in a hospital setting, prevent the onset of further damage and accelerate the path of rehabilitation.

or read more about the other Stepping Strong Innovator Awards finalists:

mikeweaver_ortho21st Century Tools to Measure
the Progress of Bone Healing

jay-zampiniDetecting Early Neurological Decline
to Prevent Paralysis

This year’s BRIght Futures Prize finalists are pursuing forward-thinking and inventive research to improve patient care. Each of the three finalists hopes to receive the $100,000 BRIght Futures Prize, which will be awarded at Discover Brigham on Nov. 10. Read about their work below, and vote for your choice.

Giovanni Traverso, MD, PhD

Giovanni Traverso, MD, PhD

Ultrasound Device for Ulcerative Colitis – Giovanni Traverso, MD, PhD

What problem are you trying to solve and why?

Ulcerative colitis is a lifelong, debilitating disease that causes severe inflammation of the gastrointestinal tract—specifically, the colon. It affects almost 800,000 people in the U.S., with an additional 60,000 new cases diagnosed every year. Symptoms include abdominal pain, rectal bleeding and chronic diarrhea. More than 20 percent of patients eventually undergo surgery to remove part or all of the colon. The disease also carries a social stigma and can significantly diminish quality of life. Better treatment options are urgently needed.

Today, patients are often prescribed medicated enemas that require them to retain the medication overnight to maximize its absorption in the colon. It is an uncomfortable experience that a patient may have to endure nightly for weeks. While some drugs are highly effective at quelling the inflammation that causes UC’s symptoms, they are too large and delicate to be delivered directly into the colon. They must be injected, which has many drawbacks.

What is your solution?

We have developed a device that uses ultrasound to deliver therapies directly to the site of disease with a brief enema, stopping inflammation without the need for an injection or overnight enema. Patients can use this device themselves in their homes, enabling them to take back control and live happier, healthier lives.

By using ultrasound to gently propel medication into the tissue, significantly greater amounts of the drugs can be delivered. And it only takes one minute—as opposed to several hours—for this device to administer medication. We also anticipate that we will be able to use our method to deliver a wide variety of drugs and new treatments as they become available—not just for treating ulcerative colitis, but also for other diseases.

How will your research project benefit people?

This device will be easier and more convenient for patients to use, with better clinical outcomes for those who suffer from ulcerative colitis. Not only will our device reduce the burden of enema administration, but it will also enable patients to receive highly effective medications that currently may only be injected. This will reduce patients’ medical expenses, improve their outcomes and prevent the worsening of symptoms or the development of related diseases. Finally, the technology this device runs on has the potential to be used in treating a wide range of other diseases, and due to its simplicity, our device can be used continuously for days, like an IV infusion. Many apheresis treatments for hospitalized patients are staggered three times a week because of the staffing complexity and large blood volumes involved. With this device, patients won’t have to wait between treatments, and we can remove more disease-causing antibodies and blood cells than is currently feasible.

or read more about the other BRIght Futures finalists:

tracyyoungpearse_headshot2Predicting Alzheimer’s

davidlevine_headshot1Home Hospital

This year’s BRIght Futures Prize finalists are pursuing forward-thinking and inventive research to improve patient care. Each of the three finalists hopes to receive the $100,000 BRIght Futures Prize, which will be awarded at Discover Brigham on Nov. 10. Read about their work below, and vote for your choice.

Tracy Young-Pearse, PhD

Tracy Young-Pearse, PhD

Predicting Alzheimer’s – Tracy Young-Pearse, PhD

What problem are you trying to solve and why?

Alzheimer’s disease is devastating for patients and their families. Unfortunately, it’s also incredibly common: More than 5 million Americans are living with Alzheimer’s. One of the reasons why we have not been able to successfully treat it is that by the time patients enter the clinic and are diagnosed, many of their brain cells have already died. Many doctors and scientists agree that early intervention, prior to the onset of memory loss and cognitive decline, may be the key. But in order to intervene early, we must be able to predict who will develop the disease. Further complicating our efforts today is that Alzheimer’s disease can come in different forms, and some patients may respond to a given therapy while others may need a different kind of intervention. If we could predict who would respond to particular therapies, this could transform how we treat Alzheimer’s disease.

What is your solution?

We want to understand why some people develop Alzheimer’s disease when others don’t so that we can intervene early to prevent disease progression in those who are at risk. Our idea is to take blood cells from individual people, turn these into brain cells in a dish and use measurements from these cells to predict Alzheimer’s.

For this project, we first are making stem cells from blood samples from three groups of people: 1) those who lived to be in their 90s and 100s with excellent cognitive abilities and no signs of disease in their brain, 2) those with Alzheimer’s disease who had plaques or tangles in their brain and 3) those who had plaques and tangles in their brain but had excellent cognition.

Through a series of manipulations, we can efficiently turn these stem cells into brain cells in just a few weeks. From these living brain cells, we will acquire measurements of the proteins that accumulate and cause the disease, and develop predictive tools that will help us assess who is at risk of developing Alzheimer’s. In addition, we will examine which cells respond to a new therapy in clinical development.

How will your research project benefit people?

If successful, our project could transform how we test new therapies for Alzheimer’s disease, allowing us to treat the disease before brain cells die. Importantly, it could also help us identify which treatment will be the most effective for which patients, and if no treatment exists for a given patient, test for new interventions that would work for them. Together, this could potentially mean reducing the suffering of the millions of families affected by this devastating disease. 

or read more about the other BRIght Futures finalists:

giotraverso_headshot2Ultrasound Device for Ulcerative Colitis

davidlevine_headshot1Home Hospital

This year’s BRIght Futures Prize finalists are pursuing forward-thinking and inventive research to improve patient care. Each of the three finalists hopes to receive the $100,000 BRIght Futures Prize, which will be awarded at Discover Brigham on Nov. 10. Read about their work below, and vote for your choice.

The Home Hospital – David Levine, MD, MA

David Levine, MD, MA

David Levine, MD, MA

What problem are you trying to solve and why?

When an older adult has to be hospitalized, it can be uncomfortable. They may not sleep well, there can be a lack of privacy, they may not like the food and it can be hard for family to visit. And sometimes, it can be more than just uncomfortable. They may fall in the hospital, catch an infection, become confused or lose strength that is never regained, keeping them from returning home. Hospitalization can also be very expensive: Medical bills and time away from work put many Americans into debt.

We think there is a better option: “hospitalization” at home, where visits from doctors and nurses, treatment with medications, blood tests and monitoring all occur at home. For over a decade, the home hospital model has been practiced in Europe and Australia, where these patients have experienced the same level of safety and quality as traditional hospital stays, in addition to improved patient satisfaction and reduced costs. But this model has rarely been tried or rigorously tested in the U.S.

What is your solution?

We plan to bring the hospital to the home for patients in the United States. We will ask carefully selected patients to participate in a randomized, controlled study, which is the best way to evaluate this model. Patients will benefit from state-of-the-art technology in their own home, including a remote vital-sign monitoring device that enables their doctor and nurse to check their heart rate, among other metrics, with a skin patch. Another technology will monitor patient activity and sleep tracking, which will allow us to test our hypothesis that patients move and sleep more at home. Patients will be able to video conference with health care providers and, best of all, doctors and nurses will visit patients in their homes. They won’t need to come to a hospital setting to receive world-class care. Lastly, patients will be in the ideal setting to receive the education and coaching from community health workers so that they’ll be able to take care of themselves once the acute illness is over.

How will your research project benefit people?

We want to build a better model of care for ill adults in need of hospitalization. Some procedures will always need to be done in a hospital setting, but in certain cases, home may be the best place for a patient to receive care, monitoring and treatment. We believe receiving care at home puts the patient first, improves patient satisfaction, and reduces cost. Patients can sleep in their own bed, eat their own food and spend more time with friends and family. For many conditions, home hospital will transform our concept of safe, high-quality, cost-effective care.

or read more about the other BRIght Futures finalists:

giotraverso_headshot2Ultrasound Device for Ulcerative Colitis

tracyyoungpearse_headshot2Predicting Alzheimer’s

Two compelling competitions to advance innovation—the BRIght Futures Prize and Stepping Strong Innovator Awards—are currently underway at BWH, and voters from the Brigham and beyond will determine the winners. Both competitions feature inventive ideas from across the hospital community, and each competition’s winner will receive a $100,000 prize.

Both competitions embody the Brigham’s ongoing focus on scalable innovation—research discoveries that can rapidly translate into clinical therapies for patients here and around the world.

The BRIght Futures Prize supports BWH investigators as they work to answer provocative questions or solve vexing problems in medicine. The fifth annual BRIght Futures Prize competition features three projects that have the potential to make dramatic improvements in patients’ lives.

Learn more about the finalists—Giovanni Traverso, MD, PhD, of the Division of Gastroenterology, Tracy Young-Pearse, PhD, of the Department of Neurology, and David Levine, MD, MA, of the division of Internal Medicine and Primary Care—in this issue of BWH Bulletin. The BRIght Futures prize will be presented at Discover Brigham on Thursday, Nov. 10.

The Stepping Strong Innovator Awards program is part of The Gillian Reny Stepping Strong Center for Trauma Innovation, established by the Reny family following the 2013 Boston Marathon bombings. The attack left Gillian Reny, a student and aspiring dancer, with severe injuries to both of her legs. The center seeks to mobilize the full potential of interdisciplinary innovation for the benefit of citizens and military personnel worldwide who have suffered from the devastation of traumatic injuries and events. The Stepping Strong Innovator Awards program, one of three funded areas in the center, supports multidisciplinary, groundbreaking projects to inspire innovative research in trauma treatment and recovery.

Learn more about the three Stepping Strong Innovator Awards finalists—Giorgio Giatsidis, MD, of the Department of Surgery, Michael J. Weaver, MD, of the Department of Orthopaedic Surgery, and Jay Zampini, MD, of Orthopaedic Surgery—and their projects in this issue, as well. The Stepping Strong Innovator Awards winner will be announced online on Monday, Oct. 17.


StrategyIcon_WordpressBWHC’s Strategy in Action: Scalable Innovation
Learn more about our strategic priorities at