External ventricular drainage in the management of pediatric patients with posterior fossa tumors and hydrocephalus: a retrospective cohort study.

PURPOSE: To determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes compared to those who did not receive an EVD. METHODS: Patients were grouped as those who underwent routine intraoperative adjunctive EVD insertion and those who did not at time of PFT resection. Patients who pre-operatively required a clinically indicated EVD insertion were excluded. Comparative analyses between both groups were conducted to evaluate clinical, radiological, and pathological outcomes. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were computed for post-operative outcomes. RESULTS: Fifty-five selected patients were included, 15 who had an EVD placed at the time of PFT resection surgery, and 40 who did not. Children without an EVD did not experience a higher rate of complications or poorer post-operative outcomes compared to those with an EVD placed during resection surgery. There was no significant difference in the degree of gross total resection (p = 0.129), post-operative CSF leak (p = 1.000), and post-operative hemorrhage (p = 0.554) between those with an EVD and those without. The frequency of new cranial nerve deficits post-operatively was higher in those with an EVD (40%) compared to those without (3%, p = 0.001). There was a trend towards more frequently observed post-operative hydrocephalus in the EVD group (p = 0.057). CONCLUSION: The routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.

Comparison of longitudinal trends in self-reported symptoms and COVID-19 case activity in Ontario, Canada.

BACKGROUND: Limitations in laboratory diagnostic capacity impact population surveillance of COVID-19. It is currently unknown whether participatory surveillance tools for COVID-19 correspond to government-reported case trends longitudinally and if it can be used as an adjunct to laboratory testing. The primary objective of this study was to determine whether self-reported COVID-19-like illness reflected laboratory-confirmed COVID-19 case trends in Ontario Canada. METHODS: We retrospectively analyzed longitudinal self-reported symptoms data collected using an online tool-Outbreaks Near Me (ONM)-from April 20th, 2020, to March 7th, 2021 in Ontario, Canada. We measured the correlation between COVID-like illness among respondents and the weekly number of PCR-confirmed COVID-19 cases and provincial test positivity. We explored contemporaneous changes in other respiratory viruses, as well as the demographic characteristics of respondents to provide context for our findings. RESULTS: Between 3,849-11,185 individuals responded to the symptom survey each week. No correlations were seen been self-reported CLI and either cases or test positivity. Strong positive correlations were seen between CLI and both cases and test positivity before a previously documented rise in rhinovirus/enterovirus in fall 2020. Compared to participatory surveillance respondents, a higher proportion of COVID-19 cases in Ontario consistently came from low-income, racialized and immigrant areas of the province- these groups were less well represented among survey respondents. INTERPRETATION: Although digital surveillance systems are low-cost tools that have been useful to signal the onset of viral outbreaks, in this longitudinal comparison of self-reported COVID-like illness to Ontario COVID-19 case data we did not find this to be the case. Seasonal respiratory virus transmission and population coverage may explain this discrepancy.

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

CONTEXT: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.

Analysis of factors that influence neurosurgical length of hospital stay among newly diagnosed pediatric brain tumor patients.

BACKGROUND: Postoperative length of stay (LOS) carries a high burden of healthcare costs. In resource-intense specialties such as neurosurgery, it is imperative to identify factors that influence LOS to improve care. The current study investigates the potential for variables that affect clinical presentation, tumor characteristics, treatment modalities, and postoperative complications to impact overall LOS in pediatric brain tumor patients. METHODS: A retrospective cohort study design was used with patients enrolled in the McMaster Pediatric Brain Tumor Study Group database. All patients up to 18 years of age, presenting with a newly diagnosed brain tumor admitted to and discharged from neurosurgery, were included. Patients were sorted into three cohorts: short LOS (≤3 days), extended LOS (≥20 days), and control LOS (4-19 days). RESULTS: Of the 124 patients included, 20 (65% male; median age: 9.1 years; range, 0.8-17.4 years) were considered short LOS, 28 (61% male; median age: 4.7 years; range, 0.4-14.7 years) were considered extended LOS, and 76 (57% male; median age: 8.5 years; range, 0.3-17.9 years) were considered control LOS. Variables that prolonged LOS were emesis at presentation (P < 0.001), developmental delay (P = 0.02), multiple surgeries (P = 0.004), tumor location (P < 0.05), subtotal resection (P = 0.02), feeding tube (P < 0.001), adjuvant chemoradiotherapy (P < 0.001), and posterior fossa syndrome (P = 0.004). CONCLUSIONS: This study identifies variables related to clinical presentation, tumor characteristics, treatment modalities, and postoperative complications associated with extended LOS. These findings uncover novel predictors of LOS that can be used to guide future research and improve health resource management.

Contribution of rare coding mutations in CD36 to type 2 diabetes and cardio-metabolic complications.

We sequenced coding regions of the cluster of differentiation 36 (CD36) gene in 184 French individuals of European ancestry presenting simultaneously with type 2 diabetes (T2D), arterial hypertension, dyslipidemia, and coronary heart disease. We identified rare missense mutations (p.Pro191Leu/rs143150225 and p.Ala252Val/rs147624636) in two heterozygous cases. The two CD36 mutation carriers had no family history of T2D and no clustering of cardio-metabolic complications. While the p.Pro191Leu mutation was found in 84 heterozygous carriers from five ethnic groups from the genome aggregation database (global frequency: 0.0297%, N = 141,321), only one European carrier of the p.Ala252Val mutation was identified (global frequency: 0.00040%, N = 125,523). The Pro191 and Ala252 amino acids were not conserved (74.8% and 68.9% across 131 animal species, respectively). In vitro experiments showed that the two CD36 mutant proteins are expressed and trafficked to the plasma membrane where they bind modified low-density-lipoprotein (LDL) cholesterol as normal. However, molecular modelling of the recent CD36 crystal structure showed that Pro191 was located at the exit/entrance gate of the lipid binding chamber and Ala252 was in line with the chamber. Overall, our data do not support a major contribution of CD36 rare coding mutations to T2D and its cardio-metabolic complications in the French population.

Predictive measures and outcomes of extent of resection in juvenile pilocytic astrocytoma.

PURPOSE: The present study aims to determine the tumor-related, clinical, and demographic factors associated with extent of resection (EOR) and post-operative outcomes in JPA patients. METHODS: All patients with JPA, identified from a single-center brain tumour data base, were included in this retrospective analysis. Pre-operative MRI scans were reviewed by a single neurosurgeon blinded to the EOR. JPA cases that exhibited no residual tumor post-operatively were assigned to the GTR group, all other tumors were assigned to the

Salvage Therapy for Childhood Medulloblastoma: A Single Center Experience.

INTRODUCTION: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. METHODS: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. RESULTS: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. CONCLUSION: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Traitement de sauvetage dans le cas du médulloblastome chez l'enfant : une expérience menée au sein d'un établissement hospitalier. Introduction: Les enfants chez qui l'on a diagnostiqué un médulloblastome réfractaire à un traitement initial ou qui sont victimes d'une récidive présentent d'habitude des pronostics de guérison vraiment défavorables. Bien qu'il existe des traitements basés sur des essais cliniques de phases I et II, ces traitements ont tendance à produire des taux notables de morbidité et de mortalité. Méthodes: Nous avons ainsi mené à l'Université McMaster une analyse rétrospective des dossiers d'enfants chez qui l'on avait diagnostiqué entre 2002 et 2015 une récidive de médulloblastome. Résultats: La réapparition de cette maladie chez 10 patients a provoqué un phénomène de diffusion leptoméningée, trois d'entre eux étant victimes d'une récidive locale. Sur ces 10 jeunes patients, la maladie a progressé de façon importante : ces enfants ont alors été transférés aux soins palliatifs. Quant aux autres 10 enfants, ils ont subi un certain type de traitement de sauvetage (des résections chirurgicales, de la radiothérapie, de la chimiothérapie), que ce soit de façon exclusive ou en variant les combinaisons possibles. Sur les 13 enfants réfractaires à un traitement initial ou victimes d'une récidive, 4 sont toujours en vie, leur suivi médian ayant été de 38,5 mois (75,5 mois). Sur les 8 patients pour qui on a pu obtenir des données moléculaires, aucun de ceux qui étaient atteints d'un médulloblastome du sous-type Wnt n'a connu de récidive. Conclusion: Les médulloblastomes qui réapparaissent après une période de guérison complète présentent un pronostic de guérison défavorable. Leur taux de survie globale est en effet de 18,2 % au cours d'une période de 5 ans, et ce, même après avoir bénéficié d'un traitement de sauvetage. Ajoutons aussi que le type de traitement initial reçu, la disponibilité des traitements ainsi que la tolérance à l'égard des traitements de sauvetage proposés a entraîné une grande hétérogénéité dans le traitement de ces jeunes patients victimes d'une récidive.