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Bioavailable estradiol concentrations are elevated and predict mortality in septic patients: a prospective cohort study

Overview of attention for article published in Critical Care, October 2016
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Title
Bioavailable estradiol concentrations are elevated and predict mortality in septic patients: a prospective cohort study
Published in
Critical Care, October 2016
DOI 10.1186/s13054-016-1525-9
Pubmed ID
Authors

Greg Tsang, Michael B. Insel, Justin M. Weis, Mary Anne M. Morgan, Michael S. Gough, Lauren M. Frasier, Cynthia M. Mack, Kathleen P. Doolin, Brian T. Graves, Michael J. Apostolakos, Anthony P. Pietropaoli

Abstract

Experimental studies demonstrate beneficial immunological and hemodynamic effects of estradiol in animal models of sepsis. This raises the question whether estradiol contributes to sex differences in the incidence and outcomes of sepsis in humans. Yet, total estradiol levels are elevated in sepsis patients, particularly nonsurvivors. Bioavailable estradiol concentrations have not previously been reported in septic patients. The bioavailable estradiol concentration accounts for aberrations in estradiol carrier protein concentrations that could produce discrepancies between total and bioavailable estradiol levels. We hypothesized that bioavailable estradiol levels are low in septic patients and sepsis nonsurvivors. We conducted a combined case-control and prospective cohort study. Venous blood samples were obtained from 131 critically ill septic patients in the medical and surgical intensive care units at the University of Rochester Medical Center and 51 control subjects without acute illness. Serum bioavailable estradiol concentrations were calculated using measurements of total estradiol, sex hormone-binding globulin, and albumin. Comparisons were made between patients with severe sepsis and control subjects and between hospital survivors and nonsurvivors. Multivariable logistic regression analysis was also performed. Bioavailable estradiol concentrations were significantly higher in sepsis patients than in control subjects (211 [78-675] pM vs. 100 [78-142] pM, p < 0.01) and in sepsis nonsurvivors than in survivors (312 [164-918] pM vs. 167 [70-566] pM, p = 0.04). After adjustment for age and comorbidities, patients with bioavailable estradiol levels above the median value had significantly higher risk of hospital mortality (OR 4.27, 95 % CI 1.65-11.06, p = 0.003). Bioavailable estradiol levels were directly correlated with severity of illness and did not differ between men and women. Contrary to our hypothesis, bioavailable estradiol levels were elevated in sepsis patients, particularly nonsurvivors, and were independently associated with mortality. Whether estradiol's effects are harmful, beneficial, or neutral in septic patients remains unknown, but our findings raise caution about estradiol's therapeutic potential in this setting. Our findings do not provide an explanation for sex-based differences in sepsis incidence and outcomes.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 13%
Student > Ph. D. Student 3 10%
Student > Bachelor 3 10%
Researcher 2 7%
Student > Doctoral Student 1 3%
Other 6 20%
Unknown 11 37%
Readers by discipline Count As %
Medicine and Dentistry 13 43%
Immunology and Microbiology 2 7%
Biochemistry, Genetics and Molecular Biology 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Agricultural and Biological Sciences 1 3%
Other 0 0%
Unknown 12 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 October 2016.
All research outputs
#15,739,529
of 25,373,627 outputs
Outputs from Critical Care
#5,130
of 6,554 outputs
Outputs of similar age
#185,023
of 323,795 outputs
Outputs of similar age from Critical Care
#103
of 116 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,554 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.8. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 323,795 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 116 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.