Thompson, Eric M.

OBJECTIVE The American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) Section on Pediatric Neurological Surgery domestic traveling fellowship was created to cover the travel and living expenses for a North American neurosurgery resident for 1 month at another institution to gain experience in pediatric neurosurgery. The objective of this work was to guide future direction by surveying past recipients about the fellowship and its impact on their training and career. METHODS Historical data have been maintained by the AANS/CNS Executive Committee and past and current chairs of the Traveling Fellowship Subcommittee. A 10-question REDCap survey was emailed to all previous fellowship recipients. RESULTS There have been 58 recipients of the traveling fellowship since 1998. The most common host program was Boston Children’s Hospital (n = 21), followed by The Hospital for Sick Children (n = 12). Excluding recent recipients after 2017 who may still be working toward certification, 20 of 38 (53%) recipients have been certified by the American Board of Pediatric Neurological Surgery (ABPNS). Twenty-four of 49 (49%) recipients completed the survey. Twenty (83.3%) respondents were either ABPNS certified or planning to seek certification, 17 (70.8%) respondents’ practices consisted of > 50% patients aged ≤ 21 years, and 18 (75%) spent 4–8 weeks at the host program, which was longer than the 1 month funded by the stipend. Twenty-two (91.7%) respondents would recommend the traveling fellowship to a resident interested in pediatric neurosurgery, and 18 (75%) believed the traveling fellowship helped them decide to pursue a career in pediatric neurosurgery, while 17 (70.8%) found that the professional connections they made were the most useful aspect of the fellowship. Fifteen (62.5%) respondents believed that the stipend of $2500 was inadequate to cover the cost of traveling and housing. CONCLUSIONS The majority of respondents are currently practicing pediatric neurosurgeons, would recommend the traveling fellowship to residents interested in neurosurgery, and believed that the experience helped them decide to pursue a career in pediatric neurosurgery. Opportunities for improvement include increasing the stipend to more appropriately fund rotations that have mostly been longer than 1 month.

Abstract Posterior Fossa Group A (PFA) ependymomas are pediatric brain tumors with extremely poor survival outcomes. As protein-coding mutations in PFA are exceedingly rare, the underlying etiology of these tumors remains elusive. Elevated CpG island methylation and depletion of H3K27me3 have been described in PFA, leading to the hypothesis that PFA may be driven by a dysregulated epigenetic state. In this study, we sought to determine how three-dimensional (3D) genome features (such as DNA loops, domains, and compartments) differ between pediatric brain tumors. We performed Hi-C sequencing on a collection of 64 patient specimens and patient-derived primary cultures that collectively span multiple subgroups of ependymoma, medulloblastoma, high-grade glioma, and non-neoplastic brain. For certain samples, we further performed RNA-seq, histone modification ChIP-seq, or whole-genome bisulfite sequencing to allow multiomic data integration. Overall, the 3D genome organization of PFA samples appeared distinct from other tumor types. We identified and defined TULIPs: a subset of type B compartments, separated by genomic distances greater than 10 Mbp, that exhibit a striking fivefold increase in reciprocal interaction strength. These TULIPs recurred at the same genomic positions across the vast majority of PFA samples with minimal representation among other tumor or non-tumor samples. TULIPs displayed enrichment for heterochromatic features such as H3K9me3 and late replication timing and were depleted of euchromatic features such as H3K27ac and protein-coding genes. By using immuno-fluorescence for H3K9me3 and oligo-FISH to label TULIP regions, we demonstrated that TULIP regions are more compact in PFA than other tumors. Finally, by applying inhibitors of H3K9 lysine methylation to PFA cultures we showed that TULIPs become more diffuse and cell viability is reduced. Altogether, this work defines TULIPs as highly recurrent epigenetic features of PFA tumors.

OBJECTIVEIn children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty.METHODSThe authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty.RESULTSA total of 359 patients met the inclusion criteria. The patients’ mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17–4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03–5.79), and ventilator dependence (OR 8.45, 95% CI 1.10–65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection.Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98–0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts.CONCLUSIONSThis is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.