Vestibular Function and Quality of Life in Vestibular Schwannoma: Does Size Matter?

Objectives: Patients with vestibular schwannoma (VS) frequently suffer from disabling vestibular symptoms. This prospective follow-up study evaluates vestibular and auditory function and impairment of quality of life due to vertigo, dizziness, and imbalance in patients with unilateral VS of different sizes before/after microsurgical or radiosurgical treatment. Methods: Thirty-eight patients with unilateral VS were included. Twenty-two received microsurgery, 16 CyberKnife radiosurgery. Two follow-ups took place after a median of 50 and 186.5 days. Patients received a standardized neuro-ophthalmological examination, electronystagmography with bithermal caloric testing, and pure-tone audiometry. Quality of life was evaluated with the Dizziness Handicap Inventory (DHI). Patient data was grouped and analyzed according to the size of the VS (group 1: <20 mm vs group 2: ≥20 mm). Results: In group 1, the median loss of vestibular function was +10.5% as calculated by Jongkees Formula (range −43 to +52; group 2: median +36%, range −56 to +90). The median change of DHI scores was −9 in group 1 (range −68 to 30) and +2 in group 2 (−54;+20). Median loss of hearing was 4 dB (−42; 93) in group 1 and 12 dB in group 2 (5; 42). Conclusion: Loss of vestibular function in VS clearly correlates with tumor size. However, loss of vestibular function was not strictly associated with a long-term deterioration of quality of life. This may be due to central compensation of vestibular deficits in long-standing large tumors. Loss of hearing before treatment was significantly influenced by the age of the patient but not by tumor size. At follow-up 1 and 2, hearing was significantly influenced by the size of the VS and the manner of treatment

Rapid, label-free classification of glioblastoma differentiation status combining confocal Raman spectroscopy and machine learning

Label-free identification of tumor cells using spectroscopic assays has emerged as a technological innovation with a proven ability for rapid implementation in clinical care. Machine learning facilitates the optimization of processing and interpretation of extensive data, such as various spectroscopy data obtained from surgical samples. The here-described preclinical work investigates the potential of machine learning algorithms combining confocal Raman spectroscopy to distinguish non-differentiated glioblastoma cells and their respective isogenic differentiated phenotype by means of confocal ultra-rapid measurements. For this purpose, we measured and correlated modalities of 1146 intracellular single-point measurements and sustainingly clustered cell components to predict tumor stem cell existence. By further narrowing a few selected peaks, we found indicative evidence that using our computational imaging technology is a powerful approach to detect tumor stem cells in vitro with an accuracy of 91.7% in distinct cell compartments, mainly because of greater lipid content and putative different protein structures. We also demonstrate that the presented technology can overcome intra- and intertumoral cellular heterogeneity of our disease models, verifying the elevated physiological relevance of our applied disease modeling technology despite intracellular noise limitations for future translational evaluatio

Diagnosis and management of complications from the treatment of primary central nervous system tumors in adults

Central nervous system (CNS) tumor patients commonly undergo multimodality treatment in the course of their disease. Adverse effects and complications from these interventions have not been systematically studied, but pose significant challenges in clinical practice and impact function and quality of life, especially in the management of long-term brain tumor survivors. Here, the European Association of Neuro-Oncology (EANO) has developed recommendations to prevent, diagnose, and manage adverse effects and complications in the adult primary brain CNS tumor (except lymphomas) patient population with a specific focus on surgery, radiotherapy, and pharmacotherapy. Specifically, we also provide recommendations for dose adaptations, interruptions, and reexposure for pharmacotherapy that may serve as a reference for the management of standard of care in clinical trials. We also summarize which interventions are unnecessary, inactive or contraindicated. This consensus paper should serve as a reference for the conduct of standard therapy within and outside of clinical trials

Diagnosis and management of complications from the treatment of primary central nervous system tumors in adults.

Central nervous system (CNS) tumor patients commonly undergo multimodality treatment in the course of their disease. Adverse effects and complications from these interventions have not been systematically studied, but pose significant challenges in clinical practice and impact function and quality of life, especially in the management of long-term brain tumor survivors. Here the European Association of Neuro-Oncology (EANO) has developed recommendations to prevent, diagnose and manage adverse effects and complications in the adult primary brain CNS tumor (except lymphomas) patient population with a specific focus on surgery, radiotherapy and pharmacotherapy. Specifically, we also provide recommendations for dose adaptations, interruptions and re-exposure for pharmacotherapy that may serve as a reference for the management of standard of care in clinical trials. We also summarize which interventions are unnecessary, inactive or contraindicated. This consensus paper should serve as a reference for the conduct of standard therapy within and outside of clinical trials

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management

Abstract Background Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. Methods DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. Results The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03–0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8–7.2, P &lt; 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22–0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3–11.1, P &lt; 0.001) with clinical implications. Conclusions The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone. </jats:sec

CFD-based sensitivity-analysis and performance investigation of a Hydronic Road-heating System

To minimize the impact of snowfall and ice formation on safety of transportation, salt is sprinkled on the asphalt every winter. However, the use of salt has economical as well as ecological disadvantages. To resolve these problems, road heating systems are used in the northern regions of Europe and America. Despite their widespread usage, considerable potential of the operational optimization is evident. The current systems are controlled under predefined weather conditions such as start of operation at 5 °C air temperature, even when snowfall is absent. Consequently, loss of energy input to heat the system is caused. To avoid unnecessary financial and energetic expense, this study presents CFD-based performance investigation as a basis for a novel predictive controller to increase the operational efficiency of hydronic road heating systems (HRS). The simulation model was developed based on a real operational HRS located in Ingolstadt and composed of bridges and ramps for a total surface of 1989 m2. Climate data of the years 2019–2020 from local weather stations were implemented in the simulation model for performance prediction on extreme climate conditions. This investigation identified that up to 70% of operational hours in terms of energy input can be saved by using a hypothetical predictive controller, thus making the HRS a more economically efficient and environmentally attractive alternate to conventional de-icing techniques

Expression of CD40 Correlates Negatively with Overall and Progression-Free Survival of LOW- and High-Grade Gliomas

BACKGROUND: Low-grade gliomas (LGGs) are known to progress to glioblastoma (GBM), decreasing the chances of survival. The tumor necrosis factor receptor CD40 and its ligand CD40L have shown value as biomarkers for GBM. The present study evaluated the role of CD40/CD40L in LGG and GBM in differentiating isocitrate dehydrogenase (IDH) wild-type and IDH-mutant GBM. METHODS: The present study was based on patient-derived samples (74 grade II gliomas, 36 grade III gliomas, and 40 cases of GBM) and expression analysis using real-time polymerase chain reaction. Open-access data from The Cancer Genome Atlas (TCGA) and the strong cohorts of TCGA data sets brain lower grade glioma and glioblastoma were used to run the analysis on mRNA expression as a validation data set. RESULTS: We found that patients with LGG and CD40 overexpression experienced shorter progression-free survival (43 vs. 29 months; hazard ratio, 0.5715; P = 0.0262) and overall survival (116 vs. 54 months; hazard ratio, 0.3431; P < 0.0001). Consistently, relapsed grade II glioma showed greater CD40 expression compared with primary grade II glioma (P = 0.0028). Just as with LGG, CD40 was a negative marker for overall survival in GBM (12 vs. 10 months; hazard ratio, 0.5178; P = 0.0491). In this context, we found greater CD40 expression in IDH wild-type GBM than in IDH-mutant GBM. The data obtained from TCGA supported our findings, with similar results for PFS and OS in LGG and GBM. CD40L expression showed no correlation with the survival data. CONCLUSION: High CD40 expression showed a significant correlation with poor outcomes for both LGG and GBM and was overexpressed in IDH wild-type GBM

Interdisciplinary Treatment of Intracranial Infectious Aneurysms

Objective: Intracranial infectious aneurysms (IIAs) are a rare clinical entity without a definitive treatment guideline. In this study, we evaluate the treatment options of these lesions based on our own clinical experience and review the current knowledge of therapy as portrayed in the literature. Methods: We conducted a single-center retrospective analysis of all patients with an IIA and performed a systematic review of the literature using the MEDLINE database. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950-October 2015) using the following keywords (in combination): 'infectious', 'mycotic', 'cerebral aneurysm', 'intracranial aneurysm'. 1,721 potentially relevant abstracts were identified and 63 studies were selected for full review. The studies were analysed regarding ruptured versus unruptured aneurysms, aneurysm localization and treatment, as well as clinical and radiological outcome. Results: Our institutional series consisted of 6 patients (median age 57 [32-76]) treated between 2011 and 2015. All patients presented with ruptured IIAs located on the middle cerebral artery (MCA, 5 patients) and anterior cerebral artery (ACA, 1 patient). Five patients were treated by clipping and resecting the aneurysm, 1 patient underwent coiling. All patients received antibiotic therapy and 1 patient died. We further identified 814 patients (median age 35.5 [0-81]) in 63 studies. Locations of the aneurysms were mentioned in 55 studies. The most frequent locations of the aneurysms were: MCA (63.5%), posterior cerebral artery (14%), ACA (9.0%) and others (13.5%). Treatment for IIAs was described in 62 studies: antibiotic treatment (56.1%), a combination of antibiotics and surgery (20.9%) or antibiotics and endovascular treatment (23.0%). Outcome was mentioned in 82.4% of the patients with a mortality rate of 16.8%. An evaluation of treatment outcome was limited due to the heterogeneity of patients in the published case series. Conclusion: Antibiotic therapy of patients with IIA is mandatory. However, due to the complexity of the disease and its accompanying comorbidities, a general treatment algorithm could not be defined. Analogous to non-mycotic aneurysms, further treatment decisions require an interdisciplinary approach involving neurosurgeons, interventionists and infectious disease specialists. (C) 2016 S. Karger AG, Base