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  • 1
    In: Clinical and Translational Science, Wiley, Vol. 17, No. 3 ( 2024-03)
    Abstract: The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis‐3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid‐chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro‐inflammatory signaling lipids from ω‐6 poly‐unsaturated fatty acids (PUFAs), including 15‐hydroxyeicosatetraenoic (HETE), 12‐HETE, and 11‐HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro‐resolving lipid mediator from ω‐3 PUFAs, 14(S)‐hydroxy docosahexaenoic acid (14S‐HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor‐outcome patients with sepsis and may serve as targets for future therapies.
    Type of Medium: Online Resource
    ISSN: 1752-8054 , 1752-8062
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2433157-0
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  • 2
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 3 ( 2022-03-16), p. e222735-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 3
    In: Western Journal of Emergency Medicine, California Digital Library (CDL), Vol. 24, No. 3 ( 2023-05-11)
    Type of Medium: Online Resource
    ISSN: 1936-9018 , 1936-900X
    Language: Unknown
    Publisher: California Digital Library (CDL)
    Publication Date: 2023
    detail.hit.zdb_id: 2375700-0
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  • 4
    In: BMJ Open, BMJ, Vol. 9, No. 9 ( 2019-09), p. e029348-
    Abstract: Sepsis is a life-threatening, dysregulated response to infection. Both high-density lipoprotein and low-density lipoprotein cholesterol should protect against sepsis by several mechanisms; however, for partially unknown reasons, cholesterol levels become critically low in patients with early sepsis who experience poor outcomes. An anti-inflammatory lipid injectable emulsion containing fish oil is approved by the Food and Drug Administration as parenteral nutrition for critically ill patients and may prevent this decrease in serum cholesterol levels by providing substrate for cholesterol synthesis and may favourably modulate inflammation. This LIPid Intensive Drug therapy for Sepsis Pilot clinical trial is the first study to attempt to stabilise early cholesterol levels using lipid emulsion as a treatment modality for sepsis. Methods and analysis This is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours − enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function. Ethics and dissemination Investigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial. Trial registration number NCT03405870 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2599832-8
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  • 5
    In: Critical Care Explorations, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 6 ( 2023-06), p. e0929-
    Type of Medium: Online Resource
    ISSN: 2639-8028
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3015728-6
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  • 6
    In: AEM Education and Training, Wiley, Vol. 4, No. 3 ( 2020-07), p. 262-265
    Abstract: The goal of this research was to determine the gender distribution of chief residents in emergency medicine (EM) residencies in the United States to explore whether the gender leadership gap is present at the resident level in EM. Methods The investigators compiled a list of EM residency programs accredited by the Accreditation Council for Graduate Medical Education. Investigators reached out to the programs using established best practices in survey distribution collecting the following: program name, program location, program length, total number of residents, total number of female residents, total number of chief residents, and the total number of female chief residents. Results Of the 223 programs contacted 194 programs responded and 182 programs were included in the study (a response rate of 82%). As of the 2019 to 2020 academic year, female EM residents account for 37.0% (2,459/6,718) of all EM residents and female EM chief residents account for 42.2% (250/593) of EM chief residents. The proportion of female EM chief residents was significantly higher than the proportion of both female EM residents (42.2% vs. 37%, p = 0.007) and female EM attending physicians (42.2% vs. 27.5%, p  〈  0.001). When comparing proportions of female residents based on duration of program, female physicians comprised 35.0% (1,652/4,720) of residents at 3‐year programs and 40.4% (807/1998) of residents at 4‐year programs (p  〈  0.01). Conclusions While the proportion of female EM residents remains significantly lower than the proportion of male residents, females and males are similarly represented at the chief resident role.
    Type of Medium: Online Resource
    ISSN: 2472-5390 , 2472-5390
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2881270-0
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  • 7
    In: Journal of Intensive Care Medicine, SAGE Publications, Vol. 36, No. 7 ( 2021-07), p. 808-817
    Abstract: Reduced cholesterol levels are associated with increased organ failure and mortality in sepsis. Cholesterol levels may vary by infection type (gram negative vs positive), possibly reflecting differences in cholesterol-mediated bacterial clearance. Methods: This was a secondary analysis of a combined data set of 2 prospective cohort studies of adult patients meeting Sepsis-3 criteria. Infection types were classified as gram negative, gram positive, or culture negative. We investigated quantitative (levels) and qualitative (dysfunctional high-density lipoprotein [HDL]) cholesterol differences. We used multivariable logistic regression to control for disease severity. Results: Among 171 patients with sepsis, infections were gram negative in 67, gram positive in 46, and culture negative in 47. Both gram-negative and gram-positive infections occurred in 11 patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels were lower for culture-positive sepsis at enrollment (TC, P 〈 .001; LDL-C, P 〈 .001; HDL-C, P = .011) and persisted after controlling for disease severity. Similarly, cholesterol levels were lower among culture-positive patients at 48 hours (TC, P = .012; LDL-C, P = .029; HDL-C, P = .002). Triglyceride (TG) levels were lower at enrollment ( P =.033) but not at 48 hours ( P = .212). There were no differences in dysfunctional HDL. Among bacteremic patients, cholesterol levels were lower at enrollment (TC, P = .010; LDL-C, P = .010; HDL-C, P ≤ .001; TG, P = .005) and at 48 hours (LDL-C, P = .027; HDL-C, P 〈 .001; TG, P = .020), except for 48 hour TC ( P = .051). In the bacteremia subgroup, enrollment TC and LDL-C were lower for gram-negative versus gram-positive infections (TC, P = .039; LDL-C, P = .023). Conclusion: Cholesterol levels are significantly lower among patients with culture-positive sepsis and bacteremia.
    Type of Medium: Online Resource
    ISSN: 0885-0666 , 1525-1489
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2001472-7
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Journal of the American College of Emergency Physicians Open Vol. 1, No. 3 ( 2020-06), p. 222-230
    In: Journal of the American College of Emergency Physicians Open, Wiley, Vol. 1, No. 3 ( 2020-06), p. 222-230
    Abstract: Research evaluating the relationship between vasopressor initiation timing and clinical outcomes is limited and conflicting. We investigated the association between time to vasopressors, worsening organ failure, and mortality in patients with septic shock. Methods This was a retrospective study of patients with septic shock (2013–2016) within 24 hours of emergency department (ED) presentation. The primary outcome was worsening organ failure, defined as an increase in Sequential Organ Failure Assessment (SOFA) score ≥2 at 48 hours compared to baseline, or death within 48 hours. The secondary outcome was 28‐day mortality. Time to vasopressor initiation was categorized into 6, 4‐hour intervals from time of ED triage. Multiple logistic regression was used to identify predictors of worsening organ failure. Results We analyzed data from 428 patients with septic shock. There were 152 patients with the composite primary outcome (SOFA increase ≥2 or death at 48 hours). Of these, 77 patients died in the first 48 hours and 75 patients had a SOFA increase ≥2. Compared to the patients who received vasopressors in the first 4 hours, those with the longest time to vasopressors (20–24 hours) had increased odds of developing worsening organ failure (odds ratios [OR] = 4.34, 95% confidence intervals [CI] = 1.47–12.79, P  = 0.008). For all others, the association between vasopressor timing and worsening organ failure was non‐significant. There was no association between time to vasopressor initiation and 28‐day mortality. Conclusions Increased time to vasopressor initiation is an independent predictor of worsening organ failure for patients with vasopressor initiation delays 〉 20 hours.
    Type of Medium: Online Resource
    ISSN: 2688-1152 , 2688-1152
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 3005425-4
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  • 9
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2020
    In:  Journal of Clinical and Translational Science Vol. 4, No. s1 ( 2020-06), p. 36-37
    In: Journal of Clinical and Translational Science, Cambridge University Press (CUP), Vol. 4, No. s1 ( 2020-06), p. 36-37
    Abstract: OBJECTIVES/GOALS: Septic shock is a lethal condition. Research suggests that overall sepsis mortality varies by race, but less is known about demographic differences in septic shock mortality. Our objectives were to describe the septic shock population using a large, state-wide data repository and identify demographic predictors of septic shock mortality. METHODS/STUDY POPULATION: This was a retrospective review of patients with septic shock in the One Florida Data Trust from 2012-2018. Patients were classified as having septic shock if they received vasopressors and had either 1) an ICD-9 or 10 code for septic shock or 2) an ICD-9 or 10 code for infection and an ICD-9 or 10 code for organ dysfunction. Demographic data and place of residence prior to admission was collected. The primary outcome was 90 day mortality. T-test and chi-square tests were used to test association of individual predictors and mortality. Multiple logistic regression was used to identify predictors of mortality after adjustment for other variables. Level of significance was set at 0.05. SAS v9.4 (Cary, NC) was used for analyses. RESULTS/ANTICIPATED RESULTS: There were 11,790 patients with septic shock. The mean(SD) age was 61(16) years. With regard to race/ethnicity 66% identified as white, 27% as black, 3.7% as Hispanic, and 3.5% as other races (non-white, non-black, non-Hispanic). Most came from home (57%). Overall, 39% died. Mortality varied by race (p 〈 0.01): white 39%, black 39%, Hispanic 31%, other races 51%. In the logistic regression model, age, race, and residence were significant predictors of mortality, after adjustment for other variables. Each additional year of age had a 2.7% increased odds of mortality (OR 1.03; 95% CI 1.02-1.03; p 〈 0.01). Compared to white patients, odds of death were 1.6 times higher for other races (95% CI 1.3-2.0; p 〈 0.01) and non-significantly higher for black patients (OR 1.1; 95% CI 1.0-1.2; p = 0.05). Compared to those from home, odds of death were highest for those from a skilled nursing facility (OR 1.5; p 〈 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Patients who identified as other races had increased mortality from septic shock compared to white patients after adjusting for other variables. Septic shock mortality also increased with age and varied by residence. Further analyses are needed to examine racial disparities and control for comorbidities, severity of illness, and aspects of resuscitation. CONFLICT OF INTEREST DESCRIPTION: The authors report no conflicts of interest, except for Dr. Fernandez, who reports personal payment from Physio-Control, Inc. for speaker fees.
    Type of Medium: Online Resource
    ISSN: 2059-8661
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2898186-8
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  • 10
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2021
    In:  Journal of Clinical and Translational Science Vol. 5, No. s1 ( 2021-03), p. 117-118
    In: Journal of Clinical and Translational Science, Cambridge University Press (CUP), Vol. 5, No. s1 ( 2021-03), p. 117-118
    Abstract: ABSTRACT IMPACT: Identifying racial disparities in septic shock mortality, a common and lethal condition, can inform future research and policy efforts aimed at understanding the drivers these disparities and addressing the underlying factors in order to reduce disparities and improve health. OBJECTIVES/GOALS: Septic shock is a major public health problem with significant mortality. Existing data indicate racial disparities in sepsis incidence, but evidence is limited on differences in septic shock outcomes. Our objective was to determine the association between race and septic shock mortality in a statewide cohort while controlling for clinical factors. METHODS/STUDY POPULATION: This was a retrospective analysis of septic shock patients in the One Florida Data Trust between 2012-18. Data was collected regarding age, sex, race, insurance status, and selected comorbid conditions [liver disease, hypertension, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), end-stage renal disease (ESRD), and human immunodeficiency virus infection (HIV)]. To account for severity of illness, we assigned Sequential Organ Failure Assessment scores for components based on laboratory values (labSOFA), and collected data on mechanical ventilation use and initial lactate. The primary outcome was 90-day mortality. The Least Absolute Shrinkage and Selection Operator (LASSO) method was used for variable selection for the multivariable regression model. RESULTS/ANTICIPATED RESULTS: There were 13,932 septic shock patients with a mean (SD) age of 61(16) years. Of these, 68% identified as white, 28% as black, 2.1% as Hispanic, and 2.0% as other races. 90-day mortality was 32% (n=4,437) and 59% required mechanical ventilation. Significant independent predictors of mortality in the regression model were age (OR 1.04; p 〈 0.01), black race (1.72; p 〈 0.01), lactate (1.10; p 〈 0.01), mechanical ventilation (3.62; p 〈 0.01), labSOFA (1.18; p 〈 0.01), history of liver disease (1.75; p 〈 0.01), hypertension (0.70; p 〈 0.01), COPD (0.87; p 〈 0.01), CHF (1.18; p 〈 0.01), HIV (1.30; p=0.05), and the interaction between age and black race. Black patients had 1.72 times the odds of mortality compared to white patients. For every one-year decrease in age, black patients had a 1% increased odds of mortality (OR 1.01; p 〈 0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Black patients have increased odds of dying from septic shock compared to white patients after controlling for age, selected comorbid conditions, and markers of illness severity. Future work is needed to move beyond demonstrating septic shock disparities and towards understanding the underlying factors.
    Type of Medium: Online Resource
    ISSN: 2059-8661
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2898186-8
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