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Background and Objectives: Stereo-EEG-guided radiofrequency thermocoagulation (RFTHC) has been proposed as relatively safe from a cognitive perspective; however, there is a lack of evidence based on neuropsychological assessments supporting this. This study is the first prospective evaluation of neuropsychological outcomes associated with stereo-EEG-guided RFTHC in patients with focal drug-resistant epilepsy., Methods: This cohort study involved prospective recruitment of consecutive patients undergoing stereo-EEG from 2 Australian centers. A comprehensive neuropsychological assessment was administered before implantation and 3 months after RFTHC (M = 104.51 days, SD = 29.25). Outcomes across cognitive domains were assessed at a group level with repeated measures t tests. Factorial repeated measures analyses of variance compared memory and language outcomes according to whether dominant mesial temporal lobe (mTL) structures were coagulated. Reliable change indices (RCIs) were computed to explore psychometrically reliable changes at an individual level., Results: The sample comprised 39 patients who underwent stereo-EEG (M = 37.08 ± 9.67 years, range = 17-56 years, 54% female). Nineteen (49%) had a language dominant epileptogenic zone (EZ), 16 (41%) a nondominant EZ, and 4 (10%) a bilateral EZ. All patients underwent RFTHC with a mean of 11.87 (SD = 6.82, range = 2-29) coagulation sites. Ten patients (26%) had RFTHC within the dominant mTL. At a group level, RFTHC was not associated with a significant decline on any neuropsychological measures (all comparisons p > 0.05). Subgroup analyses revealed a decline in delayed verbal recall after RFTHC of dominant mTL structures ( F (1,37) = 4.46, p = 0.04, η p 2 = 0.11, 95% CI [0-0.30]; medium to large effect), although it did not remain statistically significant after correction for false discovery rate. No statistically significant group differences were observed on visual memory or language measures post-RFTHC (all comparisons p > 0.05). RCI revealed that after RFTHC within the dominant mTL, 20% of patients experienced a decline in verbal memory and 10% in visual memory. By contrast, 7% declined in verbal memory and 10% in visual memory post-RFTHC outside the dominant mTL., Discussion: While these findings support the current view that RFTHC is cognitively benign for most cases, the results raise the question of a verbal memory decline after coagulation of the dominant mTL. Individualized neuropsychological counseling before stereo-EEG is essential to avoid unanticipated deficits.

Glioblastoma is the most aggressive and lethal primary brain malignancy with limited treatment options and poor prognosis. Self-renewing glioblastoma cancer stem cells (GSCs) facilitate tumour progression, resistance to conventional treatment and tumour recurrence. GSCs are resistant to standard treatments. There is a need for novel treatment alternatives that effectively target GSCs. The purinergic P2X receptor 7 (P2X7R) is expressed in glioblastomas and has been implicated in disease pathogenesis. However, the roles of P2X7R have not been comprehensively elucidated in conventional treatment-resistant GSCs. This study characterised P2X7R channel and pore function and investigated the effect of pharmacological P2X7R inhibition in GSCs. Immunofluorescence and live cell fluorescent dye uptake experiments revealed P2X7R expression, and channel and pore function in GSCs. Treatment of GSCs with the P2X7R antagonist, AZ10606120 (AZ), for 72 hours significantly reduced GSC numbers, compared to untreated cells. When compared with the effect of the first-line conventional chemotherapy, temozolomide (TMZ), GSCs treated with AZ had significantly lower cell numbers than TMZ-treated cultures, while TMZ treatment alone did not significantly deplete GSC numbers compared to the control. AZ treatment also induced significant lactate dehydrogenase release by GSCs, indicative of treatment-induced cytotoxic cell death. There were no significant differences in the expression of apoptotic markers, Annexin V and cleaved caspase-3, between AZ-treated cells and the control. Collectively, this study reveals for the first time functional P2X7R channel and pore in GSCs and significant GSC depletion following P2X7R inhibition by AZ. These results indicate that P2X7R inhibition may be a novel therapeutic alternative for glioblastoma, with effectiveness against GSCs resistant to conventional chemotherapy., Competing Interests: Declaration of Competing Interest TJO has received support from the National Health and Medical Research Council (APP1176426), The Medical Research Future Fund, The National Institute of Neurological Disorders and Stroke and Monash University. He has been supported by research grants and consultancies to his institution from Eisai, UCB Pharma, Praxis Precision Medicines, BioGen and Supernus. MM has served on advisory board for Merck and has received speaker honoraria from Merch and Biogen. Her institution receives funding from Merck, Australian National Health Medical Research Council, Brain Foundation, Charles and Sylvia Viertel Foundation, and MS Research Australia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Stereoelectroencephalography (SEEG) is a procedure used to localize the epileptogenic zone in patients with medically refractory epilepsy, involving the stereotactic implantation of electrodes into brain parenchyma. Magnetic Resonance Imaging (MRI), Digital Subtraction Angiography, and Computed Tomography have been used preoperatively to prevent Intracranial Hemorrhage (ICH) by identifying electrode-vessel conflicts (EVC's) on planned electrode trajectories. There is variation in the use of Digital Subtraction Angiography and non-invasive sequences for vascular planning. Digital Subtraction Angiography provides high spatial resolution, but carries risks of arterial dissection, groin and retroperitoneal hematoma, and a 0.5-1.9% risk of stroke. Our group has incorporated Intravenous Cone Beam Computed Tomography (CBCT A/V) Brain into our SEEG workflow, given its effective implementation in other neurosurgical domains. Primary aims include validating the safety of our CBCT A/V sequence for SEEG planning and determining if CBCT A/V is comparable to other modalities in detecting EVC's. Secondary aims include elucidating the relationship of conflicting vessel calibre with ICH incidence in SEEG using CBCT A/V imaging., Methods: A single-center retrospective study was conducted of 20 patients who underwent preoperative CBCT A/V Brain and MRI Brain with gadolinium enhancement, encompassing 273 electrode implantations from August 2020 - July 2023. The incidence and grade of post-implant, post-explant symptomatic ICH and asymptomatic ICH was noted. The total number of EVC's identifiable on MRI and CBCT A/V was recorded, along with average diameter of conflicting vessels., Results: Across 20 patients and 273 implanted electrodes, there were four ICH events, where two were symptomatic and two were asymptomatic. The mean diameter of EVC's across all patients was 1.4 mm (±0.5). A significant difference (P < 0.0001) was observed between the number of EVC's that CBCT A/V could identify (20) compared to MRI (6). Two EVC's were identified in the region of two symptomatic ICH's, with the mean diameter of these conflicted vessels being 1.5 mm (±0.4). The two symptomatic ICH-associated EVC's were observed on CBCT A/V but not MRI., Conclusions: In our series, CBCT A/V demonstrates an acceptable safety profile for SEEG planning compared to other imaging modalities. CBCT A/V identified significantly more EVC's compared to MRI, including those contributing to transient symptomatic intracranial hemorrhage. A conflicting vessel calibre of less than 1.2 mm on CBCT A/V did not contribute to ICH in our SEEG series., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Study Design: Retrospective Cohort., Objectives: To validate the most concise risk stratification system to date, the 5-item modified frailty index (mFI-5), and compare its effectiveness with the established 11-item modified frailty index (mFI-11) in the elderly population undergoing posterior instrumented spine surgery., Methods: A single centre retrospective review of posterior instrumented spine surgeries in patients aged 65 years and older was conducted. The primary outcome was rate of post-operative major complications (Clavien-Dindo Classification ≥ 4). Secondary outcome measures included rate of all complications, 6-month mortality and surgical site infection. Multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated and compared by DeLong's test. The indices were correlated with Spearman's rho., Results: 272 cases were identified. The risk of major complications was independently associated with both the mFI-5 (OR 1.89, 95% CI 1.01-3.55, P = .047) and mFI-11 (OR 3.73, 95% CI 1.90-7.30, P = .000). Both the mFI-5 and mFI-11 were statistically significant predictors of risk of all complications ( P = .007 and P = .003), surgical site infection ( P = .011 and P = .003) and 6-month mortality ( P = .031 and P = .000). Adjusted ROC curves determined statistically similar c-statistics for major complications (.68 vs .68, P = .64), all complications (.66 vs .64, P = .10), surgical site infection (.75 vs .75, P = .76) and 6-month mortality (.83 vs .81, P = .21). The 2 indices correlated very well with a Spearman's rho of .944., Conclusions: The mFI-5 and mFI-11 are equally effective predictors of postoperative morbidity and mortality in this population. The brevity of the mFI-5 is advantageous in facilitating its daily clinical use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Glioblastomas are highly aggressive and deadly brain tumours, with a median survival time of 14-18 months post-diagnosis. Current treatment modalities are limited and only modestly increase survival time. Effective therapeutic alternatives are urgently needed. The purinergic P2X7 receptor (P2X7R) is activated within the glioblastoma microenvironment and evidence suggests it contributes to tumour growth. Studies have implicated P2X7R involvement in a range of neoplasms, including glioblastomas, although the roles of P2X7R in the tumour milieu remain unclear. Here, we report a trophic, tumour-promoting role of P2X7R activation in both patient-derived primary glioblastoma cultures and the U251 human glioblastoma cell line, and demonstrate its inhibition reduces tumour growth in vitro. Primary glioblastoma and U251 cell cultures were treated with the specific P2X7R antagonist, AZ10606120 (AZ), for 72 h. The effects of AZ treatment were also compared to cells treated with the current first-line chemotherapeutic drug, temozolomide (TMZ), and a combination of both AZ and TMZ. P2X7R antagonism by AZ significantly depleted glioblastoma cell numbers compared to untreated cells, in both primary glioblastoma and U251 cultures. Notably, AZ treatment was more effective at tumour cell killing than TMZ. No synergistic effect between AZ and TMZ was observed. AZ treatment also significantly increased lactate dehydrogenase release in primary glioblastoma cultures, suggesting AZ-induced cellular cytotoxicity. Our results reveal a trophic role of P2X7R in glioblastoma. Importantly, these data highlight the potential for P2X7R inhibition as a novel and effective alternative therapeutic approach for patients with lethal glioblastomas., (© 2023. The Author(s).)

Study Design: Retrospective cohort., Objectives: To validate the 11-item modified Frailty Index (mFI) as a perioperative risk stratification tool in elderly patients undergoing spine surgery., Methods: All consecutive cases of spine surgery in patients aged 65 years or older between July 2016 and June 2018 at a state-wide trauma center were retrospectively reviewed. The primary outcome was post-operative major complication rate (Clavien-Dindo Classification ≥ III). Secondary outcome measures included the rate of all complications, 6-month mortality and surgical site infection., Results: A total of 348 cases were identified. The major complication rate was significantly lower in patients with an mFI of 0 compared to ≥ 0.45 (18.3% versus 42.5%, P = .049). As the mFI increased from 0 to ≥ 0.45 there was a stepwise increase in risk of major complications ( P < .001). Additionally, 6-month mortality rate was considerably lower when the mFI was 0 rather than ≥ 0.27 (4.2% versus 20.4%, P = .007). Multivariate analysis demonstrated an mFI ≥ 0.27 was significantly associated with an increased incidence of major complication (OR 2.80, 95% CI 1.46-5.35, P = .002), all complication (OR 2.93, 95% CI 1.70-15.11, P < .001), 6-month mortality (OR 7.39, 95% CI 2.55-21.43, P < .001) and surgical site infection (OR 4.43, 95% CI 1.71-11.51, P = .002). The American Society of Anesthesiologists' (ASA) index did not share a stepwise relationship with any outcome., Conclusion: The mFI is significantly associated in a gradated fashion with increased morbidity and mortality. Patients with an mFI ≥ 0.27 are at greater risk of major complications, all-complications, 6-monthy mortality, and surgical site infection.

Immunotherapy with T-cell checkpoint inhibitors have changed the treatment landscape for patients with melanoma brain metastases (MBMs), offering increased survival compared with historical outcomes. We sought to identify clinical features associated with intracranial tumour responses or progression-free survival (PFS) in patients with MBMs treated with immunotherapy. Patients with MBMs treated with immunotherapy from August 2013 to March 2020 were identified through local databases. Melanoma disease burdens and immune-related adverse events (irAEs) were assessed retrospectively by review of patient medical records. Efficacy was evaluated by determining objective response rates (ORRs) in brain metastases using immune-Response Evaluation Criteria in Solid Tumours criteria, MBM-specific survival and overall PFS. Twenty-six patients were identified as eligible for this study. The presence and volume of extracranial metastases (ECM) were associated with a non-significant trend of reduced intracranial ORRs and PFS. Patients with irAEs, on the other hand, had significantly increased intracranial ORRs and PFS compared to those without irAEs. Severe, grade ≥3 irAEs and co-occurrence of ≥2 irAEs were also significantly associated with longer PFS. The presence and volume of ECM correlated inversely with development and severity of irAEs. We report a strong association between the development of irAEs and favourable melanoma-specific outcomes in patients with MBMs receiving immunotherapy. Contrary to previous studies, we found that co-occurrence of ECM in these patients was associated with fewer irAEs and reduced treatment efficacy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although it is often assumed that preinjury anticoagulant (AC) or antiplatelet (AP) use is associated with poorer outcomes among those with acute subdural hematoma (aSDH), previous studies have had varied results. This study examines the impact of preinjury AC and AP therapy on aSDH thickness, 30-day mortality, and extended Glasgow Outcome Scale at 6 months in elderly patients (aged ≥65)., Methods: A level 1 trauma center registry was interrogated to identify consecutive elderly patients who presented with moderate or severe traumatic brain injury (TBI) and associated traumatic aSDH between the first of January 2013 and the first of January 2018. Relevant demographic, clinical, and radiological data were retrieved from institutional medical records. The 3 primary outcome measures were aSDH thickness on initial computed tomography scan, 30-day mortality, and unfavorable outcome at 6 months (extended Glasgow Outcome Scale)., Results: One hundred thirty-two elderly patients were admitted with moderate or severe TBI and traumatic aSDH. The mean (±SD) age was 78.39 (±7.87) years, and a majority of patients (59.8%, n = 79) were male. There was a statistically significant difference in mean aSDH thickness, but there were no significant differences in 30-day mortality (P = 0.732) and unfavorable outcome between the AP, AC, combined AP and AC, and no antithrombotic exposure groups (P = 0.342)., Conclusions: Further studies with larger sample sizes are necessary to confirm these observations, but our findings do not support the preconceived notion in clinical practice that antithrombotic use is associated with poor outcomes in elderly patients with moderate or severe TBI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Design: Systematic review and meta-analysis., Objectives: To compare biomechanical and functional outcomes between implant removal and implant retention following posterior surgical fixation of thoracolumbar burst fractures., Methods: A search of the MEDLINE, EMBASE, Google Scholar and Cochrane Databases was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines., Results: Of the 751 articles initially retrieved, 13 published articles pooling 673 patients were included. Meta-analysis revealed there was a statistically significant improvement in sagittal Cobb Angle by 16.48 degrees (9.13-23.83, p < 0.01) after surgical stabilization of thoracolumbar burst fractures. This correction decremented to 9.68 degrees (2.02-17.35, p < 0.01) but remained significant at the time of implant removal approximately 12 months later. At final follow-up, the implant removal group demonstrated a 10.13 degree loss (3.00-23.26, p = 0.13) of reduction, while the implant retention group experienced a 10.17 degree loss (1.79-22.12, p = 0.10). There was no statistically significant difference in correction loss between implant retention and removal cohorts (p = 0.97). Pooled VAS scores improved by a mean of 3.32 points (0.18 to 6.45, p = 0.04) in the combined removal group, but by only 2.50 points (-1.81 to 6.81, p = 0.26) in the retention group. Oswestry Disability Index scores also improved after implant removal by 7.80 points (2.95-12.64, p < 0.01) at 1 year and 11.10 points (5.24-16.96, p < 0.01) at final follow-up., Conclusions: In younger patients with thoracolumbar burst fractures who undergo posterior surgical stabilization, planned implant removal results in superior functional outcomes without significant difference in kyphotic angle correction loss compared to implant retention.

Implementing a health promotion program for children is a complex endeavor. In this review, we outline the key lessons learned over 10 years of experience in implementing the SI! Program (Salud Integral-Comprehensive Health) for cardiovascular health promotion in preschool settings in 3 countries: Colombia (Bogotá), Spain (Madrid), and the United States (Harlem, New York). By matching rigorous efficacy studies with implementation science, we can help bridge the divide between science and educational practice. Achieving sustained lifestyle changes in preschool children through health promotion programs is likely to require the integration of several factors: 1) multidisciplinary teams; 2) multidimensional educational programs; 3) multilevel interventions; 4) local program coordination and community engagement; and 5) scientific evaluation through randomized controlled trials. Implementation of effective health promotion interventions early in life may induce long-lasting healthy behaviors that could help to curb the cardiovascular disease epidemic., Competing Interests: Funding Support and Author Disclosures This work is supported by the SHE Foundation and “la Caixa” Foundation (LCF/CE16/10700001). The project in Colombia was funded by Santo Domingo Foundation; the study in the United States (FAMILIA) was funded by the American Heart Association (grant no. 14SFRN20490315); and the study in Spain (SI! Program) was funded by the SHE Foundation, the research grant FIS-PI11/01885 (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III), and Fundació la Marató de TV3 (369/C/2016). Dr Santos-Beneit is the recipient of grant LCF/PR/MS19/12220001 funded by “la Caixa” Foundation (ID 100010434). Dr Fernández-Jiménez is the recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III and co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future.” The Centro Nacional de Investigaciones Cardiovasculares is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies., Methods: A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted., Results: Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39-7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03-7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78-2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35-1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27-2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%)., Conclusions: Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

To investigate cerebral autoregulatory status in patients with severe traumatic brain injury (TBI), guidelines now suggest active manipulation of mean arterial pressure (MAP). There is a paucity of data, however, describing the effect on intracranial pressure (ICP) when MAP is raised. Consecutive patients with TBI requiring ICP monitoring were enrolled from November 2019 to April 2020. The MAP and ICP were recorded continuously, and clinical annotations were made whenever intravenous vasopressors were commenced or adjusted to defend cerebral perfusion pressure (CPP) targets. A significant change in MAP burden was defined as MAP >100min.mm Hg over 15 min. The primary outcome was the change in ICP burden over the same 15-min period. Bedside and clinical parameters were then compared between these groups. Twenty-eight patients were enrolled, providing 212 clinical events, of which 60 were deemed significant. Over the first 15 min, 65% were associated with a net negative ICP burden. A greater reduction in ICP burden was observed with events occurring in patients without a history of hypotension at scene ( p  = 0.016), after three days post-injury ( p  = 0.0018), and where the pressure-reactivity index (PRx) was <0.25 ( p  = 0.0005) or the ICP amplitude to CPP correlation coefficient (RAC) was <-0.10 ( p  = 0.0036) at the initiation of vasopressor changes. The ICP burden in the first 15 min was highly correlated with the next 15-min period. In patients with severe TBI requiring ICP monitoring, increasing MAP to pursue a CPP target was followed by a net negative ICP burden in approximately two-thirds of events. These data suggest a MAP challenge may be a useful adjunct in managing intracranial hypertension.

The P2X receptor 7 (P2X7R) is a plasma membrane receptor sensing extracellular ATP associated with a wide variety of cellular functions. It is most commonly expressed on immune cells and is highly upregulated in a number of human cancers where it can play a trophic role in tumorigenesis. Activation of this receptor leads to the formation of a non-selective cation channel, which has been associated with several cellular functions mediated by the PI3K/Akt pathway and protein kinases. Due to its broad range of functions, the receptor represents a potential therapeutic target for a number of cancers. This review describes the range of mechanisms associated with P2X7R activation in cancer settings and highlights the potential of targeted inhibition of P2X7R as a therapy. It also describes in detail a number of key P2X7R antagonists currently in pre-clinical and clinical development, including oxidised ATP, Brilliant Blue G (BBG), KN-62, KN-04, A740003, A438079, GSK1482160, CE-224535, JNJ-54175446, JNJ-55308942, and AZ10606120. Lastly, it summarises the in vivo studies and clinical trials associated with the use and development of these P2X7R antagonists in different disease contexts.

Study Design: This was an ambispective clinical quality registry study., Objective: To evaluate utility of 11-variable modified Frailty Index (mFI) in predicting postoperative outcomes among patients ≥80 years undergoing spinal surgery., Methods: Consecutive patients ≥80 years who underwent spinal surgery between January 1, 2013, and June 30, 2018, were included. Primary outcome measure was rate of major complication. Secondary outcome measures were (1) overall complication rate, (2) surgical site infection, and (3) 6-month mortality., Results: A total of 121 operations were performed. Demographic metrics were (1) age (mean ± SD) = 83.1 ± 2.8 years and (2) mFI (mean ± SD) = 2.1 ± 1.4 variables. As mFI increased from 0 to ≥4 variables, risk of major complication increased from 18.2% to 40.0% ( P = .014); overall complication increased from 45.5% to 70.0% ( P = .032); surgical site infection increased from 0.0% to 25.0% ( P = .007). There were no significant changes in risk of 6-month mortality across mFIs ( P = .115). Multivariate analysis showed that a higher mFI score of ≥3 variables was associated with a significantly higher risk of (1) major complication ( P = .025); (2) overall complication ( P = .015); (3) surgical site infection ( P = .007); and (4) mortality ( P = .044)., Conclusions: mFI scores of ≥3/11 variables were associated with a higher risk of postoperative morbidity in patients aged ≥80 years undergoing spinal surgery. The mFI-associated risk stratification provides a valuable adjunct in surgical decision making for this rapidly growing subpopulation of patients.

Background: The survival outcomes of clear cell ependymomas are poorly understood. This study clarifies the role of surgery and adjuvant therapy when this morphologically distinct tumor is encountered., Methods: A systematic search for studies relating to clear cell ependymomas was conducted. Primary outcomes were progression-free survival and overall survival. Prognostic variables were age, sex, tumor consistency, extent of resection, and postoperative adjuvant therapy. Kaplan-Meier survival curves were generated and compared by the log-rank test. Multivariate Cox regression models were constructed, interrogated with Schoenfeld residuals, and used to identify independent prognostic factors., Results: Of the 384 articles retrieved, 8 articles comprising 77 cases of clear cell ependymoma were included. Five-year overall survival and progression-free survival were 58.1% (95% confidence interval [CI], 46.3%-72.9%) and 46.3% (95% CI, 34.2%-62.8%), respectively. Kaplan-Meier analysis with the log-rank test showed that gross total resection was superior to subtotal resection in prolonging survival (P = 0.047) and delayed time to recurrence (P < 0.01). Multivariate analysis confirmed gross total resection as an independent protective factor against relapse (odds ratio, 0.39; 95% CI, 0.17-0.89; P = 0.03). Age <50 years predicted longer overall survival (odds ratio, 0.16; 95% CI, 0.05-0.49; P < 0.01). Postoperative adjuvant therapy after gross total resection did not affect overall survival (P = 0.98) or progression-free survival (P = 0.93). Adjuvant therapy after subtotal resection favored improved overall survival (P = 0.052)., Conclusions: Clear cell ependymomas are particularly aggressive in those aged >50 years. Gross total resection remains the cornerstone of management. Postoperative adjuvant therapy is likely to be of survival benefit only after subtotal resection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% ( p  = 0.023) and 6-month unfavorable outcome risk increased from 40.51% to 96.43% ( p  < 0.001). Multi-variate analysis showed that greater mFI score of ≥3/11 variables (≥0.27) suggested a significantly higher risk of 30-day mortality ( p  = 0.009) and unfavorable outcome ( p  < 0.001). We conclude that increasing frailty, as measured by the mFI, was associated with significantly higher risk of 30-day mortality and 6-month unfavorable outcome in elderly patients presenting with aSDH to a level 1 neurotrauma center. Assessment of mFI in elderly patients with aSDH may be a useful determinant of outcome for this rapidly growing population.

Gliomas are the most common central nervous system malignancies and present with significant morbidity and mortality. Treatment modalities are currently limited to surgical resection, chemotherapy and radiotherapy. Increases in survival rate over the previous decades are negligible, further pinpointing an unmet clinical need in this field. There is a continual struggle with the development of effective glioma diagnostics and therapeutics, largely due to a multitude of factors, including the presence of the blood-brain barrier and significant intertumoural and intratumoural heterogeneity. Importantly, there is a lack of reliable biomarkers for glioma, particularly in aiding tumour subtyping and measuring response to therapy. There is a need for biomarkers that would both overcome the complexity of the disease and allow for a minimally invasive means of detection and analysis. This is a comprehensive review evaluating the potential of current cellular, proteomic and molecular biomarker candidates for glioma. Significant hurdles faced in glioma diagnostics and therapy are also discussed here., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Design: Systematic review., Objectives: Cyanoacrylate glue closure has been utilized for dermal closure in surgical incisions. Its safety and efficacy in spine surgery are not established. The authors perform a systematic review to determine the rate of surgical site infection (SSI), wound dehiscence, and wound erythema with cyanoacrylate dermal closure in spine surgery., Methods: A systematic review adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed utilizing the PubMed/MEDLINE, EMBASE, and Cochrane databases on patients undergoing spine surgery with cyanoacrylate dermal closure. Pooled analysis was performed with stratification of patients according to spinal level and the presence/absence of instrumentation. Risk-of-bias and methodological quality was appraised using 17 prespecified criteria., Results: Five articles (1 retrospective cohort study, 4 cases series) with a total of 1282 patients were included. A total of 967 patients, all diagnosed with degenerative spine disease, were suitable for pooled analysis. In 290 patients who underwent anterior cervical discectomy and fusion, and in 23 patients with posterior cervical decompression (without instrumentation), there was 0% rate of SSI, wound dehiscence, and erythema. In 489 patients who underwent lumbar microdiscectomy, there was 0.41% rate of SSI, 0.20% rate of wound dehiscence, and 0.20% rate of wound erythema. In 165 lumbar laminectomy patients, there was a 1.82% rate of SSI, 0.61% rate of wound dehiscence, and 0% rate of wound erythema., Conclusion: Cyanoacrylate dermal closure for the aforementioned procedures is associated with low rates of wound complications (SSI, dehiscence, and erythema). Further studies should be performed, especially in nondegenerative surgery, instrumented thoracic and lumbar spine surgery., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Background: Long-term evaluations of child health promotion programs are required to assess their sustainability and the need for reintervention., Objectives: This study sought to explore the long-term impact of a preschool health promotion intervention delivered in an urban low-income area of Colombia (phase 1) and to assess the effect of a new community-based intervention (phase 2)., Methods: In phase 1, a cross-sectional analysis of knowledge, attitudes, and habits (KAH) toward a healthy lifestyle and ideal cardiovascular health (ICH) scores of 1,216 children 9 to 13 years old was performed. Of the total, 596 had previously received a preschool health promotion intervention at 3 to 5 years old, whereas the remaining 620 were not previously intervened (intervention-naive group). In phase 2, all children were cluster randomized 1:1 to receive either a 4-month educational intervention (the SI! Program) to instill healthy behaviors in community centers (24 clusters, 616 children) or to control (24 clusters, 600 children). Previously intervened and intervention-naive children were not mixed in the same cluster. The primary outcomes were the change from baseline in KAH and ICH scores. Intervention effects were tested for with linear mixed-effects models., Results: In phase 1, ∼85% of children had nonideal cardiovascular health, and those who previously received a preschool intervention showed a negligible residual effect compared with intervention-naive children. In phase 2, the between-group (control vs. intervention) differences in the change of the overall KAH and ICH scores were 0.92 points (95% confidence interval [CI]: -0.28 to 2.13; p = 0.133) and -0.20 points (95% CI: -0.43 to 0.03; p = 0.089), respectively. No booster effect was detected. However, a dose-response effect was observed, with maximal benefit in children attending >75% of the scheduled intervention; the difference in the change of KAH between the high- and low-adherence groups was 3.72 points (95% CI: 1.71 to 5.73; p < 0.001)., Conclusions: Although overall significant differences between the intervention and control groups were not observed, high adherence rates to health promotion interventions may improve effectiveness and outcomes in children. Reintervention strategies may be required at multiple stages to induce sustained health promotion effects (Salud Integral Colombia [SI! Colombia II]; NCT03119792)., (Copyright © 2020. Published by Elsevier Inc.)

Background: The incidence of cardiovascular (CV) risk factors is increasing globally, with a disproportionate burden in the low and low-middle income countries (L/LMICs). Peer support, as a low-cost lifestyle intervention, has succeeded in managing chronic illness. For global CV risk reduction, limited data exists in LMICs., Aim: The GHP-CHANGE was designed as a community-based randomized trial to test the effectiveness of peer support strategy for CV risk reduction in the island of Grenada, a LMIC., Methods: We recruited 402 adults from the Grenada Heart Project (GHP) Cohort Study of 2827 subjects with at least two CV risk factors. Subjects were randomized in a 1:1 fashion to a peer-group based intervention group (n = 206) or a self-management control group (n = 196) for 12 months. The primary outcome was the change from baseline in a composite score related to Blood pressure, Exercise, Weight, Alimentation and Tobacco (FBS, Fuster-BEWAT Score), ranging from 0 to 15 (ideal health = 15). Linear mixed-effects models were used to test for intervention effects., Results: Participants mean age was 51.4 years (SD 14.5) years, two-thirds were female, and baseline mean FBS was 8.9 (SD 2.6) and 8.5 (SD 2.6) in the intervention and control group, respectively (P = .152). At post intervention, the mean FBS was higher in the intervention group compared to the control group [9.1 (SD 2.7) vs 8.5 (SD 2.6), P = .028]. When balancing baseline health profile, the between-group difference (intervention vs. control) in the change of FBS was 0.31 points (95% CI: -0.12 to 0.75; P = .154)., Conclusions: The GHP-CHANGE trial showed that a peer-support lifestyle intervention program was feasible; however, it did not demonstrate a significant improvement in the FBS as compared to the control group. Further studies should assess the effects of low-cost lifestyle interventions in LMICs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Glioblastoma is a heterogeneous glial cell malignancy with extremely high morbidity and mortality. Current treatment is limited and provide minimal therapeutic efficacy. Previous studies were reliant on cell lines that do not accurately reflect the heterogeneity of the glioma microenvironment. Developing reliable models of human glioblastoma is therefore essential. Direct culture of human brain tumours is often difficult and there is a limited number of protocols available. Hence, we have developed an effective method for the primary culture of human glioblastoma samples obtained during surgical resection. Culturing tumour tissue direct from human brain is advantageous in that cultures (1) more closely resemble true human disease, relative to the use of cell lines; (2) comprise a range of cellular components present in the natural tumour microenvironment; and (3) are free of added antibodies and reagents. Additionally, primary glioblastoma cultures are valuable in studies examining the effects of anti-cancer pharmaceuticals and therapeutic agents, and can be further used in live cell imaging, immunocytochemistry, flow cytometry and immunoassay experiments. Via this protocol, cells are maintained in supplemented medium at 37 °C (5% CO 2 ) and are expected to achieve sufficient confluency within 7 days of initial culture., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Study Design: Ambispective observational cohort study., Objectives: Synthetic graft usage avoids morbidity associated with harvest and reduces operative time. This study aims to evaluate outcomes of anterior cervical stabilization surgery using a synthetic cage in comparison with iliac crest bone graft (ICBG) following cervical spine trauma., Methods: An ambispective review was conducted on patients from the Alfred Trauma Registry. Consecutive patients treated at a level 1 trauma center, aged 18 years and older who were treated with standalone anterior cervical stabilization following spine trauma (2011-2016) were included in the study. Primary outcome measures were patient overall satisfaction, Neck Disability Index (NDI), neck pain 10-point visual analogue scale (VAS-neck) and arm pain 10-point visual analogue scale (VAS-arm). Secondary outcome measures were radiographic evidence of fusion and rate of revision surgery. All patients had follow-up for at least 1 year., Results: Between 2011 and 2016, 114 traumatic disc levels in 104 patients were treated. ICBG was used in 32% and polyetheretherketone (PEEK) cage in 68% of the patients. Both groups had similar demographic metrics. There was no significant difference in primary outcome measures between the graft types: (1) patient satisfaction ( P = .15), (2) NDI ( P = .11), (3) VAS-neck ( P = .13), and (4) VAS-arm ( P = .20). Radiology based fusion assessment 6 months postsurgery did not show statistical significance ( P = .10). The rates of revision surgery were similar., Conclusions: This study showed no significant difference in patient-reported outcome measures when comparing the usage of PEEK cage and ICBG in anterior stand alone cervical spine stabilization. Level 1 evidence studies are required to further investigate this finding., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Hydrocephalus remains an important aspect of neurosurgical care and in select circumstances, the endoscopic third ventriculostomy (ETV) continues to remain an important treatment. In our initial experience of ETV using the commercially available plastic ventricular ports we found them both restrictive and expensive. Following this experience, we developed a stainless steel ventricular access port (VAP). We present our novel method of access involving this non-disposable ventricular port., Method: We have developed a series of custom-made, 316-grade stainless steel VAPs designed specifically for our ventricular endoscopes. Following a standard Burr-hole, cannulation of the lateral ventricle is performed inserting this port and removing the trocar allowing free access using a standard ventriculoscope without the requirement for disposable plastic ports. Since 2008 our unit has used a standard method of ventricular access using this device. We present our long-term experience of cases of endoscopic ventriculoscopy and ventriculostomy using this method of ventricular access., Results: From December 2008 to January 2016, 56 patients underwent an endoscopic third ventriculostomy using the stainless steel ventricular port. Two 2 patients (3.6%) had a recorded complication in the form of minor self-limiting intraventricular haemorrhage. No cases of infection or mortality were noted in this patient series., Conclusion: We demonstrate our long-term experience with a non-disposable VAP for ventricular access. This method remains safe with results that are comparable to published series. We suggest this method may be a less expensive and safe alternative to standard disposable methods of ventricular access.

Several theories suggest that self-focused attention plays an important role in the maintenance of depression. However, previous studies have predominantly relied on self-report and laboratory-based measures such as sentence completion tasks to assess individual differences in self-focus. We present a prospective, longitudinal study based on a sample of 29 inpatients with clinical depression, investigating whether an implicit, behavioural measure of self-focused attention, i.e., the relative frequency of first-person singular pronouns in naturally spoken language, predicts depressive symptoms at follow-up over and above initial depression. We did not find a significant cross-sectional association between depressive symptoms and first-person singular pronoun use. However, first-person singular pronoun use significantly predicted depressive symptoms approximately 8 months later, even after controlling for depressive symptoms at baseline or discharge. Exploratory analyses revealed that this effect was mainly driven by the use of objective and possessive self-references such as 'me' or 'my'. Our findings are in line with theories that highlight individual differences in self-focused attention as a predictor of the course of depression. Moreover, our findings extend previous work in this field by adopting an unobtrusive approach of non-reactive assessment, capturing naturally occurring differences in self-focused attention. We discuss possible clinical applications of language-based assessments and interventions with regard to self-focus. Copyright © 2016 John Wiley & Sons, Ltd., Key Practitioner Message: Naturally occurring individual differences in first-person singular pronoun use provide an unobtrusive way to assess patients' automatic self-focused attention. Frequent use of first-person singular pronouns predicts an unfavourable course of depression. Self-focused language might offer innovative ways of tracking and targeting therapeutic change., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Educational interventions in preschool children could improve dietary behavior and physical activity, and prevent unhealthy body weights in low- and middle-income countries. Previously, we have reported the beneficial impact of an educational intervention in preschoolers in a 6-month trial. We now report extended results after 36 months., Methods: Evaluating the cohort of previously intervened children, baseline measurements were made in May 2009 in 14 preschool facilities in Usaquén (Bogotá, Colombia). Follow-up measurements were performed at 18 and 36 months. The primary outcome was the mean change in children's knowledge and attitudes scores regarding healthy eating and living an active lifestyle, including habits scores related to physical activity. Secondary outcomes were the change over time of children's nutritional status and the mean change in parent's knowledge, attitudes, and habits., Results: We included 1216 children, 3-5 years of age, and 928 parents. After adjusting by sex and age of children, socioeconomic status, age of parents, and age and education level of teachers, we found a significant increase in mean knowledge, attitudes, and habits scores at 36 months, compared with baseline: 87.94 vs 76.15 (P <.001); 86.39 vs 57.03 (P <.001); and 66.29 vs 48.72 (P <.001), respectively. We observed a similar increase in knowledge and attitude scores in parents: 73.45 vs 70.01 (P <.001); and 78.08 vs 74.65 (P <.001). The proportion of eutrophic children increased from 62.1% at baseline to 75.0% at 36 months (P <.0001)., Conclusions: After 36 months, the educational intervention maintained a beneficial trend toward a healthy lifestyle in children and their parents., (Copyright © 2013. Published by Elsevier Inc.)

Background: School programs can be effective in modifying knowledge, attitudes, and habits relevant to long-term risk of chronic diseases associated with sedentary lifestyles. As part of a long-term research strategy, we conducted an educational intervention in preschool facilities to assess changes in preschoolers' knowledge, attitudes, and habits toward healthy eating and living an active lifestyle., Methods: Using a cluster design, we randomly assigned 14 preschool facilities in Bogotá, Colombia to a 5-month educational and playful intervention (7 preschool facilities ) or to usual curriculum (7 preschool facilities ). A total of 1216 children aged 3-5 years, 928 parents, and 120 teachers participated. A structured survey was used at baseline, at the end of the study, and 12 months later to evaluate changes in knowledge, attitudes, and habits., Results: Children in the intervention group showed a 10.9% increase in weighted score, compared with 5.3% in controls. The absolute adjusted difference was 3.90 units (95% confidence interval [CI], 1.64-6.16; P <.001). Among parents, the equivalent statistics were 8.9% and 3.1%, respectively (absolute difference 4.08 units; 95% CI, 2.03 to 6.12; P <.001), and among teachers, 9.4% and 2.5%, respectively (absolute difference 5.36 units; 95% CI, -0.29-11.01; P = .06). In the intervened cohort 1 year after the intervention, children still showed a significant increase in weighted score (absolute difference of 6.38 units; P <.001)., Conclusions: A preschool-based intervention aimed at improving knowledge, attitudes, and habits related to healthy diet and active lifestyle is feasible, efficacious, and sustainable in very young children., (Copyright © 2013. Published by Elsevier Inc.)

Objective: The Grenada Heart Project aims to study the clinical, biological, and psychosocial determinants of the cardiovascular health in Grenada in order to develop and implement a nationwide cardiovascular health promotion program., Methods: We recruited 2,827 adults randomly selected from the national electronic voter list. The main outcome measures were self-reported cardiovascular disease and behavioral risk factors, anthropometric measures, blood pressure, point-of-care testing for glucose and lipids, and ankle-brachial index. Risk factors were also compared with the U.S. National Health and Nutritional Survey data., Results: Prevalence of cardiovascular disease risk factors were: overweight and obesity-57.7% of the population, physical inactivity-23.4%, diabetes-13.3%, hypertension-29.7%, hypercholesterolemia-8.6%, and smoking-7%. Subjects who were physically active had a significantly lower 10-year Framingham risk score (p<0.001). Compared with the U.S. National Health and Nutrition Survey data, Grenadian women had higher rates of adiposity, diabetes, hypertension, and elevated low-density lipoprotein cholesterol, whereas Grenadian men had a higher rate of diabetes, a similar rate of hypertension, and lower rates of the other risk factors. Prevalence of peripheral arterial disease was 7.6%; stroke and coronary heart disease were equally prevalent at ∼2%., Conclusions: This randomly selected adult sample in Grenada reveals prevalence rates of obesity, hypertension, and diabetes significantly exceeding those seen in the United States. The contrasting, paradoxically low levels of prevalent cardiovascular disease support the concept that Grenada is experiencing an obesity-related "risk transition." These data form the basis for the implementation of a pilot intervention program based on the Institute of Medicine recommendations and may serve as a model for other low- and middle-income countries., (Copyright © 2012 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

A retrospective analysis of 301 patients was undertaken between 1993 and 2003 to evaluate the relationship of ethnicity with incidence, treatment and survival in patients undergoing surgery for high grade glioma (HGG) in New Zealand. There was no difference in age standardised incidence of HGG in Māori compared to non-Māori patients; 4.2/100,000 person years (95% confidence interval [CI] 2.6-6.9) versus 4.1 (95% CI 3.6-4.6). Māori were more likely to have complete tumour resection (odds ratio 3.59 (95% CI 1.01-12.76)) but waited 1.32 (95% CI 0.98-1.79) times longer for radiotherapy. Median survival was 29 weeks with poorer survival in Māori compared to non-Māori (hazard ratio 1.55 [95% CI 0.95-2.55]). We concluded that the incidence of HGG in Māori is similar to non-Maori. However, Māori with HGG have higher rates of complete resection but wait longer for radiotherapy and may have poorer overall survival than non-Māori., (Copyright 2010 Elsevier Ltd. All rights reserved.)