Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: a single-center analysis.

Background: This retrospective observational cohort study aimed to evaluate whether tenecteplase's use for acute ischemic stroke (AIS) has time management advantages and clinical benefits. Methods: 144 AIS patients treated with alteplase and 120 with tenecteplase were included. We compared baseline clinical characteristics, key reperfusion therapy time indices [onset-to-treatment time (OTT), door-to-needle time (DNT), and door-to-puncture time (DPT)] and clinical outcomes (24-h post-thrombolysis NIHSS improvement, and intracranial hemorrhage incidence) between the groups using univariate analysis. We assessed hospital stay durations and used binary logistic regression to examine tenecteplase's association with DNT and DPT target times, NIHSS improvement, and intracranial hemorrhage. Results: Baseline characteristics showed no significant differences except hyperlipidemia and atrial fibrillation. OTT (133 vs. 163.72, p = 0.001), DNT (36.5 vs. 50, p < 0.001) and DPT (117 vs. 193, p = 0.002) were significantly faster in the tenecteplase group. The rates of DNT ≤ 45 min (65.83% vs. 40.44%, p < 0.001) and DPT ≤ 120 min (59.09% vs. 13.79%, p = 0.001) were significantly higher in the tenecteplase group. Tenecteplase was an independent predictor of achieving target DNT (OR 2.951, 95% CI 1.732-5.030; p < 0.001) and DPT (OR 7.867, 95% CI 1.290-47.991; p = 0.025). Clinically, the proportion NIHSS improvement 24 h post-thrombolysis was higher in the tenecteplase group (64.17% vs. 50%, p = 0.024). No significant differences were observed in symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (ICH). Patients receiving tenecteplase had shorter hospital stays (6 vs. 8 days, p < 0.001). Tenecteplase was an independent predictor of NIHSS improvement at 24 h (OR 1.715, 95% CI 1.011-2.908; p = 0.045). There was no significant association between thrombolytic choice and sICH or any ICH. Conclusion: Tenecteplase significantly reduced DNT and DPT. It was associated with early neurological function improvement (at 24 h), without compromising safety compared to alteplase. The findings support tenecteplase's application in AIS.

Net water uptake within the ischemic penumbra predicts the presence of the midline shift in patients with acute ischemic stroke.

Objective: The study aimed to explore the association between midline shift (MLS) and net water uptake (NWU) within the ischemic penumbra in acute ischemic stroke patients. Methods: This was a retrospective cohort study that examined patients with anterior circulation stroke. Net water uptake within the acute ischemic core and penumbra was calculated using data from admission multimodal CT scans. The primary outcome was severe cerebral edema measured by the presence of MLS on 24 to 48 h follow-up CT scans. The presence of a significant MLS was defined by a deviation of the septum pellucidum from the midline on follow-up CT scans of at least 3 mm or greater due to the mass effect of ischemic edema. The net water uptake was compared between patients with and without MLS, followed by logistic regression analyses and receiver operating characteristics (ROCs) to assess the predictive power of net water uptake in MLS. Results: A total of 133 patients were analyzed: 50 patients (37.6%) with MLS and 83 patients (62.4%) without. Compared to patients without MLS, patients with MLS had higher net water uptake within the core [6.8 (3.2-10.4) vs. 4.9 (2.2-8.1), P = 0.048] and higher net water uptake within the ischemic penumbra [2.9 (1.8-4.3) vs. 0.2 (-2.5-2.7), P < 0.001]. Penumbral net water uptake had higher predictive performance than net water uptake of the core in MLS [area under the curve: 0.708 vs. 0.603, p < 0.001]. Moreover, the penumbral net water uptake predicted MLS in the multivariate regression model, adjusting for age, sex, admission National Institutes of Health Stroke Scale (NIHSS), diabetes mellitus, atrial fibrillation, ischemic core volume, and poor collateral vessel status (OR = 1.165; 95% CI = 1.002-1.356; P = 0.047). No significant prediction was found for the net water uptake of the core in the multivariate regression model. Conclusion: Net water uptake measured acutely within the ischemic penumbra could predict severe cerebral edema at 24-48 h.

Evaluating the role of Ginkgo biloba extract in the secondary prevention of acute ischemic stroke with cerebral microbleeds by quantitative susceptibility mapping (QSM).

BACKGROUND: EGb 761, a standardized dry extract of Ginkgo biloba leaves, has certain anti-inflammatory and thrombotic effects and can be used to treat cerebrovascular diseases. METHODS: A total of 49 patients were randomly assigned to the Aspirin group (24 cases in Controlled group) and the Aspirin + Ginkgo biloba group (25 cases in Treatment group). The quantitative magnetic sensitivity and venous oxygen saturation of cerebral microbleeds were analyzed at admission, discharge, and after follow-up for 3 and 6 months. RESULTS: The demographic details age, gender, and admission to NIHSS were not significantly different between the two groups (p < 0.05). Quantitative susceptibility mapping (QSM) showed that the magnetic sensitivity of patients in both groups remained stable after 3 and 6 months of follow-up, while the venous oxygen saturation of the Treatment group increased. The venous oxygen saturation at 3 and 6 months of follow-up was negatively correlated with the modified mRS grade score. CONCLUSIONS: QSM can be used as a quantitative follow-up tool in monitoring both oxygen saturation and Magnetic susceptibility of microbleeds noninvasively in ischemic stroke patients with cerebral microbleeds. EGB combined with Aspirin can improve blood oxygen saturation in those patients and this effect is particularly significant in the long-term efficacy of secondary prevention.

Quantitative assessment of collateral time on perfusion computed tomography in acute ischemic stroke patients.

Background and aim: Good collateral circulation is recognized to maintain perfusion and contribute to favorable clinical outcomes in acute ischemic stroke. This study aimed to derive and validate an optimal collateral time measurement on perfusion computed tomography imaging for patients with acute ischemic stroke. Methods: This study included 106 acute ischemic stroke patients with complete large vessel occlusions. In deriving cohort of 23 patients, the parasagittal region of the ischemic hemisphere was divided into six pial arterial zones according to pial branches of the middle cerebral artery. Within the 85 arterial zones with collateral vessels, the receiver operating characteristic analysis was performed to derive the optimal collateral time threshold for fast collateral flow on perfusion computed tomography. The reference for fast collateral flow was the peak contrast delay on the collateral vessels within each ischemic arterial zone compared to its contralateral normal arterial zone on dynamic computed tomography angiography. The optimal perfusion collateral time threshold was then tested in predicting poor clinical outcomes (modified Rankin score of 5-6) and final infarct volume in the validation cohort of 83 patients. Results: For the derivation cohort of 85 arterial zones, the optimal collateral time threshold for fast collateral flow on perfusion computed tomography was a delay time of 4.04 s [area under the curve = 0.78 (0.67, 0.89), sensitivity = 73%, and specificity = 77%]. Therefore, the delay time of 4 s was used to define the perfusion collateral time. In the validation cohort, the perfusion collateral time showed a slightly higher predicting power than dynamic computed tomography angiography collateral time in poor clinical outcomes (area under the curve = 0.72 vs. 0.67; P < 0.001). Compared to dynamic computed tomography angiography collateral time, the perfusion collateral time also had better performance in predicting final infarct volume (R-squared values = 0.55 vs. 0.23; P < 0.001). Conclusion: Our results indicate that perfusion computed tomography can accurately quantify the collateral time after acute ischemic stroke.

Understanding the pathogenesis of brain arteriovenous malformation: genetic variations, epigenetics, signaling pathways, and immune inflammation.

Brain arteriovenous malformation (BAVM) is a rare but serious cerebrovascular disease whose pathogenesis has not been fully elucidated. Studies have found that epigenetic regulation, genetic variation and their signaling pathways, immune inflammation, may be the cause of BAVM the main reason. This review comprehensively analyzes the key pathways and inflammatory factors related to BAVMs, and explores their interplay with epigenetic regulation and genetics. Studies have found that epigenetic regulation such as DNA methylation, non-coding RNAs and m6A RNA modification can regulate endothelial cell proliferation, apoptosis, migration and damage repair of vascular malformations through different target gene pathways. Gene defects such as KRAS, ACVRL1 and EPHB4 lead to a disordered vascular environment, which may promote abnormal proliferation of blood vessels through ERK, NOTCH, mTOR, Wnt and other pathways. PDGF-B and PDGFR-ß were responsible for the recruitment of vascular adventitial cells and smooth muscle cells in the extracellular matrix environment of blood vessels, and played an important role in the pathological process of BAVM. Recent single-cell sequencing data revealed the diversity of various cell types within BAVM, as well as the heterogeneous expression of vascular-associated antigens, while neutrophils, macrophages and cytokines such as IL-6, IL-1, TNF-α, and IL-17A in BAVM tissue were significantly increased. Currently, there are no specific drugs targeting BAVMs, and biomarkers for BAVM formation, bleeding, and recurrence are lacking clinically. Therefore, further studies on molecular biological mechanisms will help to gain insight into the pathogenesis of BAVM and develop potential therapeutic strategies.

Lipoprotein(a) and stroke: a two-sample Mendelian randomization study.

Background: To evaluate the causal relationship between lipoprotein(a) Lp(a) and stroke risk. Method: Adopting two grand scale genome-wide association study (GWAS) databases, the instrumental variables were selected on the basis that the genetic loci met the criteria of being independent of each other and closely related to Lp(a). Summary-level data for outcomes, ischemic stroke and its subtypes were acquired from the UK Biobank and MEGASTROKE consortium databases. Two-sample MR analyses were achieved using inverse variance-weighted (IVW) meta-analysis (primary analysis), weighted median analysis, and the MR Egger regression method. Multivariable-adjusted Cox regression models were also used for observational analysis. Result: Genetically predicted Lp(a) was marginally related with higher odds of total stroke (odds ratio (OR) [95% confidence intervals (CI)]: 1.003 [1.001-1.006], p = 0.010), ischemic stroke (OR [95% CI]: 1.004[1.001-1.007], p = 0.004), and large-artery atherosclerotic stroke (OR [95% CI]: 1.012 [1.004-1.019], p = 0.002) when the IVW estimator was used on the MEGASTROKE data. The associations of Lp(a) with stroke and ischemic stroke were also remarkable in the primary analysis using the UK Biobank data. Higher Lp(a) levels were also related with increased total stroke and ischemic stroke risk in the observational research data in the UK Biobank database. Conclusion: Genetically predicted higher Lp(a) perhaps rise the risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke.

Poor collateral flow with severe hypoperfusion explains worse outcome in acute stroke patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with poorer functional outcomes in acute stroke patients. It has been hypothesized that this is due to poor collateral recruitment. AIMS: This study aimed to investigate the relationship between AF and collaterals with outcome in thrombectomy patients. METHODS: This retrospective cohort study identified 1036 acute ischemic patients from the INternational Stroke Perfusion Imaging REgistry. The cohort was divided into two groups: 432 with AF and 604 without AF. Patients were stratified by collateral grades as good, moderate, and poor. Within each collateral grade, the prediction of AF versus No AF for good outcome (3-month modified Rankin Scale of 0-2) was determined. Then, within each collateral grade, perfusion was compared between those with and without AF. RESULTS: AF was negatively associated with good outcome in patients with poor collaterals (26.7% vs 51.2% for AF vs No AF, odds ratio = 0.32 (95% confidence interval = 0.22-0.50), p < 0.001), but not in patients with good (50.9% vs 58.1% for AF vs No AF, odds ratio = 0.75 (0.46-1.23), p = 0.249) or moderate collaterals (43.6% vs 50.9% for AF vs No AF, odds ratio = 0.75 (0.47-1.18), p = 0.214). AF was associated with severe hypoperfusion only in patients with poor collateral flow (54.0 vs 35.5 mL for AF vs No AF, p < 0.001). CONCLUSIONS: AF-related stroke is associated with more severe hypoperfusion and worse outcome in those with poor collaterals.

Differentiating benign from malignant gallbladder wall thickening in non-contrast MRI imaging: Preliminary study of a combined diagnostic indicator.

To synthetically evaluate the diagnostic accuracy of image features for differentiating benign from malignant gallbladder wall thickening disease with non-contrast MRI and establish the optimal diagnostic indicator. A total of 23 patients with wall thickening type gallbladder carcinoma and 61 patients with benign wall thickening disease were included. The diagnostic performance of six image features including the layered pattern on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) images, T2WI signal intensity, papillary growth, the apparent diffusion coefficient (ADC) value, and the lesion to liver parenchyma ratio (LLR) of gallbladder were evaluated and compared. The receiver operating characteristic (ROC) curve and binary logistic regression analysis were used to construct the optimally combined indicator. All six indicators showed high diagnostic accuracy. The layered pattern on DWI and LLR had the highest area under the curve (AUC) value (0.904), followed by the layered pattern on T2WI (0.883), T2WI signal intensity (0.859), ADC value (0.836), and papillary growth (0.796). There was no statistically significant difference in the AUC among indicators for pairwise comparisons. A combination of layered patterns on DWI and papillary growth was shown to be the optimal indicator by binary logistic regression analysis. The AUC value of the combination (0.972) was higher than the layered pattern on DWI (0.904) and papillary growth (0.796) (P < .001). Non-contrast MRI provides several reliable indicators for differentiating benign from malignant gallbladder thickening disease. The combination of layered patterns on DWI and papillary growth is the optimal indicator.

Net water uptake, a neuroimaging marker of early brain edema, as a predictor of symptomatic intracranial hemorrhage after acute ischemic stroke.

Objective: We hypothesized that quantitative net water uptake (NWU), a novel neuroimaging marker of early brain edema, can predict symptomatic intracranial hemorrhage (sICH) after acute ischemic stroke (AIS). Methods: We enrolled patients with AIS who completed admission multimodal computed tomography (CT) within 24 h after stroke onset. NWU within the ischemic core and penumbra was calculated based on admission CT, namely NWU-core and NWU-penumbra. sICH was defined as the presence of ICH in the infarct area within 7 days after stroke onset, accompanied by clinical deterioration. The predictive value of NWU-core and NWU-penumbra on sICH was evaluated by logistic regression analyses and the receiver operating characteristic (ROC) curve. A pure neuroimaging prediction model was built considering imaging markers, which has the potential to be automatically quantified with an artificial algorithm on image workstation. Results: 154 patients were included, of which 93 underwent mechanical thrombectomy (MT). The median time from symptom onset to admission CT was 262 min (interquartile range, 198-368). In patients with MT, NWU-penumbra (OR =1.442; 95% CI = 1.177-1.766; P < 0.001) and NWU-core (OR = 1.155; 95% CI = 1.027-1.299; P = 0.016) were independently associated with sICH with adjustments for age, sex, time from symptom onset to CT, hypertension, lesion volume, and admission National Institutes of Health Stroke Scale (NIHSS) score. ROC curve showed that NWU-penumbra had better predictive performance than NWU-core on sICH [area under the curve (AUC): 0.773 vs. 0.673]. The diagnostic efficiency of the predictive model was improved with the containing of NWU-penumbra (AUC: 0.853 vs. 0.760). A pure imaging model also presented stable predictive power (AUC = 0.812). In patients without MT, however, only admission NIHSS score (OR = 1.440; 95% CI = 1.055-1.965; P = 0.022) showed significance in predicting sICH in multivariate analyses. Conclusions: NWU-penumbra may have better predictive performance than NWU-core on sICH after MT. A pure imaging model showed potential value to automatically screen patients with sICH risk by image recognition, which may optimize treatment strategy.

Biological Effects and Mechanisms of Caspases in Early Brain Injury after Subarachnoid Hemorrhage.

Caspases are an evolutionarily conserved family of proteases responsible for mediating and initiating cell death signals. In the past, the dysregulated activation of caspases was reported to play diverse but equally essential roles in neurodegenerative diseases, such as brain injury and neuroinflammatory diseases. A subarachnoid hemorrhage (SAH) is a traumatic event that is either immediately lethal or induces a high risk of stroke and neurological deficits. Currently, the prognosis of SAH after treatment is not ideal. Early brain injury (EBI) is considered one of the main factors contributing to the poor prognosis of SAH. The mechanisms of EBI are complex and associated with oxidative stress, neuroinflammation, blood-brain barrier disruption, and cell death. Based on mounting evidence, caspases are involved in neuronal apoptosis or death, endothelial cell apoptosis, and increased inflammatory cytokine-induced by apoptosis, pyroptosis, and necroptosis in the initial stages after SAH. Caspases can simultaneously mediate multiple death modes and regulate each other. Caspase inhibitors (including XIAP, VX-765, and Z-VAD-FMK) play an essential role in ameliorating EBI after SAH. In this review, we explore the related pathways mediated by caspases and their reciprocal regulation patterns after SAH. Furthermore, we focus on the extensive crosstalk of caspases as a potential area of research on therapeutic strategies for treating EBI after SAH.

Early Edema Within the Ischemic Core Is Time-Dependent and Associated With Functional Outcomes of Acute Ischemic Stroke Patients.

Objective: To investigate the difference in early edema, quantified by net water uptake (NWU) based on computed tomography (CT) between ischemic core and penumbra and to explore predictors of NWU and test its predictive power for clinical outcome. Methods: Retrospective analysis was conducted on patients admitted to Ningbo First Hospital with anterior circulation stroke and multi-modal CT. In 154 included patients, NWU of the ischemic core and penumbra were calculated and compared by Mann-Whitney U test. Correlations between NWU and variables including age, infarct time (time from symptom onset to imaging), volume of ischemic core, collateral status, and National Institutes of Health Stroke Scale (NIHSS) scores were investigated by Spearman's correlation analyses. Clinical outcome was defined using the modified Rankin Scale (mRS) at 90 days. Logistic regression and receiver operating characteristic analyses were performed to test the predictive value of NWU. Summary statistics are presented as median (interquartile range), mean (standard deviation) or estimates (95% confidence interval). Results: The NWU within the ischemic core [6.1% (2.9-9.2%)] was significantly higher than that of the penumbra [1.8% (-0.8-4.0%)]. The only significant predictor of NWU within the ischemic core was infarct time (p = 0.004). The NWU within the ischemic core [odds ratio = 1.23 (1.10-1.39)], the volume of ischemic core [1.04, (1.02-1.06)], age [1.09 (1.01-1.17)], and admission NHISS score [1.05 (1.01-1.09)] were associated with the outcome of patients adjusted for sex and treatment. The predictive power for the outcome of the model was significantly higher when NWU was included (area under the curve 0.875 vs. 0.813, p < 0.05 by Delong test). Conclusions: Early edema quantified by NWU is relatively limited in the ischemic core and develops in a time-dependent manner. NWU estimates within the ischemic core may help to predict clinical outcomes of patients with acute ischemic stroke.

DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner.

Objective: We performed a case-control study to investigate the correlation between DNA methylation and mRNA expression of the glutathione S-transferase alpha 4 (GSTA4) gene and the risk of intracranial aneurysm (IA) in the Chinese Han population. Methods: After propensity score matching, 44 pairs of cases and controls were collected in this study. Fasting blood samples were collected for DNA and RNA extraction within 24 h of admission. Nine CpG dinucleotides were selected from the GSTA4 promoter region for DNA methylation pyrosequencing. mRNA expression of GSTA4 was measured by quantitative real-time polymerase chain reaction (RT-qPCR). In vitro cell experiments were conducted to verify the association between 5-aza-2'-deoxycytidine induced DNA hypomethylation and GSTA4 mRNA expression. Results: The mean methylation level of GSTA4 was much lower in IA patients, especially in IA patients, especially in unruptured IA (UIA), than that in controls (IA vs. Control, p < .001; ruptured IA (RIA) vs. Control, p = .005; UIA vs. Control, p < .001). With sex stratification, we further found that the association between GSTA4 methylation and IA risk presented only in women (mean methylation level: IA vs. Control, p < .001; RIA vs. Control, p = .009; UIA vs. Control, p < .001). GSTA4 mRNA expression was significantly higher in the IA group than in the control group (p < .01) and negatively correlated with DNA methylation in all individuals (r = -.746, p < .001). DNA hypomethylation can increase GSTA4 mRNA expression in human primary artery smooth muscle cells. The receiver operating characteristic (ROC) curve showed that GSTA4 mean methylation (AUC = .80, p < .001) was a reliable predictor of women intracranial aneurysm, among which CpG 1 exhibited the best predictive value (AUC = .89, p < .001). In addition, GSTA4 expression levels could also predict the risk of IA in women (AUC = .87, p = .005). Conclusion: Decreased DNA methylation and increased mRNA expression of the GSTA4 gene are associated with the risk of IA in women.

Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: This study aimed to evaluate the treatment effect of intraarterial versus intravenous tirofiban during endovascular thrombectomy in acute ischemic stroke. METHODS: This study retrospectively examined 503 patients with acute ischemic stroke with large vessel occlusion who received endovascular thrombectomy within 24 hours of stroke onset. Patients were divided into 3 groups: no tirofiban (n=354), intraarterial tirofiban (n=79), and intravenous tirofiban (n=70). The 3 groups were compared in terms of recanalization rate, symptomatic intracerebral hemorrhage, in-hospital death rate, 3-month death, and 3-month outcomes measured by modified Rankin Scale score (good clinical outcome of 0-2, poor outcome of 5-6). The comparison was statistically assessed by propensity score matching, followed by Freidman rank-sum test and pairwise Wilcoxon signed-rank test with Bonferroni correction. RESULTS: The propensity score matching resulted in 92 matched triplets. Compared with the no-tirofiban group, the intravenous tirofiban group showed significantly increased recanalization (96.7% versus 64.1%, P<0.001), an increased rate of 3-month good outcome (69.5% versus 51.2%, P=0.034), and a lower rate of 3-month poor outcome (12.2% versus 41.4%, P<0.001). There was no significant difference between the tirofiban intravenous and no-tirofiban groups in terms of symptomatic intracerebral hemorrhage (2.2% versus 0%, P=1.000). However, symptomatic intracerebral hemorrhage was significantly increased in the intraarterial-tirofiban group compared with the no-tirofiban group (19.1% versus 0%, P<0.001), with an increased rate of in-hospital death (23.6% versus 0% P<0.001), and increased rate of 3-month death (26.8% versus 11.1%, P=0.021). The intraarterial-tirofiban and no-tirofiban group showed no significant difference in recanalization rate (66.3% versus 64.1%, P=1.000). CONCLUSIONS: As an adjunct to endovascular thrombectomy, intravenous tirofiban is associated with high recanalization rate and good outcome, whereas intraarterial tirofiban is associated with high hemorrhagic rate and death rate.

Robust integral of neural network and precision motion control of electrical-optical gyro-stabilized platform with unknown input dead-zones.

Parametric uncertainty associated with unmodeled disturbance always exist in physical electrical-optical gyro-stabilized platform systems, and poses great challenges to the controller design. Moreover, the existence of actuator deadzone nonlinearity makes the situation more complicated. By constructing a smooth dead-zone inverse, the control law consisting of the robust integral of a neural network (NN) output plus sign of the tracking error feedback is proposed, in which adaptive law is synthesized to handle parametric uncertainty and RISE robust term to attenuate unmodeled disturbance. In order to reduce the measure noise, a desired compensation method is utilized in controller design, in which the model compensation term depends on the reference signal only. By mainly activating an auxiliary robust control component for pulling back the transient escaped from the neural active region, a multi-switching robust neuro adaptive controller in the neural approximation domain, which can achieve globally uniformly ultimately bounded (GUUB) tracking stability of servo systems recently. An asymptotic tracking performance in the presence of unknown dead-zone, parametric uncertainties and various disturbances, which is vital for high accuracy tracking, is achieved by the proposed robust adaptive backstepping controller. Extensively comparative experimental results are obtained to verify the effectiveness of the proposed control strategy.

Endovascular Thrombectomy.

Background and Purpose- This study aimed to explore safety of tirofiban in endovascular treatment of acute ischemic stroke. Methods- Two hundred eighteen ischemic stroke patients receiving endovascular thrombectomy were prospectively recruited, with 94 treated with intra-arterial tirofiban and 124 were not. The 2 groups were compared in terms of symptomatic intracranial hemorrhage (ICH) and fatal ICH rate by the χ2 test and logistic regression. Results- Patients treated with tirofiban compared with those without tirofiban had significantly higher rate of symptomatic ICH (14.6% versus 5.7%; P=0.027) and fatal ICH (8.8% versus 1.6%; P=0.014). Tirofiban-treated patients had increased odds of symptomatic ICH by 2.9-fold (95% CI, 1.1-7.5), and odds of fatal ICH increased by 5.9-fold (95% CI, 1.2-28.4). Conclusions- Tirofiban treatment increases risk of major ICH after endovascular thrombectomy for acute ischemic stroke in this nonrandomized study.

Survivin-targeted nanoparticles for pancreatic tumor imaging in mouse model.

We investigated the potential of targeting survivin, an inhibitor of apoptosis, in visualize pancreatic tumor in mouse model using targeted magnetic nanoparticles (MNPs) and magnetic resonance imaging (MRI). Chitosan-coated MNPS and survivin antisense oligonucleotide(ASON) were conjugated to give Sur-MNPs. Accumulations of targeted, non-targeted nanoparticles or nonsense oligonucleotide-MNPs (NSON-MNPs) in the liver, spleen, kidney and tumors were determined. Targeted nanoparticles were highly accumulated in BxPC-3 cells but not in non-cancer cells. In vivo MRI showed a significant T2 signal reduction in tumors of mice injected with targeted nanoparticles but slight signal change in tumors of mice injected with non-targeted nanoparticles or NSON-MNPs. Prussian blue staining demonstrated highly accumulated Sur-MNPs in tumor mass compared with normal pancreatic, kidney and liver tissues. Our data show that the MNPs functionalized with ASON lead to the targeted localization in pancreatic tumors. Survivin targeted nanoparticles could be used for detection of pancreatic tumors.

VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model.

The aim of this study was to assess the inhibitory efficacy of short hairpin RNA (ShRNA) targeting vascular endothelial growth factor C (VEGF-C) in an orthotopic pancreatic cancer mouse model. BxPC-3 human pancreatic cancer cells expressing green fluorescent protein (GFP) were orthotopically implanted onto the pancreas of nude mice. All mice were randomly divided into four groups when the average tumor size had reached 100 mm(3) and were treated with either vehicle or gemcitabine at 150 mg/kg; or intravenous VEGF-C ShRNA at 150 mg/kg; or intratumoral VEGF-C ShRNA at 150 µg/kg. In vivo fluorescence imaging was performed to monitor tumor growth and metastasis during the study. Real-time quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein level of VEGF-C in tumor tissues. Lymphatic vessel marker D2-40, blood vessel marker CD31 and proliferation marker Ki67 expression of the tumor tissues were analyzed by immunohistochemistry staining. Intravenous and intratumoral VEGF-C ShRNA treatment significantly inhibited tumor growth, downregulated the expression of VEGF-C mRNA, reduced tumor microlymphatic vessel density (MLVD), and inhibited cancer cell proliferation. Gemcitabine, as the standard treatment for pancreatic cancer, demonstrated a stronger inhibitory effect on tumor growth, with less inhibition of MLVD and more inhibition of microvessel density (MVD) and proliferation than VEGF-C ShRNA. These results indicate that different mechanisms are associated with the efficacy of gemcitabine and VEGF-C ShRNA.