Tracheostomy in the extremely premature neonate - Long term outcomes in a multi-institutional study.

OBJECTIVES: To describe the long-term outcomes related to breathing, feeding, and neurocognitive development in extremely premature infants requiring tracheostomy. STUDY DESIGN: Pooled cross-sectional survey. SETTING: Multi-institutional academic children's hospitals. METHODS: Extremely premature infants who underwent tracheostomy between January 1, 2012, and December 31, 2019, at four academic hospitals were identified from an existing database. Information was gathered from responses to a questionnaire by caregivers regarding airway status, feeding, and neurodevelopment 2-9 years after tracheostomy. RESULTS: Data was available for 89/91 children (96.8%). The mean gestational age was 25.5 weeks (95% CI 25.2-25.7) and mean birth weight was 0.71 kg (95% CI 0.67-0.75). Mean post gestational age at tracheostomy was 22.8 weeks (95% CI 19.0-26.6). At time of the survey, 18 (20.2%) were deceased. 29 (40.8%) maintained a tracheostomy, 18 (25.4%) were on ventilatory support, and 5 (7%) required 24-h supplemental oxygen. Forty-six (64.8%) maintained a gastrostomy tube, 25 (35.2%) had oral dysphagia, and 24 (33.8%) required a modified diet. 51 (71.8%) had developmental delay, 45 (63.4%) were enrolled in school of whom 33 (73.3%) required special education services. CONCLUSIONS: Tracheostomy in extremely premature neonates is associated with long term morbidity in the pulmonary, feeding, and neurocognitive domains. At time of the survey, about half are decannulated, with a majority weaned off ventilatory support indicating improvement in lung function with age. Feeding dysfunction is persistent, and a significant number will have some degree of neurocognitive dysfunction at school age. This information may help caregivers regarding expectations and plans for resource management.

Primary cervical ganglioneuroblastoma, nodular subtype.

Primary cervical ganglioneuroblastoma is rare and reports of its subtypes are limited. This case series describes two pediatric patients with the nodular subtype of primary cervical ganglioneuroblastoma with lymphatic spread. Clinical course, diagnosis, and management of this rare tumor are discussed with emphasis on the importance of including neuroblastic tumors in the differential diagnosis of pediatric neck masses. We also report the use of nerve monitoring of the recurrent laryngeal nerve as a surrogate for the vagus nerve during a pediatric neck dissection.

Exposure to Low (≤10 cGy) Doses of 4He Particles Leads to Increased Social Withdrawal and Loss of Executive Function Performance.

Astronauts on the planned mission to Mars will be exposed to galactic cosmic radiation (GCR), with proton and He particles accounting (in approximately equal amounts) for ∼75% of the equivalent dose. Exposure to ≤15 cGy of space radiation ions with Z ≥ 15 particles has been shown to impair various executive functions, including attentional set shifting and creative problem-solving in rats. Executive functions also regulate social interactions and mood. Should space radiation exposure alter these executive functions as it does cognitive flexibility, there is the possibility of altered interactions among crew members and team cooperativity during prolonged space exploration. This study characterized the effects of ≤10 cGy 400 MeV/n of 4He particles on cognitive flexibility and social interaction (within freely interacting dyads) in male Wistar rats. Exposure to ≥1 cGy 4He ions induced deficits in the SD and/or CD stages of the attentional set shifting (ATSET) task, as reported after exposure to Z ≥ 15 space radiation ions. Should similar effects occur in astronauts, these data suggest that they would have a reduced ability to identify key events in a new situation and would be more easily distracted by extraneous variables. The irradiated rats were also screened for performance in a task for unconstrained cognitive flexibility (UCFlex), often referred to as creative problem-solving. There was a marked dose-dependent change in UCFlex performance with ∼30% of rats exposed to 10 cGy being unable to solve the problem, while the remaining rats took longer than the sham-irradiated animals to resolve the problem. Importantly, performance in the ATSET test was not indicative of UCFlex performance. From a risk assessment perspective, these findings suggest that a value based on a single behavioral end point may not fully represent the cognitive deficits induced by space radiation, even within the cognitive flexibility domain. Rats that received 5 cGy 4He ion irradiation had a significantly lower level of interaction toward their sham-irradiated partners in a non-anxiogenic (uncaged) dyad interactions study. This is consistent with the social withdrawal previously observed in space radiation-exposed male mice in a three-chamber test. 4He-irradiated rats exhibited a significantly higher incidence and duration of self-grooming, which is even more concerning, given that their dyad partners were able to physically interact with the irradiated rats (i.e., touching/climbing over them). This study has established that exposure of male rats to "light" ions such as He affects multiple executive functions resulting in deficits in both sociability and cognitive flexibility, and possibly affective behavior (reward valuation). Further studies are needed to determine if these space radiation-induced co-morbidities are concomitantly induced within individual rats.

Glycine transporter type 1 (GlyT1) inhibition improves conspecific-provoked immobility in BALB/c mice: Analysis of corticosterone response and glucocorticoid gene expression in cortex and hippocampus.

Stress reactivity and glucocorticoid signaling alterations are reported in mouse models of autism spectrum disorder (ASD). BALB/c mice display decreased locomotor activity in the presence of stimulus mice and spend less time exploring enclosed stimulus mice; this mouse strain has been validated as an ASD model. VU0410120, a glycine type 1 transporter (GlyT1) inhibitor, improved sociability in BALB/c mice, consistent with data that NMDA Receptor (NMDAR) activation regulates sociability, and the endogenous tone of NMDAR-mediated neurotransmission is altered in this strain. Effects of a prosocial dose of VU0410120 on conspecific-provoked immobility, and relationships between conspecific-provoked immobility and corticosterone response were explored. VU0410120-treated BALB/c mice showed reduced immobility in the presence of conspecifics and increased the conspecific-provoked corticosterone response. However, the intensity of conspecific-provoked immobility in VU0410120-treated BALB/c mice did not differ as a function of corticosterone response. Expression profiles of 88 glucocorticoid signaling associated genes within frontal cortex and hippocampus were examined. BALB/c mice resistant to prosocial effects of VU0410120 had increased mRNA expression of Ddit4, a negative regulator of mTOR signaling. Dysregulated mTOR signaling activity is a convergent finding in several monogenic syndromic forms of ASD. Prosocial effects of VU0410120 in the BALB/c strain may be related to regulatory influences of NMDAR-activation on mTOR signaling activity. Because corticosterone response is a marker of social stress, the current data suggest that the stressfulness of a social encounter alone may not be the sole determinant of increased immobility in BALB/c mice; this strain may also display an element of social disinterest.