Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Complication accrual impacts pediatric extracorporeal life support mortality.

INTRODUCTION: This study tested the hypothesis that complication accrual during pediatric extracorporeal life support (ECLS) increases mortality irrespective of indication for support. METHODS: Prospectively collected Extracorporeal Life Support Organization (ELSO) registry data for all neonatal and pediatric patients cannulated for ECLS at our institution from 1/1/2015 to 12/31/2020 was stratified based on the presence or absence of complications. We excluded renal replacement therapy from complications, as this is frequently and empirically applied within our practice. RESULTS: Of 114 patients, overall survival to discharge was 66%. 62 patients (54%) had 149 total complications: 29% were mechanical (circuit related), and the rest were patient related. Age (neonatal versus pediatric), sex, race/ethnicity, support type, presence of pre-ECLS arrest, pre-ECLS pH and intubation-to-ECLS duration were not significantly associated with the development of complications. Patients with complications required longer ECLS duration (168 versus 86 median hours, p < 0.001) and were more likely to be decannulated due to death or poor prognosis (25% versus 8%, p = 0.022). One or more ECLS complications was associated with significantly decreased survival by Cox proportional hazard regression (p = 0.003). CONCLUSION: Complications on ECLS are associated with longer support duration and predict decreased survival independent of pre-ECLS variables, suggesting a multidisciplinary ECLS team target for improved outcomes.

Emanuel syndrome and congenital diaphragmatic hernia: A systematic review.

BACKGROUND: Emanuel Syndrome (ES), a rare chromosomal disorder caused by a supernumerary chromosome 22 derivative (der(22)t(11;22)), was identified in a fetus with congenital diaphragmatic hernia (CDH) at our fetal center. We aimed to identify a precedent for clinical care and patient outcomes to guide family decision-making. METHODS: This non-funded and non-registered study queried the entire CDH Registry (CDHR) including >10,000 patients since 1995 and conducted a systematic literature review for patients with concomitant ES and CDH. RESULTS: Literature review captured 12 citations and identified 9 patients with CDH+ES from over 400 known ES cases. Given the rarity of the disease and to reduce bias, there were no exclusion criteria aside from non-English language. Of these 9, two underwent surgical CDH repair with neither surviving. The CDHR identified 6 patients with ES, all reported after 2013 and prenatally diagnosed. Median estimated gestational age was 39 weeks (range 37-40) and median birth weight was 2.72 kg (range 2.4-3.4 kg). 3 patients died within the first few postnatal days; surgical repair was not offered due to "anomalies" and "pulmonary hypertension" in two and one family chose comfort measures. The other 3 patients underwent surgical repair, and 2 were supported with ECMO. Two patients survived to discharge, incurring surgical comorbidities associated with severe CDH including gastrostomy dependence, tracheostomy, and CDH recurrence. CONCLUSIONS: ES patients with CDH have potential to tolerate repair and survive to discharge, however with significant additional morbidity combined with severe challenges inherent to ES. This represents the largest series of patients with CDH and ES to date. LEVEL OF EVIDENCE: IV (Case series with no comparison group).

NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats.

Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately after endotoxin-sensitized HI (LPS-HI). We hypothesized that LPS-HI would acutely deplete reduced glutathione (GSH), indicating overwhelming oxidative stress in spite of hypothermia treatment in neonatal rats. Post-natal day 7 rats were randomized to sham ligation, or severe LPS-HI (0.5 mg/kg 4 h before right carotid artery ligation, 90 min 8% O2), followed by hypothermia alone or with N-acetylcysteine (25 mg/kg) and vitamin D (1,25(OH)2D3, 0.05 µg/kg) (NVD). We quantified in vivo CNS metabolites by serial 7T MR Spectroscopy before, immediately after LPS-HI, and after treatment, along with terminal plasma drug concentrations. GSH was significantly decreased in all LPS-HI rats compared with baseline and sham controls. Two hours of hypothermia alone did not improve GSH and allowed glutamate + glutamine (GLX) to increase. Within 1 h of administration, NVD increased GSH close to baseline and suppressed GLX. The combination of NVD with hypothermia rapidly improved cellular redox status after LPS-HI, potentially inhibiting important secondary injury cascades and allowing more time for hypothermic neuroprotection.

Barriers and facilitators to all-terrain vehicle helmet use.

BACKGROUND: The burden of all-terrain vehicle (ATV)-related injuries and deaths in the pediatric population has increased dramatically during the past decade. Brain injuries represent a large proportion of these injuries and are the leading cause of death among those injured. Despite the risk involved in operating these vehicles, helmet use remains low. The aim of this study was to identify and understand common barriers and facilitators to helmet use among ATV users. METHODS: Focus groups were conducted in Arkansas with adolescent and adult ATV users to discuss ATV and safety equipment use. Standard methods of qualitative research were used to interpret focus group data. Moderator guides were framed using the Health Belief Model of behavior change. Transcript-based analysis was used, and data were managed using HyperRESEARCH (version 2.8.3). The transcribed data were coded to identify important themes. RESULTS: Eleven focus groups were conducted with 58 participants, who discussed ATV use patterns, current safety practices, and barriers to helmet use. Major themes were a lack of perceived risk with operating an ATV and lack of perceived severity of injury resulting from ATV crashes. Participants discussed other barriers to helmet use including helmet discomfort and inconvenience. Suggested solutions included passage of helmet laws for riders younger than 18 years, helmet redesign, and development of visual aids/crash simulations to convey the dangers of ATV use. CONCLUSION: This study identifies a gap in risk perception among ATV users. Injury prevention should focus on education about risks of engaging in unsafe ATV behaviors and the danger of the vehicles themselves.

Transcranial red and near infrared light transmission in a cadaveric model.

BACKGROUND AND OBJECTIVE: Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. STUDY DESIGN/MATERIALS AND METHODS: To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. RESULTS: Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. CONCLUSION: These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue.