University of Florida Health has been awarded a $12 million, five-year grant from the National Institutes of Health to create a one-of-a-kind center to help generate treatments and prevention strategies for one of the most devastating issues critically ill patients face.
The Sepsis and Critical Illness Research Center, the first of its kind in the nation, will study long-term outcomes in patients treated for sepsis in the surgical and trauma intensive care units at UF Health Shands Hospital, with the goal of developing clinical solutions for sepsis as well as illnesses that stem from it and their enduring, dismal effects.
Sepsis is a severe, systemic combination of infection and inflammation that can shut down organs, depress or overactivate the immune system and cause death. Death from sepsis was once common, but improved treatments help many people survive to leave the hospital after battling it. Severe sepsis leaves lasting effects, however, that scientists are only beginning to understand.
In 2012, UF researchers identified a condition they call persistent inflammation, immunosuppression and catabolism syndrome, after decades of research involving critically ill patients. They say the syndrome, also known as PICS, afflicts thousands of people each year, mostly elderly people who are successfully treated for sepsis. It prevents them from recovering fully and returning to a normal lifestyle. PICS will be a major focus of the UF Sepsis and Critical Illness Research Center.
"They get sent to long-term acute care facilities and many of them never really ever rehabilitate," said Frederick A. Moore, M.D., head of the new center and chief of acute care surgery at UF Health. "This is increasingly being recognized, and we think we at least have a partial understanding of how this happens. It's really just a chronic inflammatory disease and people lose a lot of lean body mass. After they lose all their lean body mass, they really can't get rehabilitated."
UF Health work on sepsis got another boost with the publication of a July 24 New England Journal of Medicine article describing similarities between the body's response to cancer and inflammatory diseases. Lyle Moldawer, Ph.D., a professor and vice chair of research in the UF College of Medicine's department of surgery, and Richard Hotchkiss, M.D., a professor of anesthesiology, medicine and surgery at Washington University in St. Louis, wrote the article promoting the testing of anti-cancer drugs for use against inflammatory and immunosuppressive diseases, and the other way around.
"If these drugs are effective in one of these diseases, they may well be effective in many others. The article is a plea to investigators not to work in silos," Moldawer said. "Oncologists work alone; infectious disease people work alone; drug companies are broken up into sections. Each is developing drugs in their own silo. The host response (to these diseases) is common and drugs going through development in cancer should be considered more rapidly for these other chronic inflammatory diseases, such as PICS."
With significant increases in the nation's elderly population expected over the next several decades, sepsis and PICS are poised to demand even more health care resources.
The number of people in the U.S. age 65 and older is expected to reach 92 million by 2060, according to data from the U.S. Census Bureau. That's more than double the 43.1 million in that age group in 2012.
"This NIH-funded center on sepsis and critical illness addresses the increasingly significant problems of long-term mortality and functional recovery in patients with sepsis," said David S. Guzick, M.D., Ph.D., UF senior vice president for health affairs and UF Health president. "Doctors Moore and Moldawer have brought together a multidisciplinary team to tackle different aspects of the problem from a fresh scientific perspective, with the goal of improving the survival and quality of life of patients with sepsis and critical illness."
Moore will lead one of four main projects to be initiated in the center's first five years of operation. The project will study the course and outcomes of chronic, critical illness that follows sepsis in patients who have been in surgical and trauma ICUs. In collaboration with the UF Institute on Aging, the researchers will look at long-term cognitive and physical effects in patients.
This and other center projects will draw on a central database that stores de-identified information on markers of PICS in patients' blood, tissue and urine samples, as well as data on patients' cognitive and physical function.
Mark Segal, M.D., Ph.D., an associate professor and chief of the UF department of medicine's division of nephrology, hypertension and renal transplantation, and Azra Bihorac, M.D., an assistant professor of anesthesiology, medicine and surgery in the UF College of Medicine, will lead another project to study how sepsis affects the kidneys and how these organs in turn may contribute to PICS and other forms of chronic illness.
Moldawer, Philip Efron, M.D., an assistant professor of surgery and anesthesiology, and Christiaan Leeuwenburgh, Ph.D., a professor and chief of the division of biology of aging in the UF department of aging and geriatric research, will explore the possible role of immature immune system cells called myeloid-derived suppressor cells in the onset of PICS.
The fourth project will focus on one of the most debilitating effects of sepsis and PICS: muscle wasting. A. Daniel Martin, Ph.D., P.T., a professor in the UF College of Public Health and Health Professions' department of physical therapy, will lead the project, which will involve Leeuwenburgh and several other researchers.
"Dr. Martin and I will determine whether clinically practical rehabilitation techniques - administered at the ICU patient's bedside - can improve diaphragm and lower-limb muscle strength," said Leeuwenburgh, "and examine whether strength training can interfere with the vicious cycle of inactivity, inflammation and protein catabolism in these patients."
Weakness in the diaphragm and legs prevents patients from breathing and walking independently, and is thought to create a slew of other problems.
In addition to the departments already named, the College of Medicine's department of molecular genetics and microbiology and the College of Public Health and Health Professions' department of biostatistics also will be involved in the center.