Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study.

Background: Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised D-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk.

Methods: This was a phase Ib/IIa open-label multi-centre, randomised controlled trial.

Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units.

Extracellular vesicles in disorders of hemostasis following traumatic brain injury.

Traumatic brain injury (TBI) is a global health priority. In addition to being the leading cause of trauma related death, TBI can result in long-term disability and loss of health. Disorders of haemostasis are common despite the absence of some of the traditional risk factors for coagulopathy following trauma.

Twelve tips for developing and implementing an effective critical care simulation programme.

Simulation training in healthcare settings has become a valuable training tool. It provides an ideal formative assessment for interdisciplinary teaching. It provides a high fidelity and highly immersive environment where healthcare staff and students can practice developing their skills in a safe and controlled manner.

Pressure ulcer risk assessment in the ICU. Is it time for a more objective measure?

Background: The Braden scale, one of the most widely used risk assessment tools is often criticized when used in the Intensive Care Unit. Most patients in the Intensive Care Unit are at risk of pressure ulcer development meaning that the Braden score will usually indicate high risk for these patients. This study set out to determine the correlation between Sub-Epidermal Moisture measurements and Braden scores among Intensive Care Unit patients.

Cell-based Therapies for Acute Respiratory Distress Syndrome: Where Are We Now?

There is considerable interest in the potential for cell-based therapies, particularly mesenchymal stromal cells (MSCs) and their products, as a therapy for acute respiratory distress syndrome (ARDS). MSCs exert effects via diverse mechanisms including reducing excessive inflammation by modulating neutrophil, macrophage and T-cell function, decreasing pulmonary permeability and lung edema, and promoting tissue repair. Clinical studies indicate that MSCs are safe and well tolerated, with promising therapeutic benefits in specific clinical settings, leading to regulatory approvals of MSCs for specific indications in some countries.

Evaluation of severe traumatic brain injury referrals to the National Tertiary Neurosurgical Centre in the Republic of Ireland.

Background: Transfer of all severe TBI patients to a neurosurgical unit (NSU) has been advocated irrespective of levels of complexity and prognostic factors. Previous publications have suggested that only 50% of severe TBI patients in Ireland were managed in NSUs.

Aims: This study aims to audit severe TBI referrals to the National Neurosurgical Centre, to evaluate reasons for nonacceptance, assess for differences in the transferred and not transferred cohorts and to analyse observed and expected mortality rates.

Amplitude Integrated Electroencephalography: Simulated Assessment of Neonatal Seizure Detection in PICU Patients.

Objectives: Amplitude integrated electroencephalography (aEEG) is a mainstay of care in neonatal ICUs; however, knowledge gaps exist in relation to its accuracy for identifying seizures in older children. We aimed to review the diagnostic accuracy of existing neonatal seizure detection criteria for seizure detection in older children in hospital.

Design: Retrospective study.

The impact of brain tissue oxygenation monitoring on the Glasgow Outcome Scale/Glasgow Outcome Scale Extended in patients with moderate to severe traumatic brain injury: A systematic review.

Background: Traumatic brain injuries (TBIs) are one of the leading causes of death or long-term disability around the world. As a result of improvements in supportive care, patients are surviving more severe insults with more pronounced dependency on their families, hospitals, and long-term care facilities. The introduction of brain tissue oxygenation (PbtO2) monitoring aims to recognize episodes of reduced cerebral perfusion with and without associated increased intracranial pressure (ICP).

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).

Tracheostomy insertion in COVID-19: insertion practice and factors leading to unplanned tube exchange.

Background: Tracheostomy insertion in patients with coronavirus disease 2019 (COVID-19) presents unique challenges. Patients frequently have high ventilatory requirements, and as an aerosol generating procedure, tracheostomy insertion creates the potential for staff transmission. Problems with tracheostomies contribute to morbidity and mortality, and tracheostomy changes may increase risks of staff transmission.

Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis in severe COVID-19.

Background: Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined.

Objectives: We investigated EC activation in patients with acute COVID-19, and specifically focused on how proteins stored within Weibel-Palade bodies may impact key aspects of disease pathogenesis.

Pressure ulcers in patients with COVID-19 acute respiratory distress syndrome undergoing prone positioning in the intensive care unit: A pre- and post-intervention study.

Background: Prone positioning has been widely used to improve oxygenation and reduce ventilator-induced lung injury in patients with severe COVID-19 acute respiratory distress syndrome (ARDS). One major complication associated with prone positioning is the development of pressure ulcers (PUs).

Aim: This study aimed to determine the impact of a prevention care bundle on the incidence of PUs in patients with COVID-19 ARDS undergoing prone positioning in the intensive care unit.

The CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial.

Background: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs.

Use of a novel "Split" ventilation system in bench and porcine modeling of acute respiratory distress syndrome.

Split ventilation (using a single ventilator to ventilate multiple patients) is technically feasible. However, connecting two patients with acute respiratory distress syndrome (ARDS) and differing lung mechanics to a single ventilator is concerning. This study aimed to: (1) determine functionality of a split ventilation system in benchtop tests, (2) determine whether standard ventilation would be superior to split ventilation in a porcine model of ARDS and (3) assess usability of a split ventilation system with minimal specific training.

Human endothelial cell-derived exosomal microRNA-99a/b drives a sustained inflammatory response during sepsis by inhibiting mTOR expression.

The pathophysiology of sepsis and its accompanying hyper-inflammatory response are key events that lead to multi-organ failure and death. A growing body of literature now suggests that the vascular endothelium plays a critical role in driving early events of sepsis progression. In this study, we demonstrate how endothelial-derived exosomes contribute to a successive pro-inflammatory phenotype of monocytes.

Biomarkers for the early detection of pressure ulcers in the intensive care setting: A comparison between sub-epidermal moisture measurements and interleukin-1α.

Pressure ulcer (PU) prevention in the intensive care unit (ICU) is an important clinical issue as critically unwell patients are at high risk of developing PUs. However, current methods of PU detection are limited, especially for early detection. This study aimed to establish the correlation between Interleukin-1α (IL-1α)/total protein (TP) and sub-epidermal moisture (SEM) measurements in the early identification of PUs in ICU patients.

Measuring subepidermal moisture to detect early pressure ulcer development: a systematic review.

Objective: The aim was to assess evidence related to the measuring of subepidermal moisture (SEM) to detect early, nonvisible development of pressure ulcers (PUs).

Method: Using systematic review methodology, all quantitative animal and human research studies written in English were considered. In January 2021, PubMed, CINAHL, SCOPUS, Cochrane and EMBASE databases were searched.

Amplitude integrated electroencephalography - Reference values in children aged 2 months to 16 years.

Aim: Amplitude integrated electroencephalography (aEEG) is a bedside neuromonitoring tool, standard within neonatal critical care provision. Its application in children is increasing but normative data underpinning such use are lacking. We present a dataset of normative aEEG values for children aged 2 months to 16 years.

Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction.

Background: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance.

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.