ABSTRACT
Niemann-Pick disease Type C (NPC) is a neurodegenerative disease mainly caused by the mutation in NPC1 gene, leading to massive accumulation of unesterified cholesterol in the late endosome/lysosome of cells. Impaired phenotype of microglia is a hallmark in Npc1 mutant mice (Npc1-/- mice). However, the mechanism of Npc1 in regulating microglial function is still unclear. Here, we showed that the reactive microglia in the neonatal Npc1-/- mice indicated by the increased lysosome protein CD68 and phagocytic activity were associated with disrupted TREM2-mTOR signaling in microglia. Furthermore, in Npc1-deficient BV2 cells, genetic deletion of Trem2 partially restored microglial function, probably via restored mTOR signaling. Taken together, our findings indicated that loss of Npc1 in microglia caused changes of their morphologies and the impairment of lysosomal function, which were linked to the TREM2-mTOR signaling pathway.
ABSTRACT
OBJECTIVES: A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. METHODS: We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. RESULTS: We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90-day (OR 1.132 95% CI 0.367-3.487 p = 0.829; OR 1.070 95% CI 0.375-3.047 p = 0.900) or 1-year follow-up (OR 1.217 95% CI 0.407-3.637 p = 0.725; OR 1.068 95% CI 0.359-3.173 p = 0.906). INTERPRETATION: Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.
Subject(s)
Endovascular Procedures , Registries , Thrombectomy , Humans , Male , Female , Aged , Middle Aged , Retrospective Studies , Vertebrobasilar Insufficiency/surgery , Thrombolytic Therapy , Aged, 80 and over , Cerebral Infarction/therapy , Outcome Assessment, Health Care , Prognosis , ReperfusionABSTRACT
Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (â¢OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant â¢OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.
Subject(s)
Ferroptosis , Hyaluronic Acid , Magnesium Oxide , Nanocomposites , Palladium , Photothermal Therapy , Tumor Microenvironment , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Ferroptosis/drug effects , Tumor Microenvironment/drug effects , Magnesium Oxide/chemistry , Magnesium Oxide/pharmacology , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Photothermal Therapy/methods , Animals , Humans , Palladium/chemistry , Palladium/pharmacology , Palladium/therapeutic use , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Hydrogen PeroxideABSTRACT
BACKGROUND: Current studies on the impact of sex in the prognosis of childhood arterial ischemic stroke (AIS) are limited. We aimed to explore the sex differences in outcomes in patients with childhood AIS. METHODS: A retrospective analysis was conducted using the prospective data from the Chinese Pediatric Ischemic Stroke Registry. Baseline characteristics between sexes were compared in the total population cohort, propensity score (PS)-matched cohort, and inverse probability of treatment weighting cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was applied to further analyze the improvement in pediatric modified Rankin Scale (mRS) scores between sexes from 90 days to one year. Survival analysis was used to estimate the recurrence rates during the follow-up period. RESULTS: A total of 468 patients were finally included. Multivariate logistic regression showed that there were no significant differences between females and males in achieving favorable outcome (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.63 to 1.72), functional independence (OR 0.98, 95% CI 0.59 to 1.63), or shift to worse pediatric mRS scores (OR 0.83, 95% CI 0.59 to 1.17) at 90-day. Mixed-effects regression and survival analysis indicated that females and males exhibited comparable functional recovery from 90 days to one year and had similar recurrent risk during the follow-up period. CONCLUSIONS: This nationally-representative observational study indicated that both male and female pediatric patients with AIS exhibited comparable similar clinical outcomes at 90 days, as well as similar improvements and risks of recurrence during the follow-up period.
Subject(s)
Ischemic Stroke , Registries , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , China/epidemiology , East Asian People , Ischemic Stroke/epidemiology , Prognosis , Retrospective Studies , Sex FactorsABSTRACT
BACKGROUND AND PURPOSE: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics. METHODS: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining. RESULTS: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033). CONCLUSION: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.
ABSTRACT
This study aimed to explore the topographic features of thalamic subregions, functional connectomes and hierarchical organizations between thalamus and cortex in poststroke fatigue patients. We consecutively recruited 121 acute ischemic stroke patients (mean age: 59 years) and 46 healthy controls matched for age, sex, and educational level. The mean age was 59 years (range 19-80) and 38% of acute stroke patients were females. Resting-state functional and structural magnetic resonance imaging were conducted on all participants. The fatigue symptoms were measured using the Fatigue Severity Scale. The thalamic functional subdivisions corresponding to the canonical functional network were defined using the winner-take-all parcellation method. Thalamic functional gradients were derived using the diffusion embedding analysis. The results suggested abnormal functional connectivity of thalamic subregions primarily located in the temporal lobe, posterior cingulate gyrus, parietal lobe, and precuneus. The thalamus showed a gradual increase from the medial to the lateral in all groups, but the right thalamus shifted more laterally in poststroke fatigue patients than in non- poststroke fatigue patients. Poststroke fatigue patients also had higher gradient scores in the somatomotor network and the right medial prefrontal and premotor thalamic regions, but lower values in the right lateral prefrontal thalamus. The findings suggested that poststroke fatigue patients had altered functional connectivity and thalamocortical hierarchical organizations, providing new insights into the neural mechanisms of the thalamus.
Subject(s)
Connectome , Ischemic Stroke , Stroke , Female , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Connectome/methods , Ischemic Stroke/pathology , Thalamus/pathology , Magnetic Resonance Imaging/methods , Stroke/complications , Stroke/diagnostic imaging , Stroke/pathology , Fatigue/diagnostic imaging , Fatigue/etiologyABSTRACT
INTRODUCTION: The role of serum uric acid (UA) levels in the functional recovery of ischemic stroke remains uncertain. To evaluate whether UA could predict clinical outcomes in patients with ischemic stroke. PATIENTS AND METHODS: A three-stage study design was employed, combining a large-scale prospective cohort study, a meta-analysis and a Mendelian randomization (MR) analysis. Firstly, we conducted a cohort study using data from the Nanjing Stroke Registry Program (NSRP) to assess the association between UA levels and 3-month functional outcomes in ischemic stroke patients. Secondly, the meta-analysis was conducted to integrate currently available cohort evidence. Lastly, MR analysis was utilized to explore whether genetically determined UA had a causal link to the functional outcomes of ischemic stroke using summary data from the CKDGen and GISCOME datasets. RESULTS: In the first stage, the cohort study included 5631 patients and found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke. In the second stage, the meta-analysis, including 10 studies with 14,657 patients, also showed no significant association between UA levels and stroke prognosis. Finally, in the third stage, MR analysis using data from 6165 patients in the GISCOME study revealed no evidence of a causal relationship between genetically determined UA and stroke functional outcomes. DISCUSSION AND CONCLUSION: Our comprehensive triangulation approach found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke.
Subject(s)
Ischemic Stroke , Stroke , Humans , Uric Acid , Ischemic Stroke/genetics , Cohort Studies , Prospective Studies , Mendelian Randomization Analysis , Prognosis , Stroke/epidemiologyABSTRACT
BACKGROUND: Neurological recovery after endovascular treatment (EVT) for large vessel occlusion stroke often has diverse timelines. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence (DFI) and highly delayed functional independence (HDFI), in patients who do not improve early is essential for prognostication and rehabilitation. We aimed to analyze the prevalence and predictors of DFI and HDFI after EVT in acute vertebrobasilar artery occlusions (VBAO). METHODS: Patients with VBAO who received EVT in China were retrospectively enrolled. Early functional independence (EFI) was defined as a modified Rankin Scale (mRS) score of 0-2 at discharge. The incidence and predictors of DFI (mRS score 0-2 at 90 days in non-EFI patients) and HDFI (mRS score 0-2 at 1 year in non-DFI patients) were analyzed. RESULTS: 2422 patients met the study criteria. EFI was observed in 20% (483) of patients. Among non-EFI patients, DFI was observed in 21% (395/1880). HDFI was observed in 13% (191/1439) of non-DFI patients. Younger age (P=0.006), lower pre-EVT National Institutes of Health Stroke Scale (NIHSS) score (P<0.001), higher posterior circulation-Alberta Stroke Program Early CT Score (PC-ASPECTS) (P=0.012), and absence of symptomatic intracranial hemorrhage (sICH) (P<0.001) were predictors of DFI. Predictors of HDFI were younger age (P<0.001) and lower pre-EVT NIHSS score (P<0.001). CONCLUSION: A considerable proportion of patients have DFI and HDFI. The independent predictors of DFI were younger age, lower pre-EVT NIHSS score, higher PC-ASPECTS, and absence of sICH. Predictors of HDFI included younger age and lower pre-EVT NIHSS score.
ABSTRACT
BACKGROUND AND PURPOSE: The purpose of the present study was to evaluate the agreement on pc-ASPECTS (posterior circulation Acute Stroke Prognosis Early Computed Tomography Scores) based on non-contrast CT (NCCT) and CT angiography (CTA) source images in patients with acute basilar artery occlusion (BAO). METHODS: We prospectively enrolled consecutive patients with acute BAO from January 2022 to August 2022 at The First Affiliated Hospital of University of Science and Technology of China. The NCCT and CTA were scored independently by 15 raters during 2 different reading sessions at least 3 weeks apart. The pc-ASPECTS based on NCCT and CTA were analyzed on the full scale or were dichotomized (0-6 versus 7-10, 0-7 versus 8-10 and 0-8 versus 9-10). The level of agreement was measured using Fleiss κ Statistics. RESULTS: The median (IQR) CT-based pc-ASPECTS was 8 (6.75-9). The interrater agreement for CT-based pc-ASPECTS (κ=0.133 [0.132-0.133]) and CTA-based pc-ASPECTS (κ=0.204 [0.203-0.204]) was slight for all raters. Dichotomizations obtaining the highest concordance for the CT-based pc-ASPECTS (0-6 versus 7-10) and the CTA-based pc-ASPECTS (0-8 versus 9-10) failed to increase the interrater agreement to a substantial level (κ=0.350 [0.348-0.351] and 0.396 [0.395-0.398], respectively). Intrarater agreement for global CT-based pc-ASPECTS was less than substantial for the 14/15 raters and reached the level of substantial for the 3/15 raters with dichotomization. CONCLUSIONS: Agreement between clinicians assessing CT-based and CTA-based pc-ASPECTS cannot be sufficient to make reproducible clinical decisions and assessments. The dichotomization failed to improve interrater and intrarater agreement to the level of substantial.
ABSTRACT
BACKGROUND: Current studies on the role of sex in the prognosis of acute vertebrobasilar artery occlusion (VBAO) are limited. We aimed to explore whether there are sex differences on outcomes in patients treated with endovascular therapy (EVT) for VBAO. METHODS: Patients from December 2015 to December 2018 with acute VBAO within 24 h of the estimated occlusion time in 21 stroke centers in China were retrospectively analyzed. Baseline data between sexes were compared in the total population cohort and propensity score (PS)-matched cohort. Multivariate logistic regression and ordinal regression were used to analyze the association of sex with outcomes. Mixed-effects regression model was performed for changes in modified Rankin Scale (mRS) scores in men and women from 90 days to 1 year after discharge. RESULTS: A total of 577 patients (28.4% women) were finally included. Multivariate logistic regression showed that women had a lower probability of favorable outcome (mRS score 0-3 at 90 days; OR 0.544; 95% CI 0.329-0.899) and functional independence (mRS score 0-2 at 90 days; OR 0.391; 95% CI 0.228-0.670) as well as a higher possibility of shifting to worse mRS (OR 1.484; 95% CI 1.020-2.158) than men. After PS matching, 391 patients (39.4% women) were analyzed, confirming the same results regarding favorable outcome (OR 0.580; 95% CI 0.344-0.977), functional independence (OR 0.394; 95% CI 0.218-0.712), and shift mRS (OR 1.504; 95% CI 1.023-2.210). However, the results of repeated ANOVA showed that men and women had a comparable functional recovery from 90 days to 1 year. CONCLUSIONS: Stroke due to VBAO treated with EVT is associated with worse outcomes in women than in men. However, men and women showed similar long-term improvement trends.
Subject(s)
Arterial Occlusive Diseases , Endovascular Procedures , Stroke , Humans , Male , Female , Sex Characteristics , Retrospective Studies , Thrombectomy/adverse effects , Endovascular Procedures/adverse effects , Stroke/surgery , Arterial Occlusive Diseases/surgery , ArteriesABSTRACT
OBJECTIVES: Besides plaque enhancement grade, the incremental value of enhancement-related high-resolution MRI features in defining culprit plaques needs further evaluation. This study was focused on assessing whether plaque enhancement features contribute to culprit plaque identification and further risk stratification. METHODS: We retrospectively studied patients who experienced an acute ischaemic stroke and transient ischaemic attack due to intracranial atherosclerosis from 2016 to 2022. The enhancement features included enhancement grade, enhanced length, and enhancement quadrant. Associations between plaque enhancement features and culprit plaques, as well as diagnostic value, were investigated using logistic regression and receiver operating characteristic analyses. RESULTS: Overall, 287 plaques were identified, of which 231 (80.5%) and 56 (19.5%) were classified as culprit and non-culprit plaques, respectively. Comparison of the pre- and post-enhancement images revealed enhanced length longer than the plaque length in 46.32% of the culprit plaques. Multivariate logistic regression showed that enhanced length longer than plaque length (OR 6.77; 95% CI 2.47-18.51) and grade II enhancement (OR 7.00; 95% CI 1.69-28.93) were independently associated with culprit plaques. The area under the curve value for the combination of stenosis and plaque enhancement grade for the diagnosis of culprit plaques was 0.787, which increased significantly to 0.825 on the addition of enhanced length longer than the plaque length (p = 0.026 for DeLong's test). CONCLUSIONS: Enhanced length longer than the plaque length and grade II enhancement were independently associated with culprit plaques. The combination of the enhanced plaque features resulted in better culprit plaque identification.
ABSTRACT
BACKGROUND: Identifying high-risk patients based on modifiable clinical characteristics, such as malnutrition, is critical to intervening with these variables to reduce the risk of post-stroke depression (PSD). The aim of this study was to investigate the effect of nutritional status on the risk of incident PSD and the trajectory of PSD risk. METHODS: Consecutive patients with acute ischemic stroke were recruited in this observational cohort and followed up for 1 year. Multivariate logistic regressions and multilevel mixed-effects logistic regressions with random intercepts and slopes were used to investigate the effects of nutritional indexes [the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI)] and body mass index (BMI) on the risk of incident PSD and the trajectory of PSD risk over the 12-month observation period. RESULTS: A total of 538 patients were included in the final analysis. Worsening CONUT [odds ratio (OR) = 1.36; confidence interval (CI): 1.15-1.61], NRI (OR = 0.91; CI: 0.87-0.96) and PNI (OR = 0.89; CI: 0.84-0.95) scores were significantly associated with an increased risk of incident PSD. Moderate and severe risk malnutrition statuses were associated with higher incidences of PSD regardless of the malnutrition index (CONUT, NRI or PNI). Additionally, PSD risk decreased over time with a significant two-way interaction between time and CONUT, NRI, and PNI, implying that patients with elevated exposure to malnutrition showed a slower decline in PSD risk. BMI had no significant effect on the occurrence and development of PSD. CONCLUSION: Malnutrition, but not BMI, was associated with a higher probability of incident PSD and was more likely to lead to a slower rate of decline in PSD risk.
Subject(s)
Ischemic Stroke , Malnutrition , Stroke , Humans , Ischemic Stroke/complications , Depression/epidemiology , Depression/etiology , Prognosis , Malnutrition/epidemiology , Nutritional Status , Stroke/complications , Stroke/epidemiology , Retrospective StudiesABSTRACT
Background: The optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT). Methods: Patients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0-3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0-2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8). Results: In the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06-12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found. Conclusions: Patients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8). Registration: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.
ABSTRACT
Network pharmacology is widely used to predict the mechanism of traditional Chinese medicines (TCM), but the framework in traditional network pharmacology analysis ignores the relationship between the concentration of components and drug efficacy. Lanqin oral solution (LOS) is a TCM formulation that widely used in the clinical treatment of pharyngitis, but its pharmacodynamic mechanism is still unknown. The present study was designed to elaborate the anti-inflammatory mechanism of LOS based on the quality markers (Q-markers). The efficacy of LOS was correlated with the fingerprint common peaks by chemometrics to select key peaks, and the Q-markers were further confirmed by mass spectrometry. Network pharmacology analysis was performed based on the chosen Q-markers to elaborate the potential pharmacodynamic mechanisms. Four efficacy-related chromatographic peaks were screened by the novel competitive adaptive reweighted sampling (CARS) spectrum-effect relationship analysis and series of other chemometrics methods. Four peaks were further characterized as the Q-markers in the LOS by mass spectrometry, i.e., geniposide, berberine, palmatine and baicalin. The ingredient-target network demonstrated that the LOS showed more impact on the NF-κB signaling pathway to elicit anti-inflammatory ability. Overall, the present study has introduced CARS into the spectrum-effect relationship analysis for the first time, which complemented the commonly applied chemometric methods. The network established based on the screened Q-markers was highly interpretable and successfully achieved the prediction of the anti-inflammatory mechanism of LOS. The proposed workflow provides a systematic method for exploring the mechanism of TCM based on identifying efficacy indicators. More importantly, it offers a reference for clarifying the mechanisms for other TCM formulations.
Subject(s)
Drugs, Chinese Herbal , Drugs, Chinese Herbal/pharmacology , Network Pharmacology , Medicine, Chinese Traditional , Anti-Inflammatory Agents/pharmacologyABSTRACT
BACKGROUND: Few studies have focused on the effect of systemic inflammation in vertebrobasilar artery occlusion (VBAO). The aim of this study was to investigate the relationship between inflammatory indicators and the prognosis of VBAO patients receiving endovascular treatment (EVT). METHOD: Patients with VBAO who were treated with EVT within 24 hours of the estimated occlusion time were included in this study. Multivariate logistic regression and elastic net regularization were performed to analyze the effects of inflammatory indicators on the prognosis of patients with VBAO. The primary outcome was unfavorable outcome (a modified Rankin Scale score of 4-6) at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, 90 day mortality, 1 year unfavorable outcome, and mortality. RESULTS: 560 patients were included in the study. Multivariate analysis showed that white blood cells (W), neutrophils (N), neutrophil to lymphocyte ratio (NLR), platelet to neutrophil ratio, platelet to white blood cell ratio, and NLR to platelet ratio were associated with the primary outcome. Elastic net regularization indicated that W, N, and NLR were the major inflammatory predictors of unfavorable outcome at 90 days. For long term prognosis, we found that the inflammatory indicators that predicted 1 year outcomes were consistent with those that predicted 90 day outcomes. CONCLUSION: Inflammatory indicators, especially W, N, and NLR, were associated with moderate and long term prognosis of patients with VBAO treated with EVT.
Subject(s)
Arterial Occlusive Diseases , Endovascular Procedures , Stroke , Humans , Retrospective Studies , Prognosis , Lymphocytes , Neutrophils , Registries , Arteries , Treatment OutcomeABSTRACT
Background: Achieving rapid and complete vascular recanalization in patients with acute large vessel occlusion can significantly improve patients' prognosis. Objective: We aimed to investigate the potential contribution of the first-pass effect (FPE) to the clinical outcome of patients with acute vertebrobasilar artery occlusion (VBAO). Methods: We retrospectively analyzed the data of patients who underwent endovascular thrombectomy (EVT) caused by VBAO in a multicentered retrospective registry dataset. FPE was defined as successful recanalization [modified thrombolysis in cerebral infarction (mTICI) 2b/3 as modified FPE (mFPE); mTICI 3 as true FPE (tFPE)] after one pass of the device without rescue therapy. The baseline characteristics and procedural and clinical outcomes were analyzed. Multivariate analysis was used to explore the predictors of FPE and the relationship between FPE and 90-day prognosis. Results: A total of 508 patients (age, 63.7 ± 13.1 years, male, 71.6%) were finally included, 29.9% (152/508) of whom achieved mFPE, and 21.1% (107/508) of whom achieved tFPE. FPE was significantly associated with improved clinical outcomes, regardless of mFPE [odds ratio (OR): 0.601, 95% confidence interval (CI): 0.370-0.977, p = 0.040] and tFPE (OR: 0.547, 95% CI: 0.318-0.940, p = 0.029). The use of contact aspiration, favorable collateral status, cardioembolic etiology, and basilar artery occlusion were statistically significant predictors of mFPE and tFPE, whereas hypertension was a negative predictor. Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) prior to EVT was a positive predictor of mFPE but not of tFPE. Conclusion: FPE was associated with significantly favorable outcomes in EVT patients with VBAO. The predictors of FPE include infarct etiology, the site of occlusion, collateral status, EVT strategies, and IV rt-PA bridging strategies. Trial registration number: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.
ABSTRACT
Objective: Endovascular treatment (EVT) is, to date, the most promising treatment of vertebrobasilar artery occlusion (VBAO). The study aimed to determine the influence of perioperative glucose levels on clinical outcomes in patients with acute VBAO treated with EVT. Methods: We retrospectively collected consecutive VBAO patients received EVT in 21 stroke centers in China. The associations between perioperative glycemic indicators (including fasting blood glucose[FBG], admission hyperglycemia, stress hyperglycemia ratio [SHR] and short-term glycemic variability [GV]) and various clinical outcomes were analyzed in all patients and subgroups stratified by diabetes mellitus (DM). Results: A total of 569 patients were enrolled. Admission hyperglycemia significantly correlated with increased risk of symptomatic intracranial hemorrhage (sICH) (odds ratio [OR] 3.24, 95% confidence interval [CI]: 1.40-7.46), poor functional outcomes at 90 days (OR 1.91, 95%CI: 1.15-3.18) and 1 year (OR 1.96, 95%CI: 1.20-3.22). Similar significant correlations exist between FBG, SHR, GV and all the adverse outcomes except higher levels GV was not associated with increased risk of sICH (OR 1.04, 95% CI: 0.97-1.12). Subgroup analyses showed that admission hyperglycemia, FBG and SHR were significantly associated with adverse outcomes in non-diabetic patients, but not in DM patients. While, GV was associated with poor functional outcomes regardless of diabetes history. Conclusions: Admission hyperglycemia, FBG, SHR and short-term GV in VBAO patients treated with EVT were associated with adverse outcomes. The results suggested that comprehensive evaluation and appropriate management of perioperative glucose might be important for patients with VBAO and treatment with EVT.
Subject(s)
Diabetes Mellitus , Endovascular Procedures , Hyperglycemia , Humans , Pregnancy , Female , Blood Glucose , Retrospective Studies , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Treatment Outcome , Intracranial Hemorrhages/etiology , Hyperglycemia/complications , Diabetes Mellitus/etiology , ArteriesABSTRACT
BACKGROUND: Homocysteine is correlated with several imaging features of cerebral small vessel disease including white matter hyperintensities, lacunes, and enlarged perivascular spaces (EPVS) in the basal ganglia. However, little is known about EPVS in the brainstem. This study aimed to investigate the correlation between serum total homocysteine (tHcy) and EPVS in the brainstem in patients with acute isolated pontine infarction. METHODS: Consecutive patients with isolated pontine infarction were retrospectively enrolled. Clinical characteristics and laboratory tests including tHcy were recorded. Imaging markers of cerebral small vessel disease including EPVS in the basal ganglia (BG-EPVS), EPVS in the centrum semiovale, and EPVS in the midbrain or pons (brainstem-EPVS) were assessed using conventional magnetic resonance imaging. The relation between tHcy and EPVS of different parts in the brain was analyzed using univariate and multivariate regression model. RESULTS: A total of 227 patients were included (mean age 67.10 ± 9.38 years, male sex 58.6%). The frequencies of brainstem-EPVS and moderate to severe BG-EPVS accounted for 40.1% (91/227) and 40.5% (92/227) respectively. After controlling for confounding factors, multivariate logistic regression analyses showed that tHcy was an independent risk factor for both moderate to severe BG-EPVS (P = 0.003, P for trend < 0.001) and the presence of brainstem-EPVS (P < 0.001, P for trend < 0.001) in a dose-dependent manner. Furthermore, multivariate linear regression model indicated that the presence of brainstem-EPVS (ß = 0.264, 95% confidence interval = 0.143-0.402, P < 0.001) and the severity of BG-EPVS (ß = 0.162, 95% confidence interval = 0.024-0.197, P = 0.013) were positively associated with serum tHcy. CONCLUSIONS: Serum tHcy is correlated with brainstem-EPVS and BG-EPVS dose-dependently. This study may support a contributing role for homocysteine in the pathophysiology of EPVS in the brainstem and the basal ganglia.
