Meningioma animal models: a systematic review and meta-analysis.

BACKGROUND: Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types. METHODS: We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies. RESULTS: We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43). CONCLUSION: This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages). SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42022308833.

Retinal vessel dynamics analysis as a surrogate marker for raised intracranial pressure in patients with suspected idiopathic intracranial hypertension.

INTRODUCTION: Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension. METHODS: Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure. RESULTS: Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with (n = 17) and without (n = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate -0.0043 (95% CI -0.0073 to -0.0023), p = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H2O) (slope regression estimate -0.0080 (95% CI -0.0123 to -0.0039), p < 0.001). Estimated cerebrospinal fluid pressure predicted increased lumbar opening pressure >20 mm Hg (27 cm H2O) with 78% sensitivity and 92% specificity (AUC 0.81, p = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H2O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p = 0.002). CONCLUSION: Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. METHODS: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256.

Virtual magnetic resonance elastography predicts the intraoperative consistency of meningiomas.

BACKGROUND AND PURPOSE: Virtual magnetic resonance elastography (vMRE) is an experimental imaging modality designed to non-invasively predict the haptic properties of tissues. The modality is sensitive to tissue stiffness and fibrosis. Information about meningioma consistency prior to resection is of great interest in neurological surgery as the surgical plan and outcome may be affected by the tumor's stiffness. In this study, we assessed the ability of vMRE to predict the intraoperative consistency and mechanical heterogeneity of intracranial meningiomas. MATERIALS AND METHODS: We included 12 patients scheduled for meningioma resection, of which one patient was found to have a solitary fibrous tumor on histological examination. All participants underwent preoperative vMRE and intraoperative consistency grading. RESULTS AND CONCLUSIONS: Intraoperative qualitative consistency correlated positively with vMRE-based consistency assessment (odds ratio 5.63, 95% CI 1.12-28.30, p = 0.04) at b1000. Mechanically homogenous tumors had significantly lower ∆ mean stiffness than heterogeneous tumors (8.13 vs 18.07 kPa, p = 0.01). This study thus demonstrates a possible clinical application of vMRE in predicting the intraoperative consistency and mechanical heterogeneity of meningiomas.

The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis.

After severe traumatic brain injury (sTBI) proteins, neurotrophic factors and inflammatory markers are released into the biofluids. This review and meta-analysis searched the literature for prognostic candidate cerebrospinal fluid markers and their relation to sTBI patient outcome. A systematic search of the literature was carried out across PubMed, EMBASE, PubMed Central (PMC), and Cochrane Central Library. Biomarker concentrations were related to the Glasgow Outcome Scale dichotomized into favorable and unfavorable outcomes. When a biomarker was reported in ≥ 3 studies, it was included in meta-analysis. The search returned 1527 articles. After full-text analysis, 54 articles were included, 34 from the search, and 20 from the reference lists. Of 9 biomarkers, 8 were significantly different compared to controls (IL-4, IL-6, IL-8, IL-10, TNFα, sFas, BDNF, and cortisol). Of these, 5 were significantly increased in sTBI patients with unfavorable outcome (IL-6, IL-8, IL-10, TNFα, and cortisol), compared to patients with favorable outcome. This review demonstrated a correlation between 5 biomarkers and clinical outcome in sTBI patients. The paucity of included studies, however, makes it difficult to extrapolate further on this finding.

Magnetic resonance elastography in normal pressure hydrocephalus-a scoping review.

BACKGROUND: Magnetic resonance elastography (MRE) of the brain allows quantitative measurement of tissue mechanics. Multiple studies are exploring possible applications in normal pressure hydrocephalus (NPH) in clinical and paraclinical contexts. This is of great interest in neurological surgery due to challenges related to diagnosis and prediction of treatment effects. In this scoping review, we present a topical overview and discuss the current literature, with particular attention to clinical implications and current challenges. METHODS: The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), the articles were screened for relevance. Thirty articles were subject to detailed screening, and key technical and clinical data items were extracted. The inclusion criteria included the use of MRE on human subjects with NPH. RESULTS: Seven articles were included in the final study. These studies had various objectives including the role of MRE in the assessment of regional elastic changes in NPH, shunt effect, and evaluation of NPH symptoms. MRE revealed patterns of mechanical changes in NPH that differed from other dementias. Regional MRE changes were associated with specific NPH signs and symptoms. Neurosurgical shunting caused partial normalization in tissue scaffold parameters. The studies were highly heterogeneous in technical aspects and design. CONCLUSION: MRE studies in NPH are still limited by few participants, variable cohorts, inconsistent methodologies, and technical challenges, but the approach shows great potential for future clinical application.

Diagnosis, treatment, and outcome of primary CNS lymphoma-a single-center experience.

BACKGROUND: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) that occurs in the CNS (e.g. brain, meninges, spinal cord, cerebrospinal fluid, or intraocular involvement) in the absence of systemic NHL. Tumor resection does not improve survival, and neurosurgical intervention is generally limited to stereotactic biopsy to provide a histopathological diagnosis. OBJECTIVE: The objective of this single-center study was to evaluate the management and outcome of PCNSL patients diagnosed by biopsy, using overall survival and progression-free survival as endpoints. METHODS: At our department of neurosurgery, 140 patients were diagnosed with PCNSL by biopsy between January 1, 2009, and December 31, 2018. Of these, 37 patients were included in the study and were divided into three groups according to their postoperative therapy. RESULTS: Median OS was 35.7 months for the intensive treatment group, 29.5 months for the moderate treatment group, and 8.6 months for the palliative treatment group. The intensive and moderate treatment groups had similar progression-free survival, while the palliative treatment group had poor overall and progression-free survival. Six patients were long-term survivors (> 80 months). Age under 65 years was the main significant parameter affecting overall survival. CONCLUSION: In this cohort, patients with PCNSL had an overall fair prognosis if they (1) were under 65 years old, (2) had a performance score < 2 at the time of diagnosis, and (3) received either intensive or moderate chemotherapeutic treatment. Biopsy is still the primary diagnostic tool; other methods have been investigated but are not yet recommended.

The Danish Chronic Subdural Hematoma Study-comparison of hematoma age to the radiological appearance at time of diagnosis.

INTRODUCTION: Chronic subdural hematomas (CSDH) show different radiological characteristics on CT scans at the time of diagnosis. The reason for this is largely unknown. We hypothesize that the imaging characteristics reflect a time-linked pathophysiological evolution. We therefore conducted a retrospective study to examine a possible relation between the hematoma age and the radiological subtype of a CSDH. METHODS: Demographic data on patients with CSDH were retrieved from a Danish national cohort from 2010 to 2012. CT scans obtained on admission to a neurosurgical department were categorized as homogenous, separated, mixed, or membranous hematoma subtypes. The time from a known date of head injury to time of diagnostic CT was defined as hematoma age. The hematoma age was correlated to radiological hematoma subtype at the time of diagnosis by analysis of variance testing. RESULTS: In total, 543 patients were analyzed for hematoma age and classified in the following hematoma subtypes: 231 homogenous, 44 separated, 119 mixed, and 149 membranous. Patients with homogenous, separated, mixed, and membranous hematoma subtypes had a median interval of 37, 36, 40, and 60 days from head injury to diagnostic CT. We found that membranous hematoma is significantly older than other subtypes. Comparison between the other radiological subtypes showed no statistical hematoma age difference. The distribution of radiological subtypes in 590 patients without a known head injury was similar to that of patients with a known head injury. Additionally, we found that hematoma age was significantly younger for patients on antiplatelet medication. CONCLUSION: In this large national cohort, patients with membranous CSDH had a significantly longer interval between head injury and diagnosis compared to other radiological subtypes. This indicates that the radiological appearance of CSDH evolves over time, causing an alteration from different early radiological subtypes to a radiological subtype with membranes. CLINICAL TRIAL REGISTRATION NUMBER: The study was approved by the Danish Data Protection Agency (journal no.30-1145).

