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Introduction Lung biopsy is infrequently utilized in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities, or discern those with an extremely poor prognosis. Both might alter the clinical management of a subset of infants diagnosed with BPD. Methods In this tertiary referral center, we drew on a retrospective cohort of 306 preterm infants with severe BPD. Of these, nine underwent lung biopsy between 2012 and 2017. Our aim was to assess the indication of lung biopsy, the prior clinical history, safety of the procedure, and describe the biopsy findings. Finally, we considered management decisions in relation to the biopsy results in these patients. Results The average gestational age and birth weight of the 9 patients were 30±3 (range 27-34) weeks and 1421±571 (range 611-2140) grams. All infants had serial echocardiograms to assess for pulmonary hypertension, genetic testing, and computed tomography angiography (CTA) prior to biopsy. All patients showed moderate to severe alveolar simplification and 8 had some degree of pulmonary interstitial glycogenosis (PIG) ranging from focal to diffuse. Following biopsy, 2 infants with findings of PIG received high dose systemic steroids and 2 separate infants had care redirected. Conclusion In our cohort, lung biopsy was safe and well tolerated. Findings from lung biopsy may aid decision making in selected patients when used as a part of a step-wise diagnostic algorithm.

RATIONALE Aerosolized albuterol is widely used, but its tolerability and efficacy in infants with severe bronchopulmonary dysplasia (sBPD) is not well established. OBJECTIVES To compare the tolerability and efficacy of two dose levels of aerosolized albuterol to saline placebo in infants with sBPD. METHODS Single-center, multiple-crossover trial in 24 ventilated very preterm infants with sBPD. Albuterol (1.25 mg, 2.5 mg) and 3 ml of normal saline were administered every 4 h during separate 24-h treatment periods assigned in random order with a 6-h washout phase between periods. The primary outcome was the absolute change (post and pretherapy) in expiratory flow at 75% of exhalation (EF75). Secondary endpoints were changes in ventilator parameters, vital signs, and heart arrhythmia. RESULTS Average within subject EF75 values improved with each therapy: saline placebo ( + 0.45 L/min ± 2.5, p = .04), 1.25 mg of albuterol ( + 0.70 L/min ± 2.4, p

Rationale Infants with severe bronchopulmonary dysplasia (sBPD) and airway obstruction may develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi ), which impairs patient/ventilator synchrony. Objectives To determine if PEEPi is present in infants with sBPD during spontaneous breathing and if adjusting ventilator PEEP improves patient/ventilator synchrony and comfort. Methods Interventional study in infants with sBPD. PEEPi measured by esophageal pressure (Pes) and pneumotachometer, during pressure-supported breaths. PEEP i defined as the difference between Pes at start of the inspiratory effort minus Pes at onset of inspiratory flow. The set PEEP was adjusted to minimize PEEP i . "Best PEEP" was the setting with minimal wasted efforts (WE), an inspiratory effort seen on the Pes waveform without a corresponding ventilator breath. FiO 2 and SpO 2 measured pre- and post-PEEP adjustment. Sedation requirements evaluated 72 hours preprocedure and postprocedure. Results Twelve infants were assessed (gestational age, 24.9 ± 1.4 weeks; study age, 48.8 ± 1.5 weeks, postmenstrual age). Mean baseline ventilator PEEP was 16.4 cm H2 O (14-20 cm H 2 O). Eight infants required an increase, one, a reduction, and three, no change in the set PEEP. For the eight infants requiring an increase in set PEEP, there was an 18.9% reduction in WE and a reduction in FiO 2 (0.084 ± 0.058) requirements in the subsequent 24 hours. Conditional sedation was reduced in five infants postprocedure. No adverse events occurred during testing. Conclusion PEEPi is measurable in infants with sBPD with concurrent esophageal manometry and flow-time tracings without the need for pharmacological paralysis. In those with PEEP i , increasing ventilator PEEP to offset PEEP i improves synchrony.

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

OBJECTIVES: This study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18–22 months. METHODS: Retrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at

Gastroesophageal reflux may exacerbate lung disease in infants with bronchopulmonary dysplasia (BPD). Anti-reflux surgery may therefore reduce the severity of this disease in some infants. We report a retrospective series of 22 infants with severe BPD who underwent anti-reflux surgery. Our experience indicates that these procedures can be safely performed in this population and that early post-operative initiation of gastric feeds is well tolerated. Modest post-operative reductions in required oxygen and median respiratory rate were observed.

Efficient gene transfer is a critical goal in retroviral transduction. Several peptides capable of forming amyloid fibrils, such as the 39-residue semen-derived infection-enhancing peptide (SEVI), have demonstrated the ability to boost retroviral gene delivery. Here, a 13-residue peptide P13 (Ac-(671) NWFDITNWLWYIK(683)) derived from the membrane-proximal external region of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane protein, together with its 16-residue peptide derivative (P16) were found to enhance HIV-1 infection significantly. Both peptides, P13 and P16, could form amyloid fibril structures to potently enhance HIV-1 infectivity. Further investigations showed that both aromatic Trp residues and cationic Lys residues contributed to the enhancement of HIV-1 infection by these two active peptides. P16 could more effectively augment HIV-1 YU-2 infection than SEVI, implying its potential applications as a tool in the lab to improve gene transfer rates.

Eliciting a broadly neutralizing antibody response against the HIV-1 membrane-proximal external region (MPER) mimicking the activity of 4E10 and 2F5 monoclonal antibodies remains a major challenge. In this study, two novel tetra-branched peptide immunogens, 4E10- and 2F5-MAP4, were designed and synthesized using a MAP system. Guinea pigs were immunized with either of these two synthetic immunogens emulsified in an oil-phase adjuvant at 3-week intervals. After four immunizations, epitope-specific antibody responses were induced successfully, and moderate neutralizing activities against tier 1 (clades B, BC, AE) and tier 2 (clade C) HIV-1 pseudoviruses were detectable in unfractionated sera and purified IgGs. The synthetic gp41 membrane-proximal external region peptide mimetics, 4E10- and 2F5-MAP4, assisted by an appropriate adjuvant, are promising prophylactic vaccine candidates potentially capable of eliciting broadly neutralizing antibody responses against HIV-1. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.