Subject(s)
Cerebral Small Vessel Diseases , Nervous System Malformations , Aged , Brain Stem , Cerebral Small Vessel Diseases/pathology , Homocysteine , Humans , Infarction , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective StudiesABSTRACT
Background: Whether endovascular treatment (EVT) is safe and effective for vertebrobasilar artery occlusion (VBAO) is yet incompletely understood. Two RCTs, the endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST) trail and the Basilar Artery International Cooperation Study (BASICS), concentrating on this field were recently reported. Objective: We use real-world registry data of VBAO to compare the outcome of EVT inside and outside the inclusion and exclusion criteria of the BEST and BASICS study to testify the feasibility of the selection paradigms of VBAO in these trials. Methods: Consecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. The safety outcomes [3-month mortality, symptomatic intracranial hemorrhage (sICH), and effectiveness outcomes (the proportion of 3-month functional independence (mRS of 0-2) and favorable outcome (mRS of 0-3)] were compared between VBAO patients who meet or failed to meet the BEST/BASICS selection criteria for EVT. Results: Our study cohort consisted of 577 VBAO patients who underwent EVT. Of them, 446 patients had pc-ASPECTS â§8. Successful reperfusion (mTICI 2b or 3) was achieved in 85.4% (n = 493). There were 418 patients fulfilling the BEST criterion for EVT and 194 fulfilling the BASICS criterion. Regression analysis indicated that adherence to BEST or BASICS criterion for EVT was not independently related to most of the safety and effectiveness outcome except that adherence to BEST was significantly associated with the 3-month favorable outcome (ORBEST: 1.742, 95% CI: 1.087-2.790). However, when we put pc-ASPECTS into both criteria with a cut-off value of 8, meeting both BEST criterion plus pc-ASPECTS and BASICS criterion plus pc-ASPECTS was independently related to 3-month functional independence (ORBEST: 1.687, 95% CI: 1.077-2.644; ORBASIC: 1.653, 95% CI: 1.038-2.631) and favorable outcome (ORBEST: 2.280, 95% CI: 1.484-3.502; ORBASIC: 2.153, 95% CI: 1.372-3.378). Conclusion: Our study indicated that, based on real-world data of EVT, adherence to BEST or BASICS criterion for EVT was not independently associated with the safety and effectiveness outcome except that adherence to BEST was significantly related to the 3-month favorable outcome. However, the BEST or BASICS selection criterion and pc-ASPECTS â§8 might be better paradigms for EVT patient selection.
ABSTRACT
Background: Poststroke fatigue (PSF) is a common symptom in stroke survivors, yet its anatomical mechanism is unclear. Our study was aimed to identify which brain lesions are related to the PSF in patients with acute stroke. Method: Patients with first-ever acute ischemic stroke consecutively admitted from the first affiliated hospital of the University of Science and Technology of China (USTC) between January 2017 and June 2020. Fatigue was scored using the Fatigue Severity Scale. All the participants were assessed by 3.0 T brain MRI including diffusion-weighted imaging. The infarct lesions were delineated manually and transformed into a standard template. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and the occurrence and severity of fatigue. The same analyses were carried out by flipping the left-sided lesions. Multivariate logistic regressions were applied to verify the associations. Results: Of the 361 patients with acute stroke, 142 (39.3%) patients were diagnosed with fatigue in the acute phase and 116 (35.8%) at 6 months after the index stroke. VLSM analysis indicated clusters in the right thalamus which was significantly associated with the occurrence and severity of PSF at 6-month follow-up. In contrast, no significant cluster was found in the acute phase of stroke. The flipped analysis did not alter the results. Multivariate logistic regression verified that lesion load in the right thalamus (OR 2.67, 95% CI 1.46-4.88) was an independent predictor of 6-month PSF. Conclusion: Our findings indicated that lesions in the right thalamus increased the risk of fatigue symptoms 6 months poststroke.