A nomogram for predicting thrombus composition in stroke patients with large vessel occlusion: combination of thrombus density and perviousness with clinical features.

PURPOSE: To establish a nomogram incorporating pretreatment imaging parameters and clinical characteristics for predicting the thrombus composition of acute ischemic stroke (AIS) with large vessel occlusion (LVO). METHODS: We retrospectively enrolled patients with occlusion of the Middle Cerebral Artery (MCA) who underwent Mechanical Thrombectomy (MT). Retrieved thrombi were stained with Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB). Thrombi are assigned to the Fibrin-rich or RBC-rich group based on the relative fractions of Red Blood Cells (RBC), fibrin, and platelet. The independent risk factors for Fibrin-rich clots were determined via univariate and multivariate logistic regression analysis and were then integrated to establish a nomogram. RESULTS: In total, 98 patients were included in this study. Patients with fibrin-rich clots had worse functional outcome [modified Rankin scale (mRS) 0-2, 34.7% vs 63.2%, p = 0.005], longer procedure time (76.8 min vs 50.8 min, p = 0.001), and increased maneuvers of MT (1.84 vs 1.46, p = 0.703) than those with RBC-rich clots. The independent risk factors for Fibrin-rich clots were lower perviousness measured by Non-Contrast Computer Tomography (NCCT) and CT Angiography (CTA), lower thrombus relative attenuation on NCCT, elevated Platelet-WBC ratio (PWR) of admission peripheral blood, and previous antithrombotic medication. The nomogram showed good discrimination with an area under the Receiver Operating Characteristic (ROC) curve (AUC) of 0.852 (95% CI: 0.778-0.926). The calibration curve and decision curve analysis also displayed satisfactory accuracy and clinical utility. CONCLUSION: This study has developed and internally validated an easy-to-use nomogram which can help predict clot composition and optimize therapeutic strategies for thrombectomy.

Incremental value of Alberta Stroke Program Early CT Score to collateral score for predicting target mismatch in stroke patients with extended time window or unknown onset time.

PURPOSE: To evaluate whether Alberta Stroke Program Early CT Score (ASPECTS) could provide incremental value to collateral score, and their integration could be an effective surrogate of CTP in predicting target mismatch. MATERIAL AND METHODS: One hundred and fifty-nine stroke patients (onset time 6-16 h or with unknown onset time) with MCA and/or ICA occlusion underwent non-contrast computed tomography (NCCT) and CT perfusion (CTP) scan for initial assessment. Simulated single-phase CT angiography (sCTA, peak arterial phase) and multiphase CTA (mCTA) were reconstructed from CTP. ASPECTS was assessed on NCCT and sCTA. Collateral score was evaluated on mCTA. Target mismatch was defined as infarct core volume < 70 mL, the mismatch ratio ≥ 1.8, and the absolute mismatch volume ≥ 15 mL. Pearson correlation analysis, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve analyses were performed. RESULTS: Median CTA source image (CTA-SI) ASPECTS was significantly lower than NCCT ASPECTS (p = 0.001). NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score correlated significantly with infarct core volume and mismatch ratio (all p < 0.05). Mismatch group showed significantly higher NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score than non-mismatch group (all p < 0.001). NCCT ASPECTS and CTA-SI ASPECTS showed comparable predicting performance with mCTA collateral score (p > 0.05). Adding CTA-SI ASPECTS to mCTA collateral score improved the performance of mCTA in predicting target mismatch (area under curve, 0.905 vs. 0.804, p = 0.003). CONCLUSION: ASPECTS can provide incremental information to collateral score in predicting target mismatch. If CTP scan fails, clinical decision based on ASPECTS and collateral score might be reasonable.

Comparison of time consumption and success rate between CT angiography- and CT perfusion- based imaging assessment strategy for the patients with acute ischemic stroke.

BACKGROUND: Our study aimed to compare the time consumption and success rate between CTA- and CTP- based assessment strategy, and to clarify the risk factors associated with the CTP scan failure. METHODS: Clinical and radiological data of 437 consecutive AIS patients who underwent multiphase CTA or CTP for pre-treatment evaluation were retrospectively enrolled (CTA group, n = 302; CTP group, n = 135). Time consumption and success rate of CTA- and CTP- based assessment strategy were compared using Mann-Whitney U test and Chi-Squared Test. Univariate analysis and receiver operating curve analysis were used to clarify the risk factors, and their performance in predicting the CTP scan failure. RESULTS: Time consumption of CTP scan and reconstruction was significantly longer than that of CTA [775 s vs 263.5 s, P < 0.001]. CTP scan showed significantly higher failure rate than CTA (11% vs 1%, P < 0.001). Severe motion was the most common cause of CTP failure (n = 12, 80%). Baseline National Institute of Health Stroke Scale (NIHSS) score in CTP failure group was significantly higher than that in CTP success group [17 vs 13, P = 0.007]. Baseline NIHSS score of 11 was the optimal threshold value to predict CTP failure with an area under the curve of 0.715, a sensitivity of 86.7%, and a specificity of 45.0%. CONCLUSIONS: CTP- based strategy showed longer time consumption and higher failure rate than CTA- based strategy. High baseline NIHSS score was significantly associated with CTP scan failure in AIS patients.

Cerebral blood volume Alberta Stroke Program Early Computed Tomography Score predicts intracranial hemorrhage after thrombectomy in patients with acute ischemic stroke in an extended time window.

BACKGROUND: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). PURPOSE: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. MATERIAL AND METHODS: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. RESULTS: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score (P<0.001 and P<0.001, respectively), more passes of retriever (P = 0.007 and P = 0.019, respectively), low NCCT-ASPECTS (P = 0.013 and P = 0.034, respectively), and low CBV-ASPECTS (P < 0.001 and P < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P < 0.001), respectively. CONCLUSION: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

Hyperperfusion on Arterial Spin Labeling MRI Predicts the 90-Day Functional Outcome After Mechanical Thrombectomy in Ischemic Stroke.

BACKGROUND: The prognostic significance of hyperperfusion after reperfusion therapy in patients with acute ischemic stroke (AIS) remains controversial. PURPOSE: To investigate the clinical factors associated with hyperperfusion, and the 90-day prognostic value of hyperperfusion after mechanical thrombectomy in AIS patients. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Fifty-four AIS patients who underwent mechanical thrombectomy. FIELD STRENGTH/SEQUENCE: Time-of-flight MR angiography, pulsed arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and susceptibility-weighted imaging were performed at 3.0T within 1 week after thrombectomy. ASSESSMENT: Clinical factors including demographics, risk factors, stroke and treatment characteristics were collected and assessed. Hyperperfusion on ASL was defined as a focal increased cerebral blood flow on the affected side ≥130% of its mirror counterpart. Good clinical outcome at 90 days was defined as modified Rankin Scale score of 0-2. STATISTICAL TESTS: The interrater agreement was assessed using Cohen's kappa or the intraclass correlation coefficient. The relationship between hyperperfusion and clinical factors were analyzed by appropriate univariate statistics. Predictors of 90-day functional outcome were assessed by univariate analyses followed by multivariate logistic regression analysis and receiver-operating-characteristic curves. RESULTS: Thirty-six (66.7%) patients developed hyperperfusion on ASL after thrombectomy. Hyperperfusion was significantly correlated with successful recanalization (P < 0.05) and improvement of National Institutes of Health Stroke Scale scores at 24 hours (NIHSS24h ) (P < 0.05). A higher incidence of hemorrhage transformation was observed in patients with hyperperfusion than those without (63.9% vs. 50.0%), but no significant difference was found (P = 0.327). NIHSS24h (odds ratio [OR], 0.75, [95% confidence interval [CI] 0.62-0.91], P < 0.05), lesion volume on diffusion-weighted imaging (OR, 0.97, [95% CI 0.95-1.00], P < 0.05), and hyperperfusion on ASL (OR, 9.8, [95% CI 1.7-55.3], P < 0.05) were independent variables for predicting good functional outcomes. DATA CONCLUSION: Hyperperfusion on ASL correlated with successful recanalization and may be an independent prognostic marker for good neurological outcomes at 90 days in AIS patients after mechanical thrombectomy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Comparison of CT angiography collaterals for predicting target perfusion profile and clinical outcome in patients with acute ischemic stroke.

OBJECTIVES: To compare collateral status on single-phase CT angiography (sCTA) and multiphase CT angiography (mCTA) and their ability to predict a target mismatch on CT perfusion (CTP) and clinical outcome in patients with acute ischemic stroke (AIS). METHODS: Seventy-three AIS patients with stroke onset between 5 and 15 h or with unclear onset time and occlusions in the M1/M2 segment of the middle cerebral artery and/or intracranial internal carotid artery underwent head non-contrast CT and CTP. Simulated sCTA and mCTA were reconstructed from CTP data and were compared for collaterals assessment. The ability to predict target mismatch on CTP (an ischemic core < 70 ml, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 ml) and 90-day modified Rankin Scale (mRS) score of 0-2 was compared between sCTA and mCTA by using receiver operating curve analysis. RESULTS: sCTA underestimated the collateral status when compared with mCTA (p < 0.01). The ability of mCTA to predict target mismatch (AUC = 0.902, 95% confidence interval [CI] 0.809, 0.959) and clinical outcome (AUC = 0.771; 95% CI, 0.655, 0.864) was better than that of sCTA (p < 0.05 overall). A mCTA collateral score of > 3 best identified the target mismatch (sensitivity, 78.4%; specificity, 90.9%) and predicted 90-day mRS score of 0-2 (sensitivity, 84.8%; specificity, 69.4%). CONCLUSIONS: The collaterals were better estimated by mCTA compared with sCTA. A mCTA collateral score of > 3 optimized the prediction of a target mismatch on CTP and a good clinical outcome in patients with AIS. KEY POINTS: • Collateral circulation is a key determinant of ischemic core and penumbra. Better collaterals are associated with smaller ischemic core volumes and larger mismatch ratios on CT perfusion. • The collaterals can be better estimated by multiphase CTA compared with single-phase CTA. • A collateral score of > 3 on multiphase CTA best identifies patients with target mismatch on CT perfusion and predicts 90-day mRS score of 0-2.

IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation.

Liver fibrosis is a severe, life-threatening clinical condition resulting from nonresolving hepatitis of different origins. IL-17A is critical in inflammation, but its relation to liver fibrosis remains elusive. We find increased IL-17A expression in fibrotic livers from HBV-infected patients undergoing partial hepatectomy because of cirrhosis-related early-stage hepatocellular carcinoma in comparison with control nonfibrotic livers from uninfected patients with hepatic hemangioma. In fibrotic livers, IL-17A immunoreactivity localizes to the inflammatory infiltrate. In experimental carbon tetrachloride-induced liver fibrosis of IL-17RA-deficient mice, we observe reduced neutrophil influx, proinflammatory cytokines, hepatocellular necrosis, inflammation, and fibrosis as compared with control C57BL/6 mice. IL-17A is produced by neutrophils and T lymphocytes expressing the Th17 lineage-specific transcription factor Retinoic acid receptor-related orphan receptor γt. Furthermore, hepatic stellate cells (HSCs) isolated from naive C57BL/6 mice respond to IL-17A with increased IL-6, α-smooth muscle actin, collagen, and TGF-ß mRNA expression, suggesting an IL-17A-driven fibrotic process. Pharmacologic ERK1/2 or p38 inhibition significantly attenuated IL-17A-induced HSC activation and collagen expression. In conclusion, IL-17A(+) Retinoic acid receptor-related orphan receptor γt(+) neutrophils and T cells are recruited into the injured liver driving a chronic, fibrotic hepatitis. IL-17A-dependent HSC activation may be critical for liver fibrosis. Thus, blockade of IL-17A could potentially benefit patients with chronic hepatitis and liver fibrosis.

Acute Vertebrobasilar Artery Occlusion with Underlying Atherosclerosis: Balloon Angioplasty Combined with Tirofiban as Initial Salvage Therapy.

OBJECTIVE: The optimal rescue endovascular treatment for patients with intracranial atherosclerotic stenosis in acute vertebrobasilar artery occlusion is not well established. We investigated the safety and efficacy of balloon angioplasty combined with tirofiban as the initial rescue strategy in these patients. METHODS: We retrospectively analyzed the records of 41 patients admitted between January 2014 and September 2022, with vertebrobasilar artery atherosclerotic occlusion. Balloon angioplasty in combination with tirofiban was used as the first-line salvage therapy after the failure of mechanical thrombectomy. The technical success rate, recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed. RESULTS: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 38 of the 41 patients (92.7%). Acute stents were deployed in 5 patients who did not achieve successful reperfusion after balloon angioplasty. Six patients (14.6%, 6/41) underwent stent angioplasty in the stable stage for severe residual stenosis detected on follow-up imaging. There was no procedure-related complication. Hemorrhagic transformation was detected on follow-up imaging in 11 patients (26.8%), while no symptomatic intracranial hemorrhage was recorded. Good functional outcome rate was 31.7% (13/41). CONCLUSIONS: Balloon angioplasty combined with intravenous tirofiban administration is a safe and effective salvage therapy in patients with acute atherosclerotic occlusion of the vertebrobasilar artery.

Management of posterior circulation tandem occlusions in acute ischemic stroke: Recanalize the dominant vertebral artery with priority.

PURPOSE: To illustrate the characteristics of acute ostial vertebral artery (VA) and basilar artery (BA) tandem occlusions. The endovascular treatment strategy for ostial VA-BA tandem occlusion was reported. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with ostial VA-BA tandem occlusion who underwent endovascular treatment in our center between November 2018 and February 2022. We preferred to recanalize the dominant vertebral artery with priority. The imaging characteristics, treatment strategy, clinical outcomes, and complications were analyzed. RESULTS: In total, 9 patients with ostial VA-BA tandem occlusion were enrolled in this study. All the VA-BA tandem occlusion was caused by acute occlusion of the dominant VA. Endovascular revascularization was performed through the occluded dominant VA in 8 patients and was performed through contralateral non-dominant VA in 1 patient. Successful recanalization (mTICI 2b/3 grade) was achieved in all 9 patients, and 5 patients (55.5%) achieved functional independence with a mRS score of 0-2 at 90 days. CONCLUSIONS: In this case series, the occurrence of ostial VA-BA tandem occlusions was mainly caused by acute occlusion of the dominant VA. Endovascular revascularization of ostial VA-BA tandem occlusions through occluded dominant VA was feasible and recommended.

Stroke health management: Novel strategies for the prevention of recurrent ischemic stroke.

Objectives: The aim of the study was to assess the effect of the stroke health management model on the prognosis and recurrence of mild to moderate ischemic stroke, guided by the stroke health manager based on the patients' needs. In addition, up-to-date evidence of healthcare resource allocation, planning, and optimization is provided. Methods: The current research was a retrospective, observational, single-center, history-controlled study with patients divided into two groups, namely, the intervention group and the control group, following the guidance of the stroke health manager. The control group patients received standard medical care during hospitalization, which consisted of advice on healthy lifestyle choices carried out by the bed nurse, but no structured education, WeChat group, or clinical consultation was included. The intervention group patients, in addition to the standard medical care, received health management and health education from the stroke health manager, and after hospital discharge, the patients were followed up over the telephone by the health manager to see if there was any recurrence or readmission. Results: From 1 January 2018 to 31 December 2020, 382 patients with acute ischemic stroke were enrolled in this study. Through the univariate regression analysis, we found that SHM intervention was associated with a significantly lower risk of recurrence (HR = 0.459). We constructed a nomogram based on the significant variables from the regression analysis and also analyzed the association between the control group and the SHM intervention group among all subgroups using the Cox proportional hazards model to assess the effect of the stroke health management model. Most patients in this study had a total risk point between 170 and 270. The C-index value was 0.76, and the time-dependent AUC for predicting recurrence was >0.7. Conclusion: The stroke health manager-guided management model based on patients' needs can better control the risk factors of stroke and significantly reduce the recurrence rate of mild to moderate ischemic stroke within 1 year.

Time Window for Ischemic Stroke First Mobilization Effectiveness: Protocol for an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial.

OBJECTIVE: The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke. METHODS: The TIME Trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. IMPACT: The TIME Trial is designed to answer the question "when is the best time to start mobilization after stroke?" The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME Trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke.

Prognostic value of elevated high-sensitivity cardiac troponin T levels in patients with acute ischemic stroke treated with endovascular thrombectomy.

Our objective was to assess the impact of hs-cTnT elevation on functional outcome and mortality in AIS patients with large vessel occlusion (LVO) in the anterior circulation 3 months after ET and explore factors affecting hs-cTnT elevation. A total of 143 consecutive AIS patients with large vessel occlusion (LVO) in the anterior circulation following ET in a single stroke center were enrolled between January 2015 and November 2017. Hs-cTnT was quantitated on admission. Demographic characteristics, clinical data, functional outcome and all-cause mortality were compared between patients with elevated hs-cTnT levels (>14 ng/L) and those with normal hs-cTnT levels (≤14 ng/L). 58/143(40.6%) patients showed elevated hs-cTnT levels before ET. Factors independently associated with hs-cTnT elevation were admission NIHSS score (OR = 1.08, 95% CI 1.01-1.16, p = 0.032), coronary heart disease (OR = 4.89, 95% CI 1.82-13.11, p = 0.002) and congestive heart failure (OR = 4.10, 95% CI 1.07-15.68, p = 0.039). In the univariate analysis, patients with elevated hs-cTnT levels were at significantly higher risk of 3-month poor outcome (p = 0.029) and mortality (p < 0.001) than those with normal hs-cTnT levels. After multivariable analysis, hs-cTnT elevation remained an independent predictor of 3-month mortality (OR = 4.49, 95% CI 1.68-11.98, p = 0.003). In this cohort of AIS patients with LVO in the anterior circulation undergoing ET, hs-cTnT elevation is an independent predictor of 3-month mortality. Admission NIHSS score, coronary heart disease and congestive heart failure are independently associated with elevated hs-cTnT levels.

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells.

Liver fibrosis is a consequence of chronic liver disease, causing morbidity and mortality. Interleukin-33 (IL-33) is a critical mediator of inflammation, which may be involved in the development of liver fibrosis. Here, we investigated the role of IL-33 in human patients and experimental bile-duct ligation (BDL)-induced fibrosis in mice. We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis. Liver injury, inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor, and the activation of hepatic stellate cells (HSCs) was decreased in ST2-deficient mice. Recombinant IL-33 activated HSCs isolated from C57BL/6 mice, leading to the expression of IL-6, TGF-ß, α-SMA and collagen, which was abrogated in the absence of ST2 or by pharmacological inhibition of MAPK signaling. Finally, administration of recombinant IL-33 significantly increased hepatic inflammation in sham-operated BL6 mice but did not enhance BDL-induced hepatic inflammation and fibrosis. In conclusion, BDL-induced liver inflammation and fibrosis are dependent on ST2 signaling in HSCs, and therefore, the IL-33/ST2 pathway may be a potential therapeutic target in human patients with chronic hepatitis and liver fibrosis.