Comparison of outcomes between stent retriever combined with contact aspiration versus contact aspiration alone in patients without hyperdense artery sign/susceptibility vessel sign.

PURPOSE: To examine the relationship between hyperdense artery sign/susceptibility vessel sign (HAS/SVS) and thrombus composition, and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior-circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive acute anterior-circulation LVO patients (75 [63.1%] male; median age, 66 years) who underwent thrombectomy, and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was respectively assessed in noncontrast computed tomography (NCCT) and susceptibility-weighted imaging (SWI). Association of first-line thrombectomy techniques [stent retriever combined with contact aspiration (SR+CA) versus contact aspiration (CA)] with outcomes was assessed by the HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS(-), and 69 (67.0%) chose first-line SR+CA. Higher relative densities of fibrin/platelets (0.56 vs. 0.51, p<0.001) and lower relative densities of erythrocytes (0.32 vs. 0.42, p<0.001) were observed in HAS/SVS(-) than HAS/SVS(+) patients. First-line SR+CA was associated with reduced odds of distal embolization (aOR, 0.18; 95% CI, 0.04-0.83; p=0.027) and a more favorable 90-day functional outcome (aOR, 5.29; 95% CI, 1.06-26.34; p=0.042) in HAS/SVS(-) patients, and a longer recanalization time (53 min vs. 25 min, p=0.025) and higher risk of subarachnoid hemorrhage (24.2% vs. 0%, p=0.044) in HAS/SVS(+) patients. CONCLUSIONS: HAS/SVS(-) may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR+CA may have a possible better performance than CA in acute LVO patients without HAS/SVS.

Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria.

Chronic cerebral hypoperfusion (CCH) is an enduring inadequate blood flow to the brain, resulting in vascular dementia (VaD). However, the effective treatment strategies are lacking. Supplementing with nicotinamide adenine dinucleotide (NAD+) has shown neuroprotective benefits in other neurodegenerative disorders. Nicotinamide riboside (NR), as a precursor of NAD+, is believed to hold promise in improving mitochondrial health, autophagy, and cognitive function. Meanwhile, NR has unique oral bioavailability, good tolerability, and minimal side effects, and it is the most promising for clinical translation. However, the effectiveness of NR in treating CCH-related VaD is still uncertain. The present study examined the neuroprotective effects of NR supplementation and its underlying mechanisms in a CCH rat model. The rats with CCH were given NR at a daily dosage of 400 mg/kg for 3 months. NR supplementation increased blood and brain NAD+ levels and improved brain function in CCH rats, including cognitive function and oxygenation capacity. It also reduced hippocampal neuronal loss and abnormalities and mitigated the decrease in dendritic spine density. The analysis of RNA sequencing in hippocampal tissue supports these findings. Electron microscopy and protein detection results suggest that NR may maintain mitochondrial structural integrity and exert a protective role by attenuating mitochondrial fission and impaired autophagy flux caused by CCH. In conclusion, these findings offer evidence for the neuroprotective potential of NR supplementation in ameliorating cognitive impairment induced by CCH.

Analysis of factors associated with depressive symptoms in stroke patients based on a national cross-sectional study.

Post-stroke depression is commonly experienced by stroke survivors and has a significant negative impact on the physical, cognitive, and social functioning of those affected. This study aims to investigate the prevalence of depressive symptoms and their associated factors in Chinese stroke patients. Research samples were selected from the China Health and Retirement Longitudinal Study 2018 survey. Depression was evaluated using the 10-item Center for Epidemiological Studies Depression Scale, with a score ≥ 10 defined as depression. Univariate and multivariable analyses were performed to examine the associations of depressive symptoms with demographics, family relationships, health status, and lifestyle. A total of 963 stroke patients were included and 57.8% of them had depressive symptoms. Depressive symptoms were significantly associated with female sex (OR 1.762, 95% CI 1.235-2.514), lower education level (non-formal education: OR 2.148, 95% CI 1.235-3.737, primary to secondary school education: OR 1.964, 95% CI 1.272-3.033), dissatisfaction with spouse (OR 1.912, 95% CI 1.075-3.401), dissatisfaction with life (OR 1.779, 95% CI 1.080-2.931), dissatisfaction with health (OR 1.592, 95% CI 1.138-2.226), pain (OR 1.392, 95% CI 1.005-1.928) and abnormal sleep (OR 1.557, 95% CI 1.126-2.152). The findings suggest the need for regular depression screening and evaluation after a stroke, and that a well-functioning support system, effective health management, and lifestyle modifications could potentially improve the mental state of stroke patients.

Dynamic Changes and Clinical Significance of Plasma Galectin-3 in Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy.

Purpose: Galectin-3 is a key regulator of microglial proliferation and activation and may have dual and time-dependent effects on ischemic stroke. This study aimed to prospectively investigate the dynamic changes in Galectin-3 levels in patients with acute ischemic stroke receiving endovascular therapy and its clinical significance. Patients and Methods: A total of 105 patients with acute ischemic stroke who underwent endovascular therapy were prospectively enrolled. Plasma Galectin-3 was quantitatively detected by an enzyme-linked immunosorbent assay before the operation and at 1 day, 3 days and 7 days after the operation. A linear mixed-effect model, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate the dynamic changes in the plasma Galectin-3 concentration and its relationship with clinical outcomes. Results: Increases in plasma Galectin-3 levels at 1 day and 3 days after surgery were associated with early neurological deterioration and death (both P <0.05). Increased Galectin-3 levels before surgery and at 1 day and 3 days after surgery were associated with poor prognosis (P <0.05). Pearson correlation analysis revealed that Galectin-3 levels before surgery (r =0.318, P =0.002), at 1 day (r =0.318, P =0.001), 3 days (r =0.429, P < 0.001) and 7 days after surgery (r =0.340, P =0.001) were positively correlated with NIHSS scores. The ROC curve results showed that Galectin-3 concentration had a certain predictive value for death at 1 day (AUC=0.707, P=0.013), 3 days (AUC=0.708, P=0.016) and 7 days after the operation (AUC=0.708, P=0.016), but this predictive value was lower than that of the NIHSS score. Conclusion: In acute ischemic stroke patients receiving endovascular therapy, an increase in the plasma Galectin-3 levels were associated with death, poor prognosis, and early neurological deterioration. Galectin-3 levels were significantly correlated with the NIHSS score and had a certain predictive value for death.

Association of COVID-19 Infection with Subsequent Thyroid Dysfunction: An International Population-Based Propensity Score Matched Analysis.

Background: The COVID-19 pandemic's impact on thyroid function is a growing concern. Previous studies have produced inconclusive results, and there is a lack of comprehensive research into the long-term risks of thyroid dysfunction following COVID-19 infection. Methods: In this retrospective cohort study, we used data from the TriNetX international database, which includes electronic health records from a broad, diverse patient population. We compared patients with COVID-19 (cases) to those without (controls), matching for age, sex, race, and comorbidities using propensity score matching. The primary outcome was the diagnosis of thyroid dysfunction (thyrotoxicosis or hypothyroidism) within a 12-month period, analyzed using hazard ratios (HRs) and Kaplan-Meier curves, and stratified by age and sex. Results: Initially, the study included 1,379,311 COVID-19 patients and 6,896,814 non-COVID-19 patients from the TriNetX database. After matching, the cohorts were comparable in demographics and baseline characteristics. This study consistently demonstrated a significant increase in the risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, among COVID-19 patients compared to non-COVID-19 patients. In the short term (3 months postexposure), the COVID-19 group exhibited a HR of 2.07 (95% confidence interval [CI] 2.01-2.12) for thyroid dysfunction, which included both thyrotoxicosis (HR 2.10, CI 1.92-2.29) and hypothyroidism (HR 2.08, CI 2.01-2.13). This heightened risk persisted over the long term (up to 12 months), with HRs indicating an ∼2.01-fold increased risk for overall thyroid dysfunction, a 1.8-fold increased risk for thyrotoxicosis, and a 2.04-fold increased risk for hypothyroidism. Subgroup analysis, stratified by age and sex, revealed a notably higher risk of thyroid dysfunction in patients aged 65 and above (HR 2.18, CI 2.11-2.25), compared to those in the under-65 age group (HR 1.97, CI 1.91-2.03). Both male and female patients were associated with an elevated risk, with females showing a slightly higher association with thyroid dysfunction (HR 2.12, CI 2.06-2.16) compared to males (HR 1.76, CI 1.69-1.82). Conclusions: COVID-19 infection was associated with an increased risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, regardless of age or sex, during a 12-month follow-up period. Further research is required to validate these findings.

Balloon angioplasty as first-choice recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion with small clot burden.

PURPOSE: The optimal primary recanalization strategy for intracranial atherosclerosis-related emergent large vessel occlusion (ICAS-ELVO) remains controversial. We aimed to explore the safety and efficacy of balloon angioplasty as the first-choice recanalization strategy for ICAS-ELVO with small clot burden. METHODS: Consecutive ICAS-ELVO patients presenting with microcatheter "first-pass effect" during endovascular treatment (EVT) were retrospectively analyzed. Patients were divided into preferred balloon angioplasty (PBA) and preferred mechanical thrombectomy (PMT) groups based on the first-choice recanalization strategy. The reperfusion and clinical outcomes between the two groups were compared. RESULTS: Seventy-six patients with ICAS-ELVO involving the microcatheter "first-pass effect" during EVT were enrolled. Compared with patients in the PMT group, those in the PBA group were associated with (i) a higher rate of first-pass recanalization (54.0% vs. 28.9%, p = .010) and complete reperfusion (expanded thrombolysis in cerebral ischemia ≥ 2c; 76.0% vs. 53.8%, p = .049), (ii) shorter puncture-to-recanalization time (49.5 min vs. 89.0 min, p < .001), (iii) lower operation costs (¥48,499.5 vs. ¥ 99,086.0, p < .001), and (iv) better 90-day functional outcomes (modified Rankin scale:0-1; 44.0% vs. 19.2%, p = .032). Logistic regression analysis revealed that balloon angioplasty as the first-choice recanalization strategy was an independent predictor of 90-day excellent functional outcomes for ICAS-ELVO patients with microcatheter "first-pass effect" (adjusted odds ratio = 6.01, 95% confidence interval: 1.15-31.51, p = .034). CONCLUSION: Direct balloon angioplasty potentially improves 90-day functional outcomes for ICAS-ELVO patients with small clot burden, and may be a more appropriate first-choice recanalization strategy than mechanical thrombectomy for these patients.

Comparison of clinical outcomes in patients with acute ischemic stroke who underwent endovascular treatment using different perfusion modalities: a real-world multicenter study.

Background: Advanced perfusion modalities are increasingly popular for various diseases. However, few studies have focused on contrasting perfusion patterns. Objective: This study aimed to compare the time efficiency and clinical outcomes of patients with acute ischemic stroke (AIS) who underwent endovascular treatment (EVT) before one-stop arterial spin labeling (ASL) and computed tomography perfusion (CTP) protocols. Methods: This study retrospectively included 326 patients with AIS who had accepted EVT within 24 h of onset from four comprehensive stroke centers between October 2017 and September 2022. After 1:1 matching of the propensity scores, 202 patients were separated into two groups: the ASL group (n = 101) and the CTP group (n = 101). Results: Functional independence at 90 days (modified Rankin Scale [mRS] 0-2; p = 0.574), onset-to-puncture time (p = 0.231), door-to-puncture time (p = 0.136), and door-to-perfusion time (p = 0.646) were not significantly different between the two groups. The proportion of EVT complications (31.7% in the ASL group vs. 14.9% in the CTP group, p = 0.005) and symptomatic intracranial hemorrhage (sICH) at 24 h (23.8% in the ASL group vs. 9.9% in the CTP group, p = 0.008) in the CTP group were lower than the ASL group. The ischemic core volume was a common predictor of favorable outcomes in both ASL (p < 0.001) and CTP (p < 0.001) groups. Conclusion: There were no significant differences in time efficiency and efficacy outcomes between the two groups of patients receiving one-stop ASL and CTP. The proportion of sICH at 24 h and EVT complications of patients in the CTP group was lower than the ASL group. The ischemic core volume was an independent predictor for favorable outcomes.

Thrombus migration in patients with acute ischaemic stroke undergoing endovascular thrombectomy.

OBJECTIVE: The impact of thrombus migration (TM) prior to endovascular thrombectomy (EVT) on clinical outcomes and revascularisation rates remains unknown. We aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion patients. METHODS: All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicentre randomised clinical Trial were included. TM was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before EVT. The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. RESULTS: Of 627 included patients, the TM rate was 11.3% (71/627). In the multivariable logistic regression model, baseline National Institutes of Health Stroke Scale score (adjusted OR 0.956, 95% CI 0.916 to 0.999; p=0.043) and intravenous thrombolysis (adjusted OR 2.614, 95% CI 1.514 to 4.514; p<0.001) were independently associated with TM. The patients with TM were less likely to be completely recanalised than those without TM (21.27% vs 36.23%, p=0.040). The interaction of TM and the EVT treatment effect did not significantly affect mRS shift analysis (p=0.687) or mRS scores of 0 to 1 (p=0.436). CONCLUSION: Preinterventional TM does not modify the treatment effects of direct versus bridging EVT on functional outcomes in patients with acute ischaemic stroke with anterior large vessel occlusion. TM leads to a lower complete recanalisation rate.

Stroke recurrence is associated with unfavorable intracranial venous outflow in patients with symptomatic intracranial atherosclerotic large vessel severe stenosis or occlusion.

Objective: The purpose of this study was to investigate the predictive value of intracranial venous outflow for recurrent cerebral ischemic events (RCIE) in patients with symptomatic intracranial atherosclerotic large-vessel severe stenosis or occlusion (sICAS-S/O). Methods: This retrospective study included sICAS-S/O patients with anterior circulation who underwent dynamic computed tomography angiography (dCTA) and computed tomography perfusion (CTP). Arterial collaterals were evaluated using the pial arterial filling score for dCTA data, tissue-level collaterals (TLC) were assessed using the high-perfusion intensity ratio (HIR, Tmax >10 s/Tmax >6 s), and cortical veins were evaluated using the multi-phase venous score (MVS) for the vein of Labbé (VOL), sphenoparietal sinus (SPS), and superficial cerebral middle vein (SCMV). The relationships between multi-phase venous outflow (mVO), TLC, and 1-year RCIE were analyzed. Results: Ninety-nine patients were included, 37 of whom had unfavorable mVO (mVO-) and 62 of whom had favorable mVO (mVO+). Compared with the mVO+ patients, mVO- patients had a higher admission National Institutes of Health Stroke Scale (NIHSS) score (median, 4 [interquartile range (IQR), 0-9] vs. 1 [IQR, 0-4]; p = 0.048), larger ischemic volume (median, 74.3 [IQR, 10.1-177.9] vs. 20.9 [IQR, 5-86.4] mL; p = 0.042), and worse tissue perfusion (median, 0.04 [IQR, 0-0.17] vs. 0 [IQR, 0-0.03]; p = 0.007). Multivariate regression analysis showed that mVO- was an independent predictor of 1-year RCIE. Conclusion: For patients with sICAS-S/O of the anterior circulation, unfavorable intracranial venous outflow is a potential imaging indicator for predicting higher 1-year RCIE risk.

Dynamic changes in the glycocalyx and clinical outcomes in patients undergoing endovascular treatments for large vessel occlusion.

Purpose: We aimed to verify the prognostic value of the glycocalyx as a marker of blood-brain barrier damage in patients with acute ischemic stroke undergoing endovascular therapy. Methods: We recruited patients with large vessel occlusion who were undergoing recanalization and tested their glycocalyx at multiple time points. On the basis of the 90-day follow-up data, the patients were divided into a survivor group and a nonsurvivor group. In addition, neurological function was tracked, and patients were divided into a neurological deterioration group and a group without neurological deterioration. Associations between outcomes and dynamic changes in the glycocalyx were determined using a linear mixed model, and significant factors were used as covariates. Results: Nonsurvivors and patients with neurological deterioration had significantly higher syndecan-1 concentrations than survivors and patients without neurological deterioration, and syndecan-1 tended to decline after endovascular therapy (p < 0.05). The increased level of syndecan-1 at 36 h after endovascular treatment was positively correlated with the National Institute of Health Stroke Scale score for neurological deterioration (r = 0.702, p = 0.005). However, there was no significant difference in the level of hyaluronic acid or heparan sulfate in the plasma of patients with different clinical outcomes. Conclusion: Pre-reperfusion syndecan-1 levels in patients with large vessel occlusion stroke are associated with 90-day mortality and the re-degradation of syndecan-1 is positively associated with neurological deterioration.

Maf1 is an intrinsic suppressor against spontaneous neural repair and functional recovery after ischemic stroke.

INTRODUCTION: Spontaneous recovery after CNS injury is often very limited and incomplete, leaving most stroke patients with permanent disability. Maf1 is known as a key growth suppressor in proliferating cells. However, its role in neuronal cells after stroke remains unclear. OBJECTIVE: We aimed to investigate the mechanistic role of Maf1 in spontaneous neural repair and evaluated the therapeutic effect of targeting Maf1 on stroke recovery. METHODS: We used mouse primary neurons to determine the signaling mechanism of Maf1, and the cleavage-under-targets-and-tagmentation-sequencing to map the whole-genome promoter binding sites of Maf1 in isolated mature cortical neurons. Photothrombotic stroke model was used to determine the therapeutic effect on neural repair and functional recovery by AAV-mediated Maf1 knockdown. RESULTS: We found that Maf1 mediates mTOR signaling to regulate RNA polymerase III (Pol III)-dependent rRNA and tRNA transcription in mouse cortical neurons. mTOR regulates neuronal Maf1 phosphorylation and subcellular localization. Maf1 knockdown significantly increases Pol III transcription, neurite outgrowth and dendritic spine formation in neurons. Conversely, Maf1 overexpression suppresses such activities. In response to photothrombotic stroke in mice, Maf1 expression is increased and accumulates in the nucleus of neurons in the peripheral region of infarcted cortex, which is the key region for neural remodeling and repair during spontaneous recovery. Intriguingly, Maf1 knockdown in the peri-infarct cortex significantly enhances neural plasticity and functional recovery. Mechanistically, Maf1 not only interacts with the promoters and represses Pol III-transcribed genes, but also those of CREB-associated genes that are critical for promoting plasticity during neurodevelopment and neural repair. CONCLUSION: These findings indicate Maf1 as an intrinsic neural repair suppressor against regenerative capability of mature CNS neurons, and suggest that Maf1 is a potential therapeutic target for enhancing functional recovery after ischemic stroke and other CNS injuries.

An old thrombus may potentially identify patients at higher risk of poor outcome in anterior circulation stroke undergoing thrombectomy.

PURPOSE: To investigate thrombus age and its association with clinical and procedural parameters in patients with acute ischemic stroke (AIS) due to anterior circulation occlusions. METHODS: The thrombi of 107 consecutive AIS patients with occlusions in anterior circulation large-arteries were collected during mechanical recanalization. By hematoxylin-eosin staining analysis, thrombi were classified as fresh (< 3 days) or old (≥ 3 days) according to the hemosiderin positivity. Old thrombi were further classified as thrombi with focal hemosiderin or diffuse hemosiderin according to their predominant distribution. Neuro-interventional data and clinical outcomes were compared based on thrombus age. RESULTS: We identified fresh thrombi in 29 patients and old thrombi in 78 patients. Compared with patients with fresh thrombi, patients with old thrombi were associated with (i) a longer mechanical recanalization time (p = 0.027), (ii) a higher percentage of fibrin/platelets and leukocytes (all p = 0.02) and a lower percentage of erythrocytes (p = 0.001), and (iii) less favorable clinical outcomes at discharge (p = 0.019) and 90 days later (OR = 2.76, 95% CI = 1.09-6.99, p = 0.032). Furthermore, 18 (16.8%) of all patients had focal hemosiderin in old thrombi, which was independently linked to a poor clinical outcome 90 days later (adjusted OR = 5.37, 95% CI = 1.14-25.28, p = 0.034). CONCLUSION: The presence of old thrombi, particularly those with focal hemosiderin, may aid in identifying patients with acute ischemic anterior circulation stroke who are at a higher risk of poor clinical outcome at 3-month follow-up.

Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients.

Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis. Remarkably, the pre-ranked gene set enrichment analysis revealed that the co-expression modules with subgroup I-specific signature genes significantly overlapped with the differentially expressed genes in AIS patients with hemorrhagic transformation (HT). With respect to subgroup II, exclusively male patients with decreased proteasome activity were identified. Intriguingly, the majority of subgroup III was composed of female patients who showed a comparatively lower level of AIS-induced immunosuppression (AIIS). In addition, we discovered a non-linear relationship between female age and subgroup-specific gene expression, suggesting a gender- and age-dependent alteration of peripheral immunity. Taken together, our novel AIS classification approach could facilitate immunomodulatory therapies, including the administration of gender-specific therapeutics, and attenuation of the risk of HT and AIIS after ischemic stroke.

The correlation between enlarged perivascular spaces and cognitive impairment in Parkinson's disease and vascular parkinsonism.

INTRODUCTION: The widespread use of brain magnetic resonance imaging (MRI) has revealed the correlation between enlarged perivascular spaces (EPVS) and cognitive impairment (CI). However, few studies have examined the correlation between MRI-visible EPVS and CI in patients with Parkinson's disease (PD) and vascular parkinsonism (VaP). This study explored how the number and main location of EPVS in PD and VaP are correlated with the occurrence of CI in these diseases to provide radiology markers and other evidence for early clinical diagnosis in a Chinese cohort. METHODS: Clinical data were prospectively collected from 77 patients: 26 patients clinically diagnosed with PD or probable PD, 19 patients clinically diagnosed with VaP, and 32 control subjects with normal cognitive function and no stroke or parkinsonism. The patients with PD and VaP were divided into a CI group and a no CI (NCI) group according to the Montreal Cognitive Assessment Beijing version (MoCA-BJ). The relevant clinical data were statistically analysed. RESULTS: The centrum semiovale (CSO)-EPVS, lacunes, Fazekas scores, global cortical atrophy scale (GCA) scores, Koedam posterior atrophy visual scale (KS) scores, and medial temporal atrophy (MTA) scores were higher in the PD-CI and VaP-CI groups than in the control group (adjusted P < 0.017). The number of basal ganglia (BG)-EPVS in the VaP group was higher than that in the PD and control groups (adjusted P < 0.017). BG-EPVS, Fazekas scores, GCA scores, KS scores, and MTA scores were higher in the VaP-CI group than in the PD-CI group (adjusted P < 0.017). Multivariate logistic regression analysis showed that the differences in BG-EPVS and Fazekas scores were not significant between PD-CI and VaP-CI patients (P > 0.05). CONCLUSION: VaP-CI results from multiple factors and is significantly associated with BG-EPVS, lacunes, white matter hyperintensities and brain atrophy. BG-EPVS can be used as an imaging marker to distinguish VaP-CI from PD-CI.

Bacterial Signatures of Cerebral Thrombi in Large Vessel Occlusion Stroke.

It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent in situ hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of Proteobacteria, mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and Enterobacteriaceae were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. IMPORTANCE In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of Proteobacteria in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and Enterobacteriaceae in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.

Dl-3-n-butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance.

BACKGROUND: Cerebral venous disorder may have a harmful effect on ischaemic stroke; however, the underlying mechanism remains to be elucidated. Although Dl-3-n-butylphthalide is a multitarget agent for antiischaemic stroke, its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains unclear. In this study, we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins (EJVs) to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n-butylphthalide on cerebral infarction accompanied through cerebral venous disturbance. METHODS: Cerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs, and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery. 2,3,5-triphenyltetrazolium chloride staining, MRI, Evans blue extravasation and behavioural test were performed to evaluate infarction volume, cerebral blood flow (CBF), blood-brain barrier (BBB) integrity and neurological function. Immunofluorescence staining and western blot analysis were performed to detect loss of neuron, endothelial cells, pericytes and tight junctions. RESULTS: Bilateral EJVs occlusion did not cause cerebral infarction; however, it increased the infarction volume compared with the simple middle cerebral artery occlusion (MCAO) group, accompanied by severe neuron loss, worse neurological function, lower CBF, increased EJVs pressure, exacerbated Evans blue extravasation and brain oedema, as well as attenuated angiogenesis. Dl-3-n-butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss, accelerating CBF restoration, promoting angiogenesis and relieving BBB damage. CONCLUSION: Bilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic stroke. Dl-3-n-butylphthalide treatment plays a neuroprotective role in rats with MCAO accompanied by EJVs occlusion, mainly due to the promotion of CBF restoration and BBB protection.

The association between stress hyperglycemia and unfavorable outcomes in patients with anterior circulation stroke after mechanical thrombectomy.

Background and purpose: Stress hyperglycemia is common in critical and severe diseases. However, few studies have examined the association between stress hyperglycemia and the functional outcomes of patients with anterior circulation stroke, after mechanical thrombectomy (MT), in different diabetes status. This study therefore aimed to determine the relationship between stress hyperglycemia and the risk of adverse neurological functional outcomes in anterior circulation stroke patients with and without diabetes after MT. Methods: Data of 408 patients with acute anterior circulation stroke treated with MT through the green-channel treatment system for emergency stroke at the First Affiliated Hospital of Jinan University between January 2016 and December 2020 were reviewed retrospectively. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose (mmol/L) divided by glycosylated hemoglobin (%). The patients were stratified into four groups by quartiles of SHR (Q1-Q4). The primary outcome was an excellent (nondisabled) functional outcome at 3 months after admission (modified Rankin Scale score of 0-1). The relationship between stress hyperglycemia and neurological outcome after stroke was assessed using multivariate logistic regression. Results: After adjusting for potential confounders, compared with patients in Q1, those in Q4 were less likely to have an excellent outcome at 3 months (odds ratio [OR], 0.32, 95% confidence interval [CI], 0.14-0.66, p = 0.003), a good outcome at 3 months (OR, 0.41, 95% CI, 0.20-0.84, p = 0.020), and major neurological improvement (OR, 0.38, 95% CI, 0.19-0.73, p = 0.004). Severe stress hyperglycemia increased risks of 3-months all-cause mortality (OR, 2.82, 95% CI, 1.09-8.29, p = 0.041) and ICH (OR, 2.54, 95% CI, 1.21-5.50, p = 0.015). Conclusion: Stress hyperglycemia was associated with a reduced rate of excellent neurological outcomes, and increased mortality and ICH risks in patients with anterior circulation stroke after MT regardless of diabetes status.

Value of 18F-FDG PET/CT for Assessment of Advanced Lacrimal Sac Non-Keratinizing Squamous Cell Carcinoma Successfully Treated with Concurrent Chemoradiotherapy.

Non-keratinizing squamous cell carcinoma (NKSCC) of the lacrimal apparatus is extremely rare. It is usually very aggressive in destroying local tissue and has a grave prognosis for relentless recurrence and distant failures. Though the current evidence cannot make confident recommendations regarding the best management, curative surgical excision with adