Health and LifeDomain ResearchPriorities in Children, Adolescents and Young Adults With Pediatric-Onset Spinal Cord Injury: A National Cross-Sectional Survey in England.

Background: Although feedback from people with adult-onset spinal cord injury (SCI) has been considered in developing research programs, little is known about pediatric-onset SCI priorities. Objectives: To describe the health and life (H&L) domain research priorities of youth with pediatric-onset SCI living in England. Methods: Youth with pediatric-onset SCI (≥6 months) were recruited from five English rehabilitation centers and invited with their parents/caregivers to complete the age-appropriate surveys designed by the Pan-European Paediatric Spinal Cord Injury (PEPSCI) collaboration. Results: A total of 73 surveys were received (32 from participants with SCI and 41 from their parents/caregivers), providing information on 47 individuals with SCI: 2- to 7-year-olds (29.8%), 8- to 12-year-olds (19.2%), 13- to 17-year-olds (17.0%), and 18 to 25-year-olds (34.0%). The top three research priorities reported by parents/caregivers of 2- to 12-year-old and 13- to 25-year-olds were pain (81%/89%), physical function (91%/83%) and health care access (78%/78%). Eighty-nine percent of 8- to 12-year-olds emphasized schooling, peer relationships, and general mood as their research priorities. The top three research priorities for Health or Life domains reported by 13- to 25-year-olds included spasms (95%), pain (91%), pressure injuries (91%), health care access (83%), physical function (78%), and daily personal needs (74%). Conclusion: Although there should be an emphasis on addressing important life domain issues for 8- to 12-year-olds with SCI, adolescents and young adults mostly prioritized health domain research priorities in addition to health care access. This survey will aid health care and clinical research organizations to engage stakeholders to implement a comprehensive SCI research strategy in England for the pediatric population.

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition of PRMT5 suppresses the growth of a cohort of 46 patient-derived GBM stem cell cultures, with the proneural subtype showing greater sensitivity. We show that PRMT5 inhibition causes widespread disruption of splicing across the transcriptome, particularly affecting cell cycle gene products. We identify a GBM splicing signature that correlates with the degree of response to PRMT5 inhibition. Importantly, we demonstrate that LLY-283 is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts. Collectively, our findings provide a rationale for the clinical development of brain penetrant PRMT5 inhibitors as treatment for GBM.

A population-based study of fall-related traumatic brain injury identified in older adults in hospital emergency departments.

OBJECTIVE: The purpose of this study was to examine the population-based trends and factors associated with hospitalization of patients with traumatic brain injury (TBI) treated in the Emergency Department (ED) among those 65 years and older. The implications of these trends for neurosurgery and the broader society are discussed. METHOD: With a national, mandatory reporting system of ED visits, the authors used Poisson regression controlling for age and sex to analyze trends in fall-related TBI of those aged 65 years and older between 2002 and 2017. RESULTS: The overall rate of ED visits for TBI increased by 78%-from 689.51 per 100,000 (95% CI 676.5-702.8) to 1229 per 100,000 (95% CI 1215-1243) between 2002 and 2017. Females consistently experienced higher rates of fall-related TBI than did males. All age groups 65 years and older experienced significant increases in fall-related TBI rate over the study period; however, the highest rates occurred among the oldest individuals (90+ and 85-89 years). The hospital admission rate increased with age and Charlson Comorbidity Index. Males experienced both a higher admission rate and a greater percentage change in admission rate than females. CONCLUSIONS: Rates of ED visits for fall-related TBI, hospitalization, and in-ED mortality in those aged 65 years and older are increasing for both sexes. The increasing hospital admission rate is related to more advanced comorbidities, male sex, and increasing age. These findings have significant implications for neurosurgical resources; they emphasize that health professionals should work proactively with patients, families, and caregivers to clarify goals of care, and they also outline the need for more high-level and, preferably, randomized evidence to support outcomes-based decisions. Additionally, the findings highlight the urgent need for improved population-based measures for prevention in not only this age demographic but in younger ones, and the need for changes in the planning of health service delivery and long-term care.

Lower-limb exoskeletons for individuals with chronic spinal cord injury: findings from a feasibility study.

OBJECTIVE: To assess the feasibility of conducting a well-powered trial evaluating the neurological and functional effects of using an exoskeleton in individuals with chronic spinal cord injury. DESIGN: A longitudinal, prospective, self-controlled feasibility study. SETTING: Specialist Spinal Cord Injuries Centre, UK; 8 months during 2013-2014. SUBJECTS: Individuals with chronic motor complete or incomplete spinal cord injury. INTERVENTIONS: Enrolled subjects were assigned to 20 exoskeleton (ReWalk™, Argo Medical Technologies Ltd, Yokneam Ilit, Israel) training sessions over a 10-week training period. MAIN MEASURES: Feasibility measures, clinical and mobility outcome measures and measures appraising subjects' disability and attitude towards assistive technology were assessed before, during and after the study. Descriptive statistics were applied. RESULTS: Out of 60 candidates, ten (17%) were enrolled and five (8%) completed the training programme. Primary reasons for not enrolling were ineligibility (n = 24, 40%) and limited interest to engage in a 10-week training programme (n = 16, 27%). Five out of ten enrolled subjects experienced grade I/II skin aberrations. While walking speeds were higher and walking distances were longer in all exoskeleton users when compared with non-use, the exoskeleton did generally not meet subjects' high expectations in terms of perceived benefits. CONCLUSIONS: The conduct of a controlled trial evaluating the benefits of using exoskeletons that require a lengthy user-commitment to training of individuals with chronic motor complete or incomplete spinal cord injury comes with considerable feasibility challenges. Vigilance is required for preventing and detecting medical complications in spinal cord injury exoskeleton users.