Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong.

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

Rates of 30-Day and 90-Day Readmission Between Genotype-Optimal and Genotype-Suboptimal Antiplatelet Therapy Prescribing After Percutaneous Coronary Intervention.

Current evidence increasingly supports CYP2C19 genotype-guided P2Y12 inhibitor selection. Clopidogrel remains the most prescribed P2Y12 inhibitor despite higher readmission rates than those of more efficacious third-generation P2Y12 inhibitors. It remains unclear whether pharmacogenetically (PGx)-guided antiplatelet therapy directly reduces readmissions after percutaneous coronary intervention (PCI). A single-center retrospective observational cohort study at a tertiary academic medical center was conducted. Patients receiving CYP2C19 genotyping after PCI were included and stratified into 2 groups (PGx-optimal vs PGx-suboptimal P2Y12 inhibitor prescribed) on the basis of CPIC (Clinical Pharmacogenetics Implementation Consortium) recommendations. Primary outcomes included 30-day and 90-day readmissions after index PCI. Most patients (78%) were of non-European ancestry. Among patients receiving PGx-optimal therapy, 50% had acute coronary syndromes whereas 61% receiving PGx-suboptimal therapy had stable coronary artery disease. Comparable 30-day (12% vs 10%, p = 0.481) and 90-day readmission rates (24% vs 28%, p = 0.323) were observed between patients receiving PGx-optimal or PGx-suboptimal therapies. PGx-optimal therapy was associated with fewer emergency department visits (3.4% vs 4.0%, p = 0.021) within 30 days, and patients initially prescribed PGx-suboptimal therapy were switched more often to PGx-optimal therapy during a readmission than were patients prescribed PGx-suboptimal antiplatelet therapy (p <0.001). In conclusion, CYP2C19 genotype-guided P2Y12 inhibitor therapy did not improve 30- and 90-day all-cause readmission rates in a predominantly non-European population. However, P2Y12 inhibitor therapy became concordant with CYP2C19 genotype in approximately half of patients during the first readmission after PCI, which may present further opportunities to revisit and optimize dual antiplatelet therapy in patients who undergo PCI.

Gods and monsters: Greek mythology and Christian references in the neurosurgical lexicon.

BACKGROUND: Myths and religion are belief systems centered around supernatural entities that attempt to explain the observed world and are of high importance to certain communities. The former is a collection of stories that belong to a cultural tradition and the latter are organized faiths that determine codes of ethics, rituals and philosophy. Deities or monstrous creatures in particular act as archetypes instructing an individual's conduct. References to them in Greek mythology and Christianity are frequently manifested in the modern neurosurgical vernacular. METHODS: A review of the medical literature was performed using the PubMed and MEDLINE bibliographic databases. Publications from 1875 to 2021 related to neurosurgery or neuroanatomy with the medical subject headings (MeSH) terms mythology, religion, Christianity and Catholicism were reviewed. References pertaining to supernatural beings were classified to either a deity or a monstrosity according to their conventional cultural context. RESULTS: Twelve narratives associated with neurosurgery were identified, nine relating to Greek mythology and three associated with the Christian-Catholic faith. Eight accounts concerned deities and the remaining with monstrous creatures. CONCLUSION: This article explores the etymology of commonly utilized terms in daily neurosurgical practice in the context of mythology and religion. They reveal the ingenuity and creativity of early pioneers who strived to understand the brain.

Incidence and Outcomes of CNS Tumors in Chinese Children: Comparative Analysis With the Surveillance, Epidemiology, and End Results Program.

PURPOSE: Despite being the most common pediatric solid tumors, incidence and outcome of CNS tumors in Chinese children have not been systematically reported. We addressed this knowledge gap by comparing the epidemiology of pediatric CNS tumors in Hong Kong and the United States. PATIENTS AND METHODS: Data between 1999 and 2016 from a population-based cancer registry in Hong Kong, China, on patients < 18 years old with CNS tumors (Hong Kong cohort) and from the US SEER Program (Asian/Pacific Islander and all ethnicities) were compared. Incidence and overall survival (OS) by histology were evaluated. RESULTS: During the study period, 526 children were newly diagnosed with CNS tumors in Hong Kong (crude incidence rate, 2.47 per 100,000; 95% CI, 2.26 to 2.69). Adjusted incidences were significantly lower in the Hong Kong (2.51; 95% CI, 2.30 to 2.74) than in the SEER (Asian/Pacific Islander: 3.26; 95% CI, 2.97 to 3.57; P < .001; all ethnicities: 4.10 per 100,000; 95% CI, 3.99 to 4.22; P < .001) cohorts. Incidences of germ cell tumors (0.57 v 0.24; P < .001) were significantly higher, but those of glial and neuronal tumors (0.94 v 2.61; P < .001), ependymomas (0.18 v 0.31; P = .005), and choroid plexus tumors (0.08 v 0.16; P = .045) were significantly lower in Hong Kong compared with SEER (all ethnicities) cohorts. Compared with the SEER (Asian/Pacific Islander) cohort, histology-specific incidences were similar except for a lower incidence of glial and neuronal tumors in Hong Kong (0.94 v 1.74; P < .001). Among cohorts, OS differed only for patients with glial and neuronal tumors (5-year OS: Hong Kong, 52.5%; SEER [Asian/Pacific Islander], 73.6%; SEER [all ethnicities], 79.9%; P < .001). CONCLUSION: We identified important ethnic differences in the epidemiology of CNS tumors in Chinese children. These results will inform the development of pediatric neuro-oncology services in China and aid further etiologic studies.

Emergency endoscopic third ventriculostomy for blocked shunts? Univariate and multivariate analysis of independent predictors for failure.

OBJECTIVEHydrocephalus with a blocked ventriculoperitoneal (VP) shunt is a life-threatening condition. Emergency endoscopic third ventriculostomy (ETV) is a potential treatment option. The aim of the study was to identify independent risk factors associated with failure of ETV in treating patients with blocked shunts.METHODSThe authors retrospectively reviewed data from consecutive patients admitted for blocked shunt treated by ETV during the study period from 2000 to 2016. Univariate and multivariate analyses were performed to identify independent factors associated with failed ETV for blocked shunts, such as age, sex, history of CNS infection, number of previous shunt revisions, operations performed as an emergency or elective, number of specialists, and other factors.RESULTSIn total, 121 patients underwent ETV during the study period. Of these, 31 patients (25.6%) had ETV for treatment of a blocked shunt. In 25 (80.6%) of 31 ETV was performed as an emergency procedure. There was no significant difference in the success rate of ETV depending on whether it was performed as an emergency procedure (64% [16/25]) or an elective procedure (66.7% [4/6]; OR 0.062, 95% CI 0.001-2.708; p = 0.149). Univariate and multivariate analyses identified that history of a CNS infection was an independent risk factor for failure of ETV in treating patients with a blocked shunt (OR 0.030, 95% CI 0.001-0.888; p = 0.043).CONCLUSIONSEmergency ETV had a comparable success rate as elective ETV. A history of CNS infection is an independent predictor of ETV failure in treating patients with blocked shunts.

Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice.

Prolonged exposure to microgravity has shown to have deleterious effects on the human spine, indicated by low back pain during spaceflight and increased incidence of post-spaceflight herniated nucleus pulposus. We examined the effect of microgravity on biomechanical properties of lumbar and caudal discs from mice having been on 15-day shuttle mission STS-131. Sixteen C57BL/C mice (spaceflight group, n=8; ground-based control group, n=8) were sacrificed immediately after spaceflight. Physiological disc height (PDH) was measured in situ, and compressive creep tests were performed to parameterize biomechanical properties into endplate permeability (k), nuclear swelling pressure strain dependence (D), and annular viscoelasticity (G). For caudal discs, the spaceflight group exhibited 32% lower PDH, 70% lower D and crept more compared to the control mice (p=0.03). For lumbar discs, neither PDH nor D was significantly different between murine groups. Initial modulus, osmotic pressure, k and G for lumbar and caudal discs did not appear influenced by microgravity (p>0.05). Decreases in both PDH and D suggest prolonged microgravity effectively diminished biomechanical properties of caudal discs. By contrast, differences were not noted for lumbar discs. This potentially deleterious interaction between prolonged weightlessness and differential ranges of motion along the spine may underlie the increased cervical versus lumbar disc herniation rates observed among astronauts.

Intervertebral discs from spinal nondeformity and deformity patients have different mechanical and matrix properties.

BACKGROUND CONTEXT: It is well-established that disc mechanical properties degrade with degeneration. However, prior studies utilized cadaveric tissues from donors with undefined back pain history. Disc degeneration may present with pain at the affected motion segment, or it may be present in the absence of back pain. The mechanical properties and matrix quantity of discs removed and diagnosed for degeneration with patient chronic pain may be distinct from those with other diagnoses, such as spinal deformity. PURPOSE: To test the hypothesis that discs from nondeformity segments have inferior mechanical properties than deformity discs owing to differences in matrix quality. STUDY DESIGN/SETTING: In vitro study comparing the mechanical and matrix properties of discs from surgery patients with spinal nondeformity and deformity. METHODS: We analyzed nucleus and annulus samples (8-11 specimens per group) from surgical discectomy patients as part of a fusion or disc replacement procedure. Tissues were divided into two cohorts: nondeformity and deformity. Dynamic indentation tests were used to determine energy dissipation, indentation modulus, and viscoelasticity. Tissue hydration at a physiologic pressure was assessed by equilibrium dialysis. Proteoglycan, collagen, and collagen cross-link content were quantified. Matrix structure was assessed by histology. RESULTS: We observed that energy dissipation was significantly higher in the nondeformity nucleus than in the deformity nucleus. Equilibrium dialysis experiments showed that annulus swelling was significantly lower in the nondeformity group. Consistent with this, we observed that the nondeformity annulus had lower proteoglycan and higher collagen contents. CONCLUSIONS: Our data suggest that discs from nondeformity discs have subtle differences in mechanical properties compared with deformity discs. These differences were partially explained by matrix biochemical composition for the annulus, but not for the nucleus. The results of this study suggest that compromised matrix quality and diminished mechanical properties are features that potentially accompany discs of patients undergoing segmental fusion or disc replacement for disc degeneration and chronic back pain. These features have previously been implicated in pain via instability or reduced motion segment stiffness.