Abstract

Infectious diseases continue to cause an unacceptably high morbidity and mortality among elderly, critically ill, and hospitalized patients. Animal and human studies imply a significant gender-related influence on both susceptibility to and mortality from infection. All clinical studies to date, however, have been either small or based on retrospective information. One explanation for these possible differences in outcome supported by animal studies is that modulation of circulating levels of estradiol and testosterone may be immunologically """"""""protective,"""""""" mediated by changes in cytokine and biologically reactive intermediary response. Another possibility is that gender differences in social/ family values are determinants of patient death, including mode of death (withdrawal of support vs. irreversible physiologic collapse) and assumptions regarding the likelihood of long-term, high quality of life survival. The hypothesis to be tested (generated from preliminary data) is that although the incidence of infection is similar for men and women after controlling for admission diagnosis and severity of illness, high estradiol levels in both sexes is associated with higher mortality, and that mortality will also be highly dependent on end of life decisions among other social variables.
Aim 1. To prospectively determine the incidence of and associated mortality from hospital-acquired infections in a critically ill population after controlling for multiple pre-defined confounding variables, including gender.
Aim 2. To determine the relationship between sex hormonal status, systemic cytokine levels, and the incidence of and outcome from hospital-acquired infections, as well as the relative contribution of infection and end of life decisions to outcome in patients dying under study. Data obtained from this research will be used to design interventional studies utilizing hormonal manipulation, i. e., replacement or blockade, to improve outcomes from otherwise lethal infectious diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI049989-05
Application #
6923336
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Korpela, Jukka K
Project Start
2001-09-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
5
Fiscal Year
2005
Total Cost
$558,214
Indirect Cost

  Institution

Name
University of Virginia
Department
Surgery
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Guidry, Christopher A; Swenson, Brian R; Davies, Stephen W et al. (2014) Sex- and diagnosis-dependent differences in mortality and admission cytokine levels among patients admitted for intensive care. Crit Care Med 42:1110-20
Heffernan, Daithi S; Dossett, Lesly A; Lightfoot, Michelle A et al. (2011) Gender and acute respiratory distress syndrome in critically injured adults: a prospective study. J Trauma 71:878-83; discussion 883-5
Kauffmann, Rondi M; Norris, Patrick R; Jenkins, Judith M et al. (2011) Trends in estradiol during critical illness are associated with mortality independent of admission estradiol. J Am Coll Surg 212:703-12; discussion 712-3
Hranjec, Tjasa; Swenson, Brian R; Dossett, Lesly A et al. (2010) Diagnosis-dependent relationships between cytokine levels and survival in patients admitted for surgical critical care. J Am Coll Surg 210:833-44, 845-6
Collier, Bryan; Dossett, Lesly; Shipman, Jason et al. (2010) Visceral adiposity is not associated with inflammatory markers in trauma patients. J Trauma 68:57-61
Fremont, Richard D; Koyama, Tatsuki; Calfee, Carolyn S et al. (2010) Acute lung injury in patients with traumatic injuries: utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma 68:1121-7
Swenson, Brian R; Metzger, Rosemarie; Hedrick, Traci L et al. (2009) Choosing antibiotics for intra-abdominal infections: what do we mean by ""high risk""? Surg Infect (Larchmt) 10:29-39
Dossett, Lesly A; Dageforde, Leigh Anne; Swenson, Brian R et al. (2009) Obesity and site-specific nosocomial infection risk in the intensive care unit. Surg Infect (Larchmt) 10:137-42
Dossett, Lesly A; Redhage, Leigh Anne; Sawyer, Robert G et al. (2009) Revisiting the validity of APACHE II in the trauma ICU: improved risk stratification in critically injured adults. Injury 40:993-8
Dossett, Lesly A; Heffernan, Daithi; Lightfoot, Michelle et al. (2008) Obesity and pulmonary complications in critically injured adults. Chest 134:974-80

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