Performance of intraoperative neurocognitive tests during awake surgery for patients with diffuse low-grade glioma.

Despite great advancements and the diffusion of awake surgery for brain tumors, the literature shows that the tests applied during the procedure are heterogeneous and non-standardized. This prospective, observational, descriptive study collected data on intraoperative brain mapping and the performance of multiple neurocognitive tests in 51 awake surgeries for diffuse low-grade glioma. Frequency of use and rate of intraoperative findings of different neurocognitive tests were analyzed. Patients mean age at the time of surgery was 35.1 (20-57) years. We performed 26 (51.0%) surgeries on the left hemisphere (LH) and 25 (49.0%) on the right hemisphere (RH). Significant differences were observed between the total number of functional findings (cortical and subcortical) identified in the LH and RH (p = 0.004). In subcortical findings alone, the differences remained significant (p = 0.0004). The RH subcortical region showed the lowest number of intraoperative findings, and this was correlated with functional outcome: Karnofsky performance scale at five days (p = 0.022), three months (p = 0.002) and one year (p = 0.002) post-surgery. On average, more tests were used to map the RH, with a lower frequency of both cortical and subcortical functional findings. Even though subcortical findings were less frequent than cortical findings, they were crucial to defining the resection margins. Based on the intraoperative findings, frequency of use, and rate of findings per use of the tests analyzed, the most relevant tests for each hemisphere for awake brain mapping were identified.

Extent of resection in diffuse low-grade gliomas and the role of tumor molecular signature-a systematic review of the literature.

There is a lack of class I evidence concerning the impact of surgery in the treatment of diffuse low-grade glioma; the early maximal resection with preservation of eloquent brain areas has been accepted as the first therapeutic option. We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and protocol. Inclusion criteria: only case series with at least 100 patients containing supratentorial hemispheric diffuse low-grade glioma (according to any of the WHO classification used in papers published between 2000 to 2019), with pre- and postoperative MRI study were included in the qualitative and quantitative analyses. The extent of resection should be defined based on MRI at least in two categories and correlated with patients' outcomes (with univariate or multivariate analyses) using overall survival (OS) or malignant progression-free survival (MPFS). A total of 18 series with 4386 patients, published in 20 papers, were included in this systematic review. All the series that evaluates the relation between the extent of resection (EOR) and OS showed a statistically significant improvement of OS at univariate and/or multivariate analyzes with a greater EOR. Six studies showed a statistically significant improvement of MPFS with a greater EOR. We demonstrate that when a more rigorous analysis of EOR is performed, a benefit of a more aggressive resection on OS and MPFS is observed. Our review about EOR in different molecular groups of DLGG also suggests a benefit of maximum safe resection for all different subtypes, even though "radical surgery" may be associated with better OS and MPFS in tumors with a more aggressive signature.

IDH1-mutant primary intraventricular gliosarcoma: Case report and systematic review of a rare location and molecular profile.

BACKGROUND: Gliosarcoma (GS) is classified as an IDH-wild-type variant of glioblastoma (GBM). While GS is already an unusual presentation of GBM, IDH1-mutant cases are especially rare. We present an IDH1-mutant primary intraventricular GS case report and a systematic review of the molecular profile in GS correlating to the prognostic and pathogenesis of IDH1/2 mutations. CASE DESCRIPTION: A 44-years-old man presented with ongoing fatigue symptoms and a new-onset intense occipital headache. The patient complained of memory loss, dyscalculia, and concentration difficulties. An MRI revealed a bihemispheric intraventricular mass crossing the midline through the corpus callosum and infiltrating the trigone of the lateral ventricles, hypointense, and hyperintense on the T1- and T2-weighted image. We performed a microsurgical resection with a transparietal transsulcal approach; however, the contralateral mass was attached to vascular structures and we decided to reoperate the patient in another moment. The histopathological study showed a Grade IV tumor and the immunohistochemistry confirmed the diagnosis of GS. The patient presented progressive neurologic decline and died 45 days after the surgical approach. CONCLUSION: We did two systematic reviews studies from PubMed, EMBASE, MEDLINE, Cochrane, and SCOPUS databases, and included molecular and intraventricular studies of GS. We performed further meta-analysis using OpenMetaAnalyst™ software. We conducted a forest plot with the molecular profile of GS. When correlated IDH1 mutation versus tp53 mutation, we found an odds ratio (OR) of 0.018 (0.005-0.064) and P < 0.001. Moreover, we compared IDH1 mutation versus MGMT methylation (P = 0.006; OR = 0.138 [0.034-0.562]). The studies evaluating the molecular profile in GS prognostics are often extended from all GBMs despite specifics GBM variants (i.e., GS). We found a correlation between IDH1 mutation expression with tp53 and MGMT expression in GS, and future studies exploring this molecular profile in GS are strongly encouraged.

Dural-Based Frontal Lobe Hemangioblastoma.

BACKGROUND: Hemangioblastomas are benign vascular neoplasms that may be associated with von Hippel-Lindau disease. They are more common in men, with a mean age of 36 years, and rarely affect the supratentorial region and, when present in this topography, do not have meningeal impairment. Diagnosis by the radiologic and histopathologic study is difficult, since they are rare and, therefore, forgotten diagnosis, besides they are differential diagnoses with other supratentorial neoplasms. CASE DESCRIPTION: The present report describes a case of a frontal hemangioblastoma in a 64-year-old woman who presented with seizures. Our imaging studies had as a main hypothesis a frontal meningioma because of dural tail sign, lack of edema, contrast enhancement pattern, and extra-axial location in the supratentorial region, in the frontal lobe, which is uncommon for a hemangioblastoma. The patient underwent microneurosurgery for tumor resection, and the excised tissue was submitted for anatomopathologic evaluation. This study clarified the diagnosis as hemangioblastoma. We followed up the patient at the outpatient clinic for 2 years, with clinical improvement, without tumor recurrence. We also compared the clinical, radiologic, epidemiologic, and anatomopathologic data of the reported case with data from a literature review conducted through the PubMed portal. CONCLUSIONS: Definitive treatment for these lesions is surgical resection. Physicians should be aware that supratentorial meningeal hemangioblastomas can be developed in a patient without von Hippel-Lindau disease and regular follow-up is mandatory.

Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients.

BACKGROUND: Fibroblast growth factor 23 (FGF23) and endothelium-related biomarkers have been related to AKI in critically-ill patients. Also, FGF23 is associated with endothelial dysfunction. In this study, we investigated if elevated FGF23 association with severe AKI is mediated by several endothelial/glycocalyx-related biomarkers. METHODS: Prospective cohort study with critically-ill patients. Blood samples were collected within the first 24 h after ICU admission. Severe AKI (defined according to KDIGO stage 2/3) was the analyzed outcome. RESULTS: 265 patients were enrolled and 82 (30.9%) developed severe AKI-defined according to KDIGO stage 2/3. Blood samples to biomarkers measurement were collected within the first 24 h after ICU admission. After adjustment for several variables, FGF23, vascular cell adhesion protein 1 (VCAM-1), angiopoietin 2 (AGPT2), syndecan-1 and intercellular adhesion molecule-1 (ICAM-1) were associated with severe AKI. The individual indirect effects of VCAM-1, AGPT2 and syndecan-1 explained 23%, 31%, and 32% of the total observed effect of FGF23 on severe AKI, respectively. ICAM-1 showed no statistically significant mediation. When all three endothelium-related biomarkers were included in a directed acyclic graph (DAG), the Bayesian network learning suggested the following causal association pathway FGF-23 → syndecan-1 → VCAM-1 → AGPT2 → severe AKI. CONCLUSIONS: The association between FGF23 and AKI are mediated by endothelium-related biomarkers, mainly VCAM-1, AGPT2 and syndecan-1. Moreover, the statistical models show that syndecan-1, a biomarker of endothelial glycocalyx dysfunction, seems to be the initial mediator between FGF23 and severe AKI.

Angiopoietin-2 as a predictor of acute kidney injury in critically ill patients and association with ARDS.

BACKGROUND AND OBJECTIVE: Angiopoietin-2 (AGPT2) has been proposed as a key mediator of organ dysfunction, mainly in acute respiratory distress syndrome (ARDS). It has also been associated with acute kidney injury (AKI). We aimed to investigate the role of AGPT2 in patients with and without ARDS. METHODS: In a cohort study with critically ill patients, AGPT1 and AGPT2 were assayed in plasma collected within the first 24 h after admission to intensive care unit (ICU). Severe AKI and the need for dialysis were outcome measures from comparative analysis with clinical characteristics useful for AKI risk stratification. RESULTS: Among 283 patients (50.2% males), 109 (38.5%) had ARDS. AGPT2 levels at admission were higher in patients with ARDS. Although overall AGPT2 and AGPT2/AGPT1 levels were associated with severe AKI, this association was not significant in patients without ARDS; however, it remained strongly significant in ARDS patients. In patients without ARDS, AGPT2 showed only a weak discriminatory capacity to predict severe AKI (area under the curve (AUC): 0.64 vs 0.81 in the ARDS group). The continuous net reclassification improvement (NRI) in the ARDS group resulting from AGPT2 inclusion was 64.1% (P < 0.001) and the integrated discrimination improvement (IDI) index was 0.057 (P = 0.003). There was no significant difference in NRI in the no-ARDS group. CONCLUSION: AGPT2 and AGPT2/AGPT1 ratio are associated with severe AKI and there was only a need of renal replacement therapy (RRT) in patients with or at risk of ARDS, not in other critically ill patients. Adding AGPT2 to a clinical model resulted in a significant improvement in the capacity to predict severe AKI specifically in ARDS patients.