Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Asthma prevalence, lung and cardiovascular function in adolescents born preterm.

Our main objective was to study respiratory evolution and pulmonary and cardiac function in adolescents born preterm in the post-surfactant era. Observational cross-sectional study, comparing very preterm (< 32 weeks) and moderately-late preterm adolescents (≥ 32 weeks) (74 each group). We recorded respiratory symptoms, spirometry and functional echocardiogram. Very preterm adolescents required more respiratory admissions (45.9% vs. 28.4%) (p = 0.03, OR 2.1, CI95% 1.1-4.2) and had more current asthma (21.6% vs. 9.5%, p = 0.04, OR 2.3, CI95% 1.1-5.2). Preterm subjects with intrauterine growth restriction (IUGR) presented lower FEV1 (88.7 ± 13.9 vs. 95.9 ± 13.3, p = 0.027) and lower FVC (88.2 ± 13.6 vs. 95.5 ± 13.3, p = 0.025). When assessing right ventricle, very preterm showed a greater E/E' ratio (p = 0.02) and longer myocardial performance index (MPI) (p = 0.001). Adolescents with IUGR showed less shortening fraction (p = 0.016), worse E/E' ratio (p = 0.029) and longer MPI (p = 0.06). Regarding left ventricle, very preterm showed less E' wave velocity (p = 0.03), greater E/E' ratio (p = 0.005) and longer MPI (p < 0.001). Gestational age < 32 weeks is independently associated with current asthma in adolescence. Children 13-14 years old born very preterm required more respiratory admissions and had poorer diastolic and global function of both ventricles. IUGR is a risk factor for poorer lung function in preterm adolescents, regardless gestational age.

Left ventricular volumes and ejection fraction quantification using an automated three-dimensional adaptive analytic echocardiographic algorithm in pediatric population.

INTRODUCTION: The quantitative measurement of the left ventricle by echocardiography is a fundamental tool in the diagnosis and prognosis of acquired and congenital diseases in the pediatric population. The objective of this study was to validate an automated three-dimensional adaptive analytic echocardiographic algorithm, the so-called Heart Model® (HM) in the pediatric population, using as comparators the left atrial and left ventricular volumes and left ventricular ejection fraction obtained by means of conventional 2D and 3D echocardiography. METHODS: Pilot study, where a population comprised of 75 consecutive patients aged 6-17 years who attended a pediatric cardiology clinic, was evaluated. Every patient underwent a conventional 2D and 3D echocardiography and an analysis using HM. Conventional 3D echo was used as the reference method. RESULTS: Seventy-five patients were analyzed. Mean age was 11.2 (4.0) years (52.2% women). The intraclass correlation coefficient of HM vs 2D echo was poor, but it was good for the agreement between HM and 3D echo for left ventricular end-diastolic volume (ICC: 0.98; 95% CI: 0.97-0.99; P < 0.001), left ventricular end-systolic volume ICC: 0.98; 95% CI: 0.96-0.99; P = 0.001), and left ventricular ejection fraction (ICC: 0.87; 95% CI: 0.78-0.92; P < 0.001). The agreement was also good for the three parameters when the analysis was performed according to body weight. CONCLUSIONS: Heart Model® is a feasible and accurate tool for the evaluation of left atrial and left ventricular volumes and left ventricular ejection fraction in pediatric population aged above 6 years.

Parainfluenza 3 Respiratory Infection Associated with Pericardial Effusion in a Very Low Birthweight Infant.

Parainfluenza 3 virus is a frequent cause of respiratory infections in the pediatric population although it is uncommonly diagnosed in neonates, being usually reported as neonatal intensive care unit microepidemics. We report a case of parainfluenza 3 respiratory infection associated with pericardial effusion in a very low birthweight infant.