Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We and others had shown that a subset of glioblastomas (GBM), the most malignant of all primary brain tumors in adults, are responsive to TOP2 poisons. To identify genes that confer susceptibility to this drug in gliomas, we performed a genome-scale CRISPR knockout screen with etoposide. Genes involved in protein synthesis and DNA damage were implicated in etoposide susceptibility. To define potential biomarkers for TOP2 poisons, CRISPR hits were overlapped with genes whose expression correlates with susceptibility to this drug across glioma cell lines, revealing ribosomal protein subunit RPS11, 16, 18 as putative biomarkers for response to TOP2 poisons. Loss of RPS11 led to resistance to etoposide and doxorubicin and impaired the induction of pro-apoptotic gene APAF1 following treatment. The expression of these ribosomal subunits was also associated with susceptibility to TOP2 poisons across cell lines from gliomas and multiple other cancers.

BACKGROUND After MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) demonstrated that endovascular therapy improved outcomes in patients with stroke, the number of endovascular procedures has risen sharply. We describe acute transient contrast‐induced neurological deficit (ATCIND), a group of neurological syndromes associated with arterial contrast administration during angiography. Our goal is to elucidate the incidence, risk factors, outcomes, pathogenesis, and diagnostic characteristics of ATCIND. Our primary objective is to elucidate the incidence of ATCIND in the setting of coronary or cerebral angiography. Secondary outcomes include potential risk factors, demographics, treatment modalities, and patient recovery. METHODS The data that support the findings of this study are available from the corresponding author on reasonable request. The databases of the Cochrane Library, MEDLINE, Web of Science, and Embase were queried, yielding studies from 1974 to 2021. Inclusion criteria for articles were the following: (1) contrast‐induced encephalopathy, contrast‐induced neurotoxicity, or cortical blindness after contrast administration during angiography were the focus of the article; (2) incidence was reported; (3) studies included ≥3 cases; and (4) follow‐up tests were described to rule out other causes. Exclusion criteria included the following: (1) incidence was not reported; (2) unavailable in the English language; (3) abstracts and unpublished studies; and (4) did not exclude other possible causes, or findings suggested other possible causes, such as worsening ischemic injury. Of 627 articles, 7 were retained. This systematic review with meta‐analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) checklists. Independent extraction by multiple reviewers was performed. Data were pooled using a random‐effects model. RESULTS The primary study outcome was incidence of ATCIND, which was formulated before data collection began. We hypothesized that the pooled incidence of ATCIND would be similar to that of individual studies. A total of 70 of 21007 patients had the diagnosis of contrast‐induced encephalopathy, contrast‐induced neurotoxicity or angiography‐associated cortical blindness, and ATCIND. The incidence rate of ATCIND is estimated to be 0.51% (CI, 0.3%–1.0%; P <0.001 [ I 2 =29.3]), or 51 per 10 000 patients. Pooled data for risk factors for contrast‐induced encephalopathy were higher contrast dose (odds ratio [OR], 1.072; 95% CI, 0.952–1.192 [ P <0.001]; I 2 =0), and prior stroke (OR, 5.153; CI 1.726–8.581 [ P =0.003]; I 2 =0). Contrast dose >150 mL was a positive, significant predictor of visual disturbance (OR, 7.083; CI, 1.1742–42.793 [ P =0.033]). Full recovery is estimated at 89.5% (95% CI, 76.9%–95.6%; P <0.001 [ I 2 =0]). CONCLUSIONS This study confirms the rare incidence of ATCIND, although it shows moderate heterogeneity, likely reflecting the type of angiography performed. Risk factors include larger contrast dose and prior stroke. Full recovery occurs in the majority of patients. It should remain in the differential diagnosis in patients with certain risk factors for blood–brain barrier compromise.

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