A Single-Institution Retrospective Series of SARS-CoV-2 Infection in Adult Glioma Patients

A subset of cancer patients is particularly vulnerable to SARS-CoV-2 infection; however, real-world outcomes-based data on primary central nervous system tumor patients is sparse. This retrospective series describes a cohort of adult glioma patients seen at Stanford Cancer Center between January 1, 2020, and June 30, 2022 who contracted SARS-CoV-2, which, to our knowledge, currently represents the largest single-institution comprehensive analysis of this patient population. We performed a retrospective search of patients seen in the Stanford Neuro-Oncology clinic, identifying 29 cases of COVID-19 amongst glioma patients and extracted clinical data via individual chart review. At the time of COVID-19 diagnosis, 15 patients had been vaccinated against SARS-CoV-2, 8 patients were taking dexamethasone, and 8 were undergoing cancer-specific treatment. Obesity, prior tobacco use, and diabetes were the most common comorbidities. Cough, sore throat, and congestion were the most common symptoms. Five patients were admitted to the hospital and two received COVID-19-specific treatment. None died from COVID-related causes or complications. Our data suggest that glioma patients seen at Stanford Cancer Center do not experience an exceptionally high COVID-19 infectivity, hospitalization, or mortality rate, especially when compared to other vulnerable populations such as lung cancer patients. High vaccination rates, adherence to COVID-19 guidelines, and low prevalence of comorbidities may have contributed to these results

Glycogen Synthase Kinase 3 (GSK3) Inhibitor, SB-216763, Promotes Pluripotency in Mouse Embryonic Stem Cells

Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months

Mouse Intracerebral Hemorrhage Models Produce Different Degrees of Initial and Delayed Damage, Axonal Sprouting, and Recovery

The mechanisms of delayed damage and recovery after intracerebral hemorrhage (ICH) remain poorly defined. Two rodent models of ICH are commonly used: injection of the enzyme collagenase (cICH) and injection of autologous blood (bICH). In mice, we compared the effects of these two models on initial and delayed tissue damage, motor system connections, and behavioral recovery. There is no difference in lesion size between models. Injection of autologous blood causes greater mass effect and early mortality. However, cICH produces greater edema, inflammation, and cell death. Injection of the enzyme collagenase causes greater loss of cortical connections and secondary shrinkage of the striatum. Intracerebral hemorrhage occurs within the motor system connections of the striatum. Mapping of the projections of the forelimb motor area shows a significant sprouting in motor cortex projections only in cICH. Both models of ICH produce deficits in forelimb motor control. Behavioral recovery occurs by 5 weeks in cICH and 9 weeks in bICH. In summary, cICH and bICH differ in almost every facet of initial and delayed stroke pathophysiology, with cICH producing greater initial and secondary tissue damage and greater motor system axonal sprouting than bICH. Motor recovery occurs in both models, suggesting that motor system axonal sprouting in cICH is not causally associated with recovery.Journal of Cerebral Blood Flow & Metabolism advance online publication, 11 June 2014; doi:10.1038/jcbfm.2014.107

CNS Neurotoxicity of Antiretrovirals

The development of novel antiretroviral treatments has led to a significant turning point in the fight against HIV. Although therapy leads to virologic suppression and prolonged life expectancies, HIV-associated neurocognitive disorder (HAND) remains prevalent. While various hypotheses have been proposed to explain this phenomenon, a growing body of literature explores the neurotoxic effects of antiretroviral therapy. Research to date brings into question the potential role of such medications in neurocognitive and neuropsychiatric impairment seen in HIV-positive patients. This review highlights recent findings and controversies in cellular, molecular, and clinical neurotoxicity of antiretrovirals. It explores the pathogenesis of such toxicity and relates it to clinical manifestations in each medication class. The concept of accelerated aging in persons living with HIV (PLWH) as well as potential treatments for HAND are also discussed. Ultimately, this article hopes to educate clinicians and basic scientists about the neurotoxic effects of antiretrovirals and spur future scientific investigation into this important topic. Graphical Abstract

Survival patterns of oligoastrocytoma patients: A surveillance, epidemiology and end results (SEER) based analysis

Objective: The 2016 update to the World Health Organization (WHO) states that oligoastrocytoma (OA) should be classified as either oligodendroglioma or astrocytoma based on molecular biomarkers. We examined the survival patterns of patients diagnosed with OA in the Surveillance, Epidemiology and End Results (SEER) registry in the context of this revised scheme. Methods: We used data from the SEER database (1999–2010) to identify patients diagnosed with WHO grade II astrocytoma (A2, n = 4113), WHO grade II oligodendroglioma (O2, n = 2378), and oligoastrocytoma (OA, n = 1505). Survival comparison was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards analysis. Results: Similar to O2 patients, gross total resection (GTR) was not associated with improved survival in OA patients. In contrast, GTR is associated with improved survival in A2 patients. For OA patients who did not undergo surgery or radiation therapy (RT), those with tumors <5 cm in maximal diameter exhibited survival patterns similar to O2 patients, while those with tumors ≥5 cm exhibited survival patterns similar to A2 patients. Conclusions: Distinct survival patterns were observed in SEER OA patients with tumors < or ≥5 cm in maximal diameter