Notes

Perinatal morbidity along with well being utilization between moms of medically sensitive children.
Symptomatic epilepsy is a common symptom of glioblastoma, which may occur in different stages of disease. There are discrepant reports on association between early seizures and glioblastoma survival, even less is known about the background of these seizures. We aimed at analyzing the risk factors and clinical impact of perioperative seizures in glioblastoma.

All consecutive cases with de-novo glioblastoma treated at our institution between 01/2006 and 12/2018 were eligible for this study. Perioperative seizures were stratified into seizures at onset (SAO) and early postoperative seizures (EPS, ≤21days after surgery). Associations between patients characteristics and overall survival (OS) with SAO and EPS were addressed.

In the final cohort (
= 867), SAO and EPS occurred in 236 (27.2%) and 67 (7.7%) patients, respectively. SAO were independently predicted by younger age (
= .009), higher KPS score (
= .002), tumor location (parietal lobe,
= .001), GFAP expression (≥35%,
= .045), and serum chloride at admission (>102 mmol/L,
= .004). In turn, EPS were independently associated with tumor location (frontal or temporal lobe,
= .013) and pathologic laboratory values at admission (hemoglobin < 12 g/dL, [
= .044], CRP > 1.0 mg/dL [
= 0.036], and GGT > 55 U/L [
= 0.025]). Finally, SAO were associated with gross-total resection (
= .006) and longer OS (
= .030), whereas EPS were related to incomplete resection (
= .005) and poorer OS (
= .009).

In glioblastoma patients, SAO and EPS seem to have quite different triggers and contrary impact on treatment success and OS. The clinical characteristics of SAO and EPS patients might contribute to the observed survival differences.
In glioblastoma patients, SAO and EPS seem to have quite different triggers and contrary impact on treatment success and OS. The clinical characteristics of SAO and EPS patients might contribute to the observed survival differences.
Mebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers.

A single-center dose-escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose-escalation levels were 25, 50, 100, and 200 mg/kg/day of oral mebendazole. A total of 15 patients were enrolled at the highest dose studied of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8, and 16 weeks.

Twenty-four patients (18 glioblastoma and 6 anaplastic glioma) were enrolled with a median age of 49.8 years. Four patients (at 200 mg/kg) developed elevated grade 3 alanine aminotransferase (ALT) and/or aspartate transaminase (AST) after 1 month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan-Meier analysis showed a 21-month median overall survival with 41.7% of patients alive at 2 years and 25% at 3 and 4 years. Median progression-free survival (PFS) from the date of diagnosis for 17 patients taking more than 1 month of mebendazole was 13.1 months (95% confidence interval [CI] 8.8-14.6 months) but for 7 patients who received less than 1 month of mebendazole PFS was 9.2 months (95% CI 5.8-13.0 months).

Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. NaPB Further studies are needed to determine mebendazole's efficacy in patients with malignant glioma.
Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole's efficacy in patients with malignant glioma.
Stereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear.

Through a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using Net Reclassification Index (NRI > 0) and integrated discrimination improvement (IDI) metrics.

In a multivariate Cox proportional hazards model, BRAF mutation status, KPS, number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treates).
Gliomas typically escape surgical resection and recur due to their "diffuse invasion" phenotype, enabling them to infiltrate diffusely into the normal brain parenchyma. Over the past 80 years, studies have revealed 2 key features of the "diffuse invasion" phenotype, designated the Scherer's secondary structure, and include perineuronal satellitosis (PS) and perivascular satellitosis (PVS). However, the mechanisms are still unknown.

We established a mouse glioma cell line (IG27) by manipulating the histone H3K27M mutation, frequently harboring in diffuse intrinsic pontine gliomas, that reproduced the diffuse invasion phenotype, PS and PVS, following intracranial transplantation in the mouse brain. Further, to broadly apply the results in this mouse model to human gliomas, we analyzed data from 66 glioma patients.

Increased H3K27 acetylation in IG27 cells activated glucose transporter 1 (Glut1) expression and induced aerobic glycolysis and TCA cycle activation, leading to lactate, acetyl-CoA, and oncometabolite production irrespective of oxygen and glucose levels. Gain- and loss-of-function in vivo experiments demonstrated that Glut1 controls the PS of glioma cells, that is, attachment to and contact with neurons. GLUT1 is also associated with early progression in glioma patients.

Targeting the transporter Glut1 suppresses the unique phenotype, "diffuse invasion" in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.
Targeting the transporter Glut1 suppresses the unique phenotype, "diffuse invasion" in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.
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