Neighbourhood deprivation, distance to nearest comprehensive stroke centre and access to endovascular thrombectomy for ischemic stroke: a population-based study.

BACKGROUND: Endovascular thrombectomy (EVT) has revolutionized ischemic stroke care. We aimed to assess whether neighbourhood socioeconomic status is predictive of access to EVT after receipt of alteplase for ischemic stroke among patients living in Alberta, Canada, and whether this relation is mediated by the distance a person lives to the nearest comprehensive stroke centre (CSC). METHODS: We performed a retrospective study including all people older than 18 years living in Alberta who were admitted to hospital with an ischemic stroke and who received intravenous alteplase treatment between Jan. 1, 2017, and Dec. 31, 2019. Data were obtained through administrative data sets. The primary outcome was treatment with EVT. We assigned neighbourhood deprivation quintile based on the Material and Social Deprivation Index. We used logistic regression modelling to assess for a relation between deprivation and treatment with EVT. We adjusted for age, sex, stroke severity and distance to the nearest CSC. We calculated the average causal mediation effect of distance to the nearest CSC on the relation between neighbourhood deprivation level and treatment with EVT. RESULTS: The study cohort consisted of 1335 patients, of whom 181 (13.6%) had missing data and were excluded from the main regression analysis. Endovascular thrombectomy was performed or attempted in 314 patients (23.5%). In the primary model, patients from the most deprived neighbourhoods were less likely than those from less deprived neighbourhoods to have received EVT (adjusted odds ratio 0.43, 95% confidence interval 0.24 to 0.77). Neighbourhood deprivation level was not significantly associated with EVT when distance to the nearest CSC was included as a covariate. Mediation analysis suggested that 48% of the total effect that neighbourhood deprivation level had on the odds of receiving EVT was attributable to the distance a person lived from the nearest CSC. INTERPRETATION: The results suggest that people from more deprived neighbourhoods in Alberta were less likely to be treated with EVT than those from less deprived neighbourhoods. Improving access to EVT for people living in remote locations may improve the equitable distribution of this treatment.

Natural history of antiplatelet nonresponders undergoing carotid artery stenting.

OBJECTIVE: Routine antiplatelet responsiveness testing for patients undergoing carotid artery stenting procedures is not performed at most endovascular centers and remains a topic of controversy within the neurointerventional community. The objective of this study was to determine if nonresponsiveness to acetylsalicylic acid or clopidogrel was associated with the development of symptomatic thromboembolic events in patients undergoing carotid stenting procedures. METHODS: A prospective study was conducted at the Foothills Medical Centre in Calgary, Alberta, Canada, from August 2019 to July 2021. Patients undergoing carotid artery stenting procedures and who were receiving dual antiplatelet therapy were enrolled in the study. Responsiveness to the antiplatelet medications was determined through whole blood impedance aggregometry. The primary outcome was development of a symptomatic thromboembolic event within 90 days after the procedure. The treating physicians were blinded to the aggregometry results for the duration of the study. RESULTS: One hundred two procedures were performed in 100 patients. Eight thromboembolic events (8%) occurred during the study. Age (p = 0.03) and nonresponsiveness to clopidogrel (p = 0.003) were associated with the development of thromboembolic events. The multivariable model showed that clopidogrel nonresponsiveness was independently associated with the development of a thromboembolic event (adjusted OR 6.14, 95% CI 1.25-30.11, p = 0.03). CONCLUSIONS: This study demonstrated that patients who were identified as clopidogrel nonresponders, using whole blood impedance aggregometry, were at an increased risk of developing thromboembolic events. Larger studies are needed to assess the utility of routine platelet function testing prior to carotid artery stenting procedures.

Subarachnoid Hemorrhage, Delayed Cerebral Ischemia, and Milrinone Use in Canada.

INTRODUCTION: Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI. METHODS: We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods. RESULTS: The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI. CONCLUSION: DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

Optimal Glucose Target After Aneurysmal Subarachnoid Hemorrhage: A Matched Cohort Study.

BACKGROUND: Hyperglycemia has been associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, there remains debate as to what optimal glucose targets should be in this patient population. OBJECTIVE: To assess whether we could identify an optimal glucose target for patients with aSAH. METHODS: We performed a post hoc analysis of the "clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage" trial data set. Patients had laboratory results drawn daily for the entirety of their intensive care unit stay. Maximum blood glucose levels were assessed for a relationship with unfavorable outcomes using multiple logistic regression analysis. Maximum blood glucose levels were dichotomized based on the Youden index, which identified a maximum level of <9.2 mmol/L as the optimal cut point for prediction of unfavorable outcomes. Nearest neighbor matching was used to assess the relationship between maintaining glucose levels below the cut point and unfavorable functional outcomes (defined as a modified Rankin score of >2 at 3 mo post-aSAH). The matching was performed after calculation of a propensity score based on identified predictors of outcome and glucose levels. RESULTS: Three hundred eighty-nine patients were included in the matched analysis. Propensity scores were balanced on both the covariates and outcomes of interest. There was a significant average treatment effect (-0.143: 95% confidence interval -0.267 to -0.019) for patients who maintained glucose levels <9.2 mmol/L. CONCLUSION: Maintaining glucose levels below the identified cut point was associated with a decreased risk for unfavorable outcomes in this retrospective matched study.

A nationwide prospective multicenter study of external ventricular drainage: accuracy, safety, and related complications.

OBJECTIVE: External ventricular drainage (EVD) catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH), and suboptimal placement. The aim of this study was to investigate the rates of EVD catheter complications and their associated risk factor profiles in order to optimize the safety and accuracy of catheter insertion. METHODS: A total of 348 patients with urgently placed EVD catheters were included as a part of a prospective multicenter observational cohort. Strict definitions were applied for each complication category. RESULTS: The rates of misplacement, ECI/ventriculitis, and ICH were 38.6%, 12.2%, and 9.2%, respectively. Catheter misplacement was associated with midline shift (p = 0.002), operator experience (p = 0.031), and intracranial length (p < 0.001). Although mostly asymptomatic, ICH occurred more often in patients receiving prophylactic low-molecular-weight heparin (LMWH) (p = 0.002) and those who required catheter replacement (p = 0.026). Infectious complications (ECI/ventriculitis and suspected ECI) occurred more commonly in patients whose catheters were inserted at the bedside (p = 0.004) and those with smaller incisions (≤ 1 cm) (p < 0.001). ECI/ventriculitis was not associated with preinsertion antibiotic prophylaxis (p = 0.421), catheter replacement (p = 0.118), and catheter tunneling length (p = 0.782). CONCLUSIONS: EVD-associated complications are common. These results suggest that the operating room setting can help reduce the risk of infection, but not the use of preoperative antibiotic prophylaxis. Although EVD-related ICH was associated with LMWH prophylaxis for deep vein thrombosis, there were no significant clinical manifestations in the majority of patients. Catheter misplacement was associated with operator level of training and midline shift. Information from this multicenter prospective cohort can be utilized to increase the safety profile of this common neurosurgical procedure.

National adverse event profile after lumbar spine surgery for lumbar degenerative disorders and comparison of complication rates between hospitals: a CSORN registry study.

OBJECTIVE: Previous works investigating rates of adverse events (AEs) in spine surgery have been retrospective, with data collection from administrative databases, and often from single centers. To date, there have been no prospective reports capturing AEs in spine surgery on a national level, with comparison among centers. METHODS: The Spine Adverse Events Severity system was used to define the incidence and severity of AEs after spine surgery by using data from the Canadian Spine Outcomes and Research Network (CSORN) prospective registry. Patient data were collected prospectively and during hospital admission for those undergoing elective spine surgery for degenerative conditions. The Spine Adverse Events Severity system defined minor and major AEs as grades 1-2 and 3-6, respectively. RESULTS: There were 3533 patients enrolled in this cohort. There were 85 (2.4%) individual patients with at least one major AE and 680 (19.2%) individual patients with at least one minor AE. There were 25 individual patients with 28 major intraoperative AEs and 260 patients with 275 minor intraoperative AEs. Postoperatively there were 61 patients with a total of 80 major AEs. Of the 487 patients with minor AEs postoperatively there were 698 total AEs. The average enrollment was 321 patients (range 47-1237 patients) per site. The rate of major AEs was consistent among sites (mean 2.9% ± 2.4%, range 0%-9.1%). However, the rate of minor AEs varied widely among sites-from 7.9% to 42.5%, with a mean of 18.8% ± 9.7%. The rate of minor AEs varied depending on how they were reported, with surgeon reporting associated with the lowest rates (p < 0.01). CONCLUSIONS: The rate of major AEs after lumbar spine surgery is consistent among different sites but the rate of minor AEs appears to vary substantially. The method by which AEs are reported impacts the rate of minor AEs. These data have implications for the detection and reporting of AEs and the design of strategies aimed at mitigating complications.

Missed opportunities within healthcare for an earlier diagnosis of HIV.

Despite guidelines, many individuals are not routinely tested for HIV within healthcare settings. Our objective was to quantify and characterize preceding clinical encounters by newly-diagnosed persons living with HIV in southern Alberta, Canada. We discuss the clinical impact of missed HIV testing, and options for remediation. Clinical encounters prior to HIV diagnosis including the discharge diagnosis were collected between 1 April 2011 and 1 April 2016. We followed the HIV Indicator Diseases across Europe Study criteria to identify HIV Clinical Indicator Conditions (HCICs) present at clinical encounters. Patients accessing prior care were compared to those who had not previously accessed care. Of 393 individuals, 231 (58.7%) had ≥1 encounter prior to diagnosis; 224 (57%) of encounters occurred in outpatient clinics, 130 (33.1%) in emergency departments, and 39 (9.9%) in urgent care clinics. Approximately 25% (n = 57) of patients who engaged healthcare had ≥ 1 recognized HCIC but did not receive HIV testing. The most frequent HCICs were infection (n = 34; 60%) and hematological disorders (n = 12; 21%). The median CD4 cell count at HIV diagnosis for patients with an HCIC was 127 cells/mm3. In this population, three of five patients had accessed healthcare prior to diagnosis with one of four presenting with HCICs but were not offered HIV testing. Protocols beyond the current recommendations are urgently required to address missed HIV diagnostic opportunities who engaged healthcare.

Unfavorable Outcome After Good Grade Aneurysmal Subarachnoid Hemorrhage: Exploratory Analysis.

OBJECTIVE: Patients with good-grade aneurysmal subarachnoid hemorrhage (aSAH) are thought to recover well, yet some do not. This work sought to identify predictors of unfavorable functional outcome after good-grade aSAH. METHODS: We performed a post-hoc analysis of the CONSCIOUS-1 trial. Patients with World Federation of Neurosurgical Societies grades I or II aSAH were included. The primary outcome was unfavorable functional outcome (defined as a modified Rankin Scale score >2) at 12 weeks. Parametric and nonparametric testing were used as appropriate. Variables were classified as modifiable or nonmodifiable, depending on whether they were present at patient admission. Stepwise logistic regression models were created for modifiable and nonmodifiable predictors of outcome. Independent predictors in the respective multivariate analyses were combined into a final multivariate regression model. RESULTS: We included 301 patients, 67 of whom (22%) had an unfavorable outcome. Of the nonmodifiable predictors, higher admission systolic blood pressure (P = 0.002) and female sex (P = 0.011) were independently associated with unfavorable outcome. Potentially modifiable independent predictors of outcome were delayed cerebral ischemia (P = 0.039), higher maximum temperature (0.036), suffering a respiratory system complication (P = 0.004), and suffering an intracranial hemorrhagic complication (P = 0.022). All variables found to be independently predictive of poor outcome in their respective models retained statistical significance in the combined multivariate analysis. CONCLUSIONS: About 1 in 5 good-grade aSAH patients enrolled in CONSCIOUS-1 suffered an unfavorable functional outcome. Admission systolic blood pressure, female sex, hyperthermia, delayed cerebral ischemia, respiratory complications, and intracranial hemorrhagic complications may be predictive of outcome.

Lessons from the CONSCIOUS-1 Study.

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One randomized clinical trial that has been examined in detail with these questions in mind is Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1). This was a phase-2 trial testing the effect of clazosentan on angiographic vasospasm (aVSP) in patients with aSAH. Clazosentan decreased moderate to severe aVSP. There was no statistically significant effect on the extended Glasgow outcome score (GOS), although the study was not powered for this endpoint. Data from the approximately 400 patients in the study were detailed, rigorously collected and documented and were generously made available to one investigator. Post-hoc analyses were conducted which have expanded our knowledge of the management of aSAH. We review those analyses here.

Embryology of Spinal Dysraphism and its Relationship to Surgical Treatment.

Spinal dysraphism is an umbrella term that encompasses a number of congenital malformations that affect the central nervous system. The etiology of these conditions can be traced back to a specific defect in embryological development, with the more disabling malformations occurring at an earlier gestational age. A thorough understanding of the relevant neuroembryology is imperative for clinicians to select the correct treatment and prevent complications associated with spinal dysraphism. This paper will review the neuroembryology associated with the various forms of spinal dysraphism and provide a clinical-pathological correlation for these congenital malformations.

The quality of YouTube videos on endoscopic third ventriculostomy and endoscopic third ventriculostomy with choroid plexus cauterization procedures available to families of patients with pediatric hydrocephalus.

OBJECTIVE: YouTube has become an important information source for pediatric neurosurgical patients and their families. The goal of this study was to determine whether the informative quality of videos of endoscopic third ventriculostomy (ETV) and endoscopic third ventriculostomy with choroid plexus cauterization (ETV + CPC) is associated with metrics of popularity. METHODS: This cross-sectional study used comprehensive search terms to identify videos pertaining to ETV and ETV + CPC presented on the first 3 pages of search results on YouTube. Two pediatric neurosurgeons, 1 neurosurgery resident, and 2 patient families independently reviewed the selected videos. Videos were assessed for overall informational quality by using a validated 5-point Global Quality Score (GQS) and compared to online metrics of popularity and engagement such as views, likes, likes/views ratio, comments/views ratio, and likes/dislikes ratio. Weighted kappa scores were used to measure agreement between video reviewers. RESULTS: A total of 58 videos (47 on ETV, 7 on ETV + CPC, 4 on both) of 120 videos assessed met the inclusion criteria. Video styles included "technical" (62%), "lecture" (24%), "patient testimonial" (4%), and "other" (10%). In terms of GQS, substantial agreement was seen between surgeons (kappa 0.67 [95% CI 0.55, 0.80]) and excellent agreement was found between each surgeon and the neurosurgical resident (0.77 [95% CI 0.66, 0.88] and 0.89 [95% CI 0.82, 0.97]). Only fair to moderate agreement was seen between professionals and patient families, with weighted kappa scores ranging from 0.07 to 0.56. Academic lectures were more likely to be rated good or excellent (64% vs 0%, p < 0.001) versus surgical procedure and testimonial video types. There were significant associations between a better GQS and more likes (p = 0.01), views (p = 0.02), and the likes/dislikes ratio (p = 0.016). The likes/views ratio (p = 0.31) and comments/views ratio (p = 0.35) were not associated with GQS. The number of likes (p = 0.02), views (p = 0.03), and the likes/dislikes ratio (p = 0.015) were significantly associated with video style (highest for lecture-style videos). CONCLUSIONS: Medical professionals tended to agree when assessing the overall quality of YouTube videos, but this agreement was not as strongly seen when compared to parental ratings. The online metrics of likes, views, and likes/dislikes ratio appear to predict quality. Neurosurgeons seeking to increase their online footprint via YouTube would be well advised to focus more on the academic lecture style because these were universally better rated.

Natural History and Growth Patterns of Incidentally Discovered Diffusely Infiltrating Low-Grade Gliomas: A Volumetric Study.

BACKGROUND: Incidentally discovered diffusely infiltrating low-grade gliomas (iDLGGs) are rare findings on neuroimaging that pose a challenge to neurosurgeons. There is a paucity of data regarding the natural history of these lesions, and thus management is controversial. We characterize the growth rates and patterns of iDLGGs in a cohort of patients who underwent serial magnetic resonance imaging before surgical treatment. METHODS: We performed a retrospective review of all adult patients (≥18 years old) with diffuse low-grade glioma diagnosed at our institution between April 2004 and April 2016. iDLGG was defined as any lesion discovered on computed tomography or magnetic resonance imaging performed for reasons and/or symptoms not attributable to the lesion and confirmed on histopathology as low-grade glioma. Tumor growth rates and patterns of growth were analyzed in patients who had serial imaging available. RESULTS: Inclusion criteria were met by 15 patients. Mean velocity of diametric expansion was 2.93 mm/year. Of 15 patients, 11 (73.3%) had tumors with an exponential growth pattern, and 4 (26.7%) had a linear growth pattern. Initial tumor volume was positively correlated (r = 0.78) with velocity of diametric expansion. CONCLUSIONS: iDLGGs grow over time, and most exhibit an exponential pattern of growth. Tumor volume at the time of diagnosis is predictive of a faster growth rate, but not the pattern of growth.

Acute kidney injury after aneurysmal subarachnoid hemorrhage and its effect on patient outcome: an exploratory analysis.

OBJECTIVE: Acute kidney injury (AKI) is associated with death in critically ill patients, but this complication has not been well characterized after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of this study was to determine the incidence of AKI after aSAH and to identify risk factors for renal dysfunction. Secondary objectives were to examine what effect AKI has on patient mortality and functional outcome at 12 weeks post-aSAH. METHODS: The authors performed a post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial data set (clinical trial registration no.: NCT00111085, https://clinicaltrials.gov). The primary outcome of interest was the development of AKI, which was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes of interest were death and a modified Rankin Scale score greater than 2 at 12 weeks post-aSAH. Propensity score matching was used to assess for a significant treatment effect related to clazosentan administration and AKI. Univariate analysis, locally weighted scatterplot smoothing (LOWESS) curves, and stepwise logistic regression models were used to evaluate for associations between baseline or disease-related characteristics and study outcomes. RESULTS: One hundred fifty-six (38%) of the 413 patients enrolled in the CONSCIOUS-1 trial developed AKI during their ICU stay. A history of hypertension (p < 0.001) and the number of nephrotoxic medications administered (p = 0.029) were independent predictors of AKI on multivariate analysis. AKI was an independent predictor of death (p = 0.028) but not a poor functional outcome (p = 0.21) on multivariate testing. Unresolved renal dysfunction was the strongest independent predictor of death in this cohort (p < 0.001). CONCLUSIONS: AKI is a common complication following aSAH. Patients with premorbid hypertension and those treated with nephrotoxic medications may be at greater risk for renal dysfunction. AKI appears to confer an increased probability of death after aSAH.

Mobile Applications in Neurosurgery: A Systematic Review, Quality Audit, and Survey of Canadian Neurosurgery Residents.

BACKGROUND: In the past decade, smartphone applications (Apps) have experienced remarkable development across all fields of medicine, including neurosurgery. However, owing to a lack of regulatory oversight and peer review, a clear need exists for a comprehensive review and audit of the existing available Apps. In the present study, we systematically reviewed the existing mobile Apps in neurosurgery, evaluated their clinical use by neurosurgery residents in Canada, and performed a quality audit of the most popular Apps. METHODS: Indexed Apps were identified from either the Google Play Store or the iOS App Store using a comprehensive list of keywords related to neurosurgery. A subsequent cross-sectional survey of 76 Canadian neurosurgery residents was conducted, including a section on smartphone App use. We next evaluated the most popular Apps among the residents using the Healthcare Smartphone App Evaluation Tool and performed a quality audit of their content using established medical references. RESULTS: The survey identified 118 mobile Apps related to neurosurgery. The 3 most used Apps used by the current cohort of Canadian neurosurgery residents were Neurosurgery Survival Guide, Neuromind, and the Journal of Neurosurgery App. Each of these 3 Apps received an excellent score on the Healthcare Smartphone App Evaluation Tool. A quality audit of 30 pages of the Neurosurgery Survival Guide and 40 clinical scores of the Neuromind App, performed by 10 neurosurgery residents, failed to reveal inaccurate or false statements. CONCLUSION: The present study has highlighted the current landscape of neurosurgery mobile Apps and their use among neurosurgery residents.

Association between weekend admissions and mortality after aneurysmal subarachnoid hemorrhage: the "weekend effect" revisited.

OBJECTIVE: Higher mortality has been reported with weekend or after-hours patient admission across a wide range of surgical and medical specialties, a phenomenon termed the "weekend effect." The authors evaluated whether weekend admission contributed to death and long-term neurological outcome in patients following aneurysmal subarachnoid hemorrhage. METHODS: A post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) study was conducted. Univariable and stepwise multivariable logistic regression analyses were performed to assess the associations between weekend admission and mortality and long-term neurological outcome. RESULTS: Of 413 subjects included in the CONSCIOUS-1 study, 140 patients had been admitted during the weekend. A significant interaction was identified between weekend admission and neurological grade on presentation, suggesting that the outcomes of patients who had initially presented with a poor grade were disproportionately influenced by the weekend admission. On stepwise multivariable logistic regression in the subgroup of patients who had presented with a poor neurological grade (29 of 100 patients), admission on the weekend was found to be independently associated with death (OR 6.59, 95% CI 1.62-26.88, p = 0.009). Weekend admission was not associated with long-term neurological outcome. CONCLUSIONS: Weekend admission was an independent risk factor for death within 12 weeks following aneurysmal subarachnoid hemorrhage in patients presenting with a poor neurological grade. Further work is required to identify and mitigate any mediating factors.

Cognitive Impairment, Functional Outcome, and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Measures such as modified Rankin Scale (mRS) may not reflect cognitive outcome following aneurysmal subarachnoid hemorrhage. The aim of this study was to assess the relationship between functional outcome, measured by mRS, and cognition, measured by mini-mental state examination (MMSE), after aSAH. A secondary analysis evaluated the impact of delayed cerebral ischemia (DCI) on the proportion of patients who had cognitive impairment. METHODS: We performed a post hoc analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial data. MMSE and mRS scores were compared using Kruskal-Wallis equality-of-populations rank test with pairwise comparison post hoc analysis. Cognitive impairment was defined as MMSE score <27. A stepwise logistic regression model evaluated whether DCI was a predictor of cognitive impairment. RESULTS: CONSCIOUS-1 comprised 413 patients. Of these, 337 took an MMSE at their 12-week follow-up. Mean MMSE score was 27 with a median of 29 (range, 0-30; SD 5.4). There were no significant differences between MMSE scores of patients who had 12-week mRS scores of 0-2. On multivariate analysis, DCI was independently associated with cognitive impairment after aSAH. CONCLUSIONS: Patients considered to have a good outcome on mRS had varying degrees of cognitive function on MMSE, whereas development of DCI was an independent predictor of cognitive impairment after aSAH. MMSE may not be sensitive enough to discern subtle defects in cognition, as the median score was 29 out of 30.

Dendritic cell vaccines for high-grade gliomas.

Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date, various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug Administration-approved first-line chemotherapeutic option for newly diagnosed GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation and adjuvant TMZ therapy, the median overall survival remains approximately 14 months. Given the failure of conventional chemotherapeutic strategies in GBM, there has been renewed interest in the role of immunotherapy in GBM. Dendritic cells are immune antigen-presenting cells that play a role in both the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy via dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm surrounding the use of DCVs for GBM with multiple ongoing trials. In this review, we comprehensively summarize the safety, efficacy, and quality of life results from 33 trials reporting on DCV for high-grade gliomas.

Significance of fluctuations in serum sodium levels following aneurysmal subarachnoid hemorrhage: an exploratory analysis.

OBJECTIVE: Fluctuations in patient serum sodium levels are common after aneurysmal subarachnoid hemorrhage (aSAH), but their effect on patient outcome is not well described in the literature. The goal of this work was to better characterize the relationship between fluctuations in serum sodium levels, outcome, and the development of delayed cerebral ischemia (DCI) after aSAH. METHODS: The authors performed a post hoc analysis of data from the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial. Patients had their serum sodium values recorded daily for 14 days post-aSAH. Average and average absolute daily differences in sodium levels were calculated for each patient based on 3 reference points: admission sodium levels, a normal sodium level (defined as 140 mmol/L), and the previous day's sodium level. These variables were also calculated for the classic "vasospasm window" (days 3-12) post-aSAH. A stepwise logistic regression model, locally weighted scatterplot smoothing curves, and receiver operator characteristic curve analysis were used to evaluate the relationship between alterations in serum sodium levels and clinical outcome or the development of DCI after aSAH. Poor outcome was defined as a modified Rankin Scale (mRS) score of > 2 at 3 months. RESULTS: The average daily difference in sodium values from baseline (p < 0.001), average daily difference from a normal sodium level (p < 0.001), average absolute daily difference from a normal sodium level (p = 0.015), and average absolute daily difference from the previous day's sodium level (p = 0.017) were significant predictors of poor outcome in a stepwise multivariate regression model. There was a trend toward significance for average absolute daily difference from admission sodium levels during the vasospasm window as an independent predictor of DCI (p = 0.052). There was no difference in the predictive capacity for DCI when sodium fluctuations from post-aSAH days 1-14 were compared with those from the classic vasospasm window (days 3-12). CONCLUSIONS: Fluctuations in serum sodium levels may play a role in clinical outcome and the development of DCI after aSAH. The timing of these fluctuations appears to have no significant effect on the development of DCI.