Mechanism of Systemic Inflammation-Associated Endothelial and Epithelial Cell Dysfunction Following Acute Pancreatitis, Trauma, and Burns
Abstract
Acute pancreatitis is a potentially lethal inflammatory disorder with a highly variable clinical course. Acute pancreatitis accounts for over 277,000 hospitalizations (first listed diagnosis) each year in the United States alone, with an average hospital stay of 7 days. Although most patients with acute pancreatitis recover from the disease without incident, 10%-20% of patients develop a severe systemic inflammatory response that can progress to organ failure, with mortality approaching 30%. Trauma, extensive burns, and bacterial infections can also cause systemic inflammation, organ failure, and death. Despite decades of research, we still do not know why some but not other patients with acute pancreatitis undergo such a severe disease course. These processes happen quickly, over a 4- to 24-hour period. Theoretically, physicians have this window of opportunity to intervene, but we do not fully understood the process or know where or how to intervene. We first need to be able to identify, as early as possible, those patients who are likely to develop systemic inflammation and organ failure so as to start aggressive intervention before tissues throughout the body become damaged. If we can identify a marker in the blood to identify patients at risk for a severe response in acute pancreatitis, we can use this same knowledge to better manage combat injuries, such as multiple trauma and severe burns. Because it is too risky and difficult to study Soldiers injured in the combat arena, we will study patients in the intensive care unit with acute pancreatitis. We will collect blood every day for a week as well as information on their clinical status to analyze whether one or more proteins or other biomarkers in the blood correlate with the development of systemic inflammation and organ failure. We will also apply this blood to cell cultures from extra surgical tissue taken from the pancreas and small intestine of patients who do not have acute pancreatitis so we can study how these tissues react when exposed to the blood of a patient who is experiencing systemic inflammation. We will use all this new knowledge to create a computer algorithm that can predict for an individual patient the risk of developing systemic inflammation and organ failure. Our team of experts seeks to identify new biomarkers in the blood and develop new tools to assist decision-making for critically ill or injured patients. Our blood test and risk-prediction algorithm would help physicians provide the best personalized care to each patient base on insights into the status and trajectory of patients with multiple trauma, severe burns, or acute pancreatitis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710502
Entities
People
- David C Whitcomb
Organizations
- United States Army
- University of Pittsburgh