IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in cancer cells but not in the surrounding normal tissue, and 59 (82%) of 72 ICCs were IMP3 positive by immunohistochemistry. Among 35 cases with lymphovascular invasion, 26 (74%) showed IMP3 positivity in lymph node metastases. IMP3 expression was significantly correlated with tumor size, pathological grade, metastasis, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between IMP3 expression and overall survival rate. Multivariate analysis revealed that IMP3 was the only risk factor associated with survival. To further explore the mechanism of IMP3 expression in cancers, we identified 2 CpG islands at IMP3 proximal promoter. Interestingly, the IMP3 promoter was almost completely demethylated in ICCs in contrast to densely methylated promoter in normal liver tissues. IMP3 expression is a useful biomarker for ICCs and can provide an independent prognostic value for patients with ICC. To our knoweldge, this is the first direct evidence of epigenetic deregulation of IMP3 in human cancer. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

BACKGROUND: Factors influencing outcome after cerebral artery occlusion are not completely understood. Although it is well accepted that the site of arterial occlusion critically influences outcome, the majority of studies investigating this issue has focused on proximal large artery occlusion. To gain a better understanding of factors influencing outcome after distal large artery occlusion, we sought to assess predictors of outcome following isolated M2 middle cerebral artery occlusion infarcts. METHODS: We retrospectively analyzed patients with isolated acute M2 occlusion admitted to a single academic center from January 2010 to August 2012. Baseline clinical, laboratory imaging, and outcome data were assessed from a prospectively collected database. Factors associated with a modified Rankin Scale (mRS) score < /=2 in univariable analyses (p < 0.05) were entered into multivariable logistic regression analysis. The Admission National Institutes of Health Stroke Scale (aNIHSS) score, age, and infarct volume were also entered as dichotomized variables. Receiver operating characteristic curves were plotted to determine the optimal aNIHSS score, infarct volume, and age cut points predicting an mRS score < /=2. Optimal thresholds were determined by maximizing the Youden index. Respective multivariable logistic regression analyses were used to identify independent predictors of a good 90-day outcome (mRS score < /=2; primary analysis) as well as 90-day mortality (secondary outcome). RESULTS: 90 patients with isolated M2 occlusion were included in the final analyses. Of these, 69% had a good 90-day outcome which was associated with age < 80 years (p = 0.007), aNIHSS < 10 (p = 0.002), and infarct volume < /=26 ml (p < 0.001). Notably, 20% of patients (64% of those with a poor outcome) had died by 90 days. Secondary analysis for 90-day mortality was performed. This analysis indicated that infarct volume > 28 ml (OR 11.874, 95% CI 2.630-53.604, p = 0.001), age > 80 years (OR 4.953, 95% CI 1.087-22.563, p = 0.039), need for intubation (OR 7.788, 95% CI 1.072-56.604), and history of congestive heart failure (OR 5.819, 95% CI 1.140-29.695) were independent predictors of 90-day mortality (20% of all included patients). CONCLUSION: While the majority of patients with isolated M2 occlusion stroke has a good 90-day outcome, a substantial proportion of subjects dies by 90 days, as identified by a unique subset of predictors. The knowledge gained from our study may lead to an improvement in the prognostic accuracy, clinical management, and resource utilization in this patient population.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE=0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p=0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.