Posterior Reversible Encephalopathy Syndrome: Incidence and Clinical Characteristics in Children With Cancer.

The etiology and outcomes of posterior reversible encephalopathy syndrome (PRES) in children with cancer are not well understood. We aim to determine the incidence of PRES, describe associated morbidity and mortality, and better understand risk factors in this patient population. A total of 473 children with a hematologic malignancy or postallogeneic hematopoietic cell transplantation between June 2015 and June 2020 were screened for PRES to determine incidence and whether age or underlying diagnosis are associated with development of PRES. We conducted a case-control study to evaluate whether comorbidities or chemotherapeutic agents are associated with PRES. Children with PRES were matched with 2 controls based on age and underlying diagnosis to identify additional risk factors. Fourteen patients developed PRES, with an incidence of 5.9/1000 people/year. Those diagnosed with PRES had commonly described PRES symptoms: hypertension, seizures, nausea/vomiting, altered mental status, and headaches. All patients received an magnetic resonance imaging, and most had findings consistent with PRES. Hematopoietic cell transplantation was associated with the development of PRES. The use of Etoposide was associated with PRES but comorbidities, steroids and calcineurin inhibitors were not. While PRES was infrequent in this population, it is associated with high morbidity and mortality, with ICU admissions and an overall hospital mortality, because of secondary causes, of 29%.

A randomized comparison of the laryngeal mask airway supreme™ and laryngeal mask airway unique™ in infants and children: does cuff pressure influence leak pressure?

BACKGROUND: The cuff pressure for optimal airway sealing with first-generation laryngeal mask airway has been shown to be 40 cm H(2)O in children. Currently, there are no data regarding the ideal intracuff pressure for the laryngeal mask airway Supreme (Supreme) in children. OBJECTIVES: To compare the clinical performance of the laryngeal mask airway supreme with the laryngeal mask airway unique in infants and children. MATERIALS AND METHODS: One hundred eighty children were assigned to receive either a Supreme or a laryngeal mask airway-U. We hypothesized higher airway leak pressure with the Supreme at both 40 cm H(2)O and 60 cm H(2)O, when compared with the laryngeal mask airway-U. Ease and time of insertion, insertion attempts, fiber optic examination, quality of airway, efficacy of mechanical ventilation, success of gastric tube placement (Supreme), incidence of gastric insufflation, and complications were also assessed. RESULTS: Airway leak pressure at an intracuff pressure of 60 cm H(2)O for the Supreme was 17.4 (5.2) vs laryngeal mask airway-U at 18.4 (6.6) cm H(2)O and did not differ when compared to an intracuff pressure of 40 cm H(2)O for both devices; Supreme at 17.2 (5) vs laryngeal mask airway-U at 17.7 (6) cm H(2)O. The laryngeal mask airway-U was associated with higher first-attempt success rates. The Supreme was associated with less gastric insufflation than the laryngeal mask airway-U. CONCLUSIONS: Intracuff pressures of 40 cm H(2)O may be sufficient for the Supreme in children, and there may be no added benefit of an intracuff pressure of 60 cm H(2)O, as leak pressures were similar. The Supreme may be preferred over the laryngeal mask airway-U for its lower rates of gastric insufflation and provision for gastric access when mechanical ventilation is utilized.

A randomized equivalence trial comparing the i-gel and laryngeal mask airway Supreme in children.

BACKGROUND: The laryngeal mask airway Supreme (Supreme) is a new single-use supraglottic device with gastric access capability now available in all sizes for children. OBJECTIVES: To compare the i-gel with the Supreme in children for routine airway maintenance. MATERIALS/METHODS: One hundred and seventy children, aged 3 months to 11 years, 5-50 kg in weight, were randomly assigned to receive either the i-gel or the Supreme. The primary outcome measured was airway leak pressure. Secondary outcomes included the following: ease and time for insertion, insertion success rate, fiberoptic grade of view, ease of gastric tube placement, number of airway manipulations, quality of airway during anesthetic maintenance, and complications. RESULTS: A total of 168 patients were assessed for the outcomes. The median (IQR [range]) airway leak pressure for the i-gel was higher than with the Supreme, 20 (18-25 [9-40]) cm H(2)O vs 17 (14-22 [10-40]) cm H(2)O, respectively (P = 0.001). There were no differences in the time for device insertion, fiberoptic grade of view, quality of airway, and complications. Median (IQR[range]) time of successful insertion of a gastric tube was faster with the Supreme, 12 (9.2-14.3 [5.2-44.2]) s than with the i-gel, 14 (11.9-19 [6.9-75]) s; P = 0.01. The number of airway manipulations during placement was higher with the i-gel than with the laryngeal mask airway Supreme (12 vs 13 patients), P = 0.02. CONCLUSIONS: In infants and children, when a single-use supraglottic device with gastric access capabilities is required, the i-gel demonstrated higher airway leak pressures and can be a useful alternative to the Supreme.

Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets.

Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report that overexpression of sirtuin 1 (Sirt1), a mediator of the beneficial metabolic effects of calorie restriction, protects neurons against mutant HTT toxicity, whereas reduction of Sirt1 exacerbates mutant HTT toxicity. Overexpression of Sirt1 improves motor function, reduces brain atrophy and attenuates mutant-HTT-mediated metabolic abnormalities in Huntington's disease mice. Further mechanistic studies suggested that Sirt1 prevents the mutant-HTT-induced decline in brain-derived neurotrophic factor (BDNF) concentrations and the signaling of its receptor, TrkB, and restores dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) concentrations in the striatum. Sirt1 deacetylase activity is required for Sirt1-mediated neuroprotection in Huntington's disease cell models. Notably, we show that mutant HTT interacts with Sirt1 and inhibits Sirt1 deacetylase activity, which results in hyperacetylation of Sirt1 substrates such as forkhead box O3A (Foxo3a), thereby inhibiting its pro-survival function. Overexpression of Sirt1 counteracts the mutant-HTT-induced deacetylase deficit, enhances the deacetylation of Foxo3a and facilitates cell survival. These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease.

Baicalein reduces E46K alpha-synuclein aggregation in vitro and protects cells against E46K alpha-synuclein toxicity in cell models of familiar Parkinsonism.

The E46K is a point mutation in alpha-synuclein (alpha-syn) that causes familial Parkinsonism with Lewy body dementia. We have now generated a cell model of Parkinsonism/Parkinson's disease (PD) and demonstrated cell toxicity after expression of E46K in the differentiated PC12 cells. E46K alpha-syn inhibited proteasome activity and induced mitochondrial depolarization in the cell model. Baicalein has been reported to inhibit fibrillation of wild type alpha-syn in vitro, and to protect neurons against several chemical-induced models of PD. We now report that baicalein significantly attenuated E46K-induced mitochondrial depolarization and proteasome inhibition, and protected cells against E46K-induced toxicity in a cell model of PD. Baicalein also reduced E46K fibrilization in vitro, with a concentration-dependent decrease in beta sheet conformation, though it increased some oligomeric species, and decreased formation of E46K alpha-syn-induced aggregates and rescued toxicity in N2A cells. Taken together, these data indicate that mitochondrial dysfunction, proteasome inhibition and specific aspects of abnormal E46K aggregation accompany E46K alpha-syn-induced cell toxicity, and baicalein can protect as well as altering aggregation properties. Baicalein has potential as a tool to understand the relation between different aggregation species and toxicity, and might be a candidate compound for further validation by using in vivo alpha-syn genetic PD models.