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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.

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).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).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).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.

Study Design: Systematic review. Objectives: Management of stable traumatic thoracolumbar burst fractures in neurologically-intact patients remains controversial. Conservative management fails in a subset of patients who require subsequent surgical fixation. The aim of this review is to (1) determine the rate of conservative management failure, and (2) analyze predictive factors at admission influencing conservative management failure. Methods: A systematic review adhering to PRISMA guidelines was performed. Studies with data pertaining to traumatic thoracolumbar burst fractures without posterior osteoligamentous injury (e.g. AO Type A3/A4) and/or the rate and predictive factors of conservative management failure were included. Risk of bias appraisal was performed. Pooled analysis of rates of failure was performed with qualitative analysis of predictors of conservative management failure. Results: 16 articles were included in this review (11 pertaining to rate of conservative management failure, 5 pertaining to predictive risk factors). Rate of failure of conservative management from a pooled analysis of 601 patients is 9.2% (95% CI: 4.5%-13.9%). Admission factors predictive of conservative management failure include age, greater initial kyphotic angle, greater initial interpedicular distance, smaller initial residual canal size, greater Load Sharing Classification (LSC) score and greater admission Visual Analog Scale (VAS) pain scores. Conclusion: A proportion (9.2%) of conservatively managed, neurologically-intact thoracolumbar burst fractures fail conservative management. Among other factors, age, kyphotic angle, residual canal area and interpedicular distance should be investigated in prospective studies to identify the subset of patients prone to failure of conservative management. Surgical management should be carefully considered in patients with the above risk factors.

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

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.

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.

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.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.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 (P0.01). 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). Age50 years predicted longer overall survival (odds ratio, 0.16; 95% CI, 0.05-0.49; P0.01). 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).Clear cell ependymomas are particularly aggressive in those aged50 years. Gross total resection remains the cornerstone of management. Postoperative adjuvant therapy is likely to be of survival benefit only after subtotal resection.

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% (

The authors perform a retrospective trauma registry study to compare clinical, surgical and radiographical variables between anterior and posterior approaches in the management of AO Type B1 and B2 traumatic thoracolumbar fractures. Consecutive patients with surgically-managed AO Type B1 and B2 thoracolumbar fractures were included. Baseline demographics, surgical outcomes (including duration of surgery, postoperative morbidity etc.), neurological outcomes and radiographical outcomes (Cobb angle, Gardner angle) were compared between the anterior and posterior approaches. A total of 108 patients (anterior: n = 25, posterior: n = 83) were included. There were no significant between-group differences in baseline demographics and co-morbidities. Duration of surgery was longer in the anterior compared to posterior group (251 ± 91 min vs. 175 ± 69 min respectively, p 0.00003). At six-months post-surgery, there was a trend towards improvement of at least one AIS grade in the posterior compared to the anterior group (85.7% vs. 33.3% respectively, p = 0.08). Postoperative complication profile showed no difference between approaches. The posterior approach resulted in better sagittal correction (Cobb angle; anterior: +1.05 ± 8.61 deg, posterior: -3.87 ± 9.88 deg, p = 0.03) and smaller loss of correction at 6-months post-surgery (Cobb angle; anterior: 8.36 ± 9.47 deg, posterior: 4.88 ± 6.62 deg, p = 0.048). This is the first study investigating surgical approach in flexion-distraction thoracolumbar fractures. Besides a shorter operative duration, the posterior approach seems to portend more favourable radiological correction at 6 months when compared to the anterior approach. Given the inherent selection bias of this study, definitive recommendations regarding the anterior versus posterior approach cannot be made. Further well-defined, prospective studies are necessary.

BACKGROUND CONTEXT There are three phases in prophylaxis of surgical site infections (SSI): preoperative, intraoperative and postoperative. There is lack of consensus and paucity of evidence with SSI prophylaxis in the postoperative period. PURPOSE To systematically evaluate the literature, and provide evidence-based summaries on postoperative measures for SSI prophylaxis in spine surgery. STUDY DESIGN Systematic review, meta-analysis, evidence synthesis. METHODS A systematic review conforming to PRIMSA guidelines was performed utilizing PubMed (MEDLINE), EMBASE, and the Cochrane Database from inception to January 2019. The GRADE approach was used for quality appraisal and synthesis of evidence. Six postoperative care domains with associated key questions were identified. Included studies were extracted into evidence tables, data synthesized quantitatively and qualitatively, and evidence appraised per GRADE approach. RESULTS Forty-one studies (nine RCT, 32 cohort studies) were included. In the setting of preincisional antimicrobial prophylaxis (AMP) administration, use of postoperative AMP for SSI reduction has not been found to reduce rate of SSI in lumbosacral spine surgery. Prolonged administration of AMP for more than 48 hours postoperatively does not seem to reduce the rate of SSI in decompression-only or lumbar spine fusion surgery. Utilization of wound drainage systems in lumbosacral spine and adolescent idiopathic scoliosis corrective surgery does not seem to alter the overall rate of SSI in spine surgery. Concomitant administration of AMP in the presence of a wound drain does not seem to reduce the overall rate of SSI, deep SSI, or superficial SSI in thoracolumbar fusion performed for degenerative and deformity spine pathologies, and in adolescent idiopathic scoliosis corrective surgery. Enhanced-recovery after surgery clinical pathways and infection-specific protocols do not seem to reduce rate of SSI in spine surgery. Insufficient evidence exists for other types of spine surgery not mentioned above, and also for non-AMP pharmacological measures, dressing type and duration, suture and staple management, and postoperative nutrition for SSI prophylaxis in spine surgery. CONCLUSIONS Despite the postoperative period being key in SSI prophylaxis, the literature is sparse and without consensus on optimum postoperative care for SSI prevention in spine surgery. The current best evidence is presented with its limitations. High quality studies addressing high risk cohorts such as the elderly, obese, and diabetic populations, and for traumatic and oncological indications are urgently required.

Background: AO Type B3 hyperextension thoracolumbar fractures are the commonest fracture subtype in ankylosing spinal disorders. Although often considered together in spinal fractures, ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are distinct spondyloarthropathies with different pathophysiology. Few studies have compared the two entities in the setting of traumatic thoracolumbar fractures. The authors compare demographic metrics, injury profile, clinical and radiographical outcomes between patients with AS and DISH in patients suffering from AO Type B3 traumatic thoracolumbar fractures. Methods: From January 2008 to December 2018, a retrospective analysis of consecutive surgically-managed patients with AO Type B3 fractures was performed. Demographic metrics, co-morbidity [Charlson-comorbidity index, modified frailty index (mFI), etc.], injury profile (level of injury, mechanism of injury, etc.), clinical (postoperative complication, etc.) and radiographical variables were collected. Differences between patients with AS and DISH were compared. Results: Fourteen patients were identified. All patients had AS (n=6) or DISH (n=8). The mean age was 72.8±10.2 years and 78.6% of patients were neurologically intact at presentation. Medical and/or surgical complications occurred in 10 of 14 (71.4%) patients. As compared to patients with DISH, patients with AS were more likely to have low falls as the injury mechanism [odds ratio (OR): 35.0, P=0.026], have higher mFI (OR: 30.6, P=0.015), and experience a higher number of postoperative complications per patient (AS: 1.8/patient vs. DISH: 0.5/patient, P=0.024). Conclusions: In the setting of AO Type B3 fractures, patients with AS are more frail and have higher in-hospital morbidity compared to patients with DISH. Despite both pathologies being ankylosing in nature, further studies are required to fully understand the clinical differences between the two entities to enable clinicians to apply a more targeted and nuanced approach in managing fractures in ankylosing spinal disorders.

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.

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.

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.

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 MAP100min.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 (

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.

Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment imaging-based response monitoring. This systematic review aimed to present and evaluate evidence for differential expression and diagnostic accuracy of circulating biomarkers with respect to outcomes of tumor response, progression, stable disease, and treatment effects (pseudoprogression, radionecrosis, pseudoresponse, and pseudolesions) in patients undergoing treatment for World Health Organization grades II–IV diffuse astrocytic and oligodendroglial tumors. MEDLINE, EMBASE, Web Of Science, and SCOPUS databases were searched until August 18, 2019, for observational or diagnostic studies on multiple circulating biomarker types: extracellular vesicles, circulating nucleic acids, circulating tumor cells, circulating proteins, and metabolites, angiogenesis related cells, immune cells, and other cell lines. Methodological quality of included studies was assessed using an adapted Quality Assessment of Diagnostic Accuracy Studies-2 tool, and level of evidence (IA–IVD) for individual biomarkers was evaluated using an adapted framework from the National Comprehensive Cancer Network guidelines on evaluating tumor marker utility. Of 13,202 unique records, 58 studies met the inclusion criteria. One hundred thirty-three distinct biomarkers were identified in a total of 1,853 patients across various treatment modalities. Fifteen markers for response, progression, or stable disease and five markers for pseudoprogression or radionecrosis reached level IB. No biomarkers reached level IA. Only five studies contained data for diagnostic accuracy measures. Overall methodological quality of included studies was low. While extensive data on biomarker dysregulation in varying response categories were reported, no biomarkers ready for clinical application were identified. Further assay refinement and evaluation in larger cohorts with diagnostic accuracy study designs are required. PROSPERO Registration: CRD42018110658.

Acute subdural hematoma (aSDH) is among the most common injury types encountered by neurosurgeons, and carries a poor prognosis, particularly in the elderly. As the incidence of aSDH in the elderly population rises, identifying those patients who may benefit from operative intervention is crucial. This systematic review aimed to identify data on prognostic factors or indices, such as the modified frailty index, that may help predict outcome, and hence guide management. A comprehensive search of online databases was conducted by two independent authors, and data on prognostic factors and outcomes were extracted. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Of 769 studies identified in the initial search, 7 satisfied inclusion and exclusion criteria. Mortality and morbidity varied considerably among studies. Initial Glasgow Coma Scale (GCS) of 3-8 was the most consistently reported negative prognostic feature. Several studies evaluated the impact of medical comorbidities and premorbid frailty, but were limited by small sample size. A previous history of pneumonia was shown to increase the risk of Glasgow Outcome Score (GOS) 1-3 (odds ratio [OR] 6.4 [95% CI 1.6-25.2], p = 0.04) in a single study, which also reported a greater increase in GOS at 3 months in those with fewer than five comorbidities (56% vs. 19%, p 0.01). There are limited data describing prognostic factors or the use of frailty indices within the specific group of elderly patients with aSDH. Prospective research is needed to evaluate the utility of accurate and validated assessments of frailty to enhance the neurosurgeon's ability to appropriately manage this complex and expanding patient group.

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.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.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.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.

Obesity is an important consideration in neurosurgical practice. Of Australian adults, 28.3% are obese and it is estimated that more than two thirds of Australia's population will be overweight or obese by 2025. This review of the effects of obesity on neurosurgical procedures shows that, in patients undergoing spinal surgery, an increased body mass index is a significant risk factor for surgical site infection, venous thromboembolism, major medical complications, prolonged length of surgery, and increased financial cost. Although outcome scores and levels of patient satisfaction are generally lower after spinal surgery in obese patients, obesity is not a barrier to deriving benefit from surgery and, when the natural history of conservative management is taken into account, the long-term benefits of surgery may be equivalent or even greater in obese patients than in nonobese patients. In cranial surgery, the impact of obesity on outcome and complication rates is generally lower. Specific exceptions are higher rates of distal catheter migration after shunt surgery and cerebrospinal fluid leak after posterior fossa surgery. Minimally invasive approaches show promise in mitigating some of the adverse effects of obesity in patients undergoing spine surgery but further studies are needed to develop strategies to reduce obesity-related surgical complications.

We report the case of a 68-year-old male with right eye vision loss secondary to a compressive optic neuropathy from Waldenstrom macroglobulinaemia relapse in both cavernous sinuses. Central nervous system involvement is extremely uncommon in lymphoplasmacytic lymphoma. Known as Bing-Neel syndrome, this has not been previously reported to present simultaneously in bilateral cavernous sinuses. We discuss the pathophysiology, diagnostic and neuroradiological features of Bing-Neel syndrome. In this case, there was marked clinical and radiological response to chemotherapy. As outcomes following treatment for Waldenstrom macroglobulinaemia improve, greater awareness of its less common manifestations becomes important. Neurosurgical intervention may be indicated to obtain histological diagnosis or decompress critical structures.

Between July 1997 and April 2001, forty patients underwent Guglielmi detachable coil (GDC) embolization of intracranial aneurysms at Wellington Hospital.The clinical notes and imaging were reviewed retrospectively.Complete initial occlusion was achieved in 28 patients (70%). Eleven patients (27.5%) had small residual neck (90% occlusion) and one patient (2.5%) had substantial filling of the aneurysm. Follow up angiographic assessment was obtained in 28 patients (70%) of whom 24 patients (85.7%) had no recurrence or stable residual neck and four patients (14.3%) had recurrence or enlargement of the residual neck. Stable occlusion was achieved in 100% of small and medium sized aneurysms and 50% of large and giant aneurysms. Technical complications occurred in 10% including aneurysms perforated in two patients (5%) and presumed parent artery occlusion in another two (5%).The findings of the present study demonstrate the safety of GDC embolization. The initial clinical grade at presentation strongly predicted the clinical outcome. Although the number of patients in this study is small, there is evidence that the angiographic outcome is better for small and medium sized aneurysms. Our results are comparable to other published series.

Engagement of the Fas receptor promotes apoptosis by activation of caspases. In addition, alterations in plasma membrane lipid orientation and intracellular ceramide levels are often observed. In A20 B-lymphoma cells,FasL-induced cell death and phosphatidylserine (PS) externalization were completely prevented by the generic caspase inhibitor z-VAD-fmk. By contrast,the caspase-3 inhibitor Ac-DEVD-cho only partially restored cell viability and had no effect on surface exposure of PS. Flow cytometric analysis after FasL treatment identified two populations of dead cells. In one, death was dependent on caspase-3 and paralleled by DNA fragmentation and cell shrinkage. In the second, death occurred in the absence of caspase-3 activity and apoptotic features but was also blocked by zVAD-fmk. By morphological criteria these were identified as apoptotic and necrotic cells, respectively. Using fluorescent substrates, caspase-3 activity was detected only in the apoptotic cell population, whereas caspase-8 activity was detected in both. Both forms of caspase-8-dependent cell death were also detected downstream of Fas in Jurkat T-cells, where Fas-dependent PS externalization and delayed ceramide production, which is similar to results shown here in A20 cells, have been reported. However, for Raji B-cells, lacking lipid scrambling and ceramide production in response to Fas activation, only apoptosis was detected. Short-chain C2- or C6-ceramides, but not the respective inactive dihydro compounds or treatment with bacterial sphingomyelinase, induced predominantly necrotic rather than apoptotic cell death in A20 B-, Raji B- and Jurkat T-cells. Thus, delayed elevation of ceramide is proposed to promote necrosis in those Fas-stimulated cells where caspase-8 activation was insufficient to trigger caspase-3-dependent apoptosis.