Safe surgery for glioblastoma: Recent advances and modern challenges.

One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts

The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study.

INTRODUCTION The main surgical dilemma during glioma resections is the surgeon's inability to accurately identify eloquent areas when the patient is under general anaesthesia without mapping techniques. Intraoperative stimulation mapping (ISM) techniques can be used to maximise extent of resection in eloquent areas yet simultaneously minimise the risk of postoperative neurological deficits. ISM has been widely implemented for low-grade glioma resections backed with ample scientific evidence, but this is not yet the case for high-grade glioma (HGG) resections. Therefore, ISM could thus be of important value in HGG surgery to improve both surgical and clinical outcomes. METHODS AND ANALYSIS This study is an international, multicenter, prospective three-arm cohort study of observational nature. Consecutive HGG patients will be operated with awake mapping, asleep mapping or no mapping with a 1:1:1 ratio. Primary endpoints are: (1) proportion of patients with National Institute of Health Stroke Scale deterioration at 6 weeks, 3 months and 6 months after surgery and (2) residual tumour volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: (1) overall survival and (2) progression-free survival at 12 months after surgery; (3) oncofunctional outcome and (4) frequency and severity of serious adverse events in each arm. Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year. ETHICS AND DISSEMINATION The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media. TRIAL REGISTRATION NUMBER ClinicalTrials.gov ID number NCT04708171 (PROGRAM-study), NCT03861299 (SAFE-trial)

An astronomically dated record of Earth's climate and its predictability over the last 66 million years.

Much of our understanding of Earth's past climate comes from the measurement of oxygen and carbon isotope variations in deep-sea benthic foraminifera. Yet, long intervals in existing records lack the temporal resolution and age control needed to thoroughly categorize climate states of the Cenozoic era and to study their dynamics. Here, we present a new, highly resolved, astronomically dated, continuous composite of benthic foraminifer isotope records developed in our laboratories. Four climate states-Hothouse, Warmhouse, Coolhouse, Icehouse-are identified on the basis of their distinctive response to astronomical forcing depending on greenhouse gas concentrations and polar ice sheet volume. Statistical analysis of the nonlinear behavior encoded in our record reveals the key role that polar ice volume plays in the predictability of Cenozoic climate dynamics

North Atlantic Drift Sediments Constrain Eocene Tidal Dissipation and the Evolution of the Earth-Moon System

Cyclostratigraphy and astrochronology are now at the forefront of geologic timekeeping. While this technique heavily relies on the accuracy of astronomical calculations, solar system chaos limits how far back astronomical calculations can be performed with confidence. High-resolution paleoclimate records with Milankovitch imprints now allow reversing the traditional cyclostratigraphic approach: Middle Eocene drift sediments from Newfoundland Ridge are well-suited for this purpose, due to high sedimentation rates and distinct lithological cycles. Per contra, the stratigraphies of Integrated Ocean Drilling Program Sites U1408–U1410 are highly complex with several hiatuses. Here, we built a two-site composite and constructed a conservative age-depth model to provide a reliable chronology for this rhythmic, highly resolved (<1 kyr) sedimentary archive. Astronomical components (g-terms and precession constant) are extracted from proxy time-series using two different techniques, producing consistent results. We find astronomical frequencies up to 4% lower than reported in astronomical solution La04. This solution, however, was smoothed over 20-Myr intervals, and our results therefore provide constraints on g-term variability on shorter, million-year timescales. We also report first evidence that the g4–g3 “grand eccentricity cycle” may have had a 1.2-Myr period around 41 Ma, contrary to its 2.4-Myr periodicity today. Our median precession constant estimate (51.28 ± 0.56″/year) confirms earlier indicators of a relatively low rate of tidal dissipation in the Paleogene. Newfoundland Ridge drift sediments thus enable a reliable reconstruction of astronomical components at the limit of validity of current astronomical calculations, extracted from geologic data, providing a new target for the next generation of astronomical calculations

North Atlantic surface ocean warming and salinization in response to middle Eocene greenhouse warming

Quantitative reconstructions of hydrological change during ancient greenhouse warming events provide valuable insight into warmer-than-modern hydrological cycles but are limited by paleoclimate proxy uncertainties. We present sea surface temperature (SST) records and seawater oxygen isotope (δ18Osw) estimates for the Middle Eocene Climatic Optimum (MECO), using coupled carbonate clumped isotope (Δ47) and oxygen isotope (δ18Oc) data of well-preserved planktonic foraminifera from the North Atlantic Newfoundland Drifts. These indicate a transient ~3°C warming across the MECO, with absolute temperatures generally in accordance with trace element (Mg/Ca)–based SSTs but lower than biomarker-based SSTs for the same interval. We find a transient ~0.5‰ shift toward higher (δ18Osw), which implies increased salinity in the North Atlantic subtropical gyre and potentially a poleward expansion of its northern boundary in response to greenhouse warming. These observations provide constraints on dynamic ocean response to warming events, which are consistent with theory and model simulations predicting an enhanced hydrological cycle under global warming

Kortdurende bestraling plus temozolomide bij oudere patiënten met glioblastoom

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The Basics of Cancer Immunity Dc-Based Immunotherapy: Gliomas as a Paradigm Disease?

edition: 1status: publishe

Biomarkers in de neuro-oncologie: ontwikkeling en validering als uitdaging voor de toekomstige behandelstrategieën

status: publishe

Vaccines against glioblastoma: reflections on the ICT-107 phase IIb trial

status: publishe