Background Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers.Methods Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Plasma was collected for oxysterol analysis by LC-MS/MS.Results There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury.Conclusions Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers.

Background:While prolonged operative time and increased levels fused have been shown to increase the risk of prolonged intensive care unit (ICU) length-of-stay (LOS), studies are limited in guiding decision-making regarding the need for intensive care postoperatively. This is especially the case among the cohort of adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF); associations between comorbidities and ICU LOS are not well-delineated. Methods:AIS patients who underwent PSF from January 1st, 2016 to December 1st, 2016 at 101 participating centers were identified using the American College of Surgeons (ACS) National Surgical Quality Im-provement Project (NSQIP) Pediatric database. Patients were subsequently grouped by ICU LOS 0-1 day; 2-3 days; and >3 days. Multivariate regression identified predictors of increased ICU LOS. Results:2,346 AIS patients were included. The >3 days and 2-3 days groups had higher asthma rates compared to 0-1 day. The >3 days group had higher rates of structural airway abnormalities and he-matologic disorders. Cognitive impairment rates were highest for >3-day ICU LOS. Hematologic dis-orders, structural airway abnormalities, asthma and cognitive impairment were associated with prolonged ICU LOS. Conclusion:These results help inform targets for optimization of acute short-term postoperative care as well as assisting in risk stratification to improve outcomes and reduce costs for ICU-level care of AIS patients at ACS NSQIP Pediatric program-participating hospitals. Level of Evidence: III.

Prematurity is associated with surgical complications. This study sought to determine the risk of prematurity on 30-day complications, reoperations, and readmissions following ≥7-level PSF for AIS which has not been established. Utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)-Pediatric dataset, all AIS patients undergoing ≥7-level PSF from 2012–2016 were identified. Cases were 1:1 propensity score-matched to controls by age, sex, and number of spinal levels fused. Prematurity sub-classifications were also evaluated: extremely (<28 weeks), very (28–31 weeks), and moderate-to-late (32–36 weeks) premature. Univariate analysis with post hoc Bonferroni compared demographics, hospital parameters, and 30-day outcomes. Multivariate logistic regression identified independent predictors of adverse 30-day outcomes. 5531 patients (term = 5099; moderate-to-late premature = 250; very premature = 101; extremely premature = 81) were included. Premature patients had higher baseline rates of multiple individual comorbidities, longer mean length of stay, and higher 30-day readmissions and infections than the term cohort. Thirty-day readmissions increased with increasing prematurity. Very premature birth predicted UTIs, superficial SSI/wound dehiscence, and any infection, and moderate-to-late premature birth predicted renal insufficiency, deep space infections, and any infection. Prematurity of AIS patients differentially impacted rates of 30-day adverse outcomes following ≥7-level PSF. These results can guide preoperative optimization and postoperative expectations.

Hypoxic-ischemic brain injury (HIBI) leads to depletion of ATP, mitochondrial dysfunction, and enhanced oxidant formation. Measurement of acylcarnitines may provide insight into mitochondrial dysfunction. Plasma acylcarnitine levels are altered in neonates after an HIBI, but individual acylcarnitine levels in the brain have not been evaluated. Additionally, it is unknown if plasma acylcarnitines reflect brain acylcarnitine changes. In this study, postnatal day 9 CD1 mouse pups were randomized to HIBI induced by carotid artery ligation, followed by 30 min at 8% oxygen, or to sham surgery and normoxia, with subgroups for tissue collection at 30 min, 24 h, or 72 h after injury (12 animals/group). Plasma, liver, muscle, and brain (dissected into the cortex, cerebellum, and striatum/thalamus) tissues were collected for acylcarnitine analysis by LC-MS. At 30 min after HIBI, acylcarnitine levels were significantly increased, but the differences resolved by 24 h. Palmitoylcarnitine was increased in the cortex, muscle, and plasma, and stearoylcarnitine in the cortex, striatum/thalamus, and cerebellum. Other acylcarnitines were elevated only in the muscle and plasma. In conclusion, although plasma acylcarnitine results in this study mimic those seen previously in humans, our data suggest that the plasma acylcarnitine profile was more reflective of muscle changes than brain changes. Acylcarnitine metabolism may be a target for therapeutic intervention after neonatal HIBI, though the lack of change after 30 min suggests a limited therapeutic window.

Neonatal encephalopathy (NE) results from impaired cerebral blood flow and oxygen delivery to the brain. The pathophysiology of NE is complex and our understanding of its underlying pathways continues to evolve. There is considerable evidence that cholesterol dysregulation is involved in several adult diseases, including traumatic brain injury, stroke, Huntington’s disease, and Parkinson’s disease. Although the research is less robust in pediatrics, there is emerging evidence that aberrations in cholesterol metabolism may also be involved in the pathophysiology of neonatal NE. This narrative review provides an overview of cholesterol metabolism in the brain along with several examples from the adult literature where pathologic alterations in cholesterol metabolism have been associated with inflammatory and ischemic brain injury. Using those data as a background, the review then discusses the current preclinical data supporting the involvement of cholesterol in the pathogenesis of NE as well as how brain-specific cholesterol metabolites may serve as serum biomarkers for brain injury. Lastly, we review the potential for using the cholesterol metabolic pathways as therapeutic targets. Further investigation of the shifts in cholesterol synthesis and metabolism after hypoxia–ischemia may prove vital in understanding NE pathophysiology as well as providing opportunities for rapid diagnosis and therapeutic interventions. Impact This review summarizes emerging evidence that aberrations in cholesterol metabolism may be involved in the pathophysiology of NE. Using data from NE as well as analogous adult disease states, this article reviews the potential for using cholesterol pathways as targets for developing novel therapeutic interventions and using cholesterol metabolites as biomarkers for injury. When possible, gaps in the current literature were identified to aid in the development of future studies to further investigate the interactions between cholesterol pathways and NE.

OBJECTIVES:Assess trends in inpatient acute gastroenteritis (AGE) management across children's hospitals and identify elements of AGE management associated with resource use. METHODS:We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS:Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS:Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.

This is the first reported case of familial voltage-gated potassium channel (VGKC) autoimmune encephalitis. The symptoms of autoimmune encephalitis can mimic infectious encephalitis with headache, fatigue, and neuropsychiatric symptoms. Autoimmunity is emerging as a distinct cause of encephalitis in the children. Prompt recognition, diagnosis, and treatment are important to prevent brain damage. Two brothers presented two years apart with different symptoms. The explanation for their distinct symptoms lies in the multifactorial development of autoimmunity. The presentation of autoimmune encephalitis can depend on the offending antibodies. The most common are antibodies against the N-methyl-D-aspartic acid (NMDA) receptor and the VGKC complex. Antibodies to the VGKC complex are divided into three different groups depending on their antigenic target: leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), or neither. Anti-VGKC antibodies in children are associated with neuroinflammation and encephalitis. Autoimmunity to LGI1 and CASPR2 antigens is associated with distinct human leukocyte antigen (HLA) alleles. Different HLA isotypes are involved in antigen processing and presentation and can lead to a genetic predisposition to autoimmunity. VGKC autoimmune encephalitis can present with memory changes, psychiatric symptoms, and motor abnormalities. Both brothers presented with these symptoms in their own unique way. Efficient diagnosis and immunosuppression helped improve their outcomes.