Early strategy of scepter XC balloon angioplasty and simultaneous Nimodipine infusion for vasospasm following ruptured aneurysm.

BACKGROUND: Cerebral vasospasm still results in high morbidity and mortality rates in patients after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to establish a protocol for the management of vasospasm and demonstrate our experience of angioplasty using the Scepter XC balloon catheter. METHODS: In this retrospective study, a computed tomography angiography and perfusion image was arranged if early symptoms occurred or on the 7th day following aneurysmal SAH. In patients with clear consciousness, balloon angioplasties were performed for symptomatic vasospasms, which were not improved within 6-12 h after maximal medical treatments. In unconscious patients, balloon angioplasties were performed for all patients with angiographic vasospasms. RESULTS: Fifty patients underwent Scepter XC balloon angioplasty among 396 consecutive patients who accepted endovascular or surgical treatments for ruptured aneurysms. All angioplasty procedures were successful without complications. 100% angiographic improvement and 94% clinical improvement were reached immediately after the angioplasties. A favorable functional outcome (modified Rankin Score of ≤2) could be achieved in 82% of patients. Even in patients with poor clinical grading (Hunt-Hess grade 4-5), a clinical improvement rate of 87.5% and favorable outcome rate was 70.8% could be achieved. CONCLUSION: Balloon angioplasty with Scepter XC balloon catheter is safe and effective for post-SAH vasospasm. This device's extra-compliant characteristics could considerably improve the quality of angioplasty procedures. For all patients, even those with poor neurological status, early treatment with combined protocol of nimodipine and angioplasty can have good clinical outcomes.

Sleep Disturbances Following Traumatic Brain Injury in Older Adults: A Comparison Study.

OBJECTIVES: To compare the prevalence of sleep disturbances in older adults with traumatic brain injury (TBI) with that of age- and gender-matched controls and to determine the risk factors for post-TBI sleep disturbances and the effects of post-TBI disturbances on quality of life (QOL). DESIGN: Cross-sectional case-comparison study. PARTICIPANTS: Eighty older adults (aged ≥65 years) with first-time TBI more than 3 months since injury and 80 older adults controls without TBI who completed sleep and health-related QOL questionnaires. RESULTS: Older adults with TBI showed a higher prevalence of obstructive sleep apnea (OSA), insomnia, and daytime sleepiness than older adult controls. Being male, having higher levels of depression and pain, and the presence of insomnia were significantly correlated with the risks of OSA, insomnia, and daytime sleepiness following TBI, respectively. Both OSA and insomnia were significantly correlated with low QOL in older adults with TBI. CONCLUSIONS: Sleep disturbances are highly prevalent in older adults with TBI. Gender differences, depression severity, and pain level are correlated with the occurrence of post-TBI sleep disturbances. Both OSA and insomnia are regarded as major contributors to low QOL in older people with TBI. Interventions targeted at post-TBI sleep disturbances may improve QOL of older adults.

Evaluation the Effect of Sonodynamic Therapy with 5-Aminolevulinic Acid and Sodium Fluorescein by Preclinical Animal Study.

Sonodynamic therapy (SDT) is a novel tumor treatment that combines biosafe sonosensitizers and noninvasive focused ultrasound to eradicate solid tumors. Sonosensitizers such as 5-aminolevulinic acid and fluorescein have great potential in tumor treatment. Here, rodent subcutaneous and brain tumor models were used to evaluate the treatment effect of both 5-ALA- and fluorescein-mediated SDT. The subcutaneous tumor growth rates of both SDT groups were significantly inhibited compared with that of the control groups. For intracranial tumors, 5-ALA-SDT treatment significantly inhibited brain tumor growth, while fluorescein-SDT exerted no therapeutic effect in animals. The distribution of fluorescein in the brain tumor region underwent further assessment. Seven days post tumor implantation, experimental animals received fluorescein and were sacrificed for brain specimen collection. Analysis of the dissected brains revealed no fluorescence signals, indicating an absence of fluorescein accumulation in the early-stage glioma tissue. These data suggest that the fluorescein-SDT treatment response is closely related to the amount of accumulated fluorescein. This study reports the equivalent effects of 5-ALA and fluorescein on the treatment of somatic tumors. For orthotopic brain tumor models, tumor vascular permeability should be considered when choosing fluorescein as a sonosensitizer. In conclusion, both fluorescein and 5-ALA are safe and effective SDT sonosensitizers, and the tumor microenvironment and pathologic type should be considered in the selection of adequate sonosensitizers.

