BIDMC Research Brief Digest: June 2018

Beth Israel Deaconess Medical Center's (BIDMC) Researh Brief Digest is a monthly roundup of research briefs showcasing recent scientific advances led by BIDMC faculty. 

If you’d like to speak with one of our experts, please contact us at [email protected] or at 617-667-7300. You can also reach the communications team member on call through the BIDMC page operator at (617) 667-4700 and asking for pager ID #33880.

More Evidence Supports Link between Orthostatic Hypotension and CVD

Orthostatic hypotension (OH) – a rapid drop in blood pressure upon standing up from a sitting or lying down position – is a frequently encountered clinical sign among patients. Clinicians most often consider OH as indicative of dehydration. However, new research led by scientists at BIDMC bolsters the notion that adults with OH may have undiagnosed cardiovascular disease.

The team analyzed data from 9,139 participants ages 45 to 64 who enrolled in the long-running Atherosclerosis Risk in Communities (ARIC) Study between 1987 and 1989. These participants were followed for cardiovascular events and mortality through Dec. 31, 2015.

“OH was associated with all measures of subclinical cardiovascular disease and was an important predictor of clinical CVD events in the future,” said Stephen Juraschek, MD, PhD, Instructor of Medicine at BIDMC and Harvard Medical School. “When orthostatic hypotension is detected in middle-aged adults who do not have known cardiovascular disease, health care practitioners should be mindful of undetected heart disease.”

Juraschek and colleagues’ findings appeared online in the Journal of the American Heart Association on May 7.

“While there is controversy surrounding the association between OH and cardiovascular disease, our findings were unequivocal and consistent,” said Juraschek. “These findings strongly support our hypothesis about OH being an important manifestation of undetected CVD. Many treatments for OH such as increasing sodium intake or stopping blood pressure medications have the potential to worsen blood pressure control and risk for CVD. Clinicians should be aware of the possibility that undiagnosed CVD may be present in adults with OH prior to starting treatments.” (June 2018)

BIDMC Researchers Determine Exercise Dose Linked to Improved Cognitive Performance in Older Adults

While thousands of clinical trials suggest that exercising the body can protect or improve brain health as we age, few studies provide practical prescriptive guidance for how much and what kind of exercise.

Now, an exhaustive systematic review of 4,600 clinical trials – led by researchers at the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC and published online on May 30 in Neurology: Clinical Practice – provides new insight into the optimal dose of exercise for maintaining cognitive performance in healthy older adults, as well as those with mild cognitive impairment and dementia.

The team found nearly any type of exercise, from aerobic exercises such as walking, running and cycling to weightlifting and mind-body exercises such as yoga and tai chi, can contribute to improved cognitive performance. Interventions that had individuals exercising for at least 52 hours over a period of six months led to the greatest improvement in thinking abilities. Additionally, the most stable improvements in thinking abilities were found in mental processing speed, both in healthy older adults and individuals with mild cognitive impairment.

“It’s very encouraging that the evidence supports all sorts of different exercise interventions, not just aerobic, to improve thinking abilities,” said Alvaro Pascual-Leone, MD, PhD, Chief of the Division of Cognitive Neurology and the Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC. “The most stable improvements in thinking abilities were found in processing speed, both in healthy older adults and individuals with mild cognitive impairment.” (May 2018)

Traffic-Related Pollution Linked to Risk of Asthma in Children

New research led by scientists at BIDMC, the Harvard Pilgrim Health Care Institute, and the Harvard T.H. Chan School of Public Health, suggests that long-term exposure to traffic-related pollution significantly increases the risk of pediatric asthma, especially in early childhood. Their findings were published on May 3 in a Letter to the Editor in the Journal of Allergy and Clinical Immunology.

Corresponding author Mary Rice, MD, MPH, a pulmonary and critical care physician at BIDMC, and colleagues analyzed data from 1,522 Boston-area children born between 1999 and 2002 whose mothers had enrolled in a long-term study called Project Viva, established to examine how behavioral and environmental factors – such as sleep and eating habits or exposure to pollution – impact children’s health. Analysis of geographic data and Project Viva questionnaires revealed clear patterns. Most strikingly, living close to a major road was linked to childhood asthma at all ages examined.

“Children living less than 100 meters from a major road had nearly three times the odds of current asthma – children who either experience asthma symptoms or use asthma medications daily – by ages seven to 10, compared with children living more than 400 meters away from a major road,” said Rice, who is also an assistant professor of medicine at Harvard Medical School. “Even in the Boston area, where pollution levels are relatively low and within Environmental Protection Agency standards, traffic-related pollutants appear to increase the risk of asthma in childhood.” (May 2018)

Scientists Visualize the Connections Between Eye and Brain

Most of the human brain’s estimated 86 billion nerve cells, or neurons, can ultimately engage in a two-way dialogue with any other neuron. To shed more light on how neurons in this labyrinthine network integrate information – that is, precisely how multiple neurons send and combine their messages to a target neuron – a team of researchers at BIDMC and Boston Children’s Hospital (BCH) focused on a rare case in which information only travels in one direction: from the retina to the brain.

In this study published May 31 in the journal Cell, Mark Andermann, PhD, Chinfei Chen, MD, PhD, and colleagues developed a means of tracking the activity of the far-reaching ends of retinal neurons (called boutons) as they deliver visual information to the thalamus, a brain region involved in image processing.

As they relay discrete bits of visual information to the brain, different types of retinal neurons respond to distinct features of visual content such as an object’s direction of motion, brightness, or size. Conventional wisdom held that these lines of information remained separated in the thalamus. Instead, Andermann and Chen’s team found that boutons from different types of retinal neurons were often organized in local clusters and that boutons in a cluster typically make contact with a common target neuron, leading to a mixing of different lines of information. However, this mixing was not random – boutons in a cluster tended to share a common sensitivity to one or more visual features.

“The selective mixing of information from this arrangement of nearby boutons may be the retina’s version of Pointillism, the neo-expressionist art technique in which nearby dots of different colors are fused together to create new and diverse colors,” said Andermann, a member of the Division of Endocrinology, Diabetes and Metabolism at BIDMC and an Associate Professor of Medicine at Harvard Medical School. “In this way, this first interface between eye and brain is surprisingly sophisticated.” (May 2018)

‘Prepare for what we hope never happens.’ Disaster Medicine Specialist Urges Increased Training and Awareness of Chemical Weapons

In response to the troubling rise of chemical warfare agents being deployed against civilian targets, a disaster medicine specialist at BIDMC is urging health care professionals to learn how to recognize and respond safely and effectively to such an attack. In a review published April 25 in the New England Journal of Medicine, Gregory R. Ciottone, MD, Director of the Division of Disaster Medicine in the Department of Emergency Medicine at BIDMC, advocates for an overhaul to the systems currently in place to respond to a chemical weapons strike on U.S. soil.  In addition to calling for increased training and awareness, Ciottone also proposed a triage system – available online – based on recognizing the signs and symptoms of specific agents during the early phase of a chemical weapons attack.

“We are witnessing an escalation in chemical weapons attacks on civilian populations globally,” said Ciottone, who is also Director of Medical Preparedness at the National Preparedness Leadership Initiative, a joint program of Harvard’s T.H. Chan School of Public Health and the Center for Public Leadership at the Harvard John F. Kennedy School of Government. “Deadly chemical agents, originally created for the battlefield, are now being deployed in urban centers. As health care professionals, it is our responsibility to the communities we serve to become better prepared to respond to such events and treat victims.” (April 2018)

Is Relaxation Therapy Good for Your Genes?

Decades of research have demonstrated that the relaxation response – the physiological and psychological opposite of the well-known fight-or-flight stress response that can be achieved through relaxation techniques like yoga or mediation – can reduce blood pressure in people with hypertension. A new study led by investigators at BIDMC, Massachusetts General Hospital (MGH), and the Benson-Henry Institute for Mind Body Medicine at MGH identified the genes associated with the body’s response to relaxation techniques and sheds light on the molecular mechanisms by which these interventions may work to lower blood pressure. The findings were published April 4 in the Journal of Alternative and Complementary Medicine.

Co-senior author Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics, and Systems Biology Center at BIDMC said, “To our knowledge, this is the first study to test such a mind-body intervention for a population of unmedicated adults with carefully documented, persistent hypertension, and this is the first study to identify gene expression changes specifically associated with the impact of a mind-body intervention on hypertension. Our results provide new insights into how integrative medicine – especially mind-body approaches – influences blood pressure control at the molecular level.” (April 2018)

New Discovery May Calm ‘Sundown’ Agitation in Alzheimer’s Disease

Patients with Alzheimer’s disease and other forms of dementia commonly experience the sundown syndrome – a sudden worsening of confusion, agitation and aggression at the end of the day. Its daily pattern suggested that “sundowning,” as the phenomenon is also known, may be governed by the body’s internal biological clock. But whether the circadian clock regulated aggressive behavior was unknown.

Now, for the first time, a team of neuroscientists at BIDMC has demonstrated circadian control of aggression in male mice and identified the specific neurons and circuitry regulating the daily pattern. The insight opens the door to potential opportunities for managing the evening-time agitation common in patients with degenerative neurological disorders. The study was published April 9 in Nature Neuroscience.

“Sundowning is often the reason that patients have to be institutionalized, and if clinicians can control this circuit to minimize aggressiveness at the end of the day, patients may be able to live at home longer,” said senior author Clifford B. Saper, MD, Chair of the Department of Neurology at BIDMC. “We examined the biological clock’s brain circuitry and found a connection to a population of neurons known to cause violent attacks when stimulated in male mice. We wanted to know if this represented a propensity for violence at certain times of day.” (April 2018)

Working Group Offers New Guidance for Safe Opioid Prescribing for Hospitalized Patients with Acute Pain

Even as current research demonstrates that hospitalized patients’ exposure to opioids has contributed to the nationwide addiction epidemic, there is little guidance for physicians as to the safe prescribing of these pain killers in the inpatient, non-operative setting.

Now, a national working group led by an investigator at BIDMC has developed a Consensus Statement intended to inform safe prescribing of opioids for hospitalized adults with acute pain. The set of 16 recommendations, published April 5 in the Journal of Hospital Medicine, provides guidance about when to use opioids versus other pain management methods, with the goal of improving the safety of opioid use during the hospital stay and managing opioid use upon discharge.

“Hospital-based clinicians frequently treat patients with acute pain, and although opioids may sometimes be beneficial in this setting, they do carry the risk of adverse events including inadvertent overdose and physical dependence,” said lead author Shoshana J. Herzig, MD, MPH, Director of Hospital Medicine Research in BIDMC’s Division of General Medicine and Primary Care Sections of Hospital Medicine and Research. “This guidance is intended to help clinicians practicing medicine in the inpatient setting balance the benefits of opioid treatment against its risks.” (April 2018)

New Method Identifies and Determines Function of Genes Once Considered ‘Junk’

Until recently, scientific research concentrated almost exclusively on the 2 percent of the genome’s protein coding regions, virtually ignoring the other 98 percent – a vast universe of non-coding genetic material previously dismissed as ‘junk.’ In the past 10 years, scientists have discovered thousands of new long non-coding RNAs (lncRNAs). Although scientists now recognize that lncRNAs play an integral role in all biological processes, they remained largely in the dark as to their functional role.

Now, in a groundbreaking paper published April 19 in the journal Cell, a team led by investigators at the Cancer Research Institute Beth Israel Deaconess Medical Center (BIDMC) has developed a novel approach to identify and determine the functional role of lncRNAs relevant to chemotherapy resistance in Acute Myeloid Leukemia (AML). The new technique integrates information from publicly-available pharmacological data bases with leading-edge CRISPR technologies to screen for both coding and non-coding genes that influence response to treatment. Taken together, this genome-wide screening platform could be applied to identify and determine the functions of ncRNAs relevant to many health contexts.

“Although thousands of lncRNAs have now been detected and annotated in the human genome, the need to characterize their functions remains a critical challenge,” said Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at Beth Israel Deaconess Medical Center, Co-Director of the HIRM at the BIDMC Cancer Center, and the George C. Reisman Professor of Medicine at HMS. “This approach we developed integrates computational analysis of existing data bases with functional screening using CRISPR technology. This novel analysis identified functionally relevant coding and non-coding genes, enabled us to assign function to non-coding genes, as well as provided us with a wealth of biomarkers associated with response to chemotherapy. It’s a quantum leap.” (April 2018)

Studies Examine How Hospital Payments for Cardiovascular Care May Affect Patient Outcomes

In recent years, there has been a growing emphasis on improving the value of health care by incentivizing reduced spending and improved outcomes. One such effort is the Hospital Value-Based Purchasing Program administered by the Centers for Medicare and Medicaid Services (CMS). The program makes payments to hospitals based on several measures, including average spending for an episode of care and mortality rates for certain conditions, such as acute myocardial infarction (AMI), or heart attack. Hospitals that perform poorly in these measures receive reduced payments.

A new, large-scale study – led by senior corresponding author Robert W. Yeh, MD, MSc, Director of the Smith Center for Outcomes Research in Cardiology at BIDMC and published online on March 14 in Circulation: Cardiovascular Quality and Outcomes – examined the relationship between 30-day episode spending for inpatient and post-discharge care and patient mortality following a hospital admission for heart attack.

“Pay-for-performance programs such as the Hospital Value-Based Purchasing Program have recently been under fire given the absence of strong evidence that they actually improve care quality,” said first author Rishi K. Wadhera, MD, MPhil, an investigator at the Smith Center at BIDMC and a cardiology fellow at Brigham and Women’s Hospital. “In this study we found that higher 30-day spending to care for Medicare beneficiaries who recently experienced a heart attack was associated with a modest reduction in patient mortality.” (April 2018)