Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma.

BACKGROUND: BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. METHODS: Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. RESULTS: BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients' gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. CONCLUSIONS: Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

Low (0-5) Alberta Stroke Program Early Computed Tomography Score on admission predictive of worse functional outcome after mechanical thrombectomy for anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: We examined functional outcomes of mechanical thrombectomy (MT) procedures following anterior circulation large vessel occlusion (ACLVO)-related acute ischemic strokes (AIS). Results were based on admission non-contrast computed tomography (NCCT) studies, using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) as standard metric. METHODS: Qualifying subjects were consecutive patients (N = 343) at a single center undergoing MT for ACLVO-related AIS. Each was grouped according to ASPECTS status on admission, determined from NCCT images by two physicians. Primary clinical endpoint was functional independence, assessed via modified Rankin Scale (mRS) at 90 days. Secondary endpoints were vessel recanalization (i.e., modified Thrombolysis in Cerebral Infarction [mTICI] score), symptomatic intracranial hemorrhage (sICH), and mortality. RESULTS: In this study population (mean age, 63.6 ± 12.6 years; women, 30.3%; median baseline National Institute of Health Stroke Scale [NIHSS] score, 15.2 ± 4.5), patients were stratified by ASPECTS tier at presentation, either 0-5 (n = 50) or 6-10 (n = 293). Multivariate logistic regression showed a relation between ASPECTS values ≤ 5 and lesser chance of 90-day functional improvement (OR = 2.309, 95% confidence interval [CI] 1.012-5.271; p = 0.047), once adjusted for age, baseline NIHSS score, diabetes mellitus, HbA1c concentration, D-dimer level, occlusive location, numbers of device passes, and successful recanalization. CONCLUSIONS: ASPECTS values ≤ 5 correspond with worse long-term functional improvement (mRS scores > 2) in patients undergoing MT for ACLVO-related AIS. Other independent determinants of functional outcomes after MT are age, baseline NIHSS score, HbA1c concentration, and successful recanalization.

The risk and outcome of malignant brain edema in post-mechanical thrombectomy: acute ischemic stroke by anterior circulation occlusion.

BACKGROUND AND PURPOSE: Malignant brain edema (MBE) occurring after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) could lead to severe disability and mortality. We aimed to investigate the incidence, predictors, and clinical outcomes of MBE in patients with AIS after MT. METHODS: The clinical and imaging data of 155 patients with AIS of anterior circulation after MT were studied. Standard non-contrast CT was used to evaluate baseline imaging characteristics at admission. Clinical outcomes were measured using the 90-day modified Rankin Scale (mRS) score. Based on the follow-up CT scans performed within 72 h after MT, the patients were classified into MBE and non-MBE group. MBE was defined as a midline shift of ≥ 5 mm with signs of local brain swelling. Univariate and multivariate regression analyses were used to analyze the relationship between MBE and clinical outcomes and identify the predictors that correlate with MBE. RESULTS: MBE was observed in 19.4% of the patients who underwent MT and was associated with a lower rate of favorable 90-day clinical outcomes. Significant differences were observed in both MBE and non-MBE groups: baseline Alberta Stroke Program Early CT (ASPECT) score, hyperdense middle cerebral artery sign (HMCAS), baseline signs of early infarct, angiographic favorable collaterals, number of retrieval attempts, and revascularization rate. Multivariate analysis indicated that low baseline ASPECT score, absent HMCAS, angiographic poor collaterals, more retrieval attempt count, and poor revascularization independently influenced the occurrence of MBE in AIS patients with anterior circulation after MT. CONCLUSION: MBE was associated with a lower rate of favorable 90-day clinical outcomes. Low baseline ASPECT score, absent HMCAS, angiographic poor collaterals, more retrieval attempt count and poor revascularization were independently associated with MBE after MT.

Prediction model of early biomarkers of massive cerebral infarction caused by anterior circulation occlusion: Establishment and evaluation.

Objective: The purpose of this study is to establish and evaluate an early biomarker prediction model of massive cerebral infarction caused by anterior circulation occlusion. Methods: One hundred thirty-four patients with acute cerebral infarction from January 2018 to October 2020 were selected to establish the development cohort for the internal test of the nomogram. Ninety-one patients with acute cerebral infarction hospitalized in our hospital from December 2020 to December 2021 were constituted the validation cohort for the external validation. All patients underwent baseline computed tomography (CT) scans within 12 h of onset and early imaging signs (hyperdense middle cerebral artery sign, obscuration of the lentiform nucleus, insular ribbon sign) of acute cerebral infarction were identified on CT by two neurologists. Based on follow-up CT images, patients were then divided into a massive cerebral infarction group and a non-massive cerebral infarction group. The nomogram model was constructed based on logistic regression analysis with R language. The nomogram was subsequently validated in an independent external validation cohort. Accuracy and discrimination of the prediction model were evaluated by a calibration chart, receiver operating characteristic (ROC) curve, and decision curve. Results: The indicators, including insular ribbon sign, reperfusion therapy, National Institutes of Health Stroke Scale (NHISS) score, previous cerebral infarction, and atrial fibrillation, were entered into the prediction model through binary logistic regression analysis. The prediction model showed good predictive ability. The area under the ROC curve of the prediction model was 0.848. The specificity, sensitivity, and Youden index were 0.864, 0.733, and 0.597, respectively. This nomogram to the validation cohort also showed good discrimination (AUC = 0.940, 95% CI 0.894-0.985) and calibration. Conclusion: Demonstrating favorable predictive efficacy and reproducibility, this study successfully established a prediction model of CT imaging signs and clinical data as early biomarkers of massive cerebral infarction caused by anterior circulation occlusion.