Drain type and technique for subdural insertion after burr hole evacuation of chronic subdural hematoma.

Strengths and limitations of subdural versus subperiosteal drain location after burr hole evacuation of chronic subdural hematoma (CSDH) are currently debated. The safety of subdural placement of a drain has been questioned in a recent study by Soleman et al. from 2019, showing a misplacement rate of 17%, and these results have been further highlighted by the same authors, with a slightly lower misplacement rate of 15.8%, in the recent paper "When the drain hits the brain." The safety of subdural drainage for CSDH depends to a high degree on type of drain and surgical technique. In this technical note, we describe drain type and technique for drain placement which is standardized in Denmark.

Embolization of the middle meningeal artery in patients with chronic subdural hematoma-a systematic review and meta-analysis.

BACKGROUND: Chronic subdural hematoma (CSDH) remains a neurosurgical condition with high recurrence rate after surgical treatment. The primary pathological mechanism is considered to be repeated microbleedings from fragile neo-vessels within the outer hematoma membrane. The neo-vessels are supplied from peripheral branches of the middle meningeal artery, and embolization of MMA (eMMA) has been performed to prevent re-bleeding episodes and thereby CSDH recurrence. OBJECTIVE: To evaluate the published evidence for the effect of eMMA in patients with recurrent CSDH. Secondarily, to investigate the effect of eMMA as an alternative to surgery for primary treatment of CSDH. METHOD: A systematic review of the literature on eMMA in patients with recurrent CSDH was conducted. PubMed, Embase, and Cochrane databases were reviewed using the search terms: Embolization, Medial Meningeal Artery, Chronic Subdural Haematoma, and Recurrence. Furthermore, the following mesh terms were used: Chronic Subdural Haematoma AND embolization AND medial meningeal artery AND recurrence. Eighteen papers were found and included. No papers were excluded. The number of patients with primary CSDH and the number of patients with recurrent CSDH treated with eMMA were listed. Furthermore, the number of recurrences in both categories was registered. RESULTS: Eighteen papers with a total of 191 included patients diagnosed with CSDH treated with eMMA for primary and recurrent CSDH were identified. Recurrence rate for patients treated with eMMA for recurrent CSDH was found to be 2.4%, 95% CI (0.5%; 11.0%), whereas the recurrence rate for patients treated with eMMA for primary CSDH was 4.1%, 95% CI (1.4%; 11.4%). CONCLUSION: eMMA is a minimally invasive procedure for treatment of CSDH. Although this study is limited by publication bias, it seems that this procedure may reduce recurrence rates compared with burr hole craniostomy for both primary and recurrent hematomas. A controlled study is warranted.

A Prospective Observational Feasibility Study of Jugular Bulb Microdialysis in Subarachnoid Hemorrhage.

BACKGROUND: Cerebral metabolic perturbations are common in aneurysmal subarachnoid hemorrhage (aSAH). Monitoring cerebral metabolism with intracerebral microdialysis (CMD) allows early detection of secondary injury and may guide decisions on neurocritical care interventions, affecting outcome. However, CMD is a regional measuring technique that is influenced by proximity to focal lesions. Continuous microdialysis of the cerebral venous drainage may provide information on global cerebral metabolism relevant for the care of aSAH patients. This observational study aimed to explore the feasibility of jugular bulb microdialysis (JBMD) in aSAH and describe the output characteristics in relation to conventional multimodal monitoring. METHODS: Patients with severe aSAH were included at admission or after in-house deterioration when local clinical guidelines prompted extended multimodal monitoring. Non-dominant frontal CMD, intracranial pressure (ICP), partial brain tissue oxygenation pressure (PbtO2), and cerebral perfusion pressure (CPP) were recorded every hour. The dominant jugular vein was accessed by retrograde insertion of a microdialysis catheter with the tip placed in the jugular bulb under ultrasound guidance. Glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol, and glutamate were studied for correlation to intracranial measurements. Modified Rankin scale was assessed at 6 months. RESULTS: Twelve adult aSAH patients were monitored during a mean 4.2 ± 2.6 days yielding 22,041 data points for analysis. No complications related to JBMD were observed. Moderate or strong significant monotonic CMD-to-JBMD correlations were observed most often for glucose (7 patients), followed by lactate (5 patients), and pyruvate, glycerol, and glutamate (3 patients). Moderate correlation for lactate/pyruvate ratio was only seen in one patient. Analysis of critical periods defined by ICP > 20, CPP < 65, or PbtO2 < 15 revealed a tendency toward stronger CMD-to-JBMD associations in patients with many or long critical periods. Possible time lags between CMD and JBMD measurements were only identified in 6 out of 60 patient variables. With the exception of pyruvate, a dichotomized outcome was associated with similar metabolite patterns in JBMD and CMD. A nonsignificant tendency toward greater differences between outcome groups was seen in JBMD. CONCLUSIONS: Continuous microdialysis monitoring of the cerebral drainage in the jugular bulb is feasible and safe. JBMD-to-CMD correlation is influenced by the type of metabolite measured, with glucose and lactate displaying the strongest associations. JBMD lactate correlated more often than CMD lactate to CPP, implying utility for detection of global cerebral metabolic perturbations. Studies comparing JBMD to other global measures of cerebral metabolism, e.g., PET CT or Xenon CT, are warranted.

Sodium fluorescein shows high surgeon-reported usability in glioblastoma surgery.

INTRODUCTION: Glioblastoma has a high mortality rate. Current treatment includes largest possible surgical resection of the tumour using neuronavigation and fluorescence to better identify tumour tissue. In recent years, sodium fluorescein has been reintroduced in neurosurgery as a fluorescence to increase the resection rate. In this study we aimed to measure the surgeons experience of using sodium fluorescein to locate and remove tumour tissue. Furthermore we describe a case of sodium fluorescein tissue distribution. MATERIAL AND METHODS: 13 patients with glioblastoma and seven patients with cerebral metastases undergoing surgical resection were included. Surgery was performed using microscope alternating between white light and the YELLOW 560 filter, which visualized sodium fluorescein. Surgeons graded its usability in terms of location and removal on a scale from one to four. The resection rate was determined by neuroradiologists. Tissue samples obtained during surgery were analysed in relation to fluorescence and dysmorphic cells. RESULTS: Surgeons reported high usability in terms of location and removal of tumours using sodium fluorescein with medians of four in all groups, except for sub-total resections which had a median of three. Surgical complications were minimal and both resection rate and survival rate was within international standards. Histological analysis showed a visual correlation between tumorous tissue and intensity of fluorescence. CONCLUSION: Sodium fluorescence is an effective and useful tool for surgeons during fluorescence-guided surgery for the resection of glioblastoma and cerebral metastases.

The Danish chronic subdural hematoma study-predicting recurrence of chronic subdural hematoma.

BACKGROUND: An increasing incidence of chronic subdural hematoma (CSDH) and an unchanging high recurrence rate of 10-20% call for individualized treatment. The aim of this study was to establish individualized prediction models for the risk of recurrence treating death as a competing risk. METHODS: A retrospective national cohort of unilateral CSDH was included for analysis. Using competing risk survival analysis, we tested whether available covariates were associated with the risk of recurrence. We further established a pre- and a postoperative prediction model, where predictors were chosen using a LASSO approach. The models were visualized in nomograms. Predictive performance was evaluated by c index and calibrations plots. RESULTS: A total of 763 patients with surgically evacuated unilateral CSDH were included for analysis. The recurrence rate was 14% while 12% of patients died during follow-up (1 year). In our association model, hematoma size, drain type, drainage time, presence of complications, and Glasgow Coma Score were significantly associated to recurrence. Subdural drain was associated with a lower recurrence risk than subgaleal drain. The preoperative model included hematoma size, hematoma density, and history of hypertension. The postoperative model included further drain type, drainage time, and surgical complications. CONCLUSION: The nomograms allow easy assessment of the recurrence risk for the individual patient, providing a better possibility for individual adjustment of treatment and follow-up. The predictive performance indicates that significant unaccounted or unknown factors still remain. The association test found passive subdural drain superior to passive subgaleal drain in minimizing the risk of CSDH recurrence.

Early postoperative MRI after resection of brain metastases-complete tumour resection associated with prolonged survival.

BACKGROUND: This study aimed to investigate the incidence of residual tumour after resection of brain metastases using early postoperative magnetic resonance imaging (MRI) and the influence of residual tumour on overall patient survival. METHODS: Data from 72 consecutive adult patients undergoing surgery for cerebral metastases over an 18-month study period were retrospectively collected. Early postoperative MRI was used to determine the presence of postoperative residual tumour. Patients were divided into three groups according to the presence of tumour remnant on early postoperative MRI: "no residual tumour", "non-measurable residual tumour" and "measurable residual tumour". Survival analysis (mean estimate survival time) was performed using the Kaplan-Meier and log-rank (mantel cox) tests and compared between groups. Surgical reports were evaluated with regard to the surgeon statement about intraoperative extent of resection (EOR) and compared with the presence of tumour remnant found on the early postoperative MRI. RESULTS: Sixty-eight procedures were followed by early postoperative MRI. MRI verified the presence of "measurable residual tumour" following 15 procedures (22%). MRI confirmed complete resection in 57%. Gross total resection was described by the operating surgeon in 85% of the procedures. There was a significant difference in survival time after surgery between the group having no residual tumour on MRI and the group with measurable residual tumour (p = 0.025). This difference could not be explained by the differences in postoperative radiation therapy. The longest survival was found in patients with non-measurable and no residual tumour on early postoperative MRI, who also received postoperative radiotherapy. CONCLUSION: Residual tumour was seen on MRI after 22% of the procedures. The intraoperative assessment of EOR performed by the surgeon diverged from the early postoperative MRI in 40% of procedures. Correct assessment of residual tumour thus requires early postoperative MRI. Measurable residual tumour on early postoperative MRI was associated with shorter overall survival independent on postoperative radiotherapy.

Do family health conversations impact patients with glioblastoma multiforme and their family members?

AIMS AND OBJECTIVES: To assess the impact of family health conversations (FamHC) as a supplement to conventional care on health-related quality of life (HRQoL), family functioning (FFSS) and family hardiness or resilience (FHI) 4 and 14 weeks postoperatively among patients with glioblastoma multiforme and their family members. BACKGROUND: There is a lack of knowledge about the efficiency of FamHC among families experiencing glioblastoma multiforme. DESIGN: A quasi-experimental pre- and post-test design adhering to the STROBE (Strengthening the reporting of observational studies in epidemiology) guidelines for case-control studies. Patients and family members were included consecutively in the pretest period from November 2013-December 2014 for the control group (offered traditional care only), and in the post-test period from January 2015-December 2015 for the intervention group (offered traditional care and FamHC). For both groups, 4 and 14 weeks postoperative measurement were obtained. METHODS: Differences in outcomes were assessed using a difference-in-difference regression analysis approach measuring difference across pre and post groups and across 4 and 14 weeks measurements. RESULTS: The study does not reveal significant effects of FamHC (all p-values larger than 0.05) as measured by the three instruments WHOQOL-BREF, FFSS and FHI. CONCLUSIONS: The present study was not able to show significant effects of FamHC. However, it cannot be left out that the intervention might be helpful and supportive at a later state of the illness trajectory. RELEVANCE FOR CLINICAL PRACTICE: The study adds to the growing evidence-based knowledge on FamHC by questioning their potential use in different cultural contexts among families experiencing critical illness. Oncological nurses need to adapt this information to support their daily care for the patients and their close relatives. For future studies, it is recommended that the families themselves choose when the conversations should take place during the course of the illness.

Association of Antithrombotic Drug Use With Subdural Hematoma Risk.

IMPORTANCE: Incidence of subdural hematoma has been reported to be increasing. To what extent this is related to increasing use of antithrombotic drugs is unknown. OBJECTIVES: To estimate the association between use of antithrombotic drugs and subdural hematoma risk and determine trends in subdural hematoma incidence and antithrombotic drug use in the general population. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 10 010 patients aged 20 to 89 years with a first-ever subdural hematoma principal discharge diagnosis from 2000 to 2015 matched by age, sex, and calendar year to 400 380 individuals from the general population (controls). Subdural hematoma incidence and antithrombotic drug use was identified using population-based regional data (population: 484 346) and national data (population: 5.2 million) from Denmark. Conditional logistic regression models were used to estimate odds ratios (ORs) that were adjusted for comorbidity, education level, and income level. EXPOSURES: Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), a direct oral anticoagulant, and combined antithrombotic drug treatment. MAIN OUTCOMES AND MEASURES: Association of subdural hematoma with antithrombotic drug use, subdural hematoma incidence rate, and annual prevalence of treatment with antithrombotic drugs. RESULTS: Among 10 010 patients with subdural hematoma (mean age, 69.2 years; 3462 women [34.6%]), 47.3% were taking antithrombotic medications. Current use of low-dose aspirin (cases: 26.7%, controls: 22.4%; adjusted OR, 1.24 [95% CI, 1.15-1.33]), clopidogrel (cases: 5.0%, controls: 2.2%; adjusted OR, 1.87 [95% CI, 1.57-2.24]), a direct oral anticoagulant (cases: 1.0%, controls: 0.6%; adjusted OR, 1.73 [95% CI, 1.31-2.28]), and a VKA (cases: 14.3%, controls: 4.9%; adjusted OR, 3.69 [95% CI, 3.38-4.03]) were associated with higher risk of subdural hematoma. The risk of subdural hematoma was highest when a VKA was used concurrently with an antiplatelet drug (low-dose aspirin and a VKA: 3.6% of cases and 1.1% of controls; adjusted OR, 4.00 [95% CI, 3.40-4.70]; clopidogrel and a VKA: 0.3% of cases and 0.04% of controls; adjusted OR, 7.93 [95% CI, 4.49-14.02]). The prevalence of antithrombotic drug use increased from 31.0 per 1000 individuals from the general population in 2000 to 76.9 per 1000 individuals in 2015 (P < .001 for trend). The overall subdural hematoma incidence rate increased from 10.9 per 100 000 person-years in 2000 to 19.0 per 100 000 person-years in 2015 (P < .001 for trend). The largest increase was among older patients (>75 years; n = 4441) who experienced an increase from 55.1 per 100 000 person-years to 99.7 per 100 000 person-years (P < .001 for trend). CONCLUSIONS AND RELEVANCE: In Denmark, antithrombotic drug use was associated with higher risk of subdural hematoma; and the highest odds of subdural hematoma was associated with combined use of a VKA and an antiplatelet drug. The increased incidence of subdural hematoma from 2000 to 2015 appears to be associated with the increased use of antithrombotic drugs, particularly use of a VKA among older patients.

Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting.

Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall survival of only 14.6 months. Although these tumors are treated with surgery, radiation and chemotherapy, recurrence is inevitable. A critical population of tumor cells in terms of therapy, the so-called cancer stem cells (CSCs), has been identified in gliomas and many other cancers. These tumor cells have a stem cell-like phenotype and are suggested to be responsible for tumor growth, chemo- and radio-resistance as well as recurrence. However, functional evidence for migrating glioma cells having a stem cell-like phenotype is currently lacking. In the present study, the aim was to characterize the phenotype of migrating tumor cells using a novel migration assay based on serum-free stem cell medium and patient-derived spheroid cultures. The results showed pronounced migration of five different GBM spheroid cultures, but not of the commercial cell line U87MG. An in vitro limiting dilution assay showed preserved but reduced spheroid formation capacity of migrating cells. Orthotopic xenografting in mice showed preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no significant deregulation of 16 predefined CSC-related genes and the HOX-gene list in migrating cells compared to spheroids. Determination of GBM molecular subtypes revealed that subtypes of spheroids and migrating cells were identical. In conclusion, migrating tumor cells preserve expression of stem cell markers and functional CSC characteristics. Since CSCs are reported to be highly resistant to therapy, these results emphasize that the CSC phenotype should be taken into consideration in future treatment of GBMs.

Subdural hematoma cases identified through a Danish patient register: diagnosis validity, clinical characteristics, and preadmission antithrombotic drug use.

PURPOSE: This study aimed to assess the usefulness of Danish patient registers for epidemiological studies of subdural hematoma (SDH) and to describe clinical characteristics of validated cases. METHODS: Using a patient register covering a geographically defined area in Denmark, we retrieved hospital contacts recorded under SDH International Classification of Diseases version 10 codes S065 and I620 in 2000-2012. Neurosurgeons reviewed medical records of all potential cases. Based on brain scan results, verified cases were classified by SDH type (chronic SDH (cSDH) or acute SDH (aSDH)). Thirty-day mortality and preadmission antithrombotic drug use were established through linkage to population-based registers. We calculated the positive predictive value of the SDH code and compared mortality and preadmission antithrombotic drug use of cSDH with those of aSDH (age-adjusted and sex-adjusted odds ratio (OR), 95% confidence interval (95%CI)). RESULTS: We verified the diagnosis in 936 of 1185 identified patients. The positive predictive value was highest for hospital contacts with principal discharge diagnosis code S065 (96%) but was low for other contact types under code S065 (25-54%), and only moderate for patients recorded under code I620 (62%). cSDH represented 57% of verified cases, and aSDH the remaining 43%. cSDH differed markedly from aSDH with regard to a number of clinical characteristics, including a much lower mortality (OR 0.2, 95%CI 0.1-0.3). However, preadmission antithrombotic drug use did not vary by SDH type (OR 0.9, 95%CI 0.6-1.2). CONCLUSIONS: Danish patient registers are a useful resource for SDH studies. However, choice of International Classification of Diseases code markedly influences diagnostic validity. Distinction between cSDH and aSDH is not possible based on SDH diagnosis codes only. Copyright © 2016 John Wiley & Sons, Ltd.

Fewer complications with bolt-connected than tunneled external ventricular drainage.

BACKGROUND: Ventriculostomy/external ventricular drain (EVD) is a common neurosurgical procedure. Various techniques are used to fixate the drain and the objective of this study was, in a retrospective setting, to compare the incidence of complications when using bolt-connected EVD (BC-EVD) versus tunneled EVD (T-EVD). METHODS: All patients subjected to an EVD performed through a new burr hole from 2009 through 2010 at two Depts. of Neurosurgery in Denmark (Odense and Aarhus) were retrospectively identified. Patient files were evaluated for EVD fixation technique (tunneled or bolt-connected EVD) and complications including unintended removal, catheter obstruction, infection, CSF leakage, and mechanical problems. RESULTS: A total of 271 patients with 272 separate EVDs met the inclusion criteria. There was a statistically higher rate of complications leading to reinsertion in the tunneled EVD group (40 %), compared to the bolt-connected EVD group (6.5 %). There was no significant difference in infection rates. CONCLUSIONS: Tunneled EVD has a relatively high frequency of complications leading to reinsertion. The use of Bolt-connected EVD technique can lower this frequency significantly. The number needed to treat is three for preventing a complication requiring reinsertion. Infection rates are low for both types of ventriculostomies. Accordingly, we recommend use of Bolt-connected EVDs in neurosurgical practice.