Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Non-porous thrombi are less pervious and easier to be retrieved: implication from scanning electron microscopy study.

BACKGROUND: Scanning electron microscopy (SEM) studies found that the porosity of thrombi might vary among individuals. However, its relationship with the clinical presentation and efficacy of mechanical thrombectomy (MT) remains unknown. We aimed to characterize the ultrastructure of thrombi and explore its association with the complexity of MT and clot perviousness. METHODS: SEM was used to observe the morphological features of different components of thrombi obtained from patients with anterior circulation large vessel occlusion undergoing MT and to determine the porosity of thrombi by semi-quantitative analysis. Non-porous thrombi were defined as thrombi with porosity <2%. Clot perviousness was also evaluated using thrombus attenuation increase on CT perfusion (TAIctp). We assessed the complexity of MT by attempts of retrieval >3 and procedural duration >60 min, defined as the time interval between groin puncture and recanalization. RESULTS: A total of 49 thrombi were analyzed and 31 (63.3%) were classified as non-porous thrombi. The presence of non-porous thrombi was negatively associated with procedure >60 min (OR 0.152, 95% CI 0.031 to 0.734, p=0.019) and attempts >3 (OR 0.194, 95% CI 0.046 to 0.822, p=0.026) after adjustment. Additionally, receiver operating characteristic curve analysis indicated that TAIctp <17.9 Hounsfield units could predict the presence of non-porous thrombi with an area under the curve of 0.915. CONCLUSIONS: Non-porous thrombi on SEM are easier to be retrieved during MT and could be identified as less pervious clots on CT images.

Predictors of malignant middle cerebral artery infarction after endovascular thrombectomy: results of DIRECT-MT trial.

OBJECTIVES: Predictors of malignant middle cerebral artery infarction (mMCAi) in patients after intravenous thrombolysis were well documented, but the risk factors of mMCAi after endovascular thrombectomy (EVT) were not fully explored. Therefore, the present study aimed to investigate the predictors of mMCAi after EVT in stroke patients. METHODS: This was a secondary analysis of the DIRECT-MT trial. Patients who underwent EVT for the occlusions of MCA and/or intracranial internal carotid artery were analyzed. Primary outcome was the occurrence of mMCAi after EVT. Demographic, clinical, imaging, and treatment data were recorded, and multivariate logistic regression analysis was used to identify independent predictors. All of the candidate predictors were included, and forward elimination was applied to establish the most effective predictive model. Predictive ability and calibration of the model were assessed using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test, respectively. RESULTS: Of 559 enrolled patients, 74 (13.2%) patients developed mMCAi. Predictors of mMCAi included unsuccessful reperfusion, higher serum glucose, lower Alberta Stroke Project Early Computed Tomography Change Score (ASPECTS), higher clot burden score (CBS), lower collateral score, and higher pass number of thrombectomy device. AUC of predictive model integrating all independent variables was 0.836. The Hosmer-Lemeshow test showed appropriate calibration (p = 0.859). CONCLUSIONS: Reperfusion, serum glucose, ASPECTS, CBS, collateral, and pass number of thrombectomy device were associated with the occurrence of mMCAi in stroke patients after EVT, while alteplase treatment was not. Our findings might facilitate the early identification and management of stroke patients at a high risk of mMCAi. KEY POINTS: • A total of 13.2% of stroke patients with large vessel occlusion of anterior circulation developed mMCAi after EVT. • The occurrence of mMCAi had a definite negative impact on the outcome for stroke patients. • Reperfusion, serum glucose, ASPECTS, CBS, collateral score, and the pass number of thrombectomy device were associated with the occurrence of mMCAi after EVT in stroke patients.

Brain region-specific synaptic function of FUS underlies the FTLD-linked behavioural disinhibition.

Synaptic dysfunction is one of the earliest pathological processes that contribute to the development of many neurological disorders, including Alzheimer's disease and frontotemporal lobar degeneration. However, the synaptic function of many disease-causative genes and their contribution to the pathogenesis of the related diseases remain unclear. In this study, we investigated the synaptic role of fused in sarcoma, an RNA-binding protein linked to frontotemporal lobar degeneration and amyotrophic lateral sclerosis, and its potential pathological role in frontotemporal lobar degeneration using pyramidal neuron-specific conditional knockout mice (FuscKO). We found that FUS regulates the expression of many genes associated with synaptic function in a hippocampal subregion-specific manner, concomitant with the frontotemporal lobar degeneration-linked behavioural disinhibition. Electrophysiological study and molecular pathway analyses further reveal that fused in sarcoma differentially regulates synaptic and neuronal properties in the ventral hippocampus and medial prefrontal cortex, respectively. Moreover, fused in sarcoma selectively modulates the ventral hippocampus-prefrontal cortex projection, which is known to mediate the anxiety-like behaviour. Our findings unveil the brain region- and synapse-specific role of fused in sarcoma, whose impairment might lead to the emotional symptoms associated with frontotemporal lobar degeneration.

Effect of bleeding risk prediction on decision making of intravenous thrombolysis before thrombectomy: a subgroup analysis of DIRECT-MT.

BACKGROUND: The major concern for bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the potentially increased risk of symptomatic intracerebral hemorrhage (sICH). Thus we conducted this study to clarify whether evaluation of individual bleeding risk could assist in the decision to perform IVT before EVT. METHODS: The study was a subgroup analysis of a randomized trial evaluating the safety and efficacy of IVT before EVT. The SEDAN (blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign, Age, and National Institutes of Health Stroke Score) score, GRASPS (Glucose, Race, Age, Sex, systolic blood Pressure, and Severity of stroke) score, and SITS-SICH (Safe Implementation of Thrombolysis in Stroke-Symptomatic Intracerebral Hemorrhage) score were used to evaluate individual bleeding risk. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Binary logistic regression with an interaction term was used to estimate treatment effect modification to clarify whether direct EVT was more beneficial in patients with a higher sICH risk, while adjunctive IVT before EVT was more beneficial in patients with a lower sICH risk. RESULTS: Among 658 randomized patients, 639 (361 men, 56.5%; median age 69 (IQR 61-76) years) were included in the study. With the SITS-SICH score as an example, adjusted OR for functional independence with EVT alone was 1.12 (95% CI 0.68 to 1.82) in patients with a lower sICH risk (SITS-SICH score 0-4) and 0.92 (0.53 to 1.60) in those with a higher sICH risk (SITS-SICH score 5-15). There were no treatment-by-bleeding-risk interactions for all dichotomized mRS outcomes based on the three scores (all p>0.05). CONCLUSIONS: We found no evidence that clinicians can decide whether to omit IVT before EVT based on an individualized assessment of bleeding risk.

Identification of Risk Factors for Stroke in China: A Meta-Analysis of Prospective Cohort Studies.

This study aimed to identify independent risk factors for first occurrence of stroke in Chinese individuals based on prospective cohort studies. Forty prospective cohort studies assessing 1,984,552 individuals were selected for the final meta-analysis. The identified risk factors for stroke in the Chinese population included old age (RR = 1.86, 95%CI: 1.47-2.36), hypertension (RR = 2.76, 95%CI: 2.26-3.37), cardiovascular disease history (RR = 1.98, 95%CI: 1.06-3.69), chronic kidney disease (RR = 1.65, 95%CI: 1.36-2.01), diabetes mellitus (RR = 1.71, 95%CI: 1.34-2.18), metabolic syndrome (RR = 1.59, 95%CI: 1.33-1.90), hyperglycemia (RR = 1.49, 95% CI: 1.31-1.69), obesity (RR = 1.45, 95%CI: 1.29-1.63), smoking (RR = 1.42, 95% CI: 1.27-1.58), prolonged sleep time (> 7.5 h, RR = 1.44, 95%CI: 1.19-1.75), higher levels of triglyceride (RR = 1.19, 95%CI: 1.07-1.32), C-reactive protein (RR = 1.34, 95%CI: 1.07-1.69). High fruit-rich diet (RR = 0.68, 95%CI: 0.58-0.80) was associated with a lower risk of stroke. The spectrum and power of risk factors varied among different cohort inclusion years. These findings provide a comprehensive tool for the primary prevention of stroke in Chinese individuals.

Prediction of Acute Myocardial Infarction in Asian Patients With Acute Ischemic Stroke: The CTRAN Score.

Background: Patients with acute ischemic stroke (AIS) are susceptible to acute myocardial infarction (AMI), which would lead to a dramatic increase of in-hospital mortality. Objectives: The authors established and validated an easy-used model to stratify the risk of in-hospital AMI among patients with AIS. Methods: We consecutively included patients with AIS who were admitted within 7 days from symptom onset in our prospectively maintained database (NCT04487340) from January 2016 to December 2020. In the derivation cohort from 70 centers, we developed a score to predict in-hospital AMI by integrating the bedside-accessible predictors identified via multivariable logistic regression. Then in the validation cohort from 22 centers, we externally evaluated the performance of this score. Results: Overall, 96,367 patients were included. In-hospital AMI occurred in 392 (0.41%) patients. The final model, named CTRAN, incorporated 5 predictors including the history of coronary heart disease, malignant tumor, renal insufficiency, age, and baseline National Institutes of Health Stroke Scale score. The CTRAN score was confirmed in the validation cohort using receiver operating characteristic curve, which yielded an area under the curve of 0.758 (95% CI: 0.718-0.798). Conclusions: The CTRAN score could be a good tool for clinicians to identify patients with AIS at high in-hospital AMI risk.

Ensemble learning accurately predicts the potential benefits of thrombolytic therapy in acute ischemic stroke.

BACKGROUND: Finding methods to accurately predict the final infarct volumes for acute ischemic stroke patients with full or no recanalization would significantly help to evaluate the potential benefits of thrombolytic therapy. We proposed such a method by constructing a model of ensemble deep learning and machine learning using diffusion-weighted imaging (DWI) only. METHODS: The proposed prediction model (named AUNet) combines an adaptive linear ensemble model (ALEM) of machine learning and a deep U-Net network with an accelerated non-local module (U-NL-Net) to learn voxel-wise and spatial features, respectively. Of 40 patients with acute ischemic stroke who received thrombolytic therapy, 17 were fully recanalized, 14 were not recanalized, and nine were partially recanalized. The AUNet was separately trained for full recanalization conditions (AUNetR) and no recanalization (AUNetN) as the best and worst outcomes of thrombolysis, respectively. RESULTS: AUNet performed significantly better in predicting the final infarct volumes in both the recanalization and non-recanalization conditions [area under the receiver operating characteristic curve (AUC) =0.898±0.022, recanalization; AUC =0.875±0.036, non-recanalization: Matthew's correlation coefficient (MCC) =0.863±0.033, recanalization; MCC =0.851±0.025, non-recanalization] than the fixed-thresholding method (AUC =0.776±0.021, P<0.0001, recanalization; AUC =0.692±0.023, P<0.0001, non-recanalization: MCC =0.742±0.035, recanalization; MCC =0.671±0.024, non-recanalization), the logistic regression method (AUC =0.797±0.023, P<0.003, recanalization; AUC =0.751±0.030, P<0.003, non-recanalization: MCC =0.762±0.035, recanalization; MCC =0.730±0.031, non-recanalization), and a recently developed convolutional neural network (AUC =0.814±0.013, P<0.003, recanalization; AUC =0.781±0.027, P<0.003, non-recanalization: MCC =792±0.022, recanalization; MCC =0.758±0.016, non-recanalization). The potential benefit of thrombolysis calculated from AUNetR and AUNetN showed large individual differences (from 12.81% to 239.73%). CONCLUSIONS: AUNet improved predictive accuracy over current state-of-the-art methods. More importantly, the accurate prediction of infarct volumes under different recanalization conditions may provide benefitial information for physicians in selecting suitable patients for thrombolytic therapy.

Cortical degeneration detected by neurite orientation dispersion and density imaging in chronic lacunar infarcts.

BACKGROUND: Although lacunar infarcts are focal lesions, they may also have more widespread effects. A reduction in cortical thickness in the remote cortex after lacunar infarcts has been detected by structural imaging; however, its underlying microstructural changes are yet to be elucidated. This study aimed to investigate the effects of lacunar infarcts on the microstructural abnormalities associated with cortical thickness reduction in the remote cortex. METHODS: Thirty-seven patients with chronic lacunar infarcts were included. Brain structural magnetic resonance images (MRIs) and diffusion tensor images were acquired. We constructed the white matter tracts connecting with the lacunar infarcts and identified the connected cortical area based on a standard brain atlas warped into the subject space. Cortical thickness and microstructural neurite orientation dispersion and density imaging (NODDI) metrics of the ipsilesional and contralesional cortices were compared, and correlations between cortical thickness and NODDI metrics were also investigated. RESULTS: We found decreased cortical thickness and reduced neurite orientation dispersion index (ODI) in the ipsilesional cortex (2.47 vs. 2.50 mm, P=0.008; 0.451 vs. 0.456, P=0.035, respectively). In patients with precentral gyrus involvement (n=23), we found that ODI in the ipsilesional cortex was correlated with cortical thickness (r=0.437, P=0.037), and ODI in the contralesional cortex was also correlated with contralesional cortical thickness (r=0.440, P=0.036). CONCLUSIONS: NODDI metrics could reflect cortical microstructural changes following lacunar infarcts. The correlation between decreased ODI and reduced cortical thickness suggests that dendrites' loss might contribute to lacunar infarct-related cortical atrophy.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

Association of maximal systolic blood pressure with poor outcome in patients with hyperattenuated lesions on immediate NCCT after mechanical thrombectomy.

BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between blood pressure (BP) management and clinical outcome in patients with hyperattenuated lesions on non-contrast CT (NCCT) immediately after mechanical thrombectomy (MT). METHODS: We retrospectively reviewed our prospectively collected cohort for consecutive patients with acute ischemic stroke (AIS) who received MT between October 2013 and July 2018. Hourly systolic BP (SBP) and diastolic BP (DBP) values were recorded for 24 hours following MT, and then maximum SBP (SBPmax) and DBP (DBPmax) values were identified. Poor outcome was defined as 3-month modified Rankin score (mRS) 3-6 and parenchymal hemorrhage (PH) was defined according to the European Cooperative Acute Stroke Study (ECASS) II trial. Associations of BP parameters with poor outcome and PH were determined using binary logistic regression models. Receiver operating characteristics (ROC) curve analysis was used to determine the predictive value of BP. RESULTS: Initially 262 patients with AIS who received MT were reviewed and 148 patients with hyperattenuated lesions on immediate NCCT were enrolled in the final cohort for analysis. Binary logistic regression showed that every 10 mm Hg increase in SBPmax was independently associated with a poor outcome (OR 1.426; 95% CI 1.095 to 1.855; p=0.008) and PH (OR 1.025; 95% CI 1.005 to 1.480; p=0.044). SBP ≤140 mm Hg during the post-procedural 24-hour period was associated with lower odds of a poor outcome and PH compared with the other group. CONCLUSIONS: Control of maximal SBP within 24 hours might be related to a low rate of PH and poor outcome in patients with hyperattenuated lesions on immediate NCCT after intervention.

Brain Iron Deposits in Thalamus Is an Independent Factor for Depressive Symptoms Based on Quantitative Susceptibility Mapping in an Older Adults Community Population.

Objectives: With the trend of an aging population, an increasing prevalence of late-life depression has been identified. Several studies demonstrated that iron deposition was significantly related to the severity of symptoms in patients with depression. However, whether brain iron deposits influence depressive symptoms is so far unclear in the community of older adults. We measured iron deposition in deep intracranial nucleus by quantitative susceptibility mapping (QSM) and aimed to explore the relationship between iron deposition and depressive symptoms. Methods: We reviewed the data of a community population from CIRCLE study, which is a single-center prospective observational study that enrolled individuals above 40 years old with cerebral small vessel disease (SVD), while free of known dementia or stroke. We evaluated regional iron deposits on QSM, measured the volume of white matter hyperintensities (WMHs) on T2 fluid-attenuated inversion recovery, and assessed depressive symptoms by Hamilton depression scale (HDRS). We defined depressive symptom as HDRS > 7. Results: A total of 185 participants were enrolled. Participants in depressive symptom group had higher QSM value in thalamus than control group (18.79 ± 14.94 vs 13.29 ± 7.64, p = 0.003). The QSM value in the thalamus was an independent factor for the presence of depressive symptoms (OR = 1.055; 95% CI: 1.011-1.100; p = 0.013). The regional QSM values in other areas were not associated with HDRS score (all p > 0.05). No significant correlations were observed between WMHs volume and HDRS score (p > 0.05), or regional QSM values and WMHs volume (all p > 0.05). Conclusions: Our study demonstrated that iron deposits in the thalamus were related to the depressive symptoms in older adults.

Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy.

AIMS: We sought to investigate the risk factors of blood-brain barrier (BBB) disruption, and its potential impact on 90-day clinical outcome in acute ischemic stroke (AIS) patients after reperfusion therapy. METHODS: Consecutive acute anterior circulation AIS patients imaged with computed tomographic perfusion (CTP) before reperfusion therapy were included. Tmax >6 s was used for the volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was calculated as the average relative permeability-surface area product (rPS) within the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo-c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained at 90-day post-stroke. RESULTS: A total of 187 patients were included, among whom the median age was 73 (61-80) years and 76 (40.6%) were women. Median baseline NIHSS score was 12 (7- 16). Ninety-eight (52.4%) patients had mRS score >2. Increased rPShypo-i and rPShypo-c were both independently associated with males and large infarct volume. The increased rPShypo-i was also independently associated with a history of atrial fibrillation and high NIHSS score. Multivariable analysis showed higher rPShypo-c was independently associated with higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018). CONCLUSION: BBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model.

Axl, a tyrosine kinase receptor, was recently identified as an essential component regulating innate immune response. Suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 are potent Axl-inducible negative inflammatory regulators. This study investigated the role of Axl signaling pathway in immune restoration in an autologous blood-injection mouse model of intracerebral hemorrhage. Recombinant growth arrest-specific 6 (Gas6) and R428 were administrated as specific agonist and antagonist. In vivo knockdown of Axl or suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 by siRNA was applied. After intracerebral hemorrhage, the expression of endogenous Axl, soluble Axl, and Gas6 was increased, whereas the expression of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 was inhibited. Recombinant growth arrest-specific 6 administration alleviated brain edema and improved neurobehavioral performances. Moreover, enhanced Axl phosphorylation with cleavage of soluble Axl (sAxl), and an upregulation of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 were observed. In vivo knockdown of Axl and R428 administration both abolished the effect of recombinant growth arrest-specific 6 on brain edema and also decreased the expression suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3. In vivo knockdown of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 aggravated cytokine releasing despite of recombinant growth arrest-specific 6. In conclusion, Axl plays essential role in immune restoration after intracerebral hemorrhage. And recombinant growth arrest-specific 6 attenuated brain injury after intracerebral hemorrhage, probably by enhancing Axl phosphorylation and production of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3.

MiR-223 modulates hepatocellular carcinoma cell proliferation through promoting apoptosis via the Rab1-mediated mTOR activation.

Hepatocellular carcinoma (HCC) is a common digestive malignancy. MiR-223, a well-identified miRNA, exhibits diverse properties in different cancers. In this study, we demonstrated that miR-223 could suppress cell growth and promote apoptosis in HepG2 and Bel-7402 HCC cell lines. We screened and identified a novel miR-223 target, Ras-related protein Rab-1(Rab1). Upregulation of miR-223 would specifically and markedly down-regulate Rab1 expression. In addition, miR-223-overexpressing subclones showed significant cell growth inhibition by increasing cell apoptosis in HepG2 and Bel-7402 cells. To identify the mechanisms, we firstly investigated the mTOR pathway and found that pmTOR, p70S6K and Bcl-2 were dramatically down-regulated after miR-223 transfection, while no changes in the level of Bax was visualized. Furthermore, our data showed that the anti-tumor effects arising from miR-223 transfection in HCC cells may be due to the deactivation of mTOR pathway caused by the suppression of Rab1 expression when miR-223 is overexpressed. In summary, our results indicate that miR-223 functions as a tumor suppressor and plays a critical role in inhibiting the tumorigenesis and promoting the apoptosis of HCC through the mTOR signaling pathway in vitro. By targeting Rab1, miR-223 efficiently mediates the mTOR pathway. Given these, miR-223 may be a potential therapeutic target for treating HCC.

Different risk factors for poor outcome between patients with positive and negative susceptibility vessel sign.

PURPOSE: The absence of the susceptibility vessel sign (negative SVS) on gradient-recalled echo or susceptibility-weighted imaging (SWI) in thrombolytic therapy has not been well studied. Since positive and negative SVS may have different components, we aimed to investigate the difference in risk factors for clinical outcome between patients with positive and negative SVS. METHODS: We retrospectively examined clinical and imaging data from 85 consecutive patients with acute ischemic stroke with middle cerebral artery occlusion who underwent SWI before intravenous thrombolysis (IVT). We then examined the predictors of negative SVS and the risk factors for a poor outcome (defined as modified Rankin Scale score ≥3) 3 months after IVT in subgroup analysis. RESULTS: Multivariate regression analysis indicated that previous antiplatelet use (OR 0.076; 95% CI 0.007 to 0.847; p=0.036) and shorter time from onset to treatment (OR 1.051; 95% CI 1.003 to 1.102; p=0.037) were inversely associated with poor outcome in patients with negative SVS, while higher baseline National Institutes of Health Stroke Scale (NIHSS) score was associated with poor outcome in patients with positive SVS (OR 1.222; 95% CI 1.084 to 1.377; p=0.001). CONCLUSIONS: The risk factors for clinical outcome after IVT in patients with negative SVS may differ from those with positive SVS.

Unfavorable neurological outcome in diabetic patients with acute ischemic stroke is associated with incomplete recanalization after intravenous thrombolysis.

OBJECTIVE: To assess the impact of diabetes on neurological outcome and recanalization in acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: Clinical data of 419 consecutive patients with AIS who received IVT between June 2009 and April 2014. Based on the medical history and new diagnosis, the patients were divided into groups with and without diabetes. Neurological outcomes at 24 h, 7 days and 3 months after IVT were evaluated. Favorable outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score decrease ≥4 points from baseline or 0 at 24 h, NIHSS decrease ≥8 points or 0 at day 7, or modified Rankin scale ≤1 at 3 months after IVT. Recanalization on non-invasive imaging was evaluated in patients with large vessel occlusion (LVO) according to thrombolysis in myocardial infarction grades. RESULTS: Among 419 patients, 98 (23.4%) had diabetes. Multivariable analyses showed that comorbidity of diabetes was an independent predictor of unfavorable outcome at 24 h (OR=0.534, 95% CI 0.316 to 0.903, p=0.019), at day 7 (OR=0.382, 95% CI 0.220 to 0.665, p=0.001), and at 3 months (OR=0.464, 95% CI 0.266 to 0.808, p=0.007). In patients with LVO, diabetes was an independent predictor of incomplete recanalization 24 h after IVT (OR=0.268, 95% CI 0.075 to 0.955, p=0.042). CONCLUSIONS: Diabetic patients with AIS had unfavorable neurological outcome, potentially linked to incomplete recanalization after IVT.

Long-term outcomes of percutaneous cryoablation for patients with hepatocellular carcinoma within Milan criteria.

BACKGROUND: Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes. METHODS: A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed. RESULTS: A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >106 copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS. CONCLUSIONS: Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.

Incidence and risk factors for hepatocellular carcinoma in primary biliary cirrhosis.

The incidence, risk factors, and clinical features of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) have been a long-standing subject of interest. We took advantage of a large cohort of 1865 well-defined Chinese patients with PBC for whom follow-up was conducted for up to 20 years to study the incidence of HCC. Our goal was to address the incidence and prevalence of HCC in PBC and the risk factors, including hepatitis B virus (HBV) infection, and finally to compare the tumor characteristics of PBC-related HCC, including size, location, mortality, and long-term outcomes, to that of HBV-related HCC. In this cohort, HCC occurred in 70 of 1865 PBC patients with a prevalence of 3.75 % and an incidence of 0.66 cases per 100 patient-years. The 5- and 10-year cumulative incidences were 2.6 % (95 % confidence interval (CI) 1.8-3.4) and 8.9 % (95 % CI 5.5-12.3), respectively. Age >54 years (odds ratio [OR] = 5.5, 95 % CI 3.0-10.1, p = 0.001), male sex (OR = 2.2, 95 % CI 1.2-4.0, p = 0.001), co-existence of diabetes mellitus (DM) (OR = 3.1, 95 % CI 1.6-6.2, p = 0.002), and previous HBV infection (OR = 6.6, 95 % CI 3.7-11.9, p = 0.001) were independently associated with the development of HCC. The tumor size, number, location, and 5-year survival were not significantly different in PBC-related HCC compared to HBV-related HCC. Alpha-fetoprotein was elevated in only 20 % of the cases with PBC-related HCC. Although HCC was uncommon, occurring in fewer than 5 % of patients, the risk is significantly increased by age, sex, DM, and past HBV infection.

Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma.

UNLABELLED: Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child-Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment-naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1-, 3-, and 5-year tumor-free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child-Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). CONCLUSION: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5-year survival rates.