Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review.

Trientine tetrahydrochloride (TETA-4HCl, Cuvrior) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to D-penicillamine (DPA).

Non-ceruloplasmin copper and urinary copper in clinically stable Wilson disease: Alignment with recommended targets.

Background & Aims: Wilson disease (WD) is caused by accumulation of copper primarily in the liver and brain. During maintenance therapy of WD with D-penicillamine, current guidelines recommend on-treatment ranges of urinary copper excretion (UCE) of 200-500 μg/24 h and serum non-ceruloplasmin-bound copper (NCC) of 50-150 μg/L. We compared NCC (measured by two novel assays) and UCE from patients with clinically stable WD on D-penicillamine therapy with these recommendations.

Plasma Proteome Profiles Associated with Early Development of Lung Injury in Extremely Preterm Infants.

The biological mediators that initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. In this exploratory study, we used sequential window acquisition of all theoretical mass spectra mass spectrometry to identify bronchopulmonary dysplasia (BPD)-specific changes in protein abundance in plasma samples obtained in the first 72 hours of life from extremely preterm infants and bioinformatic analysis to identify BPD-related biological categories and pathways. Last, binary logistic regression analysis was used to test the BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added, with bootstrap resampling used to internally validate protein predictors and adjust for overoptimism.

Predictors of successful neonatal intubation in inexperienced operators: a secondary, non-randomised analysis of the SHINE trial.

Objective: Neonatal endotracheal intubation is a lifesaving but technically difficult procedure, particularly for inexperienced operators. This secondary analysis in a subgroup of inexperienced operators of the Stabilization with nasal High flow during Intubation of NEonates randomised trial aimed to identify the factors associated with successful intubation on the first attempt without physiological stability of the infant.

Methods: In this secondary analysis, demographic factors were compared between infants intubated by inexperienced operators and those intubated by experienced operators.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: statistical analysis plan for the international, multicenter, randomized PLUSS trial.

Background: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.

Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age.

Design, Setting, And Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries.

Maintaining normothermia immediately after birth in preterm infants <34 weeks' gestation: A systematic review and meta-analysis.

Aim: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation.

Methods: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: study protocol for the international, multicenter, randomized PLUSS trial.

Background: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth.

Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial.

Background: Wilson disease is an inherited disorder of copper transport. Whereas penicillamine is used therapeutically to re-establish copper balance, trientine is indicated for patients with penicillamine intolerance. We aimed to compare penicillamine with trientine tetrahydrochloride (TETA4) for maintenance therapy in patients with Wilson disease.

Maintaining normal temperature immediately after birth in late preterm and term infants: A systematic review and meta-analysis.

Aim: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (≥34 weeks' gestation).

Methods: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched.

Nasal High-Flow Therapy during Neonatal Endotracheal Intubation.

Background: Neonatal endotracheal intubation often involves more than one attempt, and oxygen desaturation is common. It is unclear whether nasal high-flow therapy, which extends the time to desaturation during elective intubation in children and adults receiving general anesthesia, can improve the likelihood of successful neonatal intubation on the first attempt.

Methods: We performed a randomized, controlled trial to compare nasal high-flow therapy with standard care (no nasal high-flow therapy or supplemental oxygen) in neonates undergoing oral endotracheal intubation at two Australian tertiary neonatal intensive care units.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain.

Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD).

Design, Setting, And Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.

Effects of tactile stimulation on spontaneous breathing during face mask ventilation.

Objective: We sought to determine the effect of stimulation during positive pressure ventilation (PPV) on the number of spontaneous breaths, exhaled tidal volume (VTe), mask leak and obstruction.

Design: Secondary analysis of a prospective, randomised trial comparing two face masks.

Setting: Single-centre delivery room study.

Comparison of the Pharmacokinetic Profiles of Trientine Tetrahydrochloride and Trientine Dihydrochloride in Healthy Subjects.

Background And Objective: Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt.

Extubation generates lung volume inhomogeneity in preterm infants.

Objective: To evaluate the feasibility of electrical impedance tomography (EIT) to describe the regional tidal ventilation (V) and change in end-expiratory lung volume (EELV) patterns in preterm infants during the process of extubation from invasive to non-invasive respiratory support.

Design: Prospective observational study.

Setting: Single-centre tertiary neonatal intensive care unit.

The addition of fetal scalp blood lactate measurement as an adjunct to cardiotocography to reduce caesarean sections during labour: The Flamingo randomised controlled trial.

Background: Fetal scalp blood sampling for lactate measurement (FBSLM) is sometimes used to assist in identification of the need for expedited birth in the presence of an abnormal cardiotocograph (CTG). However, there is no randomised controlled trial evidence to support this.

Aim: To determine whether adding FBSLM reduces the risk of birth by emergency caesarean section in labours complicated by an abnormal CTG, compared with CTG without FBS.

Lung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants.

Introduction: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants.

Methods: Infants born at <32 weeks were prospectively enrolled at 2 centres.

Physiological responses to facemask application in newborns immediately after birth.

Objective: Application of a face mask may induce apnoea and bradycardia, possibly via the trigeminocardiac reflex (TCR). We aimed to describe rates of apnoea and bradycardia in term and late-preterm infants following facemask application during neonatal stabilisation and compare the effects of first facemask application with subsequent applications.

Design: Subgroup analysis of a prospective, randomised trial comparing two face masks.

Documentation during neonatal resuscitation: a systematic review.

Objective: Accurate documentation in healthcare is necessary for ethical, legal, research and quality improvement purposes. In this review, we aimed to evaluate the accuracy of methods of documentation of delivery room resuscitations.

Methods: A systematic literature search in MEDLINE was conducted to identify original studies that reported the quality of documentation records during newborn resuscitation in the delivery room.

Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities.

Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/T17 polarization. In murine NEC, pro-inflammatory type 3 NKp46RORγtTbet innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46RORγt ILC3 are obliterated.

Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units.

Objective: To assess the procedural and clinical outcomes associated with the introduction of minimally invasive surfactant therapy (MIST) into standard care at 2 tertiary Australian neonatal intensive care units.

Study Design: A prospective audit was designed before the introduction of MIST in 2018, with data collected over a period of 18 months. Procedural data were completed by the clinical team performing MIST, including clinical observations, medication use, and adverse events.

A multicentre, randomised trial of stabilisation with nasal high flow during neonatal endotracheal intubation (the SHINE trial): a study protocol.

Introduction: Neonatal endotracheal intubation is an essential but potentially destabilising procedure. With an increased focus on avoiding mechanical ventilation, particularly in preterm infants, there are fewer opportunities for clinicians to gain proficiency in this important emergency skill. Rates of successful intubation at the first attempt are relatively low, and adverse event rates are high, when compared with intubations in paediatric and adult populations.