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University of Pittsburgh

February 16, 2017

Research Notes

Higher BMI linked to lower-quality end-of-life care

A study by a School of Medicine researcher suggests that the heavier someone is, the less likely they are to receive quality end-of-life care, including hospice care and the chance to die at home.

The study was led by John Harris, an obstetrics, gynecology and reproductive sciences faculty member. Harris conducted the research during his fellowship at the University of Michigan Institute for Healthcare Policy and Innovation (IHPI), and the findings were published in the Annals of Internal Medicine.

Researchers analyzed records from more than 5,600 senior citizens who took part in the long-running national Health and Retirement Study, examining how their body mass index (BMI) related to end-of-life measures, such as their use of hospice services. Results indicated that people with higher BMIs were less likely to enter hospice care and, among those who did, seniors with obesity spent fewer days in hospice than those with lower BMIs.

The study also found that about 60 percent of the seniors in the study died at home, an experience that most Americans say they would choose. But that percentage dropped as BMI rose.

The researchers focused on Medicare claims in the last six months of the participants’ lives, looking at use of hospice services and controlling for gender, race, marital status, multiple medical conditions and household assets. They also had information from surveys of the participants’ loved ones about their end-of-life care in addition to all participants’ last measured BMI.

Fifteen percent of participants were obese, with BMIs over 30, and 2 percent were morbidly obese, with BMIs over 40. Another 31 percent were overweight, with BMIs between 25 and 29.9.

The differences in end-of-life care also translated into differences in cost. In the last six months of life for a person with a normal BMI, the Medicare system spent about $43,000 for all types of care. For an obese person, the costs were about $3,500 higher.

The study was funded by the Robert Wood Johnson Foundation, the U.S. Department of Veterans Affairs and the National Institutes of Health (NIH).

Other authors included current and former IHPI members and a co-author from the Dana Farber Cancer Institute.

Genetic thyroid cancer test may preserve gland

School of Medicine scientists and doctors are embarking on the first-ever clinical trial to determine if a genetic test they pioneered could spare patients with nonaggressive thyroid cancer from complete removal of their thyroid, a gland in the neck that is important to hormone regulation and development. Such thyroid-preserving surgery minimizes surgical complications, and many patients also may avoid taking medication every day to keep thyroid hormone levels in check.

The two-year trial, which is entirely funded by individual donors affected by thyroid cancer, will investigate whether the UPMC-developed molecular genetic test ThyroSeq can correctly differentiate between thyroid cancers most likely to spread and require complete removal of the thyroid gland, and those likely to be far less invasive, warranting a thyroid-preserving surgical approach.

Said Linwah Yip, surgery faculty member and principal investigator of the trial: “We’re looking at potentially saving patients from unnecessary surgery.”

Nearly 57,000 cases of thyroid cancer are diagnosed in the U.S. every year, and about 2,000 people die of the disease, according to the American Cancer Society.

Under current guidelines of the American Thyroid Association, when patients are diagnosed preoperatively with thyroid cancer, which means a small sample of their thyroid has cancerous cells, they can start by having just half of their thyroid removed. Often, this allows the remaining part of the thyroid to continue functioning naturally without longterm medication. However, a second thyroid operation then can be required if the removed cancer is an aggressive type. Alternatively, under the current guidelines, patients can skip the initial removal of half the thyroid and proceed straight to full removal, but they will need medication for the rest of their lives.

ThyroSeq is a genetic test developed by a scientific team lead by Yuri Nikiforov, pathology faculty member and director of UPMC’s Division of Molecular and Genomic Pathology. UPMC’s latest version allows pathologists to simultaneously test 14 genes for 42 markers of thyroid cancer using just a few cells collected during the initial biopsy.

The test has performed well at differentiating between cancerous and noncancerous thyroid nodules, already sparing patients from unnecessary surgeries.

Yip and her colleagues plan to enroll about 100 patients who are newly diagnosed with thyroid cancer. Each participant’s biopsy sample will be tested with ThyroSeq to determine whether the cancer has an aggressive or nonaggressive genetic signature. The patients and their doctors then can decide whether to remove half or the entire thyroid.

In addition, the trial also will evaluate the quality-of-life parameters associated with complete removal of the thyroid gland.

This trial can be found on ClinicalTrials.gov with the identifier NCT02947035.

NIH $2.36 million grant targets development of wearable artificial lung for kids

Acute and chronic lung diseases are the most life-threatening causes of hospitalization and death among young children. This is especially true for children suffering from cystic fibrosis. The path to recovery often leads to a lung transplant, but the wait for pediatric patients can be months and the patients can require lengthy hospital stays anchored to large mechanical ventilators.

To safely bridge the time between diagnosis and transplant while allowing patient mobility, a research team led by the Swanson School of Engineering, working with the McGowan Institute for Regenerative Medicine, is developing a compact respiratory assist device for children. The Pittsburgh Pediatric Ambulatory Lung (P-PAL) would replace traditional oxygenation methods as a bridge to transplant or recovery in children with lung failure.

The project received a four-year, $2.36 million award from NIH’s National Heart, Lung and Blood Institute. Program director/principal investigator is William J. Federspiel, bioengineering faculty member. Co-PIs are William R. Wagner, director of the McGowan Institute for Regenerative Medicine and surgery, bioengineering and chemical engineering faculty member, and a colleague from the Nemours Children’s Health System in Florida.

Said Federspiel: “Standard existing therapy not only restricts children’s mobility in the hospital but can also cause lung damage and/or worsening of the child’s health. Our new approach allows the patient’s lungs to rest and heal, and if the child is a candidate for lung transplantation, the mobility afforded by the P-PAL will lead to better post-transplant outcomes.”

Co-investigators include Jonathan D’Cunha of Pitt and a faculty member from Mississippi State University.

Water reuse systems assessed

The decentralized water system at the Center for Sustainable Landscapes (CSL) at Phipps Conservatory and Botanical Gardens, which treats all nonpotable water on site, contributes to the net-zero building’s recognition as one of the greenest buildings in the world.

However, research into the efficacy of these systems versus traditional treatment has been practically nonexistent. Research by Phipps and faculty members from the Swanson school has resulted in a greater understanding of the life cycle of water reuse systems designed for living buildings, from construction through day-to-day use.

Published in Environmental Science and Technology, the research uses life-cycle assessment (LCA). The study was co-authored by Melissa M. Bilec, civil and environmental engineering faculty member and deputy director of the Mascaro Center for Sustainable Innovation (MCSI), with collaborators at Phipps, and the participation of PhD graduate student Vaclav Hasik and undergraduate Naomi Anderson.

Said Bilec: “As water becomes more of a precious resource around the globe, there is a greater focus on developing new methods of water efficiency and water conservation.”

According to Bilec, LCA scientifically analyzes the environmental impact of a product or process throughout the entire life cycle, from the materials used to build a system to their transportation, construction, use and, eventually, the estimated end of life. Although LCA has been used to compare centralized and decentralized water systems in different contexts, the Phipps CSL research is the first to consider both water supply and treatment at a comprehensive site or in the context of a net-zero energy/water building.

Bilec noted that, while the research found that a decentralized water system operates well for a facility like the CSL, the environmental benefits or trade-offs for such systems are dependent upon their lifetime of use, and may not necessarily be practical or environmentally preferable. For example, a similar system might be more environmentally and economically efficient for a development of multiple homes or buildings, rather than one structure.

Conversely, the relative impact of a decentralized system built in a water-scarce region may be more beneficial than its environmental footprint. The decision as to what water system to build and its scale, she said, should be evaluated within the context of the entire life of the structure or site it supports.

She also noted that research such as this is valuable because of the community-minded approach shared by Pitt, MCSI and Phipps, and its impact on students. For example, Hasik is using the CSL study to inform his dissertation on resilient and sustainable systems.

Other Pitt co-authors included William O. Collinge and Vikas Khanna. Colleagues from Clemson and New York University also contributed.

Innovation Institute rewards proposals

The Innovation Institute has awarded $140,000 to four Pitt teams to help them move their discoveries toward commercialization, with the aim of making a positive impact on society.

The Chancellor’s Innovation Commercialization Funds were established to provide support for promising early-stage Pitt innovations to assist in reducing the technical and/or market risk associated with the innovations and make them more attractive to investors or potential licensees. One of the paths for identifying funding opportunities is through a request for proposal program that was launched last November and recently culminated in these awards.

The teams were selected by a panel of judges from a pool of two dozen applicants that was narrowed to a group of 10 finalists.

Two awards of $35,000 each were made for innovations with a one-to-one matching partner:

• Thermoresponsive Hydrogel for Orbital Volume Augmentation, proposed by Morgan Fedorchak, faculty member in ophthalmology, chemical engineering and clinical and translational science, and Jenny Yu, faculty member and vice chair of clinical operations in ophthalmology. This nondegradable hydrogel material can be injected into the orbit of the eye following ocular trauma or as a treatment for genetic eye disorders. The material also can be used to administer anti-inflammatory or antibiotic medications. The funding will be used to provide proof-of-concept studies. Data from the successful completion of the studies will better position the innovation for application to the Department of Defense for funding to explore the therapeutic potential of the technology. Matching funds will come from the Center for Military Medicine Research, whose mission is to address combat-related injuries.

• BodyExplorer: Autonomous Simulated Patient, proposed by Douglas Nelson Jr., doctoral candidate in bioengineering; John O’Donnell, faculty member and chair of nurse anesthesia; and Joseph Samosky, bioengineering faculty member. This next-generation medical simulator is designed to help health care trainees learn anatomy and physiology and practice treating patients through naturalistic interaction with an augmented-reality enhanced full-body simulated patient. The team previously participated in the Coulter translational partners II program and the Idea Foundry’s science accelerator to advance prototype development and usability testing. The new funding will assist in improving the user interface and expanding the BodyExplorer curriculum modules to enhance access to the benefits of simulation-based learning for medical and nursing students, first responders and other health care practitioners. Idea Foundry is providing one-to-one matching cash support, in addition to $25,000 of additional in-kind support, to assist in securing additional investment.

Two projects received $35,000 awards without a matching requirement.

• Nano-LED Technology for Microdisplays, proposed by Hong Koo Kim, Bell of PA/Bell Atlantic Professor in electrical and computer engineering, and doctoral student Daud Hasan Emon. They have developed nano LED structures that have lower energy costs and longer battery life than existing LED technology. Applications include mobile device displays and other micro-display devices. The funding will support advancement of prototypes to demonstrate the breadth of the optimal applications.

• Reactive Extraction of Water: Desalination Without Membranes or Distillation, proposed by Eric Beckman, distinguished service professor in chemical engineering, has developed a chemical method for desalinating water that requires less energy than the longstanding existing methods such as reverse osmosis or flash distillation. The award will fund testing to validate the technology.

New clues show viruses entering intestine

Researchers at the School of Medicine and Washington University in St. Louis have provided the first details of how enteroviruses, which cause millions of infections worldwide annually, can enter the body through the intestine. The results of the study are published in Proceedings of the National Academy of Sciences.

Enteroviruses are a class of viruses that are the second most common human infectious agents and are primarily transmitted through close person-to-person contact, touching infected surfaces, or ingesting food or water containing the virus.

Enterovirus infections are associated with diseases that can range from mild flu-like symptoms to much more severe outcomes such as inflammation in the brain or heart, acute paralysis and even death.

Enterovirus infections acquired within neonatal intensive care units (NICU) can be devastating as newborns are particularly susceptible to infection by these viruses.

Said senior author Carolyn Coyne, faculty member in microbiology and molecular genetics in the school: “Despite their major global impact, especially on the health of children, little is known about the route that these viruses take to cross the intestine, their primary point of entry. Our approach has for the first time shed some light on this process.”

In the study, researchers isolated stem cells from premature human small intestines and grew them in the laboratory into enteroids, or so-called “mini-guts,” which contained the different cell types and tissue structures normally found in the human intestine.

Using the mini-gut model, the researchers demonstrated that echovirus 11, the enterovirus most commonly associated with NICU infections, induced significant damage to the enteroids, which could facilitate passage of the virus into the bloodstream from the infected intestine.

The results also provided the first evidence that different types of enteroviruses could target distinct cells within the gastrointestinal tract and might vary in their effectiveness at infecting intestinal cells.

Other Pitt authors of the study included Coyne G. Drummond and Congrong Ma. Colleagues from Washington University School of Medicine in St. Louis also contributed.

The study was funded by NIH, the Burroughs Wellcome Fund and Children’s Hospital of Pittsburgh of UPMC.

Heart fat linked to heart disease in postmenopausal women

A higher volume of a certain type of fat that surrounds the heart is significantly associated with a higher risk of heart disease in women after menopause and women with lower levels of estrogen at midlife, according to research led by the Graduate School of Public Health.

The findings reveal a previously unknown menopause-specific indicator of heart disease risk, pointing to potential strategies to reduce that risk and a target for future studies on the impact of hormone replacement therapy in improving cardiovascular health. The results were published online in the Journal of the American Heart Association.

Said lead author Samar R. El Khoudary, faculty member in the Department of Epidemiology: “For the first time, we’ve pinpointed the type of heart fat, linked it to a risk factor for heart disease and shown that menopausal status and estrogen levels are critical modifying factors of its associated risk in women.”

There are two types of fat surrounding the heart:

• Epicardial fat, the fat that directly covers the heart tissue (the myocardium) and is located between the outside of the heart and the pericardium (the membrane that encases the heart). It is the energy source for the heart.

• Pericardial fat, which is outside the pericardium, anterior to the epicardial fat. There are no known heart-protective functions of this fat.

El Khoudary and her team evaluated clinical data, including blood samples and heart CT scans, on 478 women enrolled in the Study of Women’s Health Across the Nation. The women were in varying stages of menopause, averaged 51 years old and were not on hormone replacement therapy.

In a previous study, the team showed that a greater volume of pericardial fat, but not epicardial fat, after menopause is explained by a decline in the sex hormone estradiol, the most potent estrogen, in midlife women. The higher volume of epicardial fat was tied to other risk factors, such as obesity.

In the new study, the researchers built on those findings to discover that not only is a greater pericardial fat volume specific to menopause, but in postmenopausal women and women with lower levels of estradiol it’s also associated with a greater risk of coronary artery calcification, an early sign of heart disease that is measured with a heart CT scan.

In the women studied, an increase in pericardial fat volume from the 25th percentile to the 75th percentile (corresponding to a 60 percent increase) was associated with a 160 percent higher risk of coronary artery calcification and a 45 percent increase in the extent of coronary artery calcification in postmenopausal women compared with pre- or early-menopausal women.

“Clearly, epicardial and pericardial fat are distinct types of heart fat that are found to be greater in postmenopausal women for different reasons with different effects on heart disease risk — and thus should be evaluated separately when searching for ways to help women avoid heart disease,” said El Khoudary.

An analysis of previous research found that heart fat volumes could be reduced with dieting and bariatric surgery. Given the uncertainty about the cardio-protective effects of hormone replacement therapy, as well as the lack of research on the impact of such therapy on heart fat volumes, El Khoudary is planning a study to evaluate hormone replacement therapy on heart fat accumulation, paying particular attention to the types of heart fat.

Karen A. Matthews of Pitt was senior author.

Colleagues from Allegheny Health Network, Rush University Medical Center, Los Angeles Biomedical Research Institute and the University of Minnesota Medical School also contributed.

This research was supported by NIH and the American Heart Association.

 

—Compiled by Marty Levine


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