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To assess the complementary value of high-resolution multi-contrast MRI (hrMRI) in identifying symptomatic patients with intracranial atherosclerosis (ICAS) who are likely to experience recurrent ischemic cerebrovascular events.In this retrospective cohort study, eighty patients with acute ischemic events attributed to ICAS who underwent hrMRI examination between January 2015 and January 2019 were included. Median follow-up for all patients was 30 months (range: 1 to 52 months) and recurrent ischemic cerebrovascular events were recorded. Cox regression analysis and time-dependent ROC were performed to quantify the association between the plaque characteristics and recurrent events.During the follow-up, 14 patients experienced recurrent ischemic cerebrovascular events. Young males and those with diabetes and poor medication persistence were more likely to experience recurrent events. ICAS in patients with recurrence had significantly higher enhancement ratio and steepness which is defined as the ratio between the plaque height and length than those without (p0.001 and p = 0.015, respectively). After adjustment of clinical factors, enhancement ratio (HR, 13.13 [95% CI, 3.58-48.20], p0.001) and plaque steepness (HR, 110.27 [95% CI, 4.75-2560.91], p = 0.003) were independent imaging biomarkers associated with recurrent events. Time-dependent ROC indicated that integrated high enhancement ratio and steepness into clinical risk factors improved discrimination power with the ROC increased from 0.79 to 0.94 (p = 0.008).The enhancement ratio and plaque steepness improved the accuracy over traditional clinical risk factors in predicting recurrent ischemic cerebrovascular events for patients with ICAS.• High-resolution magnetic resonance imaging helps clinicians to evaluate high-risk Intracranial plaque. • The higher enhancement ratio and plaque steepness (= height/length) were the primary biomarkers associated with future ischemic cerebrovascular events. • High-resolution magnetic resonance imaging combined with clinical characteristics showed a higher accuracy for the prediction of recurrent events in patients with intracranial atherosclerosis.

Introduction: Diabetes markedly affects the formation and development of intracranial atherosclerosis. The study was aimed at evaluating whether radiomics features can help distinguish plaques primarily associated with diabetes. Materials and Methods: We retrospectively analyzed patients who were admitted to our center because of acute ischemic stroke due to intracranial atherosclerosis between 2016 and 2022. Clinical data, blood biomarkers, conventional plaque features and plaque radiomics features were collected for all patients. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined from logistic regression models. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to describe diagnostic performance. The DeLong test was used to compare differences between models. Results: Overall, 157 patients (115 men; mean age, 58.7 ± 10.7 years) were enrolled. Multivariate logistic regression analysis showed that plaque length (OR: 1.17; 95% CI: 1.07–1.28) and area (OR: 1.13; 95% CI: 1.02–1.24) were independently associated with diabetes. On combining plaque length and area as a conventional model, the AUCs of the training and validation cohorts for identifying diabetes patients were 0.789 and 0.720, respectively. On combining radiomics features on T1WI and contrast-enhanced T1WI sequences, a better diagnostic value was obtained in the training and validation cohorts (AUC: 0.889 and 0.861). The DeLong test showed the model combining radiomics and conventional plaque features performed better than the conventional model in both cohorts (p < 0.05). Conclusions: The use of radiomics features of intracranial plaques on hrMRI can effectively distinguish culprit plaques with diabetes as the primary pathological cause, which will provide new avenues of research into plaque formation and precise treatment.

Background and ObjectivesSleep traits can have implications for ischemic stroke recovery in observational studies. The purpose of our present study was to explore the relationship between genetically predicted sleep traits and poststroke functional outcomes with Mendelian randomization (MR) method.MethodsInstrumental variables for insomnia and sleep duration were adopted from genome-wide association studies data of European ancestry individuals. Summary data for functional outcome after ischemic stroke were retrieved from the Genetics of Ischemic Stroke Functional Outcome network. Inverse-variance weighted approach was adopted as the main analyses. Alternative MR approaches were used in sensitivity analyses. I2and Q value statistics were used to appraise the heterogeneity among genetic variants.ResultsIn univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (odds ratio [OR] = 1.30; 95% CI: 1.10–1.54,p= 0.002). Genetic liability to short sleep, long sleep, and continuous sleep duration were not associated with poststroke functional outcome (allp> 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08–1.44,p= 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking, and alcohol consumption, the overall patterns between genetic liability to insomnia and poststroke outcome remained (allp< 0.05).DiscussionThis MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context.

Traumatic brain injury (TBI) is a worldwide health problem contributing to significant economic burden. TBI is difficult to treat partly due to incomplete understanding of pathophysiology. Ferroptosis is a type of iron-dependent programmed cell death which has gained increasing attention due to its possible role in TBI. Current studies have demonstrated that ferroptosis is related to the pathology of TBI, and inhibition of ferroptosis may improve long term outcomes of TBI. Therefore, clarification of the exact association between ferroptosis and traumatic brain injury is necessary and may provide new targets for treatment. This review describes (1) the ferroptosis pathways following traumatic brain injury, (2) the role of ferroptosis during the chronic phase of traumatic brain injury, and (3) potential therapies targeting the ferroptosis pathways.

We assessed the value of computed tomography (CT) and automated Alberta Stroke Program Early CT Score (ASPECTS) with net water uptake (NWU) to predict stroke onset time. Two-hundred forty stroke patients with anterior circulation large-vessel occlusion were included. CT-ASPECTS-NWU values were calculated by comparing the mean Hounsfield units of affected ASPECTS regions with unaffected contralateral regions. The correlation between ASPECTS-NWU and stroke onset to CT time was assessed. ASPECTS-NWU predictive values were calculated to identify a stroke onset to CT time of within 4.5/6 h. A correlation existed between stroke onset to CT time and ASPECTS-NWU (r = 0.65, p

Cerebrovascular disease is a significant global public health concern, despite the diagnosis and treatment of stroke has made great progress in recent years, however, its mainly guided by anatomical indicators, which still needs to be further improved, and there is an urgent need to explore a more accurate and comprehensive functional imaging assessment method. Rapid development of coronary CT angiography derived fractional flow reserve (CT-FFR) has become an important technique for noninvasive evaluation of coronary artery disease, and these successful application experiences inspiried neurologists to explore the functional evaluation technique of cerebral arteries and demonstrated broad application prospects. In this paper, by analyzing and comparing the coronary CT-FFR technology, the progress, existing problems and possible solutions of the functional evaluation for cerebral arterial stenosis are discussed from the aspects of coronary CT-FFR study, cerebral artery functional evaluation study, and the comparison and consideration of cerebral arterial and coronary CT-FFR.脑血管疾病是全球重大公共卫生问题，尽管脑卒中诊疗近些年取得很大进展，但以解剖学为指导的脑卒中诊疗仍有待进一步改善，迫切需要更精准、全面的功能影像评估手段。冠状动脉CT血流储备分数（CT-FFR）的快速发展已经成为无创评估冠状动脉疾病的重要技术，这些成功的经验启发神经影像医生探索脑动脉功能评估技术并展示了广阔的应用前景。本文通过分析对比冠状动脉CT-FFR技术，着重从冠状动脉CT-FFR研究、脑动脉功能评估研究及脑动脉与冠状动脉CT-FFR的对照与思考这几个方面探讨了脑动脉狭窄功能评估的进展、存在问题以及可能的解决方案。.

Objective To compare the effects of high-frequency (10 Hz) versus low-frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) on motor recovery and functional reorganization of the cortical motor network during the early phase of stroke. Methods Forty-six hospitalized, first-ever ischemic stroke patients in early stage (within two weeks) with upper limb motor deficits were recruited. They were randomly allocated to three groups with 10 Hz ipsilesional rTMS, 1 Hz contralesional rTMS, and sham rTMS of five daily session. All patients underwent motor function (Upper Extremity Fugl–Meyer), neurophysiological and resting-state functional Magnetic Resonance Imaging (fMRI) (rs-fMRI) assessments before and after rTMS intervention. Motor recovery (△Fugl–Meyer Assessment) was defined as motor function changes before and after rTMS intervention. Motor function assessment was reevaluated at time point of three month follow-up. Results The two real rTMS groups manifested greater motor improvements than the sham group. The effect sustained for at least 3 months after the end of the treatment sessions. Compared with the sham group, 10 Hz ipsilesional rTMS group presented increased resting-state functional connectivity (FC) between ipsilesional primary motor cortex (M1) and contralesional M1 (P = .007), whereas 1 Hz contralesional rTMS group presented increased FC between contralesional M1 and ipsilesional supplementary motor area (P = .010), which were positively correlated with motor recovery (P < .05). Conclusion Beneficial effect of rTMS on motor recovery might be underlaid by increased FC between stimulating site and the remote motor areas, highlighting the motor network reorganization mechanism of rTMS in early post-stroke phase.

CT densitometry-based methods to directly quantify net water uptake in ischemic brain tissue have been increasingly applied recently. There is potential for net water uptake to be used as an imaging biomarker for the pathophysiology of infarcted lesions. This review is aimed at summarizing the potential and current status of the application of net water uptake as a biomarker in the management of ischemic stroke and future directions in this context. Specifically, we provide a brief overview of the principle and different methods of net water uptake measurement, followed by a discussion of the role of net water uptake in predicting malignant brain edema and hemorrhagic transformation, evaluating lesion age, and predicting the efficacy of reperfusion therapy and long-term clinical prognosis. Artificial intelligence will help address the lack of automation and standardization in the measurement of net water absorption. Further validation of net water uptake in a prospective multicenter setting is necessary. KEY POINTS: • NWU can be used as a quantitative imaging biomarker for developing malignant brain edema in anterior and posterior circulation strokes. • The difference in NWU in edema arrest or reversibility suggests that rapid and successful revascularization can influence the progression of ischemic edema. • NWU can be used to predict the age of a lesion, with predictive power comparable to that of DWI/FLAIR mismatch.

Background A pressure wire offers a dynamic tool to assist in the measurement of the pressure gradient and assessment of the functional significance of stenosis. The author presents a patient with idiopathic intracranial hypertension who was diagnosed with cerebral venous sinus stenosis (CVSS). Venography accompanied by pressure measurement was used to guide the stent placement for CVSS. Case Description A 27-year-old woman was referred to our hospital with a chief complaint of headache and neckache lasting for 7 weeks, with an 8-day history of binocular diplopia and blurred vision. Magnetic resonance venography and digital subtraction angiography showed a filling defect in the right transverse sinus. A pressure wire was used before endovascular treatment and showed that the pressure gradient was 10 mm Hg, which meets the surgical indication. After a stent was placed, no pressure gradient was recorded by the pressure wire. Conclusions This is the first report about using a pressure wire for CVSS. The finding suggests that use of a pressure wire can be a new approach in the diagnosis and treatment of CVSS.

ObjectiveTo determine the influence of renal impairment (RI) on clinical outcomes at 3 months and the risk of recurrent stroke in patients presenting with emergent large vessel occlusion (ELVO) treated with emergent endovascular treatment (EVT).MethodsConsecutive patients with anterior circulation stroke due to ELVO treated with EVT in 21 endovascular centers were included. Multivariate regressions were used to evaluate the association of RI with mortality, functional independence (modified Rankin Scale [mRS] score 0–2), and functional improvement (shift in mRS score) at 3 months. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsA total of 628 patients with ELVO (mean age 64.7 ± 12.5 years, median NIH Stroke Scale score 17 points, 99 [15.8%] with RI) who underwent EVT were enrolled. After adjustment for other relevant variables, multivariate regression analysis indicated that RI was independently associated with functional independence (adjusted odds ratio 0.53, 95% confidence interval [CI] 0.29–0.96, p = 0.035) at 3 months but not with mortality or functional improvement. Multivariate competing-risk regression analysis showed that patients with RI who received EVT had a significantly higher risk of recurrent stroke (adjusted hazard ratio 2.56, 95% CI 1.27–5.18, p = 0.009) compared to those with normal renal function.ConclusionOur results suggest that RI is an independent predictor of functional independence at 3 months and long-term risk of recurrent stroke in patients with ELVO treated with EVT.

Introduction: Imaging-based early warning indicators and feasible stratification of acute ischemic stroke (AIS) patients with hemorrhagic transformation (HT), especially high-risk patients with parenchymal hematoma (PH), are crucial in determining subsequent treatment strategies. This study combined automated ASPECTS software with noncontrast CT (NCCT) and CTA source image (CTASI) attenuation changes using Hounsfield unit (HU) values to predict HT and PH in patients with AIS. Materials and Methods: We retrospectively enrolled 172 consecutive patients with anterior circulation large-vessel occlusion between 2016 and 2020. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) analyses were used to investigate the relationship between NCCT and CTASI-ASPECTS-HU, as well as other clinical and radiological parameters of HT and PH. Univariate and multivariate logistic regression analyses were performed to explore risk factors for HT or PH, and an ROC curve was used to evaluate their diagnostic values. Results: A multivariate analysis showed that CTASI-ASPECTS-HU and NIHSS score were independent predictors of HT (CTASI-ASPECTS-HU: odds ratio (OR), 2.22; 95% CI, 1.01–4.92; NIHSS: OR, 1.07; 95% CI, 1.02–1.13) and PH (CTASI-ASPECTS-HU: OR, 6.51; 95% CI, 2.29–18.50; NIHSS: OR, 1.07; 95% CI, 1.01–1.13). According to ROC analysis, CTASI-ASPECTS-HU >0.09 identified HT (area under the curve, 0.70; sensitivity, 70.15%; specificity, 61.90%), and CTASI-ASPECTS-HU >0.10 identified PH (area under the curve, 0.79; sensitivity, 76.19%; specificity, 73.33%). The area under the curve for predicting HT or PH increased when CTASI-ASPECTS-HU was combined with NIHSS score (HT: area under the curve, 0.74; sensitivity, 73.13%; specificity, 70.48%; PH: area under the curve, 0.81; sensitivity, 85.71%; specificity, 72.38%). Conclusion: CTASI-ASPECTS-HU is a reliable radiological predictor of HT and PH in patients with AIS. Its predictive efficacy is moderately improved when combined with NIHSS score.

BackgroundRenal impairment (RI) is associated with worse outcomes in the treatment of intravenous thrombolysis and emergent endovascular treatment (EVT) in anterior circulation stroke. The objective of this study was to investigate the association of RI with short-term and long-term outcomes in patients with vertebrobasilar artery occlusions (VBAO) who received EVT.MethodsConsecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. Multivariate regression analyses were used to evaluate the association of RI with mortality and symptomatic intracranial hemorrhage (sICH) during the hospital stay, and also mortality, favorable functional outcome (modified Rankin Scale (mRS) score of 0–3), and functional improvement (shift in mRS score) at 3 months and 1 year follow-up. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses.ResultsAfter adjustment for potential confounders, RI was independently associated with sICH (OR 3.30, 95% CI 1.55 to 7.18), as well as mortality (OR 2.54, 95% CI 1.47 to 4.38; OR 3.07, 95% CI 1.72 to 8.08), favorable functional outcome (OR 0.33, 95% CI 0.17 to 0.66; OR 0.25, 95% CI 0.12 to 0.51), and functional improvement (OR 0.45, 95% CI 0.28 to 0.74; OR 0.35, 95% CI 0.21 to 0.60) at 3 months and 1 year follow-up, respectively, but RI was not associated with in-hospital mortality. Additionally, there was no significant association between RI and recurrent stroke within 1 year.ConclusionsOur findings suggest that RI is associated with a higher risk of sICH in hospital and a decrease in survival, favorable functional outcome, and functional improvement at 90 days and 1 year follow-up.Trial registration numberURL:http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

We assessed the value of computed tomography (CT) and automated Alberta Stroke Program Early CT Score (ASPECTS) with net water uptake (NWU) to predict stroke onset time.Two-hundred forty stroke patients with anterior circulation large-vessel occlusion were included. CT-ASPECTS-NWU values were calculated by comparing the mean Hounsfield units of affected ASPECTS regions with unaffected contralateral regions. The correlation between ASPECTS-NWU and stroke onset to CT time was assessed. ASPECTS-NWU predictive values were calculated to identify a stroke onset to CT time of within 4.5/6 h.A correlation existed between stroke onset to CT time and ASPECTS-NWU (r = 0.65, p 0.001), which was affected by collateral status and infarct location. The area under the receiver operating characteristic (ROC) curve (AUC) for distinguishing a stroke onset to CT time of within 4.5 h was 0.837 (95% confidence interval [CI] 0.784-0.881; optimal cutoff 7%; sensitivity 87.10%; specificity 62.36%). The multi-index AUC was 0.884 (95% CI 0.837-0.922). The AUC for distinguishing a stroke onset to CT time of within 6 h was 0.836 (95% CI 0.783-0.880; optimal cutoff 9%; sensitivity 72.73%; specificity 81.16%). The multi-index AUC was 0.881 (95% CI 0.834-0.920).ASPECTS-NWU may be used to determine stroke onset time in patients with unwitnessed or wake-up stroke.

Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE).One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared.CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51-0.71; p 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90-0.98; p 0.001).This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.• The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment.

This study aimed to use the automated Alberta Stroke Program Early CT Score (ASPECTS) software to assess the value of different CT modalities (non-contrast CT, CT angiography [CTA]-arterial, CTA-venous, and arterial- and venous-phase mismatch-ASPECTS) in predicting the final infarct extent and clinical outcome in large-vessel occlusion stroke.This retrospective study included patients with large-vessel occlusion stroke who underwent reperfusion therapy during 2015 to 2019. Correlations between different CT-ASPECTS modalities and follow-up CT-ASPECTS and outcome were determined using Spearman rank correlation coefficient. Receiver operating characteristic curve analysis was used to assess the ability of different CT-ASPECTS modalities to identify patients with good outcomes.One hundred and thirty-five patients were included. We found almost-perfect correlation between CTA-venous-ASPECTS and follow-up CT-ASPECTS (r = 0.92; 95% CI: 0.89-0.95), better than that in other CT modalities. The 90-day modified Rankin scale (mRS) score substantially correlated with CTA-venous-ASPECTS (r = -0.64; 95% CI: -0.73 to -0.52). The ROC curve analysis showed CTA-venous-ASPECTS had the highest area under the curve (AUC: 0.82; 95% CI: 0.75-0.89; P 0.001), followed by mismatch-ASPECTS (AUC: 0.75; 95% CI: 0.65-0.85; P 0.001). When emphasizing the sensitivity for identifying patients with good outcomes, the best cut-off point of mismatch-ASPECTS was -3 with the highest sensitivity (91.30%).CTA-venous-ASPECTS is a reliable tool to predict the infarct extent and outcome. Furthermore, mismatch-ASPECTS may represent images in different angiographic phases and was sensitive for prognosis prediction.

Background: Blood pressure (BP), recanalization status, and collateral circulation are important factors for cerebral autoregulation after stroke. We aimed to investigate the association of various BP variability (BPV) parameters with clinical outcomes after mechanical thrombectomy (MT) according to recanalization and collateral status. Methods: We included 502 consecutive patients who underwent MT due to anterior circulation large vessel occlusion stroke at three comprehensive stroke centers. BPV parameters were standard deviation (SD), maximum/minimum BP, coefficient of variation (CV) and successive variation (SV). The clinical outcomes included 90-day functional outcome assessed by modified Rankin Scale score and symptomatic intracranial hemorrhage (sICH). Results: Among the included patients, 219 (43.6%) achieved good functional outcomes and 59 (11.8%) developed sICH. After adjusting for confounders, higher systolic BP (SBP) variability [CV (odds ratio (OR), 1.089, p = 0.035), SV (OR, 1.082, p = 0.004). and SD (OR, 1.074, p = 0.027)] was associated with a lower likelihood of a favorable outcome. In addition, higher SBP [CV (OR, 1.156, p = 0.001) and SD (OR, 1.118, p = 0.001)] were significantly associated with increased odds of sICH. Moreover, the relationship between BPV and the outcomes depended on recanalization status. However, regardless of collateral status, a higher BPV after MT was associated with worse outcomes. Conclusions: Higher SBP SD and CV during the first 24 h after MT was a powerful predictor of worse clinical outcomes, regardless of the collateral status. However, the effects of BPV on outcomes were more substantial among patients with successful reperfusion.

Supplemental material, sj-pdf-1-tan-10.1177_1756286421997383 for Blood pressure variability and outcomes after mechanical thrombectomy based on the recanalization and collateral status by Xianjun Huang, Hongquan Guo, Lili Yuan, Qiankun Cai, Min Zhang, Yi Zhang, Wusheng Zhu, Zibao Li, Qian Yang, Zhiming Zhou, Wen Sun and Xinfeng Liu in Therapeutic Advances in Neurological Disorders

Malnutrition is associated with poor prognosis of different diseases. This study aimed to investigate the association of malnutrition with long-term mortality of older adults with ischemic stroke in China.We selected patients aged ≥65 years with first-ever ischemic stroke from the Nanjing Stroke Registry Program. Malnutrition was defined according to the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. Multivariable Cox proportional hazards regressions and competing risk regressions were performed to explore the relationship between malnutrition and the risk of mortality in older adults with ischemic stroke.Among 1065 enrolled patients, 60.5%, 46.7%, and 30.6% of patients were malnourished according to CONUT, GNRI, and PNI score. During a median follow-up of 4.74 (3.73-5.82) years, 205 (19.2%) patients died. In multivariate analysis, malnutrition (severe risk versus normal nutrition) was associated with significantly increased risk for mortality by the CONUT (adjusted hazard ratio [HR] 4.615, 95% confidence interval [CI] 1.373-15.514, P = 0.013), GNRI (adjusted HR 3.641, 95% CI 1.924-6.891, P 0.001), and PNI score (adjusted HR 1.587, 95% CI, 1.096-2.297, P = 0.014). Furthermore, adding the malnutrition indexes to models modestly improved the predictive ability of mortality.Our study indicated that malnutrition was highly prevalent in older Chinese adults with ischemic stroke and associated with increased mortality. Further research is required to evaluate the efficacy of nutritional management in these patients.

AIM Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) × cystatin C-based glomerular filtration rate, and investigate its association with short-term complications after curative resection of CRC. METHOD Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed. RESULTS Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P

Background Preoperative neuroimaging assessment of collateral circulation is important for selecting acute ischemic stroke patients who are appropriate for endovascular treatment. We sought to validate the capillary index score system in an Asian population and compare its ability in predicting clinical outcomes with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system. Methods We continuously enrolled acute ischemic stroke patients from two neurological centers from March 2014 to March 2017. Multivariate analyses were performed to assess the capillary index score system with 90-day clinical outcome (modified Rankin scale score). The scoring systems were compared for predicting good (modified Rankin scale 0–2) and excellent (modified Rankin scale 0–1) functional outcomes using area under the receiver operating characteristic curves. Results We identified 157 patients (median age, 65 years; 96 (61.1%) males), of whom 71 (45.2%) patients with 90-day good functional outcomes were selected. Capillary index score was independently associated with clinical outcome after endovascular treatment (OR 0.63; 95% CI 0.43–0.92; P = 0.016) with its predictive ability for good functional outcome (area under the receiver operating characteristic curve 0.755). For excellent functional outcome, the capillary index score system was not inferior to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (area under the receiver operating characteristic curve 0.748 versus 0.793, P = 0.09). Conclusions The capillary index score system is a potentially useful tool for predicting 90-day functional outcomes in acute ischemic stroke patients after endovascular treatment.

ObjectiveTo investigate whether thyroid function profiles can predict poststroke fatigue (PSF) in patients with acute ischemic stroke.MethodsPatients with stroke were consecutively recruited within 3 days of onset in Jinling Hospital. Serum levels of thyroid hormones, thyroid antibodies, hematologic indexes, and biochemical indexes were measured on admission. Fatigue was scored using the Fatigue Severity Scale. Associations were analyzed with multivariate regression and restricted cubic splines.ResultsOf the 704 patients with stroke, 292 (41.5%) were diagnosed with fatigue in the acute stage and 224 (35.3%) 6 months after the index stroke. The serum levels of thyroid-stimulating hormone (TSH) were inversely associated with the risk of PSF in both the acute phase and at follow-up evaluations after adjusting for potential confounders (odds ratio 0.30, 95% confidence interval 0.24–0.37 in the acute phase, and odds ratio 0.70, 95% confidence interval 0.58–0.84 at follow-up). The subgroup analysis indicated that in the acute phase of ischemic stroke, TSH was associated with severity of PSF in the groups with euthyroidism (β = −0.70, p < 0.001), subclinical hypothyroidism (β = −0.44, p < 0.001), and low-T3 syndrome (β = −0.34, p = 0.008). Higher TSH was associated with better Fatigue Severity Scale scores in patients with low-T3 syndrome 6 months after the index stroke (β = −0.35, p = 0.01). Furthermore, in the group with low-T3 syndrome, FT3 serum level could also indicate a higher risk of PSF (β = −2.54, p < 0.001 in the acute phase, and β = −2.67, p < 0.001 at follow-up).ConclusionThyroid function profiles may predict fatigue after acute ischemic stroke, suggesting that neuroendocrine responses could have a role in PSF.

Aim Azathioprine can prevent postoperative recurrences in Crohn's disease. We compared the efficacy of azathioprine in preventing surgical recurrence to explore whether immediate prophylaxis after surgery is better than azathioprine started after endoscopic or clinical recurrence. Method Data of patients with intestinal resection and ileocolic anastomosis for Crohn's disease between 2006 and 2015 were retrieved from a prospectively maintained database. Patients were grouped according to the strategies of postoperative therapy with azathioprine. Univariate and multivariate proportional hazard Cox regression analyses were conducted to identify independent predictive factors for surgical recurrence. Results Only age equal to or less than 16 years at diagnosis was an independent risk factor for surgical recurrence in all 166 patients (P = 0.005). In patients with high risk of recurrence (27 in the symptom-driven group, 39 in the endoscopy-driven group and 69 in the immediate prophylaxis group), both immediate and endoscopy-driven azathioprine delayed and reduced surgical recurrence compared with symptom-driven azathioprine (P = 0.035, 0.019). Their efficacy in reducing surgical recurrence was confirmed by Cox regression analyses (hazard ratio 0.465, P = 0.045; hazard ratio 0.352, P = 0.028). Surgical recurrence was similar between the immediate and endoscopy-driven groups. In addition, age ≤ 16 at diagnosis was still an independent risk factor for surgical recurrence in this subgroup. Conclusions In patients with high risk of recurrence, both immediate prophylactic azathioprine after surgery and azathioprine started after endoscopic recurrence can delay and reduce surgical recurrence compared with azathioprine started after clinical recurrence. In addition, azathioprine started immediately after surgery was not superior to azathioprine started after discovery of endoscopic recurrence.

Background Inflammation and neutrophils play pivotal roles in hemorrhagic transformation (HT) after recombinant tissue plasminogen activator (rtPA) treatment in stroke; however, the contribution of Nod-like receptor protein 3 (NLRP3), a key component of the innate immune system, is not yet known. This study aimed to explore the role of NLRP3 in the delayed rtPA-induced HT and its association with the neutrophil recruitment. Methods Rats were subjected to thromboembolic focal cerebral ischemia and delayed rtPA treatment at 4 h after ischemia to mimic HT. NLRP3 short hairpin RNAs (shRNA) were administered 72 h before ischemia. Additionally, rabbit anti-rat neutrophil serum (inducing neutropenia) was administered before cerebral ischemia. The infarct volume, edema volume, neurological deficit, hemorrhages, blood-brain barrier (BBB) integrity and brain neutrophil recruitment were evaluated at 24 h after cerebral ischemia. Results Our results demonstrated that delayed rtPA treatment at 4 h after ischemia promoted the expression of NLRP3 in neurons, microglia and endothelial cells, degradation of BBB components, and HT. NLRP3 knockdown significantly attenuated NLRP3 expression, BBB disruption, and HT. It also improved neurological functions and reduced neutrophil recruitment. Rabbit anti-rat neutrophil serum, like NLRP3 shRNA, reduced hemorrhage score and hemorrhage volumes after rtPA treatment. Furthermore, the anti-rat neutrophil serum combined with NLRP3 shRNA didn't further increase the protective effect on HT compared to rabbit anti-rat neutrophil serum used alone. Conclusions Together, our data suggest that NLRP3 inhibition can reduce neutrophil recruitment, which may contribute to the inhibitory effect on HT.

A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear.A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients.A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients.Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Aim/background CD99 participate in neutrophil infiltration after inflammatory events; however, despite the important role of inflammation in ischemic stroke, the role of CD99 in ischemic stroke remains unclear. Method In the present study, we detected the protein expression of CD99, ICAM-1, and CD31 (PECAM-1) in oxygen-glucose deprivation (OGD)-induced bEnd.3 cells and neutrophils and explored the influence of HIF-1α and IL-1β on their expression. We also explored the role of CD99 in the OGD-induced transmigration of neutrophils. Results Our results showed that OGD induction upregulated CD99 in bEnd.3 cells and that this effect could be abolished by the preadministration of IL-1β and was not mediated by HIF-1α. However, the activation of ICAM-1 by OGD remained activated with IL-1β treatment. No significant influence of IL-1β on OGD-induced CD31. Finally, we found a significant increase in infiltrated neutrophils after OGD induction compared with the control and OGD + anti-CD99 groups. Conclusion Our results indicated that CD99 mediates neutrophil infiltration and transmigration via OGD induction and thus constitutes a potential therapeutic target for anti-inflammatory treatment after ischemic stroke.

Background and Purpose— Acute ischemic stroke caused by cervical artery dissection tend to result in unfavorable outcomes even with appropriate medical treatment. This study evaluated the safety and effectiveness of endovascular thrombectomy in treating acute ischemic stroke associated with cervical artery dissection. Methods— Patients with acute ischemic stroke and with large artery occlusion associated with dissection were selected. Propensity score matching was performed to increase the comparability. Patients with a 90-day modified Rankin Scale score of 0 to 2 were defined as with favorable outcome. Results— Eighty patients with and 80 patients without thrombectomy were enrolled. After propensity score matching, 48 patients with and 48 patients without thrombectomy were matched for further analysis. Proportion of favorable outcome (modified Rankin Scale score of 0–2) was higher in patients with thrombectomy than in those without (66.7% versus 39.6%; P =0.008). There were no significance differences about the incidence of symptomatic intracranial hemorrhage (8.3% versus 4.2%; P =0.677) and the 90-day mortality (10.4% versus 6.3%; P =0.714) between matched patients with and without thrombectomy. Conclusions— Endovascular thrombectomy seems to be an effective treatment in selected patients with acute ischemic stroke associated with cervical artery dissection, but the safety of thrombectomy needs further research.

Background Inflammatory response has been recognized as a pivotal pathophysiological process during cerebral ischemic stroke. NLRP3 inflammasome, involved in the regulation of inflammatory cascade, can simultaneously lead to GSDMD-executed pyroptosis in cerebral ischemia. Low-density lipoprotein receptor (LDLR), responsible for cholesterol uptake, was noted to exert potential anti-inflammatory bioactivities. Nevertheless, the role of LDLR in neuroinflammation mobilized by cerebral ischemia/reperfusion (I/R) has not been investigated. Methods Ischemic stroke mice model was accomplished by middle cerebral artery occlusion. Oxygen-glucose deprivation was employed after primary cortical neuron was extracted and cultured. A pharmacological inhibitor of NLRP3 (CY-09) was administered to suppress NLPR3 activation. Histological and biochemical analysis were performed to assess the neuronal death both in vitro and in vivo. In addition, neurological deficits and behavioral deterioration were evaluated in mice. Results The expression of LDLR was downregulated following cerebral I/R injury. Genetic knockout of Ldlr enhanced caspase-1-dependent cleavage of GSDMD and resulted in severe neuronal pyroptosis. LDLR deficiency contributed to excessive NLRP3-mediated maturation and release of IL-1β and IL-18 under in vitro and in vivo ischemic conditions. These influences ultimately led to aggravated neurological deficits and long-term cognitive dysfunction. Blockade of NLRP3 substantially retarded neuronal pyroptosis in Ldlr−/− mice and cultured Ldlr−/− neuron after experimental stroke. Conclusions These results demonstrated that LDLR modulates NLRP3-mediated neuronal pyroptosis and neuroinflammation following ischemic stroke. Our findings characterize a novel role for LDLR as a potential therapeutic target in neuroinflammatory responses to acute cerebral ischemic injury.

Summary Background Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. Methods We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov , NCT02441556 . Findings Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0–3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81–3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0–3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20–7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31–7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. Interpretation There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. Funding Jiangsu Provincial Special Program of Medical Science.

Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients.Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END.Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volumeDWI infarct volume were more frequent in patients with END than patients without (all P0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volumeDWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001).HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.

Rationale Endovascular treatment plus standard medical therapy is superior to standard medical therapy alone for acute anterior proximal intracranial large artery occlusion strokes. The benefit of endovascular treatment in acute ischemic stroke caused by basilar artery occlusion remains unproven. Aim This study compares the safety and efficacy of endovascular treatment plus standard medical therapy versus standard medical therapy alone in acute ischemic stroke due to basilar artery occlusion. Design The study is a multicenter randomized control trial with blinded outcome assessment. A projected total 344 subjects with acute basilar arterial occlusion within 8 h of estimated occlusion time will be enrolled over three years in China. Patients will be assigned to endovascular treatment plus standard medical therapy and standard medical therapy alone group in 1:1 ratio for study centers. Study outcomes The primary outcome measure is a favorable functional outcome, defined as a modified Rankin Score of 0–3 at 90 days. The primary safety measure is mortality at 90 days. Trial registration ClinicalTrials.gov (NCT 02441556). Summary The BEST trial will provide valuable insights into the safety and efficacy of endovascular treatment for acute ischemic stroke patients with basilar artery occlusion.

Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

Background Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. Methods Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd/Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. Results The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P

Purpose: To evaluate the rate of stent malapposition, plaque prolapse, and fibrous cap rupture detected by optical coherence tomography (OCT) after carotid artery stenting (CAS) based on the presence of lipid-rich plaque, which may be associated with acute stent thrombosis. Methods: A retrospective study was conducted involving 26 consecutive patients who underwent CAS with OCT imaging acquired before stent deployment and after stent dilation. Adequate imaging quality could not be obtained in 6 patients (out-of-screen images and residual blood), which left 20 patients (mean age 63 years; 13 men) for analysis. Plaque characteristics were determined from 500 selected OCT cross sections; a lipid-rich plaque was defined by lipid present in ≥2 quadrants. Cross-sectional OCT images within the stented segment were evaluated at 1-mm intervals for the presence of malapposition, plaque prolapse, and fibrous cap rupture. The data were compared between patients with and without lipid-rich plaques. The patients were examined at 6 months to determine the degree of in-stent restenosis (ISR). Results: Patients with lipid-rich plaque demonstrated a higher rate of embedded stent struts (29.4% vs 23.7%, p

Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR=2.28, 95% CI=1.15–4.51) and rs11833579 AA genotype (OR=1.92, 95% CI=1.16–3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3–4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR=2.06, 95% CI=1.26–3.36) compared to 0–2 variants. Moreover, genotype–phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population ( P =0.003 for rs12425791 and P =0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility.