The Role of Nitric oxide in the sweep gas for patients receiving Extracorporeal Membrane Oxygenation or Cardiopulmonary Bypass.

Nitric oxide (NO) was proclaimed the 1992 "molecule of the year" by Culotta in Science magazine because of its importance in neuroscience, physiology and immunology. Inhaled NO has been in clinical use for over 35 years to decrease pulmonary hypertension and improve oxygenation. Over the last 20 years there has been much research to understand the role of nitric oxide on cell surface receptors, mitochondria, and intracellular processes which involve calcium and superoxide radicals.

Hemostatic Outcome Definitions in Pediatric Extracorporeal Membrane Oxygenation: Challenges in Cohorts From Rotterdam (2019-2023) and Melbourne (2016-2022).

Objectives: To determine if a priori standardization of outcome hemostatic definitions alone was adequate to enable useful comparison between two cohorts of pediatric extracorporeal membrane oxygenation (ECMO) patients, managed according to local practice and protocol.

Design: Comparison of two separate prospective cohort studies performed at different centers with standardized outcome definitions agreed upon a priori.

Setting: General and cardiac PICUs at the Royal Children's Hospital (RCH) in Melbourne, Australia, and the Sophia Children's Hospital (SCH) in Rotterdam, The Netherlands.

Comprehensive Characterization of Surface-Bound Proteins and Measurement of Fibrin Fiber Thickness on Extracorporeal Membrane Oxygenation Circuits Collected From Patients.

Objective: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children.

Design: Single-center observational prospective study, April to November 2021.

Setting: PICU, Royal Children's Hospital, Melbourne, Australia.

Immunofluorescence Protocol for Characterization of Platelet and Leukocyte Binding in Extracorporeal Membrane Oxygenation (ECMO) Circuits.

The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients.

Clinical Effects of Nitric Oxide Added to the Oxygenator of Children on Extracorporeal Membrane Oxygenation: Pre-Post Cohort Study.

Nitric oxide (NO) can be safely delivered through the sweep gas to the oxygenator of an extracorporeal membrane oxygenation (ECMO) circuit. It has theoretical benefits such as preventing platelet adhesion to surfaces, mitigating inflammatory response and protection against ischemia-reperfusion injury. In this uncontrolled before-after study of children on ECMO, the outcomes of those who received NO were compared with those who did not.

Factors XI and XII in extracorporeal membrane oxygenation: longitudinal profile in children.

Background: Extracorporeal membrane oxygenation (ECMO) is used in children with cardiopulmonary failure. While the majority of ECMO centers use unfractionated heparin, other anticoagulants, including factor XI and factor XII inhibitors are emerging, which may prove suitable for ECMO patients. However, before these anticoagulants can be applied in these patients, baseline data of FXI and FXII changes need to be acquired.

Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial.

The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses.

Safety and feasibility of adjunct autologous cord blood stem cell therapy during the Norwood heart operation.

Background: We conducted this phase I, open-label safety and feasibility trial of autologous cord blood (CB) stem cell (CBSC) therapy via a novel blood cardioplegia-based intracoronary infusion technique during the Norwood procedure in neonates with an antenatal diagnosis of hypoplastic left heart syndrome (HLHS). CBSC therapy may support early cardiac remodeling with enhancement of right ventricle (RV) function during the critical interstage period.

Methods: Clinical grade CB mononucleated cells (CBMNCs) were processed to NetCord-FACT International Standards.

Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation.

Objectives: To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding.

Design: Prospective observational study of pediatric ECMO patients from April 2017 to May 2019.

Setting: The PICU in a large, tertiary referral pediatric ECMO center.

Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial.

Importance: In children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).

Objective: To determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.

The Evolution of Extracorporeal Membrane Oxygenation Circuitry and Impact on Clinical Outcomes in Children: A Systematic Review.

This systematic review summarizes the major developments in extracorporeal membrane oxygenation (ECMO) circuitry in pediatrics over the past 20 years and demonstrates the impacts of those developments on clinical outcomes. This systematic review followed structured Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1987 studies were retrieved, of which 82 were included in the final analysis.

Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation.

Objectives: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO).

Design: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019.

Setting: The PICU in a large tertiary referral pediatric ECMO center.

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial.

Introduction: Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality.

Dismal Outcomes of Second-Run Extracorporeal Life Support in the Paediatric Population.

Background: In 2011 we reported unfavourable outcomes of second-run extracorporeal life support (ECLS) in children. We wanted to investigate whether this previous report affected our strategy and modified our long-term outcomes.

Methods: Between 1988 and 2015, 31 patients underwent a second-run ECLS.

Ventricular assist device support in patients with single ventricles: the Melbourne experience.

Objectives: The capacity and limitations of ventricular assist device (VAD) support in single-ventricle physiology remains poorly understood. We aimed to review our experience in the use of VAD support in the single-ventricle circulation to determine its feasibility in this population.

Methods: We reviewed our experience with VAD support in patients with single ventricles over the past 25 years.

Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial.

Purpose: Cardiopulmonary bypass induces an ischaemia-reperfusion injury and systemic inflammatory response, which contributes to low cardiac output syndrome following cardiac surgery. Exogenous nitric oxide during cardiopulmonary bypass has shown potential to ameliorate such injury. We undertook a large randomised controlled trial to investigate the clinical effects of administering nitric oxide to the cardiopulmonary bypass circuit in children.

Safety of Intracoronary Human Cord Blood Stem Cells in a Lamb Model of Infant Cardiopulmonary Bypass.

Background: One potential approach for advancing univentricular heart surgical palliation outcomes is by stem cell therapy to augment right ventricular function and muscle mass. Whether the stem cell-inclusive cord blood mononuclear cells (CBMNCs) are safe to perfuse into the coronary vasculature during neonatal cardiopulmonary bypass (CPB) is unknown. We evaluated the acute safety, functional effects, and fate of human CBMNCs in a novel model of coronary vasculature delivery in a lamb model of infant CPB.

Anticoagulation strategies and difficulties in neonatal and paediatric extracorporeal membrane oxygenation (ECMO).

Objective: The aim of this review is to highlight an emerging problem with anticoagulation-related complications in neonatal and paediatric ECMO, to explore for flaws in the currently recommended anticoagulation management responsible for these problems and to discuss possible strategies mitigating further escalation of the issue.

Data Sources: Pertinent neonatal and paediatric literature on the topic of interest and international Extracorporeal Life Support Organisation (ELSO) registry data request.

Conclusions: The international ELSO registry data reveals increasing rates of anticoagulation-related complications during neonatal and paediatric ECMO worldwide.

Outcomes after operations for bicuspid aortic valve disease in the pediatric population.

Background: Outcomes after operations for bicuspid aortic valve disease in pediatric patients were determined.

Methods: Between 1977 and 2011, 146 consecutive patients underwent surgical repair of bicuspid aortic valve. Median age at operation was 207 days (range, 5 days to 16 years).

Extracorporeal membrane oxygenation circuitry.

The extracorporeal membrane oxygenation circuit is made of a number of components that have been customized to provide adequate tissue oxygen delivery in patients with severe cardiac and/or respiratory failure for a prolonged period of time (days to weeks). A standard extracorporeal membrane oxygenation circuit consists of a mechanical blood pump, gas-exchange device, and a heat exchanger all connected together with circuit tubing. Extracorporeal membrane oxygenation circuits can vary from simple to complex and may include a variety of blood flow and pressure monitors, continuous oxyhemoglobin saturation monitors, circuit access sites, and a bridge connecting the venous access and arterial infusion limbs of the circuit.

A central role for Ras1 in morphogenesis of the basidiomycete Schizophyllum commune.

Fungi have been used as model systems to define general processes in eukaryotes, for example, the one gene-one enzyme hypothesis, as well as to study polar growth or pathogenesis. Here, we show a central role for the regulator protein Ras in a mushroom-forming, filamentous basidiomycete linking growth, pheromone signaling, sexual development, and meiosis to different signal transduction pathways. ras1 and Ras-specific gap1 mutants were generated and used to modify the intracellular activation state of the Ras module.

Activated clotting time (ACT).

The standard assay for monitoring anticoagulation during extracorporeal life support (ECLS) is the activated clotting time (ACT) test, with celite, kaolin, and glass beads being the most commonly used activators to initiate contact activation. The point-of-care ACT test has been the preferred test in catheterization labs and cardiac theatres because it has a number of advantages over laboratory tests (Spinler et al., Ann Pharmacother 39(7-8):1275-1285, 2005): Shorter time between sampling and results.

Remote ischemic preconditioning in cyanosed neonates undergoing cardiopulmonary bypass: a randomized controlled trial.

Objective: The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group.