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Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites. Locoregional CAR T cell delivery via infusion through an intracranial catheter is currently under study in multiple early phase clinical trials. Here, we describe the Seattle Children's single-institution experience including the multidisciplinary process for the preparation of successful, repetitive intracranial T cell infusion for children and the catheter-related safety of our 307 intracranial CAR T cell doses.

Abstract Purpose To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. Methods We report on six patients with NF‐1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. Results Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4–28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life‐threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1–2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. Conclusion Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF‐1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Abstract While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin’s profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) and 126 controls (n = 59 female) who were 5–17 years old were included. Partial correlations and multivariable regression analyses assessed the relationship between HMW adiponectin and adiposity. HMW adiponectin was inversely associated with total and central adiposity (FM%: β − 0.21, 95% CI − 0.15, − 0.08; p value

The objective of this study was to estimate the comparative effectiveness of bisphosphonate therapy on bone mineral density (BMD) in patients with corticosteroid-treated Duchenne muscular dystrophy (DMD). A retrospective, comparative effectiveness study evaluating changes in BMD and fragility fractures in patients with DMD presenting to British Columbia Children’s Hospital from 1989 to 2017 was conducted. Marginal structural generalized estimating equation models weighted by stabilized inverse-probability of treatment weights were used to estimate the comparative effectiveness of therapy on BMD. Of those treated with bisphosphonates (N = 38), 7 (18.4%), 17 (44.7%), and 14 (36.8%) cases were treated with pamidronate, zoledronic acid, or a combination of both, respectively, while 36 cases of DMD were untreated. Mean age of bisphosphonate initiation was 9.2 (SD 2.7) years. Mean fragility fractures declined from 3.5 to 1.0 following bisphosphonate therapy. Compared to the treated group, the untreated group had an additional 0.63-SD decrease (95% confidence interval [CI]: −1.18, −0.08, P = .026) in total BMD and an additional 1.04-SD decrease (95% CI: −1.74, −0.34; P = .004) in the left hip BMD, but the change in lumbar spine BMD (0.15, 95% CI: −0.36, 0.66; P = .57) was not significant. Bisphosphonate therapy may slow the decline in BMD in boys with corticosteroid-treated DMD compared to untreated counterparts. Total number of fragility fractures decreased following bisphosphonate therapy.

Puberty is initiated by hormonal changes in the adolescent body that trigger physical and behavioral changes to reach adult maturation. As these changes occur, some adolescents experience concerning pubertal symptoms that are associated with dysfunction of the autonomic nervous system (ANS). Vasovagal syncope (VVS) and Postural Orthostatic Tachycardia Syndrome (POTS) are common disorders of the ANS associated with puberty that are related to orthostatic intolerance and share similar symptoms. Compared to young males, young females have decreased orthostatic tolerance and a higher incidence of VVS and POTS. As puberty is linked to changes in specific sex and non-sex hormones, and hormonal therapy sometimes improves orthostatic symptoms in female VVS patients, it is possible that pubertal hormones play a role in the increased susceptibility of young females to autonomic dysfunction. The purpose of this paper is to review the key hormonal changes associated with female puberty, their effects on the ANS, and their potential role in predisposing some adolescent females to cardiovascular autonomic dysfunctions such as VVS and POTS. Increases in pubertal hormones such as estrogen, thyroid hormones, growth hormone, insulin, and insulin-like growth factor-1 promote vasodilatation and decrease blood volume. This may be exacerbated by higher levels of progesterone, which suppresses catecholamine secretion and sympathetic outflow. Abnormal heart rate increases in POTS patients may be exacerbated by pubertal increases in leptin, insulin, and thyroid hormones acting to increase sympathetic nervous system activity and/or catecholamine levels. Given the coincidental timing of female pubertal hormone surges and adolescent onset of VVS and POTS in young women, coupled with the known roles of these hormones in modulating cardiovascular homeostasis, it is likely that female pubertal hormones play a role in predisposing females to VVS and POTS during puberty. Further research is necessary to confirm the effects of female pubertal hormones on autonomic function, and their role in pubertal autonomic disorders such as VVS and POTS, in order to inform the treatment and management of these debilitating disorders.