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Objective Our objective is to describe the implications, anticipated and perceived, by providers in a level-IV neonatal intensive care unit (NICU) with immediate patient access to inpatient notes and test results in the wake of the 21st Century Cures Act (CCA). Study Design Using a mixed-method approach in February 2021, a preimplementation survey of neonatologists, neonatal fellows, nurse practitioners, and neonatal nurses reported their perspectives on the new 21st CCA and how they anticipated that it would change their practices, and the experience of families in the NICU. In the follow-up to implementation, a postsurvey was completed by staff reporting their experiences in July 2021. Thematic analysis was performed. Results In the preimplementation survey, staff reported the greatest perceived benefits of the changes to be an increase in families' ability to be part of the care team and prepare questions, and faster discussion of results by the care team. Also, staff's highest concerns were that family members may incorrectly interpret results delivered electronically without the context provided by the care team and be overwhelmed by the amount of information available. In the postimplementation survey, staff reported that the Act had less impact on their practice than they had anticipated preimplementation. Conclusion To maximize benefits and limit burdens to families and staff, care teams should consider a thoughtful approach to information sharing with family members in compliance with the 21st CCA. Key Points The impact of the 21 CCA on the NICU has not been studied. NICU staff have significant concerns related to the release of results to families. This study highlights the need to set expectations and provide family-centered care. [ABSTRACT FROM AUTHOR]

Pathogenic variants in HPRT1 lead to deficiency in hypoxanthine‐guanine phosphoribosyltransferase and are responsible for a spectrum of disorders. The severe phenotype is termed Lesch–Nyhan syndrome (LNS) and is inherited in an X‐linked recessive manner. Most individuals with LNS have profound intellectual and physical disabilities throughout life including self‐mutilating behaviors. Here, we present the case of a male infant who was diagnosed with LNS at 3 weeks of age via rapid exome sequencing (ES), which revealed a hemizygous maternally inherited deletion of at least 1.3 Mb of Xq26.3, including exons 2 to 9 of HPRT1. We discuss the critical time points leading to this diagnosis while highlighting his parents' values that guided the decision‐making. Genetic testing provided an early diagnosis for this infant that led to important considerations regarding goals of care in addition to raising new ethical concerns. This highlights the important role that early and rapid diagnostic genetic testing can play in helping families make difficult decisions. Additionally, this case highlights the complexity of discussing rare genetic diagnoses with families and facilitating critical discussions to empower the family toward making an informed decision. [ABSTRACT FROM AUTHOR]

There is a growing appreciation of the role of lung stem/progenitor cells in the development and perpetuation of chronic lung disease including idiopathic pulmonary fibrosis. Human amniotic epithelial cells (hAECs) were previously shown to improve lung architecture in bleomycin-induced lung injury, with the further suggestion that hAECs obtained from term pregnancies possessed superior anti-fibrotic properties compared with their preterm counterparts. In the present study, we aimed to elucidate the differential effects of hAECs from term and preterm pregnancies on lung stem/progenitor cells involved in the repair. Here we showed that term hAECs were better able to activate bronchioalveolar stem cells (BASCs) and type 2 alveolar epithelial cells (AT2s) compared with preterm hAECs following bleomycin challenge. Further, we observed that term hAECs restored TGIF1 and TGFß2 expression levels, while increasing c-MYC expression despite an absence of significant changes to Wnt/ß-catenin signaling. In vitro, term hAECs increased the average size and numbers of BASC and AT2 colonies. The gene expression levels of Wnt ligands were higher in term hAECs, and the expression levels of BMP4, CCND1 and CDC42 were only increased in the BASC and AT2 organoids co-cultured with hAECs from term pregnancies but not preterm pregnancies. In conclusion, term hAECs were more efficient at activating the BASC niche compared with preterm hAECs. The impact of gestational age and/or complications leading to preterm delivery should be considered when applying hAECs and other gestational tissue-derived stem and stem-like cells therapeutically. [ABSTRACT FROM AUTHOR]

Background: Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD. Methods: Lipopolysaccharide was introduced intra-amniotically at day 16 of pregnancy prior to exposure to 65% oxygen (hyperoxia) at birth. hAECs were administered either 12 hours (early) or 4 days (late) after hyperoxia commenced. Collective lung tissues were subjected to histological analysis, multikine ELISA for inflammatory cytokines, FACS for immune cell populations and 3D lung stem cell culture at neonatal stage (postnatal day 7 and 14). Invasive lung function test and echocardiography were applied at 6 and 10 weeks of age. Results: hAECs improved the tissue-to-airspace ratio and septal crest density in a dose-dependent manner, regardless of administration route. Early administration of hAECs, coinciding with the commencement of postnatal hyperoxia, was associated with reduced macrophages, dendritic cells and natural killer cells. This was not the case if hAECs were administered when lung injury was established. Fittingly, early hAEC treatment was more efficacious in reducing interleukin-1β, tumour necrosis factor alpha and monocyte chemoattractant protein-1 levels. Early hAEC treatment was also associated with reduced airway hyper-responsiveness and normalisation of pressure-volume loops. Pulmonary hypertension and right ventricle hypertrophy were also prevented in the early hAEC treatment group, and this persisted until 10 weeks of age. Conclusions: Early hAEC treatment appears to be advantageous over late treatment. There was no difference in efficacy between intravenous and intratracheal administration. The benefits of hAEC administration resulted in long-term improvements in cardiorespiratory function. [ABSTRACT FROM AUTHOR]