Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality.

Background: Lipids play a critical role in defense against sepsis. We sought to investigate gene expression and lipidomic patterns of lipid dysregulation in sepsis.

Methods: Data from four adult sepsis studies were analyzed and findings were investigated in two external datasets.

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

Objectives: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours.

Design: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients.

TRENDS IN CHOLESTEROL AND LIPOPROTEINS ARE ASSOCIATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME INCIDENCE AND DEATH AMONG SEPSIS PATIENTS.

Objective: Compare changes in cholesterol and lipoprotein levels occurring in septic patients with and without acute respiratory distress syndrome (ARDS) and by survivorship. Methods: We reanalyzed data from prospective sepsis studies. Cholesterol and lipoprotein levels were analyzed using univariate testing to detect changes between septic patients with or without ARDS, and among ARDS survivors compared with nonsurvivors at enrollment (first 24 h of sepsis) and 48 to 72 h later.

Racial disparities in septic shock mortality: a retrospective cohort study.

Background: Patients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock.

Methods: Our study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018 We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics.

Expression Predicts Poor Outcomes and Mortality From Sepsis.

Unlabelled: This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

Objectives: Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

DHCR7 Expression Predicts Poor Outcomes and Mortality from Sepsis.

Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 days). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets. Secondary analysis of samples from prospectively enrolled sepsis patients and a zebrafish sepsis model for drug discovery.

Association Between Hypocholesterolemia and Mortality in Critically Ill Patients With Sepsis: A Systematic Review and Meta-Analysis.

Unlabelled: To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis.

Data Sources: Systematic review and meta-analysis of published studies on PubMed and Embase.

Study Selection: All observational studies reporting ICU admission cholesterol and triglyceride levels in critically ill patients with sepsis were included.

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed.

Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19.

A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

Objective: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity.

Design: Prospective cohort study with independent replication cohort.

HDL and persistent inflammation immunosuppression and catabolism syndrome.

Purpose Of Review: This study reviews the mechanisms of HDL cholesterol immunomodulation in the context of the mechanisms of chronic inflammation and immunosuppression causing persistent inflammation, immunosuppression and catabolism syndrome (PICS) and describes potential therapies and gaps in current research.

Recent Findings: Low HDL cholesterol is predictive of acute sepsis severity and outcome. Recent research has indicated apolipoprotein is a prognostic indicator of long-term outcomes.

Lipid and lipoprotein predictors of functional outcomes and long-term mortality after surgical sepsis.

Rationale: Sepsis is a life-threatening, dysregulated response to infection. Lipid biomarkers including cholesterol are dynamically regulated during sepsis and predict short-term outcomes. In this study, we investigated the predictive ability of lipid biomarkers for physical function and long-term mortality after sepsis.

Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.

In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules.

Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial.

Objectives: Cholesterol may be protective in sepsis. Patients with early sepsis may have critically low cholesterol levels that are associated with poor outcomes. The study objective was to test the safety of a fish oil-containing lipid injectable emulsion for stabilizing early cholesterol levels in sepsis.

Time to vasopressor initiation and organ failure progression in early septic shock.

Objective: 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.

Quantitative and Qualitative Assessments of Cholesterol Association With Bacterial Infection Type in Sepsis and Septic Shock.

Background: 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.

LIPid Intensive Drug therapy for Sepsis Pilot (LIPIDS-P): Phase I/II clinical trial protocol of lipid emulsion therapy for stabilising cholesterol levels in sepsis and septic shock.

Introduction: 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.

Admission characteristics predictive of in-hospital death from hospital-acquired sepsis: A comparison to community-acquired sepsis.

Purpose: Healthcare associated (HA) sepsis is associated with increased resource utilization and mortality compared with community acquired (CA) sepsis. The purpose of this study was to identify independent predictors of in-hospital mortality from HA-sepsis.

Materials And Methods: Retrospective study of adult patients admitted with HA or CA-sepsis.

PCSK9 loss-of-function variants and risk of infection and sepsis in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

Background: Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been associated with adverse outcomes in patients hospitalized for sepsis. PCSK9 loss-of-function (LOF) variants area associated with lower low-density lipoprotein cholesterol (LDL-C) levels. Decreased LDL-C is a biomarker of acute and chronic infection and sepsis risk.

Effect of Levocarnitine vs Placebo as an Adjunctive Treatment for Septic Shock: The Rapid Administration of Carnitine in Sepsis (RACE) Randomized Clinical Trial.

Importance: Sepsis induces profound metabolic derangements, while exogenous levocarnitine mitigates metabolic dysfunction by enhancing glucose and lactate oxidation and increasing fatty acid shuttling. Previous trials in sepsis suggest beneficial effects of levocarnitine on patient-centered outcomes.

Objectives: To test the hypothesis that levocarnitine reduces cumulative organ failure in patients with septic shock at 48 hours and, if present, to estimate the probability that the most efficacious dose will decrease 28-day mortality in a pivotal phase 3 clinical trial.

HDL inflammatory index correlates with and predicts severity of organ failure in patients with sepsis and septic shock.

Objective: High density lipoprotein (HDL) is important for defense against sepsis but becomes dysfunctional (Dys-HDL) during inflammation. We hypothesize that Dys-HDL correlates with organ dysfunction (sequential organ failure assessment (SOFA) score) early sepsis.

Methods: A prospective cohort study of adult ED sepsis patients enrolled within 24 hours.

Sequential Organ Failure Assessment Component Score Prediction of In-hospital Mortality From Sepsis.

Objectives: Early organ dysfunction in sepsis confers a high risk of in-hospital mortality, but the relative contribution of specific types of organ failure to overall mortality is unclear. The objective of this study was to assess the predictive ability of individual types of organ failure to in-hospital mortality or prolonged intensive care.

Methods: Retrospective cohort study of adult emergency department patients with sepsis from October 1, 2013, to November 10, 2015.

Development of a Simple Sequential Organ Failure Assessment Score for Risk Assessment of Emergency Department Patients With Sepsis.

Objectives: Sepsis-3 recommends using the quick Sequential Organ Failure Assessment (qSOFA) score followed by SOFA score for sepsis evaluation. The SOFA is complex and unfamiliar to most emergency physicians, while qSOFA is insensitive for sepsis screening and may result in missed cases of sepsis. The objective of this study was to devise an easy-to-use simple SOFA score for use in the emergency department (ED).