Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.

DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Imaging Characteristics and Interpretation Strategy for Renal Hyperparathyroidism: A Retrospective 4-Dimensional Computed Tomography Study.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm. METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected. RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns. CONCLUSION: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Diagnostic performance of computed tomography-digital subtraction angiography and conventional magnetic resonance imaging for evaluating the vascularity of osseous spinal tumors.

BACKGROUND AND PURPOSE: Patients with hypervascular spinal tumors may have severe blood loss during tumor resection, which increases the risks of perioperative morbidity and mortality. However, the preoperative evaluation of tumor vascularity may be challenging; moreover, the reliability of the data obtained in conventional preoperative noninvasive imaging is debatable. In this study, we compared conventional magnetic resonance imaging (MRI) and subtraction computed tomography angiography (CTA) in terms of their performance in vascularity evaluation. The catheter digital subtraction angiography (DSA) technique was used as a reference standard. METHODS: This study included 123 consecutive patients with spinal tumor who underwent subtraction CTA, catheter DSA, and subsequent surgery between October 2015 and October 2021. Data regarding qualitative and semiquantitative subtraction CTA parameters and conventional MRI signs were collected for comparison with tumor vascularity graded through catheter DSA. The diagnostic performance of qualitative CTA, quantitative CTA, and conventional MRI in assessing spinal tumor vascularity was analyzed. RESULTS: Qualitative subtraction CTA was the best noninvasive imaging modality in terms of diagnostic performance (area under the receiver operating characteristic curve [AUROC], 0.95). Quantitative CTA was relatively inferior (AUROC, 0.87). MRI results had low reliability (AUROC, 0.51 to 0.59). Intratumoral hemorrhage and prominent foraminal venous plexus were found to be the specific signs for hypervascularity (specificity 93.2%). CONCLUSIONS: Qualitative subtraction CTA offers the highest diagnostic value in evaluating spinal tumor vascularity, compared to quantitative CTA and MRI. Although conventional MRI may not be a reliable approach, certain MRI signs may have high specificity, which may be crucial for assessing spinal tumor vascularity.

Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Efficacy of preoperative embolization for metastatic spinal tumor surgery using angiographic vascularity assessment.

OBJECTIVES: Preoperative embolization (PE) for metastatic spinal tumors is a method of minimizing intraoperative blood loss during aggressive surgery. This study specified angiographic standards and investigated the influence of these and other factors on blood loss in patients with spinal metastases and various pathologies. METHODS: The cohort comprised 126 consecutive patients receiving PE from 2015 to 2021. Their clinical, surgical, and angiographic characteristics were reviewed. Standard angiographic grading was used for vascularity assessment. Degree of embolization was divided into complete (≥ 90%), near complete (67 to < 90%), and partial (< 67%). Logistic regression analysis was used to investigate factors predictive of massive blood loss (> 2500 mL). A proportional odds model was used to assess factors predictive of the degree of embolization. RESULTS: Mean intraoperative blood loss was 1676 mL. Among the patients, 62 had hypervascular tumors and 64 had nonhypervascular tumors, according to the angiographic classification. Intraoperative blood loss differed significantly with embolization degree, both overall (p < 0.001) and in the hypervascular and nonhypervascular groups (p = 0.01 and 0.03). Angiographic hypervascularity, spinal metastasis invasiveness index, and embolization degree were significant predictors of massive blood loss in univariate analysis, but only embolization degree was significant in multivariate analysis. Only the presence of the radiculomedullary artery at the target level was significant in both the univariate and multivariate analyses for embolization degree. CONCLUSIONS: In addition to pathological classification, angiographic vascularity assessment is valuable. Although complete embolization is a reasonable goal, it is challenging to achieve in cases of visible radiculomedullary artery. KEY POINTS: • Angiography has a supplementary role in vascularity assessment for spinal metastatic surgery. • Better embolization degree is associated with less intraoperative blood loss in both angiographic hypervascular and nonhypervascular groups. • Presence of radiculomedullary artery in the target level causes worse embolization outcome.

The Extent of Tumor Invasion and Therapeutic Embolization Are Associated with Recurrent Hemorrhage in Patients with External Carotid Artery Blowout Syndrome.

PURPOSE: To explore the optimal strategies of therapeutic embolization for patients with carotid blowout syndrome in the external carotid artery (ECA), who may also present with arterial tumor invasion or necrosis extending to the internal carotid artery (ICA) or common carotid artery (CCA). MATERIALS AND METHODS: The study included 110 patients with ECA blowout between 2005 and 2022. Antecedent cross-sectional imaging features were examined, including tumor size, extent of arterial invasion, and air-containing necrosis. Patients were divided into Groups 1 (n = 53, simultaneous ICA/CCA invasion + ECA therapeutic embolization), 2 (n = 18, simultaneous ICA/CCA invasion + ECA-ICA/CCA therapeutic embolization), and 3 (n = 39, no ICA/CCA invasion + ECA therapeutic embolization). Kaplan-Meier and multivariable Cox regression analyses were performed to evaluate associations of clinical, imaging, and therapeutic embolization characteristics with recurrent bleeding. RESULTS: Multivariable Cox regression revealed that Group 1 was independently associated with a higher risk of recurrent bleeding than that in Group 2 (adjusted hazard ratio, 6.3; 95% CI, 1.7‒23.4; P = .005) and Group 3 (adjusted hazard ratio, 3.8; 95% CI, 1.8‒8.3; P = .001). In the subgroup with simultaneous ICA/CCA invasion, air-containing necrosis around the ICA/CCA was independently associated with recurrent bleeding after therapeutic embolization of the ECA (adjusted hazard ratio, 5.0; 95% CI, 1.8‒13.6; P = .002). CONCLUSIONS: In patients with ECA blowout treated with therapeutic embolization, there was a lower risk of recurrent bleeding when the extents of arterial invasion and therapeutic embolization were concordant. Air-containing necrosis around the ICA/CCA was associated with recurrent bleeding, so extensive therapeutic embolization to the ICA/CCA should be evaluated in such patients.

Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment.

BACKGROUND: Long-chain ceramides are associated with the mechanisms and clinical outcomes of acute ischemic stroke (AIS). This study aimed to investigate the plasma ceramides and sphingosine-1-phosphate in AIS patients undergoing endovascular thrombectomy (EVT) and their associations with outcomes. METHODS: Plasma samples were collected from 75 AIS patients who underwent EVT before (T1), immediately after (T2), and 24 h after (T3) the procedures and 19 controls that were matched with age, sex, and co-morbidities. The levels of ceramides with different fatty acyl chain lengths and sphingosine-1-phosphate were measured by UHPLC-ESI-MS/MS. A poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months after stroke. RESULTS: The plasma levels of long-chain ceramides Cer (d18:1/16:0) at all three time points, Cer (d18:1/18:0) at T1 and T3, and Cer (d18:1/20:0) at T1 and very-long-chain ceramide Cer (d18:1/24:1) at T1 were significantly higher in AIS patients than those in the controls. In contrast, the plasma levels of sphingosine-1-phosphate in AIS patients were significantly lower than those in the controls at all three time points. Among the AIS patients, 34 (45.3%) had poor functional outcomes at 3 months poststroke. Multivariable analysis showed that higher levels of Cer (d18:1/16:0) and Cer (d18:1/18:0) at all three time points, Cer (d18:1/20:0) at T1 and T2, and Cer (d18:1/24:0) at T2 remained significantly associated with poor functional outcomes after adjustment for potential confounding factors. CONCLUSION: Plasma ceramides were elevated early in AIS patients with acute large artery occlusion. Furthermore, Cer (d18:1/16:0) and Cer (d18:1/18:0) could be early prognostic indicators for AIS patients undergoing EVT.

Effect of using G-FAST to recognize emergent large vessel occlusion: A city-wide community experience.

BACKGROUND/PURPOSE: A prehospital bypass strategy was suggested for large vessel occlusion. This study aimed to evaluate the effect of a bypass strategy using the gaze-face-arm-speech-time test (G-FAST) implemented in a metropolitan community. METHODS: Pre-notified patients with positive Cincinnati Prehospital Stroke Scale and symptom onset <3 h from July 2016 to December 2017 (pre-intervention period) and those with positive G-FAST and symptom onset <6 h from July 2019 to December 2020 (intervention period) were included. Patients aged <20 years and those with missing in-hospital data were excluded. The primary outcomes were the rates of receiving endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT). The secondary outcomes were total prehospital time, door-to-computed tomography (CT) time, door-to-needle (DTN) time, and door-to-puncture (DTP) time. RESULTS: We included 802 and 695 pre-notified patients from the pre-intervention and intervention periods, respectively. The characteristics of the patients in the two periods were similar. In the primary outcomes, pre-notified patients during the intervention period showed higher rates of receiving EVT (4.49% vs. 15.25%, p < 0.001) and IVT (15.34% vs. 21.58%, p = 0.002). In the secondary outcomes, pre-notified patients during intervention period had longer total prehospital time (mean 23.38 vs 25.23 min, p < 0.001), longer door-to-CT time (median 10 vs 11 min, p < 0.001), longer DTN time (median 53 vs 54.5 min, p < 0.001) but shorter DTP time (median 141 vs 139.5 min, p < 0.001). CONCLUSION: The prehospital bypass strategy with G-FAST showed benefits for stroke patients.

Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: Conditional survival estimates provide critical prognostic information for patients with advanced renal cell carcinoma (aRCC). Efficacy, safety, and conditional survival outcomes were assessed in CheckMate 214 (ClinicalTrials.gov identifier NCT02231749) with a minimum follow-up of 5 years. METHODS: Patients with untreated aRCC were randomized to receive nivolumab (NIVO) (3 mg/kg) plus ipilimumab (IPI) (1 mg/kg) every 3 weeks for 4 cycles, then either NIVO monotherapy or sunitinib (SUN) (50 mg) daily (four 6-week cycles). Efficacy was assessed in intent-to-treat, International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk/poor-risk, and favorable-risk populations. Conditional survival outcomes (the probability of remaining alive, progression free, or in response 2 years beyond a specified landmark) were analyzed. RESULTS: The median follow-up was 67.7 months; overall survival (median, 55.7 vs 38.4 months; hazard ratio, 0.72), progression-free survival (median, 12.3 vs 12.3 months; hazard ratio, 0.86), and objective response (39.3% vs 32.4%) benefits were maintained with NIVO+IPI versus SUN, respectively, in intent-to-treat patients (N = 550 vs 546). Point estimates for 2-year conditional overall survival beyond the 3-year landmark were higher with NIVO+IPI versus SUN (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional progression-free survival and response point estimates were also higher beyond 3 years with NIVO+IPI. Point estimates for conditional overall survival were higher or remained steady at each subsequent year of survival with NIVO+IPI in patients stratified by tumor programmed death ligand 1 expression, grade ≥3 immune-mediated adverse event experience, body mass index, and age. CONCLUSIONS: Durable clinical benefits were observed with NIVO+IPI versus SUN at 5 years, the longest phase 3 follow-up for a first-line checkpoint inhibitor-based combination in patients with aRCC. Conditional estimates indicate that most patients who remained alive or in response with NIVO+IPI at 3 years remained so at 5 years.

Long-term outcomes of moyamoya disease following indirect revascularization in middle adulthood: A prospective, quantitative study.

BACKGROUND/PURPOSE: Our previous study demonstrated that indirect revascularization is effective in the treatment of adult moyamoya patients. This prospective study aims to evaluate the long-term effectiveness of indirect revascularization in moyamoya patients in middle adulthood. METHODS: From January 2013 to June 2019, moyamoya patients more than 40 years of age underwent indirect revascularizations were studied. The hypoperfusion area of brains was revascularized. The cerebral angiography and time-to-peak (TTP) scoring (ranged 0-14) of the magnetic resonance perfusion study were used to evaluate the revascularization effect. RESULTS: During the study period, 50 consecutive adult moyamoya patients underwent indirect revascularization. Seventeen patients (27 cerebral hemispheres) more than 40 years of age were included. The mean age was 47.9 ± 6.4 years, and 13 patients were female. The pre-operative Suzuki stages were I, II, III, IV, V, and VI in 1, 1, 9, 13, 0, and 3 hemispheres, respectively. After a mean follow-up period of 52.5 ± 20.6 months, all patients had improvement or stabilization of their clinical conditions. Available post-operative angiography demonstrated Matsushima grading A in 18 of 20 hemispheres. The mean TTP score of all 27 hemispheres improved from 5.0 ± 3.3 pre-operatively to 12.0 ± 2.1 after surgery (p < 0.001). The post-operative mean TTP score of the 7 hemispheres without angiographic follow-up was 10.4 ± 1.8. One patient had persistent mild motor weakness after 56-month follow-up. Transient complications with full recovery occurred in 3 patients. CONCLUSION: Indirect revascularization is a safe method with satisfactory long-term results in moyamoya patient in middle adulthood.

Air-containing necrosis as the imaging predictor for imminent carotid blowout in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Carotid blowout syndrome (CBS) is a devastating complication of head and neck cancer (HNC). In this study, we describe radiological features that can predict imminent (<6 months) carotid blowout in patients with HNC. METHODS: Cross-sectional CT or MRI were interpreted from 25 treated HNC patients with acute CBS and 50 treated HNC patients without CBS (controls). The tumor size and the distance from the tumor to the carotid trunk was measured. The following imaging findings of the tumor were also recorded: carotid trunk involvement, enhancement pattern, and the presence of air-containing necrosis. The odds ratios of imminent CBS for each imaging finding were estimated using a multivariable logistic regression model. RESULTS: Compared to the controls, the CBS group had larger tumors (49 ± 18 mm vs. 38 ± 18 mm, p = 0.017), tumors closer to the carotid trunk (0.5 ± 1.7 mm vs. 8.2 ± 14.2 mm, p < 0.001), a higher prevalence of 360° involvement (60% vs. 18%, p < 0.001), more heterogeneous enhancement patterns (84% vs. 50% p < 0.001), and more air-containing necrosis (40% vs. 2% p < 0.001). After multivariable adjustment, the presence of air-containing necrosis remained a significant risk factor for imminent CBS (OR: 20.1, 95% CI: 1.98-204.00; p = 0.011). CONCLUSION: The presence of air-containing necrosis is associated with a higher risk of imminent CBS. This characteristic imaging finding should be evaluated in the follow-up CT or MRI of HNC patients for early warning.

Comparison of risk scores in predicting symptomatic intracerebral hemorrhage after endovascular thrombectomy.

BACKGROUND/PURPOSE: Several risk scores have been developed to predict symptomatic intracerebral hemorrhage (SICH) after acute reperfusion therapy for ischemic stroke. We compared the performance of established risk scores in predicting SICH after EVT under different SICH criteria. METHODS: A total of 258 patients with anterior circulation large vessel occlusion who received EVT in two medical centers of Taiwan were recruited. Three definitions of SICH, the European Collaborative Acute Stroke Study II (ECASS II), ECASS III, and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), were used. The HAT, SITS-SICH, SEDAN, and TAG risk scores were applied. Logistic regression and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of each risk model. RESULTS: In the 258 included patients (mean age, 71.9 ± 11.8 years; men, 48.1%), the observed rates of SICH according to ECASS II, ECASS III, and SITS-MOST criteria were 10.1%, 5.0%, and 4.7%, respectively. Higher glucose level (>160 mg/dL) and unsuccessful recanalization independently predicted SICH under all criteria. Among the different risk scores, only SEDAN and TAG consistently predicted SICH. SEDAN and TAG scores exhibited the highest AUC in predicting SICH for ECASS III (SEDAN 0.72, TAG 0.72) and SITS-MOST (SEDAN 0.73, TAG 0.70) criteria. CONCLUSION: Among various risk scores, the TAG and SEDAN scores best predict SICH after EVT. Higher glucose level and unsuccessful recanalization, which are included in the TAG and SEDAN scores, are independent risk factors of SICH in the present cohort, highlighting their detrimental effects.

Expanding resources of endovascular thrombectomy: An optimization model.

BACKGROUND/PURPOSE: Recently optimized models for selecting the locations of hospitals capable of providing endovascular thrombectomy (EVT) did not consider the accuracy of the prehospital stroke scale assessment and possibility of secondary transport. Our study aimed to propose a new model for selecting existing hospitals with intravenous thrombolysis capability to become EVT-capable hospitals. METHODS: A sequential order was provided to upgrade hospitals providing intravenous thrombolysis, using a mixed integer programming model based on current medical resource allocation. In addition, we drafted a centralized plan to redistribute existing EVT resources by redetermining locations of EVT-capable hospitals. Using historical data of 7679 on-scene patients with suspected stroke, the model was implemented to determine the hospital that maximizes the number of patients receiving EVT treatment within call-to-definitive-treatment time. RESULTS: All suspected stroke patients were sent to EVT-capable hospitals directly under the current medical resource allocation model. After upgrading one additional hospital to become an EVT-capable hospital, the percentage of patients receiving definitive treatment within the standard call-to-definitive-treatment time was elevated from 68.82% to 72.97%. In the model, assuming that there is no hospital providing EVT, all patients suspected of stroke will be sent to EVT-capable hospitals directly after upgrading three or more hospitals to be able to provide treatment. CONCLUSION: All patients eligible for acute stroke treatment are sent to EVT-capable hospitals in the simulation under the current medical resource allocation model. This model can be utilized to provide insights for capacity redistribution in other regions.

Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy.

BACKGROUND: Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT. METHODS: We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3-6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage). RESULTS: Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03-4.08), T2 (OR, 2.08; 95% CI, 1.05-4.01), and T3 (OR, 3.94; 95% CI, 1.44-10.79) were independent predictors of death or disability at 90 days. CONCLUSION: Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.

Angiographic early hyperemia in the middle cerebral artery territory after thrombectomy is associated with favorable clinical outcome in anterior circulation stroke.

OBJECTIVES: Angiographic cortical early hyperemia (EH) is frequently observed after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke. The aim of the study is to investigate the relationship between EH and clinical outcomes. METHODS: Between January 2015 and September 2018, consecutive patients who underwent EVT for anterior circulation LVO stroke with optimal recanalization (modified thrombolysis in cerebral infarction 2b or 3) were included. Angiographic studies after immediate reperfusion were used for analysis for cortical EH sign. Clinical functional outcomes were evaluated with the modified Rankin Scale (mRS) at 90 days. Safety outcomes, including mortality and intracerebral hemorrhage, were assessed. The association of EH between clinical functional and safety outcomes was analyzed. RESULTS: A total of 143 patients were analyzed (mean age: 71 years; median National Institutes of Health Stroke Scale score: 18). A positive EH sign was observed in 88 (62%) patients. Good functional outcome at 90 days was significantly different between the EH+ and EH- groups (p = .0157). Intracerebral hemorrhage and mortality did not differ between groups. In multivariate logistic regression analysis, EH was an independent predictor for good clinical outcome (mRS ≤ 2, odds ratio: 3.49, p = .0034) in addition to young age. CONCLUSION: Results revealed that the presence of EH is associated with better clinical outcome at 90 days, but not associated with increased hemorrhagic complication. These findings with clinically relevant implications require further validation. KEY POINTS: • Angiographic cortical hyperemia is a common finding immediately after endovascular thrombectomy. • Presence of cortical hyperemia is an independent prognostic factor for good clinical outcome. • Hemorrhagic complication is not associated with cortical hyperemia.

External validation of prehospital stroke scales for emergent large vessel occlusion.

BACKGROUND: It is suggested that a prehospital scale should be utilized to identify patients with emergent large vessel occlusion (ELVO). We aimed to perform external validation of nine ELVO scales. METHODS: This single center retrospective observational study included patients with ischemic stroke visiting the emergency department (ED) within 6 h of symptom onset. Participants were excluded if individual items of the National Institute of Health Stroke Scale scores were not recorded or they did not receive brain computed tomography angiography or magnetic resonance imaging before intravenous thrombolysis or endovascular thrombectomy, and within 24 h of ED admission. The first definition of ELVO was emergent occlusion of the internal carotid artery (ICA) and middle cerebral artery segment 1 (M1). The second definition was emergent occlusion of ICA, M1, basilar artery, middle cerebral artery segment 2, anterior cerebral artery segment 1, and posterior cerebral artery segment 1. Area under the receiver operating characteristic curve (AUROC) was constructed to examine discrimination. The sensitivity, specificity, positive predictive value, and negative predictive value of the nine scales under the two ELVO definitions were calculated. RESULTS: A total of 1231 patients were included in the study. No significant differences were observed in the AUROC under the two ELVO definitions. However, sensitivity values of these scales were largely different, ranging from 44.56% to 93.68% under the first ELVO definition. The sensitivity values among scales were also different under the second ELVO definition. CONCLUSION: Stakeholders in the community should choose suitable scales according to their own system conditions.

Safety and efficacy of the transbrachial approach for endovascular thrombectomy in patients with acute large vessel occlusion stroke.

BACKGROUND: The transbrachial approach (TBA) is an alternative method to the transfemoral approach (TFA). We herein aimed to evaluate the safety and efficacy of the TBA for endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke. METHODS: We reviewed the records of 297 patients who had undergone EVT from January 2015 to July 2019. Eighteen patients who had undergone 19 procedures were included. Indications for arterial access, devices, recanalization rates, complication rates, and clinical outcomes were evaluated. RESULTS: There were 15 and 4 cases of anterior and posterior circulation stroke, respectively. The mean patient age was 80.1 years. Eight patients were male. The median National Institutes of Health Stroke Scale score was 18. The total procedure duration tended to be longer when the TBA was used after failure of the TFA (n = 6, 32%, median: 60.5 min) than when the TBA was used as the first treatment approach (n = 13, 68%, median: 22 min). Optimal recanalization (a modified Thrombolysis in Cerebral Infarction score of 2b or 3) was achieved for 15 procedures. Local complications were observed in two cases: one with brachial artery pseudoaneurysm and another with brachial artery occlusion. Three patients with anterior circulation stroke exhibited good clinical outcomes (modified Rankin score ≤ 2) at 90 days. Symptomatic intracranial hemorrhage occurred in one patient. Mortality was noted in four patients. CONCLUSION: The TBA for EVT is a suitable alternative when adoption of the TFA is difficult or impossible.

Early recurrence of ischemic stroke in patients receiving endovascular thrombectomy.

BACKGROUND/PURPOSE: Endovascular thrombectomy (EVT) is effective in treating acute ischemic stroke associated with large vessel occlusion. Early recurrence of ischemic stroke (ERIS) after EVT, however, is a devastating event and could worsen the condition of patient. Current study aimed to investigate the prevalence and risk factors of ERIS after EVT. METHODS: The medical records of all patients receiving EVT at a single medical center were reviewed and analyzed. ERIS was defined as presentation of newly developed neurological deficits in previously recanalized vascular territory or another vascular territory that was not initially involved within 30 days of the index stroke. RESULTS: From January 2015 to September 2018, a total of 200 patients (71.6 ± 12.3 years, male 49%) had received EVT and 17 patients (8.5%) developed ERIS. Presence of valvular heart disease was the only clinical factor associated with ERIS (OR: 4.26, 95% CI: 1.16-17.7). Patients with ERIS had significantly worse modified Rankin scale at 3 months (common OR: 3.11, 95% CI: 1.18-8.73) and were independently associated with mortality (OR: 7.73, 95% CI: 2.00-30.6). Ten of 17 patients with ERIS had received repeated EVT and all achieved good recanalization without procedure-related complications or symptomatic intracerebral hemorrhage. CONCLUSION: ERIS in patients receiving EVT was not rare, especially in those with valvular heart disease, and was associated with worse outcome. Nevertheless, they could be safely treated by repeated EVT.

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

BACKGROUND AND PURPOSE: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. METHODS: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. RESULTS: One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P<0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02-1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P<0.001). CONCLUSIONS: In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.