Background In patients with mild ischemic stroke, small but eloquent infarcts may have devastating effects, particularly on health-related quality of life. Aim This study investigates the association between acute infarct location and three-month health-related quality of life in patients with mild ischemic stroke. Methods We evaluated consecutively enrolled patients from a single center between August 2012 and July 2013. Our primary outcome at three months was impairment in any health-related quality of life domain (upper extremity, lower extremity, executive function, and general concerns) defined by a T-score <45. We analyzed the association between acute infarct locations and impaired health-related quality of life at three months in univariate and multivariable analysis. Results Among 229 patients (mean age 64.9 years, 55% male, 29.7% black, and median initial NIHSS score 1), impaired health-related quality of life was noted in 84 (36.2%) patients at three months. In univariate analysis, patients with subcortical infarcts (56.0% vs. 39.3%, p = 0.02) and brainstem infarcts (21.4% vs. 10.3%, p = 0.02) were more likely to have impaired health-related quality of life. In multivariable analysis, patients with subcortical and/or brainstem infarcts had increased odds of impaired health-related quality of life (adjusted OR 2.54, 95% CI 1.29-5.01, p = 0.01). Conclusions After mild ischemic stroke, subcortical and brainstem infarct locations predict impairment in health-related quality of life.
Glioblastoma multiforme is the most deadly primary brain tumor, exhibiting a median survival of just 13 months despite aggressive treatments including surgery, radiation, and chemotherapy. There are two main subtypes of glioblastoma, denoted primary and secondary glioblastoma, respectively. While the former begins as a grade IV tumor, secondary glioblastomas evolve from a lineage that may include grade II astrocytomas and grade III anaplastic astrocytomas, a class of tumors which are molecularly defined by mutations in isocitrate dehydrogenase (IDH). The molecular mechanisms underlying progression of these tumors are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in a plethora of cancers and represents a probable mechanism by which malignant cells delay senescence and evade cell death. TERT activity is the primary mechanism by which malignant cells replenish telomeres with the other being the alternative lengthening of telomeres (ALT) system, known to become active in tumors harboring loss of function mutations in ATRX. In data obtained from The Cancer Genome Atlas, significantly lower rates of survival were observed in low grade glioma patients with tumors highly expressing TERT as compared to tumors with low/medium expression. However, studies comparing the expression of TERT across different grades of glioma have not been performed to date. Using immunohistochemical staining we show that, controlling for ATRX and IDH mutational status, TERT expression increases as a function of tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that as astrocytomas progress to more aggressive tumors, TERT expression likely increases to provide enhanced genomic stability. Citation Format: John L. Caniglia, Anvesh Jalasutram, Kiran K. Velpula, Maheedhara R. Guda, Sarah E. Bach, Andrew J. Tsung. TERT expression increases with tumor grade in a cohort of IDH mutant gliomas [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO043.
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