Program Director/Principal Investigator (Last, First, Middle): Guirgis, Faheem, W Dr. Guirgis? long-term career goal is to become an independent clinician scientist with the skills to design and implement the highest quality clinical and translational research studies to develop individually-tailored treatments for sepsis and other acute diseases. The long-term goal of this research program is to characterize the antecedents and mediators of morbid long-term outcomes in patients with sepsis. Despite successful early management, sepsis is a disease with a high incidence of chronic critical illness (CCI - intensive care unit stay ? 14 days with organ dysfunction) and morbid long-term outcomes (functional dependence or death at 1 year), which occur frequently in early survivors. Both the rapid identification of patients at risk for morbid outcomes and the development of novel therapies are crucial for improving outcomes after sepsis. High density lipoprotein (HDL) defends against sepsis-associated organ injury by: 1) neutralizing bacterial endotoxin, 2) modulating innate cellular immunity and preventing release of inflammatory cytokines, and 3) preventing endothelial cell activation and dysfunction. However, HDL can become dysfunctional (Dys-HDL) in the setting of inflammation, losing protective functions and becoming pro-inflammatory. Our preliminary results demonstrate that Dys-HDL is present in early sepsis and that persistent Dys-HDL elevation (first 48 hours) is associated with adverse outcomes (death, hospice or nursing home care). The overall goal of this proposal is to investigate and fully characterize the role of Dys-HDL in a diverse population of patients with both CA and HA-sepsis. The central hypothesis of this study is that structural and functional changes in HDL during sepsis are associated with the persistent presence of Dys-HDL as well as the inflammation and endothelial dysfunction that lead to acute organ dysfunction, CCI, and morbid long-term outcomes. To test this, we will enroll 160 patients in a two-site, prospective, longitudinal, cohort study. During the proposed K award period (5 years), Dr. Guirgis with the help of his mentors will develop and strengthen his skills as a translational researcher while investigating several aspects of the role of Dys-HDL in sepsis. To achieve independence as a clinical researcher, Dr. Guirgis plans to: 1) receive hands-on experience in the design and conduct of clinical research studies, 2) take didactic coursework in clinical and translational research, 3) receive training and education in translational research techniques, focusing on lipid biology, oxidative stress, HDL physiology, and inflammation biology, 4) improve his standing as an academic emergency physician and leader, and 5) learn how to become an effective mentor to others. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

Public Health Relevance

Sepsis is a disease that is complicated by acute organ dysfunction, which is frequently followed by chronic critical illness and morbid long-term outcomes. The long-term goal of this research program is to characterize the antecedents and mediators of morbid long-term outcomes in patients with sepsis. The overall goal of this proposal is to investigate and fully characterize the role of dysfunctional high density lipoprotein (HDL) in a diverse population of patients with both community-acquired and hospital-acquired sepsis. We will enroll 160 patients in a two- site, prospective, longitudinal, cohort study to answer several questions regarding the role of dysfunctional HDL in sepsis.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Dunsmore, Sarah
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Florida
Emergency Medicine
Schools of Medicine
United States
Zip Code
Guirgis, Faheem W; Leeuwenburgh, Christiaan; Grijalva, Victor et al. (2018) HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A Subanalysis of a Prospective Pilot Study. Shock 50:66-70
Guirgis, Faheem W; Puskarich, Michael A; Smotherman, Carmen et al. (2017) Development of a Simple Sequential Organ Failure Assessment Score for Risk Assessment of Emergency Department Patients With Sepsis. J Intensive Care Med :885066617741284
Javed, Adnan; Guirgis, Faheem W; Sterling, Sarah A et al. (2017) Clinical predictors of early death from sepsis. J Crit Care 42:30-34
Guirgis, Faheem W; Dodani, Sunita; Moldawer, Lyle et al. (2017) Exploring the Predictive Ability of Dysfunctional High-Density Lipoprotein for Adverse Outcomes in Emergency Department Patients with Sepsis: A Preliminary Investigation. Shock 48:539-544
Guirgis, Faheem W; Jones, Lisa; Esma, Rhemar et al. (2017) Managing sepsis: Electronic recognition, rapid response teams, and standardized care save lives. J Crit Care 40:296-302
Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F et al. (2017) The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients. Crit Care Med 45:1436-1442
Guirgis, Faheem W; Donnelly, John P; Dodani, Sunita et al. (2016) Cholesterol levels and long-term rates of community-acquired sepsis. Crit Care 20:408
Williams, Deborah J; Guirgis, Faheem W; Morrissey, Thomas K et al. (2016) End-tidal carbon dioxide and occult injury in trauma patients: ETCO2 does not rule out severe injury. Am J Emerg Med 34:2146-2149
Duran-Gehring, Petra; Bryant, Laurie; Reynolds, Jennifer A et al. (2016) Ultrasound-Guided Peripheral Intravenous Catheter Training Results in Physician-Level Success for Emergency Department Technicians. J Ultrasound Med 35:2343-2352
Guirgis, Faheem W; Brakenridge, Scott; Sutchu, Selina et al. (2016) The long-term burden of severe sepsis and septic shock: Sepsis recidivism and organ dysfunction. J Trauma Acute Care Surg 81:525-32