1/20/2024 0 Comments New horizon surgical center![]() ![]() ![]() We recognize that no single therapeutic intervention will prevent PICS, but the SCIRC's overall goal is to understand the prevalence and pathogenesis of this new syndrome at a mechanistic level. This Sepsis and Critical Illness Research Center (SCIRC) application comprises four projects and five cores drawn from two colleges (Medicine and Public Health and Health Professions) and eight University of Florida Health departments (Surgery, Medicine, Anesthesiology, Biostatistics, Molecular Genetics and Microbiology, Aging and Geriatric Research, and Physical Therapy) and will address the following questions in four projects: #1a) What is the incidence and early risk factors for CCI in septic surgical ICU patients and what are the long-term cognitive and functional consequences? #1b) Can novel biomarkers predict, early, which patients will develop CCI, and, later, which CCI patients will have morbid long-term outcomes (i.e., PICS)? #2) Is PICS inherently driven by dysregulation in myelopoiesis and inappropriate MDSC expansion, promoting persistent inflammation, immunosuppression and catabolism? #3) Does AKI, through dysregulation of anti-angiogenic and angiogenic cytokines, drive the expansion of MDSCs, inflammation, and anti-angiogenesis? and #4) Does CCI contribute significantly to muscle atrophy, especially in mechanically ventilated patients'diaphragms and extremities, and will resistance exercise improve muscle strength, reduce inflammation, and alter the trajectory of CCI away from the PICS phenotype? We will study 400 surgical ICU patients who develop sepsis for at least one year, and use murine models of chronic polymicrobial sepsis for mechanistic studies and interventional methods. We further hypothesize that PICS is caused, at least in part, by dysregulated myelopoiesis and expansion of myeloid-derived suppressor cells (MDSCs), aggravated by aging and largely driven by acute kidney injury (AKI), resulting in imbalance of angiogenic and anti-angiogenic factors. Our overarching hypothesis is that PICS is now a predominant clinical trajectory in the surgical ICU patients after sepsis, and is the greatest, near-term clinical challenge in surgical ICUs. Although recent advances in early ICU care have reduced in-hospital mortality, with the aging population a new epidemic of chronic critical illness (CCI) has emerged and its progression into what we call the persistent inflammation, immunosuppression and catabolism syndrome (PICS) has unacceptable morbid long-term consequences. Despite 30 years of intensive research, morbidity and mortality of sepsis in surgical intensive care unit (ICU) patients remain unacceptably high. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |