Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.

Introduction. Neurosurgeons are familiar with chronic subdural haematoma (CSH), a well-known clinical entity, which is usually treated by some modality of trepanation. Despite the excellent outcomes obtained by surgery, complications may occur, some of which may be potentially severe or fatal. Furthermore, up to 25% recurrence rate is reported. The authors present a novel approach to the management of CSH based on the use of dexamethasone as the treatment of choice in the majority of cases.Patients and methods. Medical records of 122 CSH patients were retrospectively reviewed. At admission, symptomatic patients were classified according to the Markwalder Grading Score (MGS). Those scoring MGS 1-2 were assigned to the Dexamethasone protocol (4mg every 8h, re-evaluation after 48-72h, slow tapering), and those scoring MGS 3-4 were, in general, assigned to the Surgical protocol (single frontal twistdrill drainage to a closed system, without irrigation). Patients were followed in the Outpatient Office with neurological assessment and serial CT scans.Results Discussion. The rationale for the use of dexamethasone in CSH lies in its anti-angiogenic properties over the subdural clot membrane, as it is derived from experimental studies and the very few clinical observations published. Surgical evacuation of CSH is known to achieve excellent results but no well-designed trials compare medical versus surgical therapies. The experience obtained from this series lets us formulate some clinical considerations: dexamethasone is a feasible treatment that positively compares to surgical drain (and avoided two thirds of operations); the natural history of CSH allows a 48-72h dexamethasone trial without putting the patient at risk of irreversible deterioration; eliminates all morbidity related to surgery and recurrences; does not provoke significant morbidity itself; reduces hospital stay; does not preclude ulterior surgical procedures; it is well tolerated and understood by the patient and relatives and it probably reduces costs. The authors propose a protocol that does not intend to substitute surgery but to offer a safe and effective alternative.Conclusion. Data obtained from this large retrospective series suggests that dexamethasone is a feasible and safe option in the management of CSH. In the author's experience dexamethasone was able to cure or improve two thirds of the patients. This fact should be confirmed by others in the future. The true effectiveness of the therapy as compared to surgical treatment could be ideally tested in a prospective randomized trial.KEY WORDS: Chronic subdural haematoma. Dexamethasone. Nonoperative treatment. Glucocorticoids. Tratamiento con dexametasona del hematoma subdural crónico

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.

Objective Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. Methods Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 μg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. Results Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104–335) and 331 (140–476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. Conclusion Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.