Physiologic Determinants of Near-Infrared Spectroscopy-Derived Cerebral and Tissue Oxygen Saturation Measurements in Critically Ill Patients.

Objectives: Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely measured physiologic parameters to tissue oxygen saturation measured by NIRS.

Design: An observational sub-study of patients enrolled in the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomized feasibility trial.

Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

Background: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions.

Methods: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14.

Vascular leak in sepsis: physiological basis and potential therapeutic advances.

Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148).

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes.

Methods: Phase 1 is a multicentre open-label dose-escalation pilot trial.

Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial.

Purpose: Fluid overload is common in critical illness and is associated with mortality. This study investigated the feasibility of a randomised trial comparing conservative fluid administration and deresuscitation (active removal of accumulated fluid using diuretics or ultrafiltration) with usual care in critical illness.

Methods: Open-label, parallel-group, allocation-concealed randomised clinical feasibility trial.

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS.

Recovery, rehabilitation and follow-up services following critical illness: an updated UK national cross-sectional survey and progress report.

Objective: To comprehensively update and survey the current provision of recovery, rehabilitation and follow-up services for adult critical care patients across the UK.

Design: Cross-sectional, self-administered, predominantly closed-question, electronic, online survey.

Setting: Institutions providing adult critical care services identified from national databases.

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial.

Objectives: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below.

Trial Design: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial.

Fluid management and deresuscitation practices: A survey of critical care physicians.

Accumulation of a positive fluid balance is common in critically ill patients, and is associated with adverse outcomes, including mortality. However, there are few randomised clinical trials to guide clinicians as to the most appropriate fluid strategy following initial resuscitation and on the use of deresuscitation (removal of accumulated fluid using diuretics and/or renal replacement therapy). To inform the design of randomised trials, we surveyed critical care physicians with regard to perceptions of fluid overload in critical care, self-reported practice, acceptability of a variety of approaches to deresuscitation, appropriate safety parameters, and overall acceptability of a randomised trial of deresuscitation.

Guidelines on the management of acute respiratory distress syndrome.

The Faculty of Intensive Care Medicine and Intensive Care Society Guideline Development Group have used GRADE methodology to make the following recommendations for the management of adult patients with acute respiratory distress syndrome (ARDS). The British Thoracic Society supports the recommendations in this guideline. Where mechanical ventilation is required, the use of low tidal volumes (<6 ml/kg ideal body weight) and airway pressures (plateau pressure <30 cmHO) was recommended.

Deresuscitation of Patients With Iatrogenic Fluid Overload Is Associated With Reduced Mortality in Critical Illness.

Objectives: To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness.

Design: Retrospective cohort study.

Setting: Ten ICUs in the United Kingdom and Canada.

Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis.

Background: It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients.

Purpose: To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness.

Methods: We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present.

Aspartate-Based CXCR4 Chemokine Receptor Binding of Cross-Bridged Tetraazamacrocyclic Copper(II) and Zinc(II) Complexes.

The CXCR4 chemokine receptor is implicated in a number of diseases including HIV infection and cancer development and metastasis. Previous studies have demonstrated that configurationally restricted bis-tetraazamacrocyclic metal complexes are high-affinity CXCR4 antagonists. Here, we present the synthesis of Cu(2+) and Zn(2+) acetate complexes of six cross-bridged tetraazamacrocycles to mimic their coordination interaction with the aspartate side chains known to bind them to CXCR4.

Mono- and Bis-Alkylation of Glyoxal-Bridged Tetraazamacrocycles Using Mechanochemistry.

Glyoxal-bridged bisaminal tetraazamacrocyclic derivatives of 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) can be N-functionalized to incorporate coordinating groups or for conjugation to biomolecules. Herein, we present an improved N-functionalization methodology using mechanochemistry which reduces reaction times in comparison with conventional synthetic routes. A range of six alkyl halides were reacted with cyclen and cyclam bisaminal derivatives in various ratios to form mono- and bis-functionalized quaternary ammonium salts.

Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis.

Background: Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.

Crystal structure of di-chlorido-(4,11-dimethyl-1,4,8,11-tetra-aza-bicyclo-[6.6.2]hexa-deca-ne)iron(III) hexa-fluorido-phosphate.

The title compound, [FeCl2(C14H30N4)]PF6, contains Fe(3+) coordinated by the four nitro-gen atoms of an ethyl-ene cross-bridged cyclam macrocycle and two cis chloride ligands in a distorted octa-hedral environment. In contrast to other similar compounds this is a monomer. Inter-molecular C-H⋯Cl inter-actions exist in the structure between the complex ions.