Acrolein produced by glioma cells under hypoxia inhibits neutrophil AKT activity and suppresses anti-tumoral activities.

Acrolein, which is the most reactive aldehyde, is a byproduct of lipid peroxidation in a hypoxic environment. Acrolein has been shown to form acrolein-cysteine bonds, resulting in functional changes in proteins and immune effector cell suppression. Neutrophils are the most abundant immune effector cells in circulation in humans. In the tumor microenvironment, proinflammatory tumor-associated neutrophils (TANs), which are termed N1 neutrophils, exert antitumor effects via the secretion of cytokines, while anti-inflammatory neutrophils (N2 neutrophils) support tumor growth. Glioma is characterized by significant tissue hypoxia, immune cell infiltration, and a highly immunosuppressive microenvironment. In glioma, neutrophils exert antitumor effects early in tumor development but gradually shift to a tumor-supporting role as the tumor develops. However, the mechanism of this anti-to protumoral switch in TANs remains unclear. In this study, we found that the production of acrolein in glioma cells under hypoxic conditions inhibited neutrophil activation and induced an anti-inflammatory phenotype by directly reacting with Cys310 of AKT and inhibiting AKT activity. A higher percentage of cells expressing acrolein adducts in tumor tissue are associated with poorer prognosis in glioblastoma patients. Furthermore, high-grade glioma patients have increased serum acrolein levels and impaired neutrophil functions. These results suggest that acrolein suppresses neutrophil function and contributes to the switch in the neutrophil phenotype in glioma.

CAN008 prolongs overall survival in patients with newly diagnosed GBM characterized by high tumor mutational burden.

BACKGROUND: A previous phase 1 dose-escalation study in Taiwan indicated CAN008 (asunercept) with standard concurrent chemoradiotherapy (CCRT) improved progression-free survival (PFS) in newly diagnosed glioblastoma (GBM) patients. This study evaluates the efficacy of CAN008 in promoting overall survival (OS) and identifies genetic alterations associated with treatment responses. METHODS: We compared OS of 5-year follow-ups from 9 evaluable CAN008 cohort patients (6 received high-dose and 3 received low-dose) to a historical Taiwanese GBM cohort with 164 newly diagnosed patients. CAN008 treatment response-associated genetic alterations were identified by whole-exome sequencing and comparing variant differences between response groups. Associations among patient survival, tumor mutational burden (TMB), and genetic alterations were analyzed using CAN008 cohort and TCGA-GBM dataset. RESULTS: OS for high-dose CAN008 patients at 2 and 5 years was 83% and 67%, respectively, and 40.1% and 8.8% for the historical GBM cohort, respectively. Better OS was observed in the high-dose CAN008 cohort (without reaching the median survival) than the historical GBM cohort (median OS: 20 months; p=0.0103). Five high-dose CAN008 patients were divided into good and poor response groups based on their PFS. A higher variant count and TMB were observed in good response patients, whereas no significant association was observed between TMB and patient survival in the newly diagnosed TCGA-GBM dataset, suggesting TMB may modulate patient CAN008 response. CONCLUSION: CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB.

CAR T Cell Therapy in Primary Brain Tumors: Current Investigations and the Future.

Chimeric antigen receptor T cells (CAR T cells) are engineered cells expressing a chimeric antigen receptor (CAR) against a specific tumor antigen (TA) that allows for the identification and elimination of cancer cells. The remarkable clinical effect seen with CAR T cell therapies against hematological malignancies have attracted interest in developing such therapies for solid tumors, including brain tumors. Glioblastoma (GBM) is the most common primary brain tumor in adults and is associated with poor prognosis due to its highly aggressive nature. Pediatric brain cancers are similarly aggressive and thus are a major cause of pediatric cancer-related death. CAR T cell therapy represents a promising avenue for therapy against these malignancies. Several specific TAs, such as EGFR/EGFRvIII, IL13Rα2, B7-H3, and HER2, have been targeted in preclinical studies and clinical trials. Unfortunately, CAR T cells against brain tumors have showed limited efficacy due to TA heterogeneity, difficulty trafficking from blood to tumor sites, and the immunosuppressive tumor microenvironment. Here, we review current CAR T cell approaches in treating cancers, with particular focus on brain cancers. We also describe a novel technique of focused ultrasound controlling the activation of engineered CAR T cells to achieve the safer cell therapies. Finally, we summarize the development of combinational strategies to improve the efficacy and overcome historical limitations of CAR T cell therapy.

The Role of Myeloid Cells in GBM Immunosuppression.

Gliomas are intrinsic brain tumors that originate from glial cells. Glioblastoma (GBM) is the most aggressive glioma type and resistant to immunotherapy, mainly due to its unique immune environment. Dimensional data analysis reveals that the intra-tumoral heterogeneity of immune cell populations in the glioma microenvironment is largely made up of cells of myeloid lineage. Conventional therapies of combined surgery, chemotherapy and radiotherapy have achieved limited improvements in the prognosis of glioma patients, as myeloid cells are prominent mediators of immune and therapeutic responses-like immunotherapy resistance-in glioma. Myeloid cells are frequently seen in the tumor microenvironment (TME), and they are polarized to promote tumorigenesis and immunosuppression. Reprogramming myeloid cells has emerged as revolutionary, new types of immunotherapies for glioma treatment. Here we detail the current advances in classifying epigenetic, metabolic, and phenotypic characteristics and functions of different populations of myeloid cells in glioma TME, including myeloid-derived suppressor cells (MDSCs), glioma-associated microglia/macrophages (GAMs), glioma-associated neutrophils (GANs), and glioma-associated dendritic cells (GADCs), as well as the mechanisms underlying promotion of tumorigenesis. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in glioma patients.

Calcium-Related Gene Signatures May Predict Prognosis and Level of Immunosuppression in Gliomas.

Gliomas are the most common primary brain cancer. While it has been known that calcium-related genes correlate with gliomagenesis, the relationship between calcium-related genes and glioma prognosis remains unclear. We assessed TCGA datasets of mRNA expressions with differentially expressed genes (DEGs) and enrichment analysis to specifically screen for genes that regulate or are affected by calcium levels. We then correlated the identified calcium-related genes with unsupervised/supervised learning to classify glioma patients into 2 risk groups. We also correlated our identified genes with immune signatures. As a result, we discovered 460 calcium genes and 35 calcium key genes that were associated with OS. There were 13 DEGs between Clusters 1 and 2 with different OS. At the same time, 10 calcium hub genes (CHGs) signature model were constructed using supervised learning, and the prognostic risk scores of the 3 cohorts of samples were calculated. The risk score was confirmed as an independent predictor of prognosis. Immune enrichment analysis revealed an immunosuppressive tumor microenvironment with upregulation of checkpoint markers in the high-risk group. Finally, a nomogram was generated with risk scores and other clinical prognostic independent indicators to quantify prognosis. Our findings suggest that calcium-related gene expression patterns could be applicable to predict prognosis and predict levels of immunosuppression.

A manzamine-derived compound as a potential therapeutic agent for glioma by inducing apoptosis and cell cycle arrest.

Glioma is a severe disease with a poor prognosis despite aggressive surgical resection and traditional chemotherapies. Therefore, new anti-neoplastic drugs are urgently needed. Bioactive compounds from natural products are potential sources of antiproliferative molecules, among which manzamine compounds extracted from the Formosan marine sponge Haliclona sp. have shown considerable promise as anticancer drugs. In the present study, the anti-neoplastic effect and mechanism of the manzamine derivative 1-(9'-propyl-3'-carbazole)-1, 2, 3, 4-tetrahydro-ß-carboline (PCTC) were investigated using in vitro cell lines and an in vivo subcutaneous animal model. Both cytotoxic and anti-proliferative effects were shown in human and murine glioma cell lines (A172, U87MG, and GL261), together with enhanced expressions of apoptotic enzymes and intracellular reactive oxygen species, and blockage of the G1/S phase of the cell cycle. In addition, combined treatment of GL261 cells with PCTC and temozolomide had a synergic antiproliferative effect. Significant safety, efficacy, and survival benefits were also demonstrated with PCTC treatment in the murine subcutaneous GL261 model. In conclusion, PCTC could effectively promote cell death through apoptosis and cell cycle arrest in glioma cell lines, and provide survival benefits in the animal model. Therefore, PCTC may be a clinically beneficial therapy for glioblastoma.

Delayed Progressive Mass Effect After Secured Ruptured Middle Cerebral Artery Aneurysm: Risk Factors and Outcomes.

Objective: Delayed progressive mass effect (DPME) after securing an aneurysm is uncommon following microsurgical or endovascular repair and leads to a poor clinical outcome. Patients with ruptured middle cerebral artery (MCA) aneurysms have a high risk of postoperative oedema and mass effect, which may require decompressive treatment. Because few studies have discussed the risk and predictive factors, we focused on ruptured MCA aneurysms and evaluated the outcomes of these patients and the necessity of salvage surgery when DPME presented. Methods: Data on 891 patients with aneurysmal subarachnoid haemorrhage (aSAH) treated between January 2011 and February 2020 were extracted from the medical database of a tertiary referral centre. A total of 113 patients with aSAH resulting from at least one MCA aneurysm were identified. After excluding patients with several clinical confounders, we enrolled 80 patients with surgically treated aSAH. We examined the characteristics of aneurysms and hematomas, perioperative contrast pooling patterns, presence of distal hematomas, perisylvian low density, occlusive treatment modality, management strategies, the need for salvage surgical decompression, and postoperative 90-day outcomes to identify possible risk factors. Results: DPME was observed in 27 of the 80 patients (33.7%). The DPME and non-DPME group differed significantly in some respects. The DPME group had a higher risk of salvage surgery (p < 0.001) and poorer outcomes (mRS at day 90; p = 0.0018). The univariate analysis indicated that the presence of hematoma, CTA spot signs, perisylvian low density, and distal hematoma were independent risk factors for DPME. We also noted that DPME remained an independent predictor of a poorer 90-day functional outcome (mRS ≤ 2). Conclusion: DPME can lead to salvage decompression surgery and directly relates to poor outcomes for patients with a ruptured MCA aneurysm. Distal hematoma, perisylvian low density, and CTA spot signs on preoperative images can predict DPME.

Receptor-Interacting Protein 140 Enhanced Temozolomide-Induced Cellular Apoptosis Through Regulation of E2F1 in Human Glioma Cell Lines.

Glioblastoma (GBM), a grade IV glioma, is responsible for the highest years of potential life lost among cancers. The poor prognosis is attributable to its high recurrence rate, caused in part by the development of resistance to chemotherapy. Receptor-interacting protein 140 (RIP140) is a very versatile coregulator of nuclear receptors and transcription factors. Although many of the pathways regulated by RIP140 contribute significantly to cancer progression, the function of RIP140 in GBM remains to be determined. In this study, we found that higher RIP140 expression was associated with prolonged survival in patients with newly diagnosed GBM. Intracellular RIP140 levels were increased after E2F1 activation following temozolomide (TMZ) treatment, which in turn modulated the expression of E2F1-targeted apoptosis-related genes. Overexpression of RIP140 reduced glioma cell proliferation and migration, induced cellular apoptosis, and sensitized GBM cells to TMZ. Conversely, knockdown of RIP140 increased TMZ resistance. Taken together, our results suggest that RIP140 prolongs the survival of patients with GBM both by inhibiting tumor cell proliferation and migration and by increasing cellular sensitivity to chemotherapy. This study helps improve our understanding of glioma recurrence and may facilitate the development of more effective treatments.

Anterior sacral meningocele repair assisted by intraoperative intrathecal fluorescence and 3D printing model: illustrative case.

BACKGROUND: Marfan syndrome is rarely accompanied by anterior sacral meningocele (ASM) resulting from erosion of the sacrum by dural ectasia. ASM may induce symptoms due to severe mass effects. ASM may also mimic ovarian cysts, and the risk of cerebrospinal fluid (CSF) leakage is high if spontaneous rupture of the cyst occurs. In this study, the authors presented a rare case of ASM with iatrogenic CSF leakage in a 34-year-old woman with suspected Marfan syndrome. OBSERVATIONS: The patient initially presented with a giant ASM that was first misdiagnosed as an ovarian cyst. Previously, it had been partially resected, which was followed by iatrogenic CSF leakage. Symptoms of intracranial hypotension, including postural headache and dizziness, developed within 1 month. Brain magnetic resonance imaging (MRI) showed pituitary enlargement, bilateral subdural effusion, and tonsillar herniation. Preoperative computed tomography myelography provided three-dimensional (3D) examination of the deformed sacrum and CSF leakage site. Transabdominal approaches led to primary repair, and repair of the meningocele was achieved by intraoperative fluorescein fluorescence and 3D printed model-guided polymethyl methacrylate bone cement reconstruction. No CSF leakage or recurrent ASM was found at the 1.5-year follow-up visit. LESSONS: Intraoperative intrathecal fluorescence and 3D-printed models are useful for ASM repair. Preoperative MRI is helpful for differentiating ASM from other causes of a huge pelvic mass, including ovarian cyst.

Roles of Neutrophils in Glioma and Brain Metastases.

Neutrophils, which are the most abundant circulating leukocytes in humans, are the first line of defense against bacterial and fungal infections. Recent studies have reported the role and importance of neutrophils in cancers. Glioma and brain metastases are the most common malignant tumors of the brain. The tumor microenvironment (TME) in the brain is complex and unique owing to the brain-blood barrier or brain-tumor barrier, which may prevent drug penetration and decrease the efficacy of immunotherapy. However, there are limited studies on the correlation between brain cancer and neutrophils. This review discusses the origin and functions of neutrophils. Additionally, the current knowledge on the correlation between neutrophil-to-lymphocyte ratio and prognosis of glioma and brain metastases has been summarized. Furthermore, the implications of tumor-associated neutrophil (TAN) phenotypes and the functions of TANs have been discussed. Finally, the potential effects of various treatments on TANs and the ability of neutrophils to function as a nanocarrier of drugs to the brain TME have been summarized. However, further studies are needed to elucidate the complex interactions between neutrophils, other immune cells, and brain tumor cells.

Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors.

Focused ultrasound (FUS) in the presence of microbubbles can transiently open the blood-brain barrier (BBB) to increase therapeutic agent penetration at the targeted brain site to benefit recurrent glioblastoma (rGBM) treatment. This study is a dose-escalating pilot trial using a device combining neuronavigation and a manually operated frameless FUS system to treat rGBM patients. The safety and feasibility were established, while a dose-dependent BBB-opening effect was observed, which reverted to baseline within 24 hours after treatment. No immunological response was observed clinically under the applied FUS level in humans; however, selecting a higher level in animals resulted in prolonged immunostimulation, as confirmed preclinically by the recruitment of lymphocytes into the tumor microenvironment (TME) in a rat glioma model. Our findings provide preliminary evidence of FUS-induced immune modulation as an additional therapeutic benefit by converting the immunosuppressive TME into an immunostimulatory TME via a higher but safe FUS dosage.

Valproic Acid Enhanced Temozolomide-Induced Anticancer Activity in Human Glioma Through the p53-PUMA Apoptosis Pathway.

Glioblastoma (GBM), the most lethal type of brain tumor in adults, has considerable cellular heterogeneity. The standard adjuvant chemotherapeutic agent for GBM, temozolomide (TMZ), has a modest response rate due to the development of drug resistance. Multiple studies have shown that valproic acid (VPA) can enhance GBM tumor control and prolong survival when given in conjunction with TMZ. However, the beneficial effect is variable. In this study, we analyzed the impact of VPA on GBM patient survival and its possible correlation with TMZ treatment and p53 gene mutation. In addition, the molecular mechanisms of TMZ in combination with VPA were examined using both p53 wild-type and p53 mutant human GBM cell lines. Our analysis of clinical data indicates that the survival benefit of a combined TMZ and VPA treatment in GBM patients is dependent on their p53 gene status. In cellular experiments, our results show that VPA enhanced the antineoplastic effect of TMZ by enhancing p53 activation and promoting the expression of its downstream pro-apoptotic protein, PUMA. Our study indicates that GBM patients with wild-type p53 may benefit from a combined TMZ+VPA treatment.

Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study.

Asunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Using cortical function mapping by awake craniotomy dealing with the patient with recurrent glioma in the eloquent cortex.

BACKGROUND: Awake craniotomy is an effective method by which to reduce postoperative neurologic deficit in newly-diagnosed glioma patients. However, the level of functional preservation in patients undergoing resection of recurrent glioma remains unknown. Therefore, this study aimed to evaluate functional outcomes in patients with recurrent glioma undergoing awake craniotomy as compared with conservative general anesthesia craniotomy for tumor resection. METHODS: We retrospectively reviewed 225 patients who had recurrent gliomas from May 2013 to January 2016 in our institution. New-onset neurological deficits were evaluated on postoperative day 7 (early) and at 3 months (late). General performance was assessed both preoperatively and at 3 months postoperatively. RESULTS: The early neurological deficit rate was 3.8% in the awake craniotomy group and 21.6% in the general anesthesia group (p. 0.032), while the late neurological deficit rates were 3.8% and 11.5%, respectively (p. 0.231). Moreover, 46.1% of patients in the awake craniotomy group and 12.6% in the general anesthesia group demonstrated an improvement in the Karnofsky performance status (KPS) score (p < 0.001). CONCLUSION: Awake craniotomy is an effective and safe method by which to perform recurrent glioma surgery. The neurological outcomes and general performance after awake craniotomy in recurrent glioma patients were better than those in patients undergoing general anesthesia craniotomy.

Incidence and Factors Associated with Postoperative Delayed Hyponatremia after Transsphenoidal Pituitary Surgery: A Meta-Analysis and Systematic Review.

INTRODUCTION: Postoperative delayed hyponatremia is a complication associated with transsphenoidal pituitary surgery. Due to a wide spectrum of symptoms, the reported incidence and predictors of postoperative delayed hyponatremia vary among studies, and this deserves to be reviewed systematically. METHODS: PubMed, EMBASE, and CENTRAL databases were searched until September 1, 2020. Studies were included when (1) the event number of delayed hyponatremia after transsphenoidal pituitary surgery was reported, or (2) the associated factors of such complication were evaluated. RESULTS: A total of 27 studies were included for meta-analysis. The pooled incidence of overall and symptomatic delayed hyponatremia was 10.5% (95% confidence interval (CI) = 7.4-14.7%) and 5.0% (95% CI = 3.6-6.9%), respectively. No overt variations of the pooled estimates were observed upon subgroups stratified by endoscopic and microscopic procedure, publication year, and patients' age. In addition, 44.3% (95% CI = 29.6-60.2%) of unplanned hospital readmissions within 30 days were caused by delayed hyponatremia. Among the predictors evaluated, older age was the only significant factor associated with increased delayed hyponatremia (odds ratio = 1.16, 95% CI = 1.04-1.29, P = 0.006). CONCLUSION: This meta-analysis and systematic review evaluated the incidence of postoperative delayed hyponatremia and found it as a major cause of unplanned readmissions after transsphenoidal pituitary surgery. Older patients are more prone to such complications and should be carefully followed. The retrospective nature and heterogeneity among the included studies and the small number of studies used for risk factor evaluation might weaken the corresponding results. Future prospective clinical studies are required to compensate for these limitations.

Glioblastoma Primary Cells Retain the Most Copy Number Alterations That Predict Poor Survival in Glioma Patients.

Gliomas are solid tumors that originate from glial cells in the brain or spine and account for 74.6% of malignant primary central nervous system tumors worldwide. As patient-derived primary cells are important tools for drug screening and new therapy development in glioma, we aim to understand the genomic similarity of the primary cells to their parental tumors by comparing their whole-genome copy number variations and expression profile of glioma clinicopathologic factors. We found that the primary cells from grade II/III gliomas lost most of the gene copy number alterations (CNAs), which were mainly located on chromosome 1p and 19q in their parental tumors. The glioblastoma (GBM) primary cells preserved 83.7% of the gene CNAs in the parental GBM tumors, including chromosome 7 gain and 10q loss. The CNA gains of LINC00226 and ADAM6 and the chromosome 16p11 loss were reconstituted in primary cells from both grade II/III gliomas and GBMs. Interestingly, we found these CNAs were correlated to overall survival (OS) in glioma patients using the Merged Cohort LGG and GBM dataset from cBioPortal. The gene CNAs preserved in glioma primary cells often predicted poor survival, whereas the gene CNAs lost in grade II/III primary cells were mainly associated to better prognosis in glioma patients. Glioma prognostic factors that predict better survival, such as IDH mutations and 1p/19q codeletion in grade II/III gliomas, were lost in their primary cells, whereas methylated MGMT promoters as well as TERT promoter mutations were preserved in GBM primary cells while lost in grade II/III primary cells. Our results suggest that GBM primary cells tend to preserve CNAs in their parental tumors, and these CNAs are correlated to poor OS and predict worse prognosis in glioma patients.

The Merits of Awake Craniotomy for Glioblastoma in the Left Hemispheric Eloquent Area: One Institution Experience.

OBJECTIVE: Awake craniotomy (AC) with intraoperative stimulation mapping is the standard treatment for gliomas, especially those on the eloquent cortex. Many studies have reported survival benefits with the use of AC in patients with glioma, however most of these studies have focused on low-grade glioma. The aim of this study was to evaluate the experience of one treatment center over 10 years for resection of left hemispheric eloquent glioblastoma. METHODS: This retrospective analysis included 48 patients with left hemispheric eloquent glioblastoma who underwent AC and 61 patients who underwent surgery under general anesthesia (GA) between 2008 and 2018. Perioperative risk factors, extent of resection (EOR), preoperative and postoperative Karnofsky Performance Score (KPS), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: The postoperative KPS was significantly lower in the GA patients compared to the AC patients (p = 0.002). The EOR in the GA group was 90.2% compared to 94.9% in the AC group (p = 0.003). The mean PFS was 18.9 months in the GA group and 23.2 months in the AC group (p = 0.001). The mean OS was 25.5 months in all patients, 23.4 months in the GA group, and 28.1 months in the AC group (p < 0.001). In multivariate analysis, the EOR and preoperative KPS independently predicted better OS. CONCLUSION: The patients with left hemispheric eloquent glioblastoma in this study had better neurological outcomes, maximal tumor removal, and better PFS and OS after AC than surgery under GA. Awake craniotomy should be performed in these patients if the resources are available.