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October 11, 2001

RESEARCH NOTES

Weight decline leads to death among elderly

Modest decline in body weight is an important marker of risk of mortality in older adults, according to a Pitt study published in the October issue of the Journal of the American Geriatrics Society.

The multi-center study, led by Anne B. Newman, associate professor in the division of geriatric medicine at Pitt's School of Medicine, found that weight loss of as little as 5 percent over a three-year period was associated with an increased risk of mortality. Weight stability was associated with optimal mortality rates.

"Although the weight loss is subtle, this study illustrates the need for physicians to closely monitor the weight of their older patients, including those who are already thin or at ideal weight," Newman reported.

People who had a weight loss of 5 percent and who had a lower starting weight over the course of three years had a mortality rate as high as 7.4 percent while people who gained weight or whose weight was stable had a mortality rate of about 2 percent.

The study included 4,255 people, age 65 or older, who are part of the multi-center Cardiovascular Health Study established in 1989. An additional group of 459 African-Americans was added to the study in 1992.

"The participants in this study were somewhat healthier than those seen in general practice. However, compared with previous studies, this group was more representative of older adults living in the community, including men and women and a sizable number of African-Americans," Newman said.

Weight change was determined by comparing the participants' baseline weight upon study entry to their weight three years later. The follow-up for mortality began at the end of the three-year period through an additional one to four years. People were excluded from the final analysis who were hospitalized or who had a new diagnosis of cardiovascular disease or cancer during the study period.

Over the three years, 18.7 percent of women and 16.2 percent of men had a weight loss of greater than 5 percent, while 6.3 percent of women and 4.1 percent of men had a weight loss greater than 10 percent.

Those who lost weight had a higher prevalence of stroke, diabetes, hypertension or gastrointestinal illness and used a higher number of medications than the weight-stable group.

The minority group was similar to the original group in that those whose weight was stable had more optimal health status and lower disability than those who gained or lost weight. However, those in the minority group who gained weight had the lowest income and education whereas in the original group, lower income and education were associated with weight loss.

"Those on a medically prescribed diet at baseline were more likely to lose weight than those who were not on a diet, suggesting that weight loss may have been a treatment goal," said Newman. "Weight loss was also associated with a self-initiated diet, again suggesting intentionality. However, those who lost weight in these two subgroups did not have either a lower or higher risk of mortality than did those who reported no special diet."

Newman also reported that "although many potentially identifiable risk factors for weight loss can be identified and treated, the extent to which weight can be regained and whether weight regain would improve survival is not known."

Other centers participating include the University of Washington, Seattle; the University of Alabama, Birmingham; the University of Arizona, Tucson; Johns Hopkins, and the National Institute on Aging.

The study is funded by the National Heart, Lung and Blood Institute.

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Human heart kept alive outside body for first time

Tucked away in an empty operating room at the University of Pittsburgh Medical Center (UPMC), a human heart continued to beat — outside the body — for nearly 12 hours with the aid of an experimental organ preservation and transportation system under development by TransMedics, Inc. of Woburn, Mass. The time the heart was preserved exceeded what is possible with current techniques and met the researchers' expectations for the first test of its kind.

This was the first time the Portable Organ Preservation System (POPS) was connected to a human heart. The company has conducted extensive testing in animals, and several weeks ago it performed its first human trial with a kidney that made urine and functioned normally for nearly 24 hours before researchers disconnected the device.

Although this phase of the trial required using a heart that could not be used for transplantation, UPMC's surgeons are optimistic about its potential to expand the pool of available organs. Using current methods — whereby organs are packed in coolers filled with ice and special solutions — organs only can be preserved safely for limited periods of time. Called cold ischemia time, the duration depends on the organ. The cold ischemic time for the heart is the shortest; once it is removed from the donor and has no blood supply, it has a "shelf life" of approximately six hours.

POPS maintained the human heart in its normal functioning physiologic state, with continuous blood flow, for about 12 hours before researchers elected to disconnect the organ for additional testing.

"Current technology provides only a small window of opportunity to transport and transplant an organ, thereby greatly limiting the availability of organs to those in need. A longer preservation time would allow us to share organs across greater distances, and more patients would benefit from life-saving transplants," said Robert L. Kormos, professor of surgery and director of thoracic transplantation and the artificial heart program at UPMC.

"POPS could provide transplant teams with sufficient time to perform a complete range of tests on organs that we currently do not consider suitable for transplantation, such as those from older donors or those with questionable function," said Kenneth R. McCurry, assistant professor of surgery and director of lung and heart-lung transplantation at UPMC. "Furthermore, perfusion with POPS may result in improved organ function by 'resuscitating' previously unusable organs. Such therapies might significantly increase the number of organs that can be used for transplantation. Additionally, POPS might allow us to use hearts and lungs from nonheart-beating donors. We'd essentially be able to resuscitate these organs, then transplant them."

The new technique also might reduce or even eliminate a type of injury to the donor organ that sometimes results when oxygenated blood is reintroduced into the organ during transplant surgery. The rush of oxygen into the organ's cells somehow causes a process of cell self-destruction, therefore compromising the function of the graft.

TransMedics' technique preserves the heart and other organs by mimicking the actions and environmental conditions of the internal body.

The system used here weighs approximately 70 pounds and is shaped like a box that can fit in an ambulance or private jet. A smaller unit, weighing about 55 pounds, could fit on the seat of a commercial airplane. The system has a four-hour battery, built-in handles and detachable wheels. It consists of a portable electro-perfusion device, bio-compatible organ-specific disposable components and proprietary chemical solutions that bathe the organ.

POPS is used in research at several sites in the United States and United Kingdom. The system was developed to prolong safe organ preservation and transport, increase the number of organ transplants and potentially improve transplant outcomes. TransMedics is conducting kidney studies for review by the U.S. Food and Drug Administration in late 2001.

More than 78,000 patients are on the national transplant waiting list, including nearly 50,000 who await donor kidneys. While those awaiting heart transplants number about 4,000, only 2,200 heart transplants are performed each year and close to 800 die annually waiting for a heart. Almost 6,000 patients in the U.S. are expected to die due to the limited supply of organs.


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