Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

Cross-sectional study of a UK cohort of neonatal vein of Galen malformation

Objective: Describe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation (VGM) identified before 28 days of life. // Methods: Neonates with angiographically confirmed vein of Galen malformation presenting to one of the two UK treatment centres (2006‐2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomised into “good” and “poor” categories. Cross‐sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors. // Results: Of 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty‐four participated in neurocognitive assessment. Outcomes were approximately evenly split between “good” and “poor” categories across all domains, namely neurological status, general cognition, neuromotor skills, adaptive behaviour, and emotional and behavioural development. Important predictors of poor cognitive outcome were initial Bicetre score </=12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariable analysis only Bicetre score </=12 remained significant. // Interpretation: Despite modern supportive and endovascular treatment, over a third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous, as well as arterial, circulation are important in pathophysiology of brain injury

Detailed statistical analysis plan for the SafeBoosC III trial : a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants

Background: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. Methods/design: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (&lt; 26 weeks) compared to higher gestational age ( 65 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. Discussion: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. Trial registration: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018

Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants : a protocol for the SafeBoosC randomised clinical phase III trial

Background: Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants. Methods/design: SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using 'opt-out' or deferred consent). Exclusion criteria will be no parental informed consent (or if 'opt-out' is used, lack of a record that clinical staff have explained the trial and the 'opt-out' consent process to parents and/or a record of the parents' decision to opt-out in the infant's clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants. Discussion: Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates. Trial registration: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018

Photoinduced Degradation of Polymer Films Using Polyglyoxylate-Polyester Blends and Copolymers

© 2018 American Chemical Society. Polymeric coatings are commonly employed to alter surface properties. While some coatings are designed to remain stable over a prolonged period, in applications such as pharmaceuticals or fertilizers, the coating is designed to erode and reveal or release the underlying material. Self-immolative polymers (SIPs) undergo depolymerization following the cleavage of stimuli-responsive end-caps from their termini, enabling controlled depolymerization in the solid state and in solution. Poly(ethyl glyoxylate) (PEtG) is a promising SIP because of its depolymerization to benign products, but its amorphous structure and low glass-transition temperature make it unsuitable alone for coating applications. This study explored the blending of PEtG with polyesters including polycaprolactone (PCL), poly(l-lactic acid), and poly(R-3-hydroxybutyrate). Block copolymers of PEtG with PCL were also synthesized and studied. It was found that the phase separation behavior and consequently the thermal and mechanical properties of the materials could be tuned according to the composition of the blend, while the stimuli-responsive degradation of PEtG was retained in the blends. This work therefore provides a framework for the application of PEtG-based coatings in applications ranging from pharmaceuticals to agricultural products