Complete response after treatment of breast cancer with isolated liver metastasis: a case report.

Background: Breast cancer has a high incidence and is prone to metastasis, while isolated liver metastasis is rare. A growing body of evidence supports the effectiveness of treating breast cancer with anti-human epidermal growth factor receptor-2 (HER2) therapy in combination with chemotherapy. However, little is known about its impact on metastatic liver disease. There is also a lack of consensus on managing liver metastases from breast cancer, and no studies have been conducted on managing the disappearance of liver metastases after treatment. Case Description: In May 2021, a 51-year-old female patient with HER2-positive breast cancer with isolated liver metastases had immunohistochemistry of estrogen receptor (ER) (-), progesterone receptor (PR) (-), and HER2 (3+) for both her primary lesion and liver metastases. After undergoing 17 cycles of anti-HER2 therapy and chemotherapy, the patient expressed a desire for surgery. Then a preoperative examination was performed, which revealed the disappearance of both the primary breast lesion and the liver metastases. Immediately afterwards, a left mastectomy was performed, and postoperative pathology showed a complete response to the breast tumor. As for the liver, where the metastatic lesions disappeared, no relevant study has reported how to deal with this situation. Finally, after a hospital-wide discussion, the patient was given trastuzumab maintenance therapy. Until now, no obvious signs of recurrence or metastasis have been observed during regular follow-ups. Conclusions: This case suggests that maintenance therapy may be the best option for patients with breast cancer whose liver metastases disappear by medication. Also, it can be inferred that in HER2-positive metastatic breast cancer (MBC), patients with isolated liver metastases may be more likely to achieve a cure-like outcome. Nevertheless, more cases and follow-up information are needed to support these views.

CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II): rationale and design.

BACKGROUND AND PURPOSE: Tenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore the efficacy and safety of TNK in Chinese patients who had an acute ischaemic stroke with large/medium vessel occlusion in an extended time window. METHODS AND DESIGN: Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II) is a multicentre, prospective, block-randomised, open-label, blinded-endpoint, phase IIb study. Eligible patients are 1:1 randomised into two groups: 0.25 mg/kg TNK versus best medical management (excluding TNK). The safety and efficacy of 0.25 mg/kg TNK are assessed through reperfusion status and presence of symptomatic intracranial haemorrhage (sICH). STUDY OUTCOMES: The primary outcome is major reperfusion without sICH at 24-48 hours after randomisation. Major reperfusion is defined as restoration of blood flow to greater than 50% of the involved ischaemic territory assessed by catheter angiography or repeated perfusion imaging. Secondary outcomes include post-thrombolytic recanalisation, neurological improvements, change in the National Institutes of Health Stroke Scale score, haemorrhagic transformation at 24-48 hours, systematic bleeding at discharge, modified Rankin Scale (mRS) 0-1, mRS 0-2, mRS 5-6, mRS distribution and Barthel index at 90 days. DISCUSSION: CHABLIS-T II will provide important evidence of intravenous thrombolysis with TNK for patients who had an acute stroke in an extended time window.

Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (ß = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (ß = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial.

BACKGROUND: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window. METHODS: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. RESULTS: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design. DISCUSSION: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).

Reperfusion measurements, treatment time, and outcomes in patients receiving endovascular treatment within 24 hours of last known well.

AIMS: The aim of this study was to explore the interaction between reperfusion and treatment time on the outcomes of patients undergoing endovascular treatment presenting within 24 h of last known well, and to compare the predictive ability of different reperfusion measurements on outcomes. METHODS: Eligible patients from a single-center cohort were enrolled in this study. Reperfusion was assessed using reperfusion index (decreased volume of hypoperfusion lesion compared with baseline) measured by repeated perfusion imaging, and modified treatment in cerebral ischemia score measured by digital subtraction angiography, respectively. The interactions between reperfusion measurements and treatment time on outcomes were explored using multivariate-adjusted logistic and linear regression models. The predictive abilities of reperfusion measurements on outcomes were compared using area under the receiver operating characteristic curve (ROC-AUC) and values of R-square. RESULTS: Reperfusion index and treatment time had significant interactions on 3-month modified Rankin Scale (mRS) 0-2 and infarct growth (p for interaction <0.05). Although the AUCs were statistically similar (AUCs of mRS 0-2 prediction, mTICI≥2b:0.63, mTICI≥2c:0.59, reperfusion index≥0.5:0.66, reperfusion index ≥0.9:0.73, P value of any of the two AUCs >0.05), reperfusion index≥0.9 showed the highest R-square values in outcome prediction (R-square values of 3-month mRS 0-2 and infarct growth = 0.21) among all the reperfusion measurements. CONCLUSION: Treatment time mitigated the effect of reperfusion on outcomes of patients receiving endovascular treatment within 24 h of last known well. Reperfusion index≥0.9 might serve as a better proxy of good outcomes compared with other reperfusion measurements.

Association of time to groin puncture with patient outcome after endovascular therapy stratified by etiology.

Background: Randomized clinical trials and large stroke registries have demonstrated a time-dependent benefit of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). The aim of this study was to investigate whether this could be applied to different stroke subtypes in a real-world single-center cohort. Materials and methods: Consecutive ischemic stroke patients with LVOs presenting within 24 h after symptom onset were prospectively registered and retrospectively assessed. Baseline multimodal imaging was conducted before EVT. Independent predictors of functional independence [90-day modified Rankin scale (mRS), 0-2] and any incidence of intracranial hemorrhage (ICH) were explored using a stepwise logistic regression model in the entire cohort and in stroke subtypes. Results: From 2015 to 2020, 140 eligible patients received EVT, of whom 59 (42%) were classified as large artery atherosclerosis (LAA)-related. Time from last known normal to groin puncture was identified as an independent predictor for functional independence in patients of cardioembolic (CE) subtype [odds ratio (OR) 0.90 per 10 min; 95% CI 0.82-0.98; P = 0.013] but not in the LAA subtype and the whole cohort. Groin puncture within 6 h after the time of last known normal was associated with a lower risk of any ICH in the whole cohort (OR 0.36, 95% CI 0.17-0.75, P = 0.007). Sensitivity analysis of patients with complete imaging profiles also confirmed the above findings. Besides, compared with patients of the CE subtype, the LAA subtype had a smaller baseline ischemic core volume, a better collateral status, a slower core growth rate, and a numerically smaller final infarct volume. Conclusion: Faster groin puncture has a more pronounced effect on the functional outcome in patients of CE subtype than those of LAA subtype. Reducing time to groin puncture is of great importance in improving the prognosis of patients after EVT, especially those of CE subtype, and reducing the incidence of any ICH in all patients.

Integrative Bioinformatics Analysis Reveals CHEK1 and UBE2C as Luminal A Breast Cancer Subtype Biomarkers.

In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein-protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.

Hemispheric cerebral blood flow predicts outcome in acute small subcortical infarcts.

The association between baseline perfusion measures and clinical outcomes in patients with acute small subcortical infarcts (SSIs) has not been studied in detail. Post-processed acute perfusion CT and follow-up diffusion-weighted imaging of 71 patients with SSIs were accurately co-registered. Relative perfusion values were calculated from the perfusion values of the infarct lesion divided by those of the mirrored contralateral area. The association between perfusion measures with clinical outcomes and the interaction with intravenous thrombolysis were studied. Additionally, the perfusion measures for patients having perfusion CT before and after thrombolysis were compared. Higher contralateral hemispheric cerebral blood flow (CBF) was the only independent predictor of an excellent clinical outcome (modified Rankin Scale of 0-1) at 3 months (OR = 1.3, 95% CI 1.1-1.4, P = 0.001) amongst all the perfusion parameters, and had a significant interaction with thrombolysis (P = 0.04). Patients who had perfusion CT after thrombolysis demonstrated a better perfusion profile (relative CBF ≥1) than those who had perfusion CT before thrombolysis (After:45.5%, Before:21.1%, P = 0.03). This study implies that for patients with SSIs, hemispheric CBF is a predictor of clinical outcome and has an influence on the effect of intravenous thrombolysis.

Association of Admission NIHSS Score with Infarct Core Volume and Target Mismatch of Infarct Core/Penumbra Volume on CT Perfusion in Acute Ischaemic Stroke.

INTRODUCTION: Neurological impairment is associated with collateral status in acute ischaemic stroke (AIS). We aimed to validate the association between admission National Institutes of Health Stroke Scale (aNIHSS) score and infarct core volume (ICV) and target infarct core/penumbra volume mismatch (TMM) on CT perfusion (CTP) in AIS patients. METHODS: Patients with acute middle cerebral artery or internal carotid artery occlusion from 2011 to 2020 were included. All patients underwent pretreatment CTP at admission. ICV and TMM were analyzed with MIStar software on CTP maps. aNIHSS scores and clinical characteristics of patients were obtained from our prospectively recorded stroke database. RESULTS: We recruited 182 patients with a median age of 69.5 years; 85 (63.7%) were male, and the median aNIHSS score was 14. Of those, 149 (81.8%) had an ICV < 70 mL, and 139 (76.3%) had TMM. Lower aNIHSS was associated with an ICV < 70 mL, with an area under the curve (AUC) of 0.74, and TMM with an AUC of 0.76. Among all 15 items of the aNIHSS, the gaze score was the only item independently associated with an ICV < 70 mL (adjusted odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.22-0.79, p = 0.008) and TMM (adjusted OR = 0.5, 95% CI: 0.28-0.9, p = 0.021). One or both aNIHSS ≤ 16 and gaze score = 0 predicted TMM with a sensitivity of 0.79 and a specificity of 0.62. CONCLUSION: aNIHSS may be a useful tool to predict an ICV < 70 mL and TMM on CTP in AIS patients.

Incident cerebral microbleeds and hypertension defined by the 2017 ACC/AHA Guidelines.

BACKGROUND: The cut-off for hypertension was lowered to blood pressure (BP) over 130/80 mmHg in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline. Whether the new definition of hypertension remains a potent risk factor of cerebral microbleeds (CMBs) is uncertain. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study. METHODS: This study is a sub-study of the Shanghai Aging Study (SAS). A total of 317 participants without stroke or dementia were included at baseline (2009-2011), and were invited to repeated clinical examinations and cerebral magnetic resonance imaging (MRI) at follow-up (2016-2018). CMBs at baseline and follow-up were evaluated on T2*-weighted gradient recalled echo (GRE) and susceptibility-weighted angiography (SWAN) sequence of MRI. We classified baseline BP into four categories: normal BP, elevated systolic BP, stage 1 hypertension and stage 2 hypertension according to the ACC/AHA guideline. We assessed the associations between BP categories and incident CMBs by generalized linear models. RESULTS: A total of 159 participants (median age, 67 years) completed follow-up examinations with a mean interval of 6.9 years. Both stage 1 and stage 2 hypertension at baseline were significantly related with a higher risk of incident CMBs (IRR 2.77, 95% CI, 1.11-6.91, P=0.028; IRR 3.04, 95% CI, 1.29-7.16, P=0.011, respectively), indicating dose-response effects across BP categories. Participants with ≥5 incident CMBs or incident CMBs in the deep locations all had baseline stage 1 and 2 hypertension. CONCLUSIONS: Participants with baseline stage 1 and stage 2 hypertension had a significantly higher risk of incident CMBs in this 7-year longitudinal community cohort.

White matter hyperintensities induce distal deficits in the connected fibers.

White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH-related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract-specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function.

Comparison of methods between CT perfusion source images and CT angiography in collateral flow assessment.

BACKGROUND: The methods used for grading leptomeningeal collateral flow (LMF) on single-phase computed tomography angiography (CTA) are heterogeneous and limited by temporal resolution. PURPOSE: To compare the reliability of relative filling time delay (rFTD) on CT perfusion source images (CTP-SI) and the currently used single-phase CTA collateral assessment methods and evaluate their ability to predict clinical outcomes in acute ischemic stroke patients. MATERIAL AND METHODS: We analyzed consecutive middle cerebral artery or internal carotid artery occlusion patients who received multimodal CT before treatment and within 12 h of stroke symptom onset from October 2015 to December 2018. Patients were dichotomized using the 90-day mRS into good (0-1) versus adverse (2-6) outcomes. CTP-SI was used to identify the rFTD score. CTA images were reconstructed to assess collateral status using the collateral score (Cs) and region leptomeningeal collateral score (rLMCs). Two observers independently assessed images. RESULTS: The baseline characteristics (n = 54) were median age of 67 years and 68.5% of the participants were men. The baseline median NIHSS was 14. Good clinical outcomes were observed in 19 (35.2%) patients. The k value was higher for rFTDs (k = 0.779, P < 0.001) than Cs (k = 0.666, P < 0.001) and rLMCs (k = 0.763, P < 0.001). Higher rFTDs were correlated with lower rLMCs (Spearman's rho -0.68, P < 0.001) and Cs (rho -0.66, P < 0.001). In multivariate logistic regression, rFTD was associated with functional outcomes (P = 0.044). CONCLUSION: The rFTDs method is comparable to single-phase CTA-based assessments in assessing LMFs in acute ischemic stroke patients. Higher rFTDs is independently associated with adverse long-term functional outcomes.

Poly(lactic-co-glycolic acid)-Chitosan-Gelatin Composite Nanomaterials for the Treatment of Diabetic Foot Ulcer Wound Infection.

In this experiment, a solid carrier was prepared with PLGA, gelatin, and chitosan as the main raw materials, so that BMSCs could exert their repairing effect directly in the ulcer area under the stimulation of Klotho protein. We chose to use electrospun PLGA as the main technical means to provide suitable adhesion growth environment for BMSCs by preparing PLGA nanofibers. At the same time, PLGA nanofibers are also a controlled release material, so that Klotho protein can remain active, thereby achieving the purpose of stimulating BMSCs for a long time. Through the nano-scale porous structure provided on the surface of the PLGA film, BMSCs can adhere well to the surface of the material and continuously receive stimulation from the inner Klotho protein. We applied this composite to mice with diabetic ulcers, and verified the effects of Klotho protein and BMSCs on DFU healing in five groups of mice. From the results, the Klotho+BMSCs group achieved the best healing effect, followed by the Klotho group alone, while the other three groups had no significant difference in healing effects. It is proved that both Klotho and BMSCs can help the healing of diabetic ulcers, but BMSCs alone cannot survive in harsh environments, and it is difficult to play a normal repair role. The purpose of this study was to investigate the effect of Klotho protein on BMSCs and ECs under high glucose conditions, and to find a suitable carrier for planting BMSCs on it. At the same time, the material also has a certain sustained release function. We have concluded that Klotho protein can promote the proliferation and migration of BMSCs and ECs under high glucose conditions. When combined with electrospinning technology to prepare a protein that can release Klotho, it also provides a microstructure suitable for BMSCs adhesion, thereby ensuring that BMSCs can successfully survive. In the end, we artificial Klotho protein can promote angiogenesis in diabetic ulcer areas by protecting BMSCs and ECs, thereby promoting healing of ulcer areas.

Research on the Treatment of Diabetic Foot with Ulcer Based on Nano-Silver Antibacterial Dressing.

The incidence of diabetes has been increasing year by year. Long-term growth in blood sugar causes complications such as diabetic foot ulcer and infections, which will increase the difficulty of ulcer treatment. The diabetes brings great pain and heavy economic burden to patients and their families. In view of the above problems, a nano-silver antibacterial dressing is synthesized in this paper to control bacterial infection on the ulcer surface and promote wound healing. This paper describes the preparation process and morphological characterization of nano-silver antibacterial dressings. 100 patients were selected, which divided into two groups for comparative experiments. The conventional group used conventional vaseline dressing, and the control group was nano-silver antibacterial dressing. The ulcer surface healing time, the number of dressing changes, and the control of infection were analyzed separately, and statistical analysis was performed with SPSS19.0. The experimental results are as follows. The use of nano-silver antibacterial dressing can significantly reduce the incidence of infection in diabetic foot patients, which is helpful to reduce the number of dressing changes, shorten the healing time of ulcer, and accelerate the turnover rate. It helps to shorten the course of diabetic foot, and it is recommended to promote its clinical application.

Sodium ion transport across the endothelial glycocalyx layer under electric field conditions: A molecular dynamics study.

In the present research, the sodium ion transport across the endothelial glycocalyx layer (EGL) under an imposed electric field is investigated, for the first time, using a series of molecular dynamics simulations. The electric field is perpendicularly imposed on the EGL with varying strengths. The sodium ion molarity difference between the inner and outer layers of EGL, Δc, is used to quantify the sodium transport in the presence of the negatively charged glycocalyx sugar chains. Results suggest that a weak electric field increases Δc, regardless of whether the electric field is imposed perpendicularly inward or outward. By contrast, a strong electric field drives sodium ions to travel in the same orientation as the electric field. Scrutiny of the charge distribution of the glycocalyx sugar chains suggests that the electric field modifies the spatial layouts of glycocalyx atoms as it drives the transport of sodium ions. The modification in glycocalyx layouts further changes the inter-molecular interactions between glycocalyx sugar chains and sodium ions, thereby limiting the electric field control of ion transport. The sodium ions, in turn, alter the apparent bending stiffness of glycocalyx. Moreover, the negative charges of the glycocalyx sugar chains play an important role in maintaining structural stability of endothelial glycocalyx. Based on the findings, a hypothesis is proposed regarding the existence of a strength threshold of the electric field in controlling charged particles in the endothelium, which offers an alternative explanation for contrasting results in previous experimental observations.

White matter hyperintensities associated with progression of cerebral small vessel disease: a 7-year Chinese urban community study.

We aimed to explore the role of white matter hyperintensities (WMH) in progression of cerebral small vessel disease (CSVD) in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline and progression) and cognitive impairment. CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. Small vessel disease (SVD) score was rated as the total burden of CSVD markers. Global cognitive function and 5 main cognitive domains (memory, language, spatial construction, attention and executive function) were evaluated by neuropsychological tests. We performed multivariable linear regression and binominal logistic regression. Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. WMH (baseline and progression) were associated with decline of executive function. WMH were associated with progression of cerebral small vessel disease and decline of executive function in a Chinese urban community study over a period of 7 years.

High Level of Serum Tissue Kallikrein Is Associated with Favorable Outcome in Acute Ischemic Stroke Patients.

BACKGROUND/OBJECTIVES: We sought to assess the association between a serum tissue kallikrein (TK) level and a 90-day outcome in acute ischemic stroke (AIS) patients who received acute reperfusion therapy. METHODS: Consecutive AIS patients within 6 hours after stroke onset between December 2015 and August 2017 were prospectively recruited. Blood samples were collected before acute reperfusion therapy for serum TK measurement. Outcome was modified Rankin scale (mRS) score at 90 days after stroke onset. Binary logistic regression was performed to analyze the association between the baseline TK level and the clinical outcome. RESULTS: Between December 2015 and August 2017, 75 patients (age range from 33 to 91 years, 72.0% male) were recruited in this study. Higher baseline TK was independently associated with a favorable functional outcome (mRS 0-2) (odds ratio 1.01, 95% confidence interval (CI) 1.00-1.02, p = 0.047) and low mortality rate (odds ratio 0.98, 95% CI 0.96-1.00, p = 0.049) at 90 days. Increased TK level was associated with 90 d mRS (0-2) with area under the curve of 0.719 (95% CI 0.596-0.842; p = 0.002). CONCLUSIONS: Serum TK can be a promising predictor of clinical outcome in AIS patients who received acute reperfusion therapy.

Permeability Surface of Deep Middle Cerebral Artery Territory on Computed Tomographic Perfusion Predicts Hemorrhagic Transformation After Stroke.

BACKGROUND AND PURPOSE: Permeability surface (PS) on computed tomographic perfusion reflects blood-brain barrier permeability and is related to hemorrhagic transformation (HT). HT of deep middle cerebral artery (MCA) territory can occur after recanalization of proximal large-vessel occlusion. We aimed to determine the relationship between HT and PS of deep MCA territory. METHODS: We retrospectively reviewed 70 consecutive acute ischemic stroke patients presenting with occlusion of the distal internal carotid artery or M1 segment of the MCA. All patients underwent computed tomographic perfusion within 6 hours after symptom onset. Computed tomographic perfusion data were postprocessed to generate maps of different perfusion parameters. Risk factors were identified for increased deep MCA territory PS. Receiver operating characteristic curve analysis was performed to calculate the optimal PS threshold to predict HT of deep MCA territory. RESULTS: Increased PS was associated with HT of deep MCA territory. After adjustments for age, sex, onset time to computed tomographic perfusion, and baseline National Institutes of Health Stroke Scale, poor collateral status (odds ratio, 7.8; 95% confidence interval, 1.67-37.14; P=0.009) and proximal MCA-M1 occlusion (odds ratio, 4.12; 95% confidence interval, 1.03-16.52; P=0.045) were independently associated with increased deep MCA territory PS. Relative PS most accurately predicted HT of deep MCA territory (area under curve, 0.94; optimal threshold, 2.89). CONCLUSIONS: Increased PS can predict HT of deep MCA territory after recanalization therapy for cerebral proximal large-vessel occlusion. Proximal MCA-M1 complete occlusion and distal internal carotid artery occlusion in conjunction with poor collaterals elevate deep MCA territory PS.

Flow diversion within seven days after stroke onset is associated with favorable outcome in anterior circulation stroke.

Anterior cerebral artery (ACA) flow diversion (FD), defined as ipsilateral mean velocity (MV) of at least 30% greater than the contralateral artery, could be seen an indirect sign of leptomeningeal collateralization in the setting of middle cerebral artery occlusion. The purpose of the study was to evaluate the association between dynamic FD and functional outcome in acute anterior stroke patients with large artery occlusion. Acute middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive stroke patients within 12h were recruited. Transcranial Doppler ultrasound was done at baseline, 24h and 7d after onset and velocities of MCA and ACA were recorded. FD ratio was calculated by dividing the ipsilateral ACA MV by the contralateral ACA MV. FD was determined positive when FD ratio ≥1.3. Outcome was assessed by 90-day modified Rankin's Scale (mRS). The association between FD at different time points and functional outcome were analyzed. 16 patients (median age of 67 and 75% were male) were recruited. FD ratio showed a trend of decline but did not reach statistical significance (p=0.056). The proportion of FD at baseline (p=0.026), 24h (p=0.001) and 7d (p=0.044) was significantly higher in patients with favorable outcome. Higher FD ratio at baseline (p=0.02) and 24h (p=0.003) were significantly associated with favorable outcome. These results suggested that FD ratio showed a trend of decline after stroke onset. Presence of FD within 7days was associated with favorable functional outcome in acute MCA/ICA occlusive stroke patients.