Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock.

A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial.

Background: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients.

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate.

Objectives: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes.

Factors influencing decisions by critical care physicians to withdraw life-sustaining treatments in critically ill adult patients with severe traumatic brain injury.

Background: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population.

Methods: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada.

Prognostic Value of Glial Fibrillary Acidic Protein in Patients With Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Objectives: Biomarkers have been suggested as potential prognostic predictors following a moderate or severe traumatic brain injury but their prognostic accuracy is still uncertain. The objective of this systematic review is to assess the ability of the glial fibrillary acidic protein to predict prognosis in patients with moderate or severe traumatic brain injury.

Data Sources: MEDLINE, Embase, CENTRAL, and BIOSIS electronic databases and conference abstracts, bibliographies of selected studies, and narrative reviews were searched.

Effect of age of transfused red blood cells on neurologic outcome following traumatic brain injury (ABLE-tbi Study): a nested study of the Age of Blood Evaluation (ABLE) trial.

Background: Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells.

Effects of Mesenchymal Stem Cell Treatment on Systemic Cytokine Levels in a Phase 1 Dose Escalation Safety Trial of Septic Shock Patients.

Objectives: Cellular Immunotherapy for Septic Shock is the first-in-human clinical trial evaluating allogeneic mesenchymal stem/stromal cells in septic shock patients. Here, we sought to determine whether plasma cytokine profiles may provide further information into the safety and biological effects of mesenchymal stem/stromal cell treatment, as no previous study has conducted a comprehensive analysis of circulating cytokine levels in critically ill patients treated with mesenchymal stem/stromal cells.

Design: Phase 1 dose-escalation trial.

Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial.

Rationale: In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death.

Objectives: To conduct a phase I dose escalation trial of MSCs in septic shock with the primary objective of examining the safety and tolerability of MSCs.

Methods: We enrolled nine participants within 24 hours of admission to the ICU.

High circulating angiopoietin-2 levels exacerbate pulmonary inflammation but not vascular leak or mortality in endotoxin-induced lung injury in mice.

Background: Elevated plasma levels of angiopoietin-2 (ANGPT2) have been reported in patients with acute lung injury (ALI); however, it remains unclear whether this increase contributes to, or just marks, the underlying vasculopathic inflammation and leak associated with ALI. Here we investigated the biological consequences of inducing high circulating levels of ANGPT2 in a mouse model of endotoxin-induced ALI.

Methods: Transgenic mice (ANGPT2) with elevated circulating levels of ANGPT2, achieved through conditional hepatocyte-specific overexpression, were examined from 3 to 72 hours following lipopolysaccharide (LPS)-induced ALI.

Lack of elevation in plasma levels of pro-inflammatory cytokines in common rodent models of pulmonary arterial hypertension: questions of construct validity for human patients.

Translational research depends on the relevance of animal models and how well they replicate human disease. Here, we investigated plasma levels of three important pro-inflammatory cytokines (TNFα, IL-6, and MCP-1), known to be elevated in human pulmonary arterial hypertension (PAH), and systematically assessed their levels in PAH patients compared to five different rodent models of pulmonary hypertension (PH). A consistent immunoassay platform (Luminex xMAP) and source (Millipore) was used to measure all specimens.

Prognostication in critically ill patients with severe traumatic brain injury: the TBI-Prognosis multicentre feasibility study.

Objective: Severe traumatic brain injury is a significant cause of morbidity and mortality in young adults. Assessing long-term neurological outcome after such injury is difficult and often characterised by uncertainty. The objective of this feasibility study was to establish the feasibility of conducting a large, multicentre prospective study to develop a prognostic model of long-term neurological outcome in critically ill patients with severe traumatic brain injury.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012".

Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference).

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012."

Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference).

Predictive value of neuron-specific enolase for prognosis in patients with moderate or severe traumatic brain injury: a systematic review and meta-analysis.

Background: Prognosis is difficult to establish early after moderate or severe traumatic brain injury despite representing an important concern for patients, families and medical teams. Biomarkers, such as neuron-specific enolase, have been proposed as potential early prognostic indicators. Our objective was to determine the association between neuron-specific enolase and clinical outcomes, and the prognostic value of neuron-specific enolase after a moderate or severe traumatic brain injury.

Resuscitation Prior to Emergency Endotracheal Intubation: Results of a National Survey.

Introduction: Respiratory failure is a common problem in emergency medicine (EM) and critical care medicine (CCM). However, little is known about the resuscitation of critically ill patients prior to emergency endotracheal intubation (EETI). Our aim was to describe the resuscitation practices of EM and CCM physicians prior to EETI.

Device and Medication Preferences of Canadian Physicians for Emergent Endotracheal Intubation in Critically Ill Patients.

Objectives: Various medications and devices are available for facilitation of emergent endotracheal intubations (EETIs). The objective of this study was to survey which medications and devices are being utilized for intubation by Canadian physicians.

Methods: A clinical scenario-based survey was developed to determine which medications physicians would administer to facilitate EETI, their first choice of intubation device, and backup strategy should their first choice fail.

Association of Blood Donor Age and Sex With Recipient Survival After Red Blood Cell Transfusion.

Importance: While red blood cells (RBCs) are administered to improve oxygen delivery and patient outcomes, they also have been associated with potential harm. Unlike solid organ transplantation, the clinical consequences of donor characteristics on recipients have not been evaluated in transfusion medicine.

Objective: To analyze the association of RBC donor age and sex with the survival of transfusion recipients.

Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review.

The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome.

Postintubation hypotension in intensive care unit patients: A multicenter cohort study.

Purpose: To determine the incidence of postintubation hypotension (PIH) and associated outcomes in critically ill patients requiring endotracheal intubation.

Materials And Methods: Medical records were reviewed for 479 consecutive critically ill adult patients who required intubation by an intensive care unit (ICU) service at 1 of 4 academic tertiary care hospitals. The primary outcome measure was the incidence of PIH.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease.

Background: Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings.

Emergency department management of early sepsis: a national survey of emergency medicine and intensive care consultants.

Objectives: Early goal-directed therapy (EGDT) is recommended for sepsis management in current guidelines, but the underpinning evidence is controversial. Clinician beliefs and the capacity to implement all recommended elements of EGDT in emergency departments (EDs) are uncertain. Our study aimed to explore self-reported management of early sepsis by Scottish emergency medicine (EM) and intensive care medicine (ICM) consultants, delineate important differences and determine the guideline recommendations rated most important and deliverable within the ED.

Inappropriate medication administration practices in Canadian adult ICUs: a multicenter, cross-sectional observational study.

Background: Critically ill patients often receive multiple medications via continuous intravenous infusion. Coadministration of multiple medications through the same port of a venous access device often is necessary but requires an assessment of compatibility.

Objective: To describe the frequency of inappropriate coadministration of continuously infused medications via a Y-site and the use of intravenous catheters in patients in Canadian intensive care units (ICUs) in a multicenter, cross-sectional observational study.

Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis.

Objectives: To determine the ability and accuracy of the S-100β protein in predicting prognosis after a moderate or severe traumatic brain injury.

Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data Sources: Medline, Embase, Cochrane Central Register of Controlled Trials, BIOSIS (from their inception to April 2012), conference abstracts, bibliographies of eligible articles, and relevant narrative reviews.

Determination of neurologic prognosis and clinical decision making in adult patients with severe traumatic brain injury: a survey of Canadian intensivists, neurosurgeons, and neurologists.

Objectives: Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care.

Design, Setting, And Participants: We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers.