This is a secondary analysis from data collected from a multi-institutional study that was supported by funding from the National Institutes of Health: RO1 AI49989-01 (Clinical Trials.gov
The aim of the original analysis was to determine the predictive ability of estradiol concentrations at 48 hours after critical illness.25,26
In this cohort, all patients, aged 18 years or older, who were admitted to the trauma intensive care unit (ICU) at Vanderbilt University Medical Center (VUMC) for at least 48 hours were eligible for enrollment. The entry criteria of a 48-hour ICU stay was used to select a patient population at risk of death and ICU complications. To be eligible for this study, patients also had to have an admission computed tomography (CT) of the abdomen and pelvis regions that could be reevaluated by the radiology department (described below). Only obese patients, defined as a BMI ≥30 kg/m2
, were included in this study population.
Independent radiologists evaluated the admission CT. For attenuation analysis, concentric freeform regions of interest were defined manually, and an area in square centimeters was calculated via picture archiving and communication system. The regions of interest were defined on axial slices at the level of the L1 vertebral body endplate in all patients. This level has been shown to influence the magnitude of the association with metabolic syndrome definitions.9,27
Two separate regions of interest were created. The most external region of interest (subcutaneous fat) included all subcutaneous structures deep to skin. The inner region of interest (visceral fat region) included all structures deep to the abdominal wall musculature. Visceral adiposity was defined as those patients who had a subcutaneous fat area to visceral fat area ratio that was greater than the median value (1.39); whereas, subcutaneous adiposity was defined as those patients who had a subcutaneous fat area to visceral fat area ration that was less than the median value (1.39; ).
For analysis, concentric freeform regions of interest (subcutaneous fat area and visceral fat region) were defined manually and an area in square centimeters was calculated via picture archiving and communication system.
Gender, age, BMI, Acute Physiology and Chronic Health Evaluation II score at ICU admission date of hospital, Trauma Injury Severity Score, Glasgow Coma Score, Multiple Organ Dysfunction Score, presence of ICU infection or ARDS, and mortality were collected. Patient care was at the discretion of the attending physician according to established trauma and critical care protocols.
One 10-mL blood sample was collected 48 hours after ICU admission (at the time of study entry) for analysis of cytokine levels. Plasma was separated from whole blood and stored at −70°C until analysis. Samples were assayed for interleukin 1, 2, 4, 6, 8, 10, and tumor necrosis factor α. This was accomplished by using a LINCOplex custom kit, following the manufacturer's instructions (Linco Research, St. Charles, MO). Twenty-five microliters of human serum from each collection time point on all patients was run in duplicates on a Luminex100 System (Miraibio, Alameda, CA) to determine the concentration of the cytokines of interest. The Luminex system is an ELISA-based technology allowing multianalyte detection in a single well. Data reduction were performed with STATLia (Brendan Scientific) and subsequently incorporated into the database.
Categorical variables were compared using the Pearson's χ2 test for independence or Fisher's exact test. Normally distributed continuous variables were summarized by reporting the mean and SD and compared using Student's t test. Nonnormally distributed continuous variables were presented by reporting the median and interquartile ranges and compared using the Wilcoxon Rank Sum test. Stata version 10.0 (Stata, College Station, TX) was used for the analysis. Tests for statistical significance were two sided with a level of significance of 0.05.
The study was approved by the institutional review board (IRB) of VUMC. A wavier of consent was obtained from both the IRB for the blood draw at 48 hours and study inclusion, because the study posed minimal risk to subjects. Families were assented during the critical illness phase, and patients were consented after their critical illness resolved when possible. Patients who died or were discharged before consent being obtained remained in the study, with IRB approval. Patients who were able to consent, but refused could either withdraw completely or refuse subsequent participation. All data are maintained in a secure, password protected database that is Health Insurance Portability and Accountability Act-compliant, and all patient information is de-identified before analysis and reporting.