Future Directions in Therapies for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is caused by a complex interplay among hyperinflammation, endothelial dysfunction, and alveolar epithelial injury. Targeted treatments toward the underlying pathways have been unsuccessful in unselected patient populations. The first reliable biological subphenotypes reflective of these biological disease states have been identified in the past decade.

Steroids and Immunomodulatory Therapies for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a dysregulated immune response to infection or injury. This framework has driven long-standing interest in immunomodulatory therapies as treatments for ARDS. In this narrative review, we first define what constitutes a dysregulated immune response in ARDS.

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity.

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values.

Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep.

Background: The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preservation by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD.

Extracorporeal carbon dioxide removal in acute hypoxaemic respiratory failure: a systematic review, Bayesian meta-analysis and trial sequential analysis.

Purpose: To assess the safety and efficacy of extracorporeal carbon dioxide removal (ECCOR) standard care in patients with acute hypoxaemic respiratory failure (AHRF).

Methods: MEDLINE, Embase and clinical trial registries were searched from 1994 to 31 December 2021. We included randomised controlled trials (RCTs) and observational studies.

Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study.

COVID-19 is clinically characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

Background: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

Background: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19.

Objective: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients.

Methods: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.

Characterizing preclinical sub-phenotypic models of acute respiratory distress syndrome: An experimental ovine study.

The acute respiratory distress syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub-phenotypes that exist within its broader envelope. These sub-phenotypes have varied outcomes and respond differently to several previously studied interventions.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes.

Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure.

Design, Setting, And Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK.

Prophylactic Postoperative High Flow Nasal Oxygen Versus Conventional Oxygen Therapy in Obese Patients Undergoing Bariatric Surgery (OXYBAR Study): a Pilot Randomised Controlled Trial.

Background: Patients with obesity are predisposed to a reduction in end-expiratory lung volume (EELV) and atelectasis after anaesthesia. High flow nasal oxygen (HFNO) may increase EELV, reducing the likelihood of postoperative pulmonary complications (PPC). We conducted a pilot randomised controlled trial (RCT) of conventional oxygen therapy versus HFNO after bariatric surgery.

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients.

Background: Heterogeneous respiratory system static compliance (C) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level.

Methods: We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe C-calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]-and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide.

Results: We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of C within the first seven days of MV.

Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review.

A plethora of leukocyte modulations have been reported in critically ill patients. Critical illnesses such as acute respiratory distress syndrome and cardiogenic shock, which potentially require extracorporeal membrane oxygenation (ECMO) support, are associated with changes in leukocyte numbers, phenotype, and functions. The changes observed in these illnesses could be compounded by exposure of blood to the non-endothelialized surfaces and non-physiological conditions of ECMO.

Dynamic data-driven meta-analysis for prioritisation of host genes implicated in COVID-19.

The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). We conducted an extensive systematic review of experiments identifying potential host factors.

Heart failure supported by veno-arterial extracorporeal membrane oxygenation (ECMO): a systematic review of pre-clinical models.

Objectives: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to treat patients with refractory severe heart failure. Large animal models are developed to help understand physiology and build translational research projects. In order to better understand those experimental models, we conducted a systematic literature review of animal models combining heart failure and VA-ECMO.

Ex vivo models for research in extracorporeal membrane oxygenation: a systematic review of the literature.

With ongoing progress of components of extracorporeal membrane oxygenation including improvements of oxygenators, pumps, and coating materials, extracorporeal membrane oxygenation became increasingly accepted in the clinical practice. A suitable testing in an adequate setup is essential for the development of new technical aspects. Relevant tests can be conducted in ex vivo models specifically designed to test certain aspects.

Incidence of early intra-cranial bleeding and ischaemia in adult veno-arterial extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation patients: a retrospective analysis of risk factors.

Background: Cerebral complications in veno-arterial extracorporeal membrane oxygenation are known to have a strong impact on mortality and morbidity. Aim of this study is to investigate the early incidence, risk factors and in-hospital mortality of intra-cranial ischaemia and haemorrhage in adults undergoing veno-arterial extracorporeal membrane oxygenation treatment.

Methods: This study is a single-centre retrospective analysis on adult patients undergoing veno-arterial extracorporeal membrane oxygenation for different indications.