Snapshot of Science for April 2020

Welcome to our Snapshot of Science for April 2020

Here's a quick look at some recent publications, press releases and stories about the Mass General Research Institute community.

In this issue we highlight:

19 new studies published in high impact journals, along with 15 summaries submitted by the research teams
11 new research-related press releases from the Mass General Public Affairs office
9 posts from the Mass General Research Institute blog

Publications

CARDIOVASCULAR MORTALITY, HEAT AND PREPARING FOR CLIMATE CHANGE
Cardiovascular Mortality and Exposure to Heat in an Inherently Hot Region: Implications for Climate Change
Alahmad B, Khraishah H, Shakarchi AF, Albaghdadi M, Rajagopalan S [et al.], Jaffer FA
Published in Circulation on March 30, 2020 | *Summary available

PRESCRIPTIONS OF STEROIDS FOR RESPIRATORY INFECTIONS IN THE U.S.
Prescribing Systemic Steroids for Acute Respiratory Tract Infections in United States Outpatient Settings: A Nationwide Population-Based Cohort Study
Lin KJ, Dvorin E, Kesselheim AS.
Published in PLoS Medicine on March 31, 2020

DIFFERING RISK FACTORS FOR COLORECTAL CANCER
Risk Factor Profiles Differ for Cancers of Different Regions of the Colorectum
Wang L, Lo CH, He X, Hang D, Wang M [et al.], Song M.
Published in Gastroenterology on April 1, 2020

EXAMINING THE IMPACT OF SERVICE USE GROUPS FOR CHILDREN WITH AUTISM
Service Use Classes Among School-aged Children From the Autism Treatment Network Registry
Lindly OJ, Chan J, Levy SE, Parker RA, Kuhlthau KA.
Published in Pediatrics on April 1, 2020 | *Summary available

RISK FACTORS FOR AGITATION DURING ADMISSION IN PATIENTS WITH AUSTISM
Agitation in Patients with Autism Spectrum Disorder Admitted to Inpatient Pediatric Medical Units
Hazen EP, Ravichandran C, Hureau AR, O'Rourke J, Madva E [et al.], McDougle CJ.
Published in Pediatrics on April 1, 2020 | *Summary available

PATIENT PREFERENCES FOR PALLIATIVE CARE VERSUS AGGRESSIVE TREATMENT
Seriously Ill Patients' Willingness to Trade Survival Time to Avoid High Treatment Intensity at the End of Life
Rubin EB, Buehler A, Halpern SD.
Published in JAMA Internal Medicine on April 6, 2020

LOSS OF REDD1 GENE MAY DRIVE PROGRESSION OF RAS MUTANT CANCERS
REDD1 Loss Reprograms Lipid Metabolism to Drive Progression of RAS Mutant Tumors
Qiao S, Koh SB, Vivekanandan V, Salunke D, Patra KC [et al.], Ellisen LW.
Published in Genes & Development on April 9, 2020 | *Summary available

ADAPTIVE ANTIBIOTIC RESISTANCE IN KLEBSIELLA PNEUMONIAE
Adaptive Evolution of Virulence and Persistence in Carbapenem-Resistant Klebsiella Pneumoniae
Ernst CM, Braxton JR, Rodriguez-Osorio CA, Zagieboylo AP, Li L [et al.], Hung DT.
Published in Nature Medicine on April 13, 2020

MISSENSE VARIANT MAY PROTECT AGAINST LIVER DISEASE
A Missense Variant in Mitochondrial Amidoxime Reducing Component 1 Gene and Protection Against Liver Disease
Emdin CA, Hass ME, Khera AV, Aragam K, Chaffin M [et al.], Kathiresan S.
Published in PLoS Genetics on April 13, 2020 | *Summary available

SMOKING ASSOCIATED WITH AAV
Association of Cigarette Smoking with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
McDermott G, Fu X, Stone JH, Wallwork R, Zhang Y [et al.], Wallace ZS.
Published in JAMA Internal Medicine on April 13, 2020 | *Summary available

RECEPTOR AXIS AS POTENTIAL TARGET FOR PREVENTING ISCHEMIC KIDNEY INJURY
Pro-inflammatory P2Y14 Receptor Inhibition Protects Against Ischemic Acute Kidney Injury in Mice
Battistone MA, Mendelsohn AC, Spallanzani RG, Allegretti AS, Liberman RN [et al.], Breton S.
Published in Journal of Clinical Investigation on April 14, 2020 | *Summary available

IMPROVING COLLECTION OF PATIENT-REPORTED OUTCOMES
Factors Associated with Increased Collection of Patient-Reported Outcomes Within a Large Health Care System
Sisodia RC, Dankers C, Orav J, Joseph B, Meyers P [et al.], Sequist TD.
Published in JAMA Open Network on April 14, 2020 | *Summary available

MEDICARE PART D AND ANTIRETROVIRAL THERAPY
Medicare Part D and Cost-Sharing for Antiretroviral Therapy and Preexposure Prophylaxis
Tseng CW, Dudley RA, Chen R, Walensky RP.
Published in JAMA Open Network on April 14, 2020 | *Summary available

FLOW RATE DETERMINES PROGNOSIS FOR AORTIC STENOSIS
Transvalvular Flow Rate Determines Prognostic Value of Aortic Valve Area in Aortic Stenosis
Namasivayam M, He W, Churchill TW, Capoulade R, Liu S [et al.], Hung J.
Published in Journal of the American College of Cardiology on April 15, 2020 | *Summary available | Press Release

GENETIC RISK SCORE ANALYSIS AND TYPE-2 DIABETES
Pleiotropy-based Decomposition of Genetic Risk Scores: Association and Interaction Analysis for Type 2 Diabetes and CAD
Chasman DI, Giulianini F, Demler OV, Udler MS.
Published in American Journal of Human Genetics on April 16, 2020 | *Summary available

EFFORTS TO MITIGATE PERCEIVED RISKS AMONG IMMIGRANTS
Assessment of Perspectives on Health Care System Efforts to Mitigate Perceived Risks Among Immigrants in the United States: A Qualitative Study
Saadi A, Molina US, Franco-Vasquez A, Inkelas M, Ryan GW.
Published in JAMA Open Network on April 17, 2020 | *Summary available

LOWER NUCLEUS ACCUMBENS VOLUME MAY SIGNAL CHRONIC PAIN
Loss of Nucleus Accumbens Low-Frequency Fluctuations Is a Signature of Chronic Pain
Makary MM, Polosecki P, Cecchi GA, DeAraujo IE, Barron DS [et al.], Geha P.
Published in PNAS on April 20, 2020 | *Summary available

DIABETES INCREASES THE PRODUCTION OF LEUKOCYTES IN BONE MARROW
Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes
Hoyer FF, Zhang X, Coppin E, Vasamsetti SB, Modugu G [et al.], Nahrendorf M.
Published in Circulation on April 22, 2020 | *Summary available

COMPARING OPERATIVE VS NONOPERATIVE FRACTURE TREATMENT
Operative vs Nonoperative Treatment of Distal Radius Fractures in Adults: A Systematic Review and Meta-analysis
Ochen Y, Peek J, van der Velde D, Beeres FJP, van Heijl M [et al.], Heng M.
Published in JAMA Network Open on April 23, 2020 | *Summary available

Summaries

To understand the underexplored consequences of climate change on cardiovascular health, our collaborative group of cardiologists, environmental health specialists and epidemiologists bridged disciplines to explore the intersection between cardiovascular medicine and climate change. Regions that are inherently hot, like Kuwait and the Arabian Peninsula, are witnessing soaring temperatures unlike ever before. We found that such populations with severe heat exposure exhibit a doubling to tripling of cardiovascular mortality rates. Accordingly, we are sounding the alarm that urgent public health interventions by the international community, including heightened awareness among cardiologists, is warranted.

(Summary submitted by Farouc Amin Jaffer, MD, PhD, Division of Cardiology, Department of Medicine)

Autism spectrum disorder (ASD) affects the health of many children. Numerous behavioral and medical services exist for ASD, and some may help to optimize child health. Yet little is known about service use patterns in children with ASD. This study examined service use among 1,378 school-aged children with ASD in North America. Four unique service use groups were identified, with the majority of children receiving multimodal services or primarily educational services. One-fifth of children had limited services use or mainly used special diets and/or natural products. Findings may better support decision-making by families and clinicians about ASD services for children.

(Summary submitted by Olivia Lindly, PhD, MPH, Northern Arizona University)

RISK FACTORS FOR AGITATION DURING ADMISSION IN PATIENTS WITH AUTISM
Agitation in Patients with Autism Spectrum Disorder Admitted to Inpatient Pediatric Medical Units
Hazen EP, Ravichandran C, Hureau AR, O'Rourke J, Madva E [et al.], McDougle CJ.
Published in Pediatrics on April 1, 2020

Medical admissions can be particularly stressful for children with Autism Spectrum Disorder (ASD). This stress can lead patients to become agitated, putting themselves and the staff caring for them at risk. In this paper, we studied the frequency of agitation in pediatric medical hospital admissions to Mass General over a five-year period and identified factors that are associated with increased risk. We found that at least one episode of agitation occurred in 12% of hospitalizations of children with ASD. A past history of agitation and a history of sensory sensitivities were associated with the greatest risk. By identifying patients at high risk of agitation, providers may be better able to take preventative measures to help protect them.

(Summary submitted by Eric Hazen, MD, Department of Psychiatry, Mass General Hospital for Children)

Activating RAS gene mutations drive many poor-prognosis cancers, yet RAS mutation alone is not sufficient for malignant progression due to profound metabolic stress induced by RAS activation. Using genetic models, we show that loss of the stress response gene REDD1 in RAS-mutant cells converts pre-cancerous lesions into aggressive and metastatic tumors by triggering a pathway for lipid uptake and processing that meets the metabolic demands of activated RAS. Correspondingly, although RAS-mutant lung and pancreas cancers with low REDD1 levels have a worse prognosis than matched tumors with high REDD1, they also have potentially actionable therapeutic vulnerabilities related to REDD1-mediated metabolic rewiring.

(Summary submitted by Leif Ellisen, MD, PhD, Mass General Cancer Center, Division of Hematology/Oncology, Department of Medicine)

Cirrhosis is a leading cause of death worldwide. However, the genetic underpinnings of cirrhosis remain poorly understood. We analyzed twelve thousand individuals with cirrhosis and identified a common missense variant in a gene called MARC1 that protects against cirrhosis. Individuals who carried this genetic variant had lower rates of cirrhosis, lower blood cholesterol levels, lower liver enzyme levels and reduced liver fat. These genetic findings suggest that MARC1 deficiency may lower blood cholesterol levels and protect against cirrhosis, identifying MARC1 as a potential therapeutic target for liver disease.

(Summary submitted by Connor Emdin, PhD, Center for Genomic Medicine)

ANCA-associated vasculitis (AAV) is a rare but serious autoimmune disease targeting small blood vessels. Prior research showed that exposure to silica and asbestos are risk factors for AAV, but the effect that cigarette smoking may have on disease risk has been unclear. This study used Partners HealthCare System data to look at the smoking history of 484 patients with AAV and 1,419 patients without AAV. The group of vasculitis patients contained significantly more former and current smokers than the group of patients without vasculitis, suggesting that cigarette smoking is a modifiable risk factor for AAV.

(Summary submitted by Gregory McDermott, MD, Department of Medicine)

Patients hospitalized for various primary conditions are often at risk of developing kidney complications, a condition known as “acute kidney injury - AKI”. AKI is known as a “silent killer” because it causes no symptoms and physicians have no early diagnostic and no specific therapy for AKI. Using a pre-clinical model of hospital-acquired AKI, the study shows the central role of the P2Y14 receptor within the kidney, which triggers an inflammatory cascade during the early phase of AKI. A particularly strong correlation was observed between urinary concentration of the P2Y14 ligand, UDP-glucose and the development of AKI in cardiac surgery patients. This study identifies the UDP-Glucose/P2Y14 receptor axis as a potential target for the prevention and/or attenuation of hospital acquired-AKI.

(Summary submitted by Sylvie Breton, PhD, MSc, Department of Medicine)

Most healthcare systems measure quality of patient care by collecting metrics such as surgical site infection and readmission to the hospital. However, these are not the outcomes that patients care most about. Patients care about things like, “Will having my knee replaced allow me to walk without pain?” or “If you perform that cancer surgery, how bad will my quality of life be afterwards?” Outcomes like this are called patient reported outcomes (PROs). PROs are a way for us, as clinicians and researchers, to ask patients about the things that matter to them in an objective way. In this study, Partners Healthcare describes their experience with building the world’s largest PRO program.

(Summary submitted by Rachel Sisodia, MD, Department of Obstetrics & Gynecology, Mass General Physicians Organization)

Nationwide Medicare formulary and pricing files from 2019 were used to determine annual costs of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for HIV treatment and prevention under a standard Medicare Part D insurance plan. The annual median prices of ART and PrEP were $35,780 and $20,570, respectively. Annual out-of-pocket costs for patients ranged from $3,000-$4,000, unless they qualified for low-income subsidies. Half to two-thirds of the overall costs were borne by Medicare, rather than insurance plans or manufacturers. High ART and PrEP prices jeopardize affordability for patients and place most of the cost burden on taxpayers.

(Summary submitted by Rochelle Walensky, MD, MPH, Division of Infectious Disease, Department of Medicine)

The aortic valve, one of the heart’s main valves, can commonly stiffen and become restricted in older age. Severe restriction (aortic stenosis) can lead to poor quality of life and risk of death. Treatment involves valve replacement, using open-heart surgery or catheter-based approaches. Determining severity of disease accurately is therefore vital in correctly timing intervention. This study sheds light on a new approach to determining aortic stenosis severity, better incorporating heart blood flow conditions using echocardiography (cardiac ultrasound). The study tracked two independent cohorts of close to 1,000 patients each and showed that the new system was superior to current approaches in disease classification in prediction of death over long-term follow-up.

(Summary submitted by Mayooran Namasivayam, MBBS, PhD, Division of Cardiology, Department of Medicine)

Genetic risk scores (GRSs) are gaining increasing attention for their potential in assessing an individual’s inherited genetic liability for disease, and potentially also the benefit from lifestyle choices or drug treatment. However, GRSs typically do not distinguish between overall genetic risk and genetic risk pertaining to particular pathophysiologic pathways. The new publication describes an approach for the latter. For incident type-2 diabetes and CAD in two large populations, the research shows how pathway-specific GRSs can inform an individual’s inherited genetic risk pertaining to specific pathophysiologic mechanisms and can enhance assessment of individual benefit from lifestyle choices or statin treatment.

(Summary submitted by Daniel Chasman, PhD, Department of Medicine, Brigham and Women's Hospital)

Anti-immigrant policies and rhetoric can have serious negative healthcare consequences for immigrants and their families. To address this, healthcare facilities have instituted policies and actions to ensure their immigrant patients feel welcome and protected while receiving care. We conducted 38 interviews at 25 health care facilities across 5 states with the largest undocumented immigrant populations to characterize the range, scope and content of policies these facilities have implemented since the 2016 U.S. presidential election. We found policies and actions mitigating: (1) exposure to immigration enforcement personnel, (2) disclosure of immigration status–related information, (3) risk associated with patient-level stressors, (4) risk associated with practitioner-level stressors, and (5) coordination of risk mitigation efforts. Understanding how health care facilities can mitigate immigration-related risks is an important step toward improving healthcare for immigrants and their families.

(Summary submitted by Altaf Saadi, MD, Department of Neurology)

The prevalence of chronic pain has reached epidemic levels with no available cure or quantitative diagnostic or prognostic tools. Using brain imaging, we found that, compared to the brain of healthy people, the brain of patients with subacute back pain at risk for becoming chronic back pain patients exhibits smaller nucleus accumbens volume, which predates the onset of chronic pain and persists in the chronic phase. We also found that loss of low frequency fluctuations of the nucleus accumbens activity is a robust signature of the chronic phase of pain and is potentially a diagnostic marker for this condition.

(Summary submitted by Meena M. Makary, PhD, Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging)

Inflammatory myeloid leukocytes contribute to cardiovascular complications in diabetes. We describe that diabetes increases the production of leukocytes in the bone marrow. Analysis of bone marrow niche cells and factors suggest that increased circulating myeloid cell levels may be regulated through aberrant bone marrow endothelium in diabetes. We showed that diabetes-induced alterations in bone marrow endothelial cells modulate the supply of inflammatory myeloid cells, and consequently the degree of diabetic complications such as atherosclerosis. The study suggests that a dysregulated hematopoietic bone marrow niche may contribute to cardiovascular sequelae in diabetes.

(Summary submitted by Friedrich Felix Hoyer, MD, Department of Radiology)

COMPARING OF OPERATIVE VS NONOPERATIVE FRACTURE TREATMENT
Operative vs Nonoperative Treatment of Distal Radius Fractures in Adults: A Systematic Review and Meta-analysis
Ochen Y, Peek J, van der Velde D, Beeres FJP, van Heijl M [et al.], Heng M.
Published in JAMA Network Open on April 23, 2020

The fracture of the distal radius is the most common injury in adults, accounting for approximately 17.5% of fractures. Previous meta-analyses have focused specifically on elderly populations, aged 60 years or older, and found no difference in functional outcome between operative and nonoperative treatment. This meta-analysis, which focused on nonelderly populations, shows that operative treatment of distal radius fractures could improve functional outcome and grip strength, with no difference in overall complication rate. Different populations were evaluated, and our findings suggest that operative treatment might be more effective and have a greater impact on the health and well-being of the younger, non-elderly patients.

(Summary submitted by Yassine Ochen, MD, Department of Orthopaedics)

Press Releases

New COVID-19 Symptom Research App Recruiting Millions of Americans to Beat the Disease
Featuring Andrew Chan, MD, MPH

As the COVID-19 coronavirus pandemic grips the U.S., a new free app is helping to track the onset and progression of symptoms of millions across the nation.

Study Reveals Sustained Benefits of 3D Mammograms for Breast Cancer Screening
Featuring Manisha Bahl, MD, MPH

A team of investigators at Mass General has verified the long-term benefits of DBT, which includes fewer false-positives.

Mind-Body Medicine Experts Urge Full Integration of Stress Reduction into Care and Research
Featuring Michelle Dossett, MD, PhD, MPH

Researchers from the Benson-Henry Institute for Mind Body Medicine at Mass General call for broader use of mind-body practices.

Study Shows That an Integrated Clinical and Behavioral Program Can Help Reduce Excess Weight Gain by Pregnant Mothers
Featuring Tiffany Blake-Lamb, MD, and Elsie Taveras, MD, MPH

A new study describes how a program known as First 1,000 Days enabled mothers who were overweight at the start of pregnancy to reduce their odds of excess weight gain by nearly a third.

Mass General Researchers Uncover Biomarkers That Could Lead to More Patients Getting Immunotherapy
Featuring Manish Gala, MD

A breakthrough class of cancer treatments – immunotherapies – may become available to a wider range of patients thanks to new research from the Mass General.

New Findings May Lead to Improved Care for Patients with Heart Valve Disease
Featuring Mayooran Namasivayam, MBBS, PhD, and Judy Hung, MD

Results from a new study may improve tests that determine when patients with heart valve disease need surgery.

Novel Imaging Application from Mass General Illuminates Processes in Cancer, COVID-19 and Other Diseases
Featuring Gordon Harris, PhD

Medical images for a wide range of diseases, including coronavirus 19 (COVID-19), can now be more easily viewed, compared and analyzed using a breakthrough web-based imaging platform developed by Mass General and collaborating researchers.

New Online COVID-19 Model Reveals How Lifting or Extending Different Social-Distancing Measures Will Affect States

A new online tool, COVID-19 Simulator, developed by researchers at Mass General and Georgia Tech can help policy makers see how lifting or extending different social-distancing measures at various times can impact each state in terms of COVID-19 cases, hospitalizations, and deaths.

Certain Scores May Predict Which Trauma Patients Face High Risk of Multiple Infections
Featuring Laurence Rahme, PhD

Trauma patients are at risk of developing multiple infections while in the hospital, but it is difficult to identify those who are especially susceptible. Now a Mass General team has found certain scores already used to assess the severity of a trauma patient's condition can provide clues.

Study Examines How the Health of Communities Relates to Party Voting
Featuring Jason Wasfy, MD

New research indicates that communities with poorer health are shifting votes towards the Republican party.

Family History Misses Identifying Individuals with High Genetic Risk of Cardiovascular Disease or Cancer
Featuring Amit Khera, MD, and Aniruddh Patel, MD

Certain genetic changes, termed "pathogenic variants," substantially increase risk for cardiovascular disease and cancer—the leading causes of death—but testing to identify individual carriers is not part of current clinical practice.

Blog Posts

A Review of How COVID-19 Could Affect the Mental Health of Health Care Workers
Featuring Roy Perlis, MD, MSc

In an effort to better understand the psychological impact that treating COVID-19 patients has on health care providers, Roy Perlis, MD, MSc, director of the Center for Qualitative Health, looked to experts in China.

Mass General Researchers Mobilize to Fight Virus
Featuring Harry W. Orf, PhD

Harry W. Orf, PhD, discusses what the closure of labs means for patients, how Mass General researchers are mobilizing in response to the COVID-19 pandemic and the impact this effort is having on medical research.

What Makes This Coronavirus So Unique? A Look at the Virology of SARS-CoV-2
Featuring Galit Alter, PhD

At a recent Grand Rounds presentation at Mass General, Galit Alter, PhD, an investigator at the Ragon Institute of Mass General, MIT and Harvard, discussed what scientists have learned so far about the virology of SARS-CoV-2, and what makes it different from diseases we have seen before.

The Story of One Researcher Who Volunteered to Join the Front Lines at Mass General
Featuring Chris Aldrighetti, BS

Chris Aldrighetti, a clinical research coordinator in Radiation Oncology, shares his experience as a volunteer on the front lines of the COVID-19 outbreak at Mass General.

A Team Effort to Fast Track New Testing Strategies for COVID-19

In a recent virtual town hall, members of the Mass General Brigham Center for COVID Innovation outlined the parameters that new diagnostic tools will have to meet.

Exploring the Mental Health Impact of COVID-19 on New Mothers
Featuring Sharon Dekel, PhD

Sharon Dekel, PhD, is launching a study that is open to all women across the globe who have recently given birth (within the past six months) to understand the impact of COVID-19 on women’s mental health, their birth experience and how they are coping with new motherhood.

More Scientist-Approved Experiments for Kids
Featuring Nitya Jain, PhD

They say necessity is the mother of invention, and in the search for educational activities to keep kids occupied, one mother and Mass General researcher has been getting particularly creative.

Three Tips to Help Manage Stress and Anxiety During the Pandemic
Featuring Luana Marques, PhD

It is okay to feel scared, but finding time to breathe, “cool off your brain” and take care of ourselves is crucial to making it through uncertain times. Here are three tips Luana Marques, PhD, recently shared to manage stress and anxiety during this time.

The Difference Between N95s, Surgical Masks and Cloth Masks
Featuring George Alba, MD

What is an N95 mask and how is it different from a surgical mask? Is a cloth mask safe? George Alba, MD, a clinician researcher in Pulmonary and Critical Care Medicine, helps explain the specifics and best practices according to CDC guidelines.

The Mass General Difference

Conditions & Treatments

Patients & Visitors

Research & Innovation

Mass General
Research Institute

Snapshot of Science for April 2020