Search

Introduction Immunological studies of adult gliomas have been numerous, whereas pediatric gliomas are relatively understudied despite the fact that they are the leading cause of cancer-related childhood mortality (1). Among [...], Despite being the leading cause of cancer-related childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole- transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapeutic strategy that could be applied to multiple preclinical glioma models. MAPK-driven pediatric gliomas have a higher IFN signature relative to other molecular subgroups. Single-cell sequencing identified an activated and cytotoxic microglia (MG) population designated MG-Act in BRAF-fused, MAPK-activated pilocytic astrocytoma (PA), but not in high-grade gliomas or normal brain. T cell immunoglobulin and mucin domain 3 (TIM3) was expressed on MG-Act and on the myeloid cells lining the tumor vasculature but not normal brain vasculature. TIM3 expression became upregulated on immune cells in the PA microenvironment, and anti-TIM3 reprogrammed ex vivo immune cells from human PAs to a proinflammatory cytotoxic phenotype. In a genetically engineered murine model of MAPK-driven, low-grade gliomas, anti-TIM3 treatment increased median survival over IgG- and anti-PD-1-treated mice. Single-cell RNA-Seq data during the therapeutic window of anti-TIM3 revealed enrichment of the MGAct population. The therapeutic activity of anti-TIM3 was abrogated in mice on the CX3CR1 MG-KO background. These data support the use of anti-TIM3 in clinical trials of pediatric low-grade, MAPK- driven gliomas.

Objective: To investigate differences and calculate pooled incidence of any intraventricular haemorrhage (IVH), severe IVH (Grade III/IV, sIVH) and ventriculoperitoneal shunt (VPS) placement in preterm infants across geographical, health and economic regions stratified by gestational age (GA).Design: MEDLINE, Embase, CINAHL and Web of Science were searched between 2010 and 2020. Studies reporting rates of preterm infants with any IVH, sIVH and VPS by GA subgroup were included. Meta-regression was performed to determine subgroup differences between study designs and across United Nations geographical regions, WHO mortality strata and World Bank lending regions. Incidence of any IVH, sIVH and VPS by GA subgroups<25, <28, 28-31, 32-33 and 34-36 weeks were calculated using random-effects meta-analysis.Results: Of 6273 publications, 97 met inclusion criteria. Incidence of any IVH (37 studies 87 993 patients) was: 44.7% (95% CI 40.9% to 48.5%) for GA <25 weeks, 34.3% (95% CI 31.2% to 37.6%) for GA <28 weeks, 17.4% (95% CI 13.8% to 21.6%) for GA 28-31 weeks, 11.3% (95% CI 7.3% to 17.0%) for GA32-33 weeks and 4.9% (95% CI 1.4% to 15.2%) for GA 34-36 weeks. Incidence of sIVH (49 studies 328 562 patients) was 23.7% (95% CI 20.9% to 26.7%) for GA <25 weeks, 15.0% (95% CI 13.1% to 17.2%) for GA <28 weeks, 4.6% (95% CI 3.5% to 6.1%) for GA 28-31 weeks, 3.3% (95% CI 2.1% to 5.1%) for GA 32-33 weeks and 1.8% (95% CI 1.2% to 2.8%) for GA 34-36 weeks. Europe had lower reported incidence of any IVH and sIVH relative to North America (p<0.05). Proportion of VPS across all GA groups was 8.4% (95% CI 4.7% to 14.7%) for any IVH and 17.2% (95% CI 12.2% to 26.2%) for sIVH. Heterogeneity was high (I2 >90%) but 64%-85% of the variance was explained by GA and study inclusion criteria.Conclusions: We report the first pooled estimates of IVH of prematurity by GA subgroup. There was high heterogeneity across studies suggesting a need for standardised incidence reporting guidelines. [ABSTRACT FROM AUTHOR]

Neurocysticercosis (NCC) is a leading cause of preventable epilepsy in lower- and upper- middle-income countries (LMICs/UMICs). NCC is a human-to-human transmitted disease caused by ingestion of Taenia solium eggs from a Taenia carrier. T. solium infection control is the key to reduce NCC incidence. This systematic review aims to identify T. solium control programs that can provide frameworks for endemic areas to prevent NCC-related epilepsy. A systematic search was conducted in PubMed/Medline, Embase, Web of Science, and Cochrane Library databases in March 2021. After title and abstract review, full texts were screened for qualitative analysis. Additional articles were identified via citation search. Of 1322 total results, 34 unique studies were included. Six major intervention types were identified: national policy (8.8%), community sanitation improvement (8.8%), health education (8.8%), mass drug administration (29.4%), pig vaccination and treatment (32.4%), and combined human and pig treatment (11.8%). Overall, 28 (82.4%) studies reported decreased cysticercosis prevalence following the intervention. Only health education and combined human and pig treatment were effective in all selected studies. NCC causes preventable epilepsy in LMICs/UMICs and its incidence can be reduced through T. solium control. Most interventions that disrupt the T. solium transmission cycle are effective. Long-term sustained results require comprehensive programs, ongoing surveillance, and collaborative effort among multisectoral agencies. [ABSTRACT FROM AUTHOR]

Objectives: Refractory epilepsy is a diagnosis of recurrent seizures that requires multiple resources for optimal chronic management. The disease negatively impacts the lives of affected patients and families and poses an economic burden to the health care system. This study compares hospital costs between pediatric patients treated with antiseizure medications (ASMs) only and ASMs plus vagus nerve stimulation (VNS). Methods: Patients 0–17 years of age who were diagnosed with refractory epilepsy between January 1, 2011 and December 31, 2016, were identified from the Children's Hospital Association's Pediatric Health Information System (PHIS) database. Patients treated with ASMs only or ASMs plus VNS were included in the study and were followed 1 year prior and 2 years after meeting pre‐determined criteria for refractory epilepsy. The difference‐in‐difference (DID) approach along with the two‐part model was used to compare the changes in mean hospital costs captured in the PHIS database over time between the two cohorts. Results: One thousand one hundred thirteen patients treated with ASMs plus VNS and 3471 patients treated with ASMs only were included. At a follow‐up time of 2 years, for the ASMs‐only cohort, the adjusted all‐cause and epilepsy‐related mean annual total costs increased by $14 715 (95% confidence interval [CI]: $12 375–$17 055) and $18 437 (95% CI: $15 978–$20 896), respectively. By comparison, the adjusted all‐cause and epilepsy‐related mean annual total costs of the ASMs plus VNS cohort increased by $12 838 (95% CI: $8171–$17 505) and $15 183 (95% CI: $10 253–$20 113), respectively. Compared to ASMs only, ASMs plus VNS generated a cost savings of $3254 for epilepsy‐related annual costs per year after the index date. Significance: Compared to ASMs alone, ASMs plus VNS is a treatment modality associated with lower annual hospital costs over time. Our study shows that VNS is a cost‐beneficial treatment for a national cohort of pediatric patients with refractory epilepsy. [ABSTRACT FROM AUTHOR]