Perianesthetic neurological adverse events in children: A review of the Wake-Up Safe Database.

BACKGROUND: Perianesthetic neurological adverse events are rare in children and have been studied in detail in the settings of cardiac surgery and regional anesthesia. Our study aims to characterize perianesthetic neurological adverse events in children in the setting of all types of surgery and diagnostic or interventional procedures, to evaluate anesthesia's role, and to identify factors amenable to prevention. METHODS: We conducted a retrospective study by reviewing all the anesthetic encounters reported in the Wake-Up Safe database between January 2010 and December 2017. RESULTS: The rate of perianesthetic neurological adverse events was 0.49 per 10 000 pediatric anesthetic encounters. The odds of NAE were significantly higher in children who were older than 6 months; had American Society of Anesthesiologists physical status (ASA PS) of 3, 4, or 5; or had American Society of Anesthesiologists Emergency (ASA E) status. Seizures were the most common NAE. Overall, 23 (18.1%) children with neurological adverse events died, and 33 (26%) experienced permanent or severe permanent harm. The risk of death was higher in infants and in children with ASA PS of 3, 4, or 5; ASA E status; preexisting neurological abnormality; or preexisting neurological deficit and in events associated with cardiac arrest or trauma. Anesthesia contributed to 24 (18.9%) events; patient disease was the primary causative factor in 95 (74.8%) adverse events, and 37 (29.1%) events were preventable, including 2 deaths. Preventable factors broadly included inadequate preoptimization, complications during airway management and central venous catheter placement, and suboptimal patient positioning. CONCLUSION: Perianesthetic neurological adverse events are rare in children and have a poor outcome. Our study has described pediatric perianesthetic neurological injury in detail and identified contributing factors that can be optimized during various phases of perianesthetic care. This information can be utilized during the informed consent process and to enhance the quality of care in children receiving anesthesia.

Clinical and organizational risk factors for mortality during deterioration events among pediatric oncology patients in Latin America: A multicenter prospective cohort.

BACKGROUND: Hospitalized pediatric hematology-oncology (PHO) patients have frequent clinical deterioration events (CDE) requiring intensive care unit (ICU) admission, particularly in resource-limited settings. The objective of this study was to describe CDEs in hospitalized PHO patients in Latin America and to identify event-level and center-level risk factors for mortality. METHODS: In 2017, the authors implemented a prospective registry of CDEs, defined as unplanned transfers to a higher level of care, use of ICU-level interventions on the floor, or nonpalliative floor deaths, in 16 PHO centers in 10 countries. PHO hospital admissions and hospital inpatient days were also reported. This study analyzes the first year of registry data (June 2017 to May 2018). RESULTS: Among 16 centers, 553 CDEs were reported in PHO patients during 11,536 admissions and 119,414 inpatient days (4.63 per 1000 inpatient days). Event mortality was 29% (1.33 per 1000 inpatient days) but ranged widely across centers (11%-79% or 0.36-5.80 per 1000 inpatient days). Significant risk factors for event mortality included requiring any ICU-level intervention on the floor and not being transferred to a higher level of care. Events with organ dysfunction, a higher severity of illness, and a requirement for ICU intervention had higher mortality. In center-level analysis, hospitals with a higher volume of PHO patients, less floor use of ICU intervention, lower severity of illness on transfer, and lower rates of floor cardiopulmonary arrest had lower event mortality. CONCLUSIONS: Hospitalized PHO patients who experience CDEs in resource-limited settings frequently require floor-based ICU interventions and have high mortality. Modifiable hospital practices around the escalation of care for these high-risk patients may contribute to poor outcomes. Earlier recognition of critical illness and timely ICU transfer may improve survival in hospitalized children with cancer.

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma.

Histone lysine demethylases (KDMs) play critical roles in oncogenesis and therefore may be effective targets for anticancer therapy. Using a time-resolved fluorescence resonance energy transfer demethylation screen assay, in combination with multiple orthogonal validation approaches, we identified geldanamycin and its analog 17-DMAG as KDM inhibitors. In addition, we found that these Hsp90 inhibitors increase degradation of the alveolar rhabdomyosarcoma (aRMS) driver oncoprotein PAX3-FOXO1 and induce the repressive epigenetic mark H3K9me3 and H3K36me3 at genomic loci of PAX3-FOXO1 targets. We found that as monotherapy 17-DMAG significantly inhibits expression of PAX3-FOXO1 target genes and multiple oncogenic pathways, induces a muscle differentiation signature, delays tumor growth and extends survival in aRMS xenograft mouse models. The combination of 17-DMAG with conventional chemotherapy significantly enhances therapeutic efficacy, indicating that targeting KDM in combination with chemotherapy may serve as a therapeutic approach to PAX3-FOXO1-positive aRMS.

Sex differences in the interaction of short-term particulate matter exposure and psychosocial stressors on C-reactive protein in a Puerto Rican cohort.

There is substantial evidence linking particulate matter air pollution with cardiovascular morbidity and mortality. However, health disparities between populations may exist due to imprecisely defined non-innate susceptibility factors. Psychosocial stressors are associated with cardiovascular disease and may increase non-innate susceptibility to air-pollution. We investigated whether the association between short-term changes in ambient particulate matter and cardiovascular health risk differed by psychosocial stressors in a Puerto Rican cohort, comparing women and men. We used data from the Boston Puerto Rican Health Study (BPRHS), a longitudinal study of cardiovascular health among adults, collected between 2004 and 2013. We used mixed effect models to estimate the association of current-day ambient particle number concentration (PNC) on C-reactive protein (CRP), a marker of systemic inflammation, and effect modification by psychosocial stressors (depression, acculturation, perceived stress, discrimination, negative life events and a composite score). Point estimates of percent difference in CRP per interquartile range change in PNC varied among women with contrasting levels of stressors: negative life events (15.7% high vs. 6.5% low), depression score (10.6% high vs. 4.6% low) and composite stress score (16.2% high vs. 7.0% low). There were minimal differences among men. For Puerto Rican adults, cardiovascular non-innate susceptibility to adverse effects of ambient particles may be greater for women under high stress. This work contributes to understanding health disparities among minority ethnic populations.