How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin.

Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015.

Role of albumin, starches and gelatins versus crystalloids in volume resuscitation of critically ill patients.

Purpose Of Review: The review focuses on fluid resuscitation of critically ill patients with either colloid or crystalloid solutions.

Recent Findings: In healthy patients, the volume expanding effect of colloids is greater than that of crystalloids. However, in critically ill patients, a similar amount of crystalloids and colloids is required for fluid resuscitation, suggesting a lower efficiency of colloids when capillary permeability is increased, and endothelial glycocalyx disrupted.

Real-time urinary electrolyte monitoring after furosemide administration in surgical ICU patients with normal renal function.

Background: Although the loop-diuretic furosemide is widely employed in critically ill patients with known long-term effects on plasma electrolytes, accurate data describing its acute effects on renal electrolyte handling and the generation of plasma electrolyte alterations are lacking. We hypothesized that the long-term effects of furosemide on plasma electrolytes and acid-base depend on its immediate effects on electrolyte excretion rate and patient clinical baseline characteristics. By monitoring urinary electrolytes quasi-continuously, we aimed to verify this hypothesis in a cohort of surgical ICU patients with normal renal function.

"Awake" extracorporeal membrane oxygenation (ECMO): pathophysiology, technical considerations, and clinical pioneering.

Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.

Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives.

Purpose: Esophageal pressure (Pes) is a minimally invasive advanced respiratory monitoring method with the potential to guide management of ventilation support and enhance specific diagnoses in acute respiratory failure patients. To date, the use of Pes in the clinical setting is limited, and it is often seen as a research tool only.

Methods: This is a review of the relevant technical, physiological and clinical details that support the clinical utility of Pes.

Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies.

Long-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T-cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical-grade tumor-redirected TSCM starting from naive precursors.

Skeletal muscle lactate overproduction during metformin intoxication: An animal study with reverse microdialysis.

Lactic acidosis during metformin intoxication is classically mainly attributed to diminished lactate clearance through liver gluconeogenesis. Here we studied 6 healthy, sedated and mechanically ventilated pigs to clarify whether high dose of metformin also increases skeletal muscle lactate production. Each animal had two microdialysis catheters inserted in gluteus muscles, one per side.

Ultra-protective ventilation and hypoxemia.

Partial extracorporeal CO2 removal allows a decreasing tidal volume without respiratory acidosis in patients with acute respiratory distress syndrome. This, however, may be associated with worsening hypoxemia, due to several mechanisms, such as gravitational and reabsorption atelectasis, due to a decrease in mean airway pressure and a critically low ventilation-perfusion ratio, respectively. In addition, an imbalance between alveolar and artificial lung partial pressures of nitrogen may accelerate the process.

BACH2 regulates CD8(+) T cell differentiation by controlling access of AP-1 factors to enhancers.

T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that the TF BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection.

Deterioration of Lung Function in a Pig Model of Uncontrolled Cardiac Death.

Introduction: Uncontrolled donors after circulatory determination of death (uDCDD) represent a yet unexplored pool of organs potentially available for transplantation. The aims of this study were to validate a protocol of cardiac death in the pig and to investigate lung function during the process.

Materials And Methods: Cardiac death was induced in preanesthetized animals with an injection of 600 mg propofol; once systolic blood pressure was <50 mm Hg (Agonal Phase), a 20 mEq bolus of KCl was given and, after asystolia was documented, cardiopulmonary resuscitation (CPR) started, followed by 5 minutes no touch (end-CPR).

Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema.

Objective: Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis.

How ARDS should be treated.

The Berlin definition criteria applied at positive end-expiratory pressure (PEEP) 5 cm H2O reasonably predict lung edema and recruitabilty. To maintain viable gas exchange, the mechanical ventilation becomes progressively more risky going from mild to severe acute respiratory distress syndrome (ARDS). Tidal volume, driving pressure, flow, and respiratory rate have been identified as causes of ventilation-induced lung injury.

Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure.

Substantial attention and resources have been directed to improving outcomes of patients with critical illnesses, in particular sepsis, but all recent clinical trials testing various interventions or strategies have failed to detect a robust benefit on mortality. Acute heart failure is also a critical illness, and although the underlying etiologies differ, acute heart failure and sepsis are critical care illnesses that have a high mortality in which clinical trials have been difficult to conduct and have not yielded effective treatments. Both conditions represent a syndrome that is often difficult to define with a wide variation in patient characteristics, presentation, and standard management across institutions.

Imaging in acute respiratory distress syndrome.

Purpose: Imaging has become increasingly important across medical specialties for diagnostic, monitoring, and investigative purposes in acute respiratory distress syndrome (ARDS).

Methods: This review addresses the use of imaging techniques for the diagnosis and management of ARDS as well as gaining knowledge about its pathogenesis and pathophysiology. The techniques described in this article are computed tomography, positron emission tomography, and two easily accessible imaging techniques available at the bedside-ultrasound and electrical impedance tomography (EIT).

Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts.

Despite expensive life-sustaining interventions delivered in the ICU, mortality and morbidity in patients with acute respiratory failure (ARF) remain unacceptably high. Extracorporeal membrane oxygenation (ECMO) has emerged as a promising intervention that may provide more efficacious supportive care to these patients. Improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARF.

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries.

Importance: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS).

Objectives: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition.

Design, Setting, And Participants: The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents.

Mechanical Power and Development of Ventilator-induced Lung Injury.

Background: The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung.

Methods: Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate.

Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach.

Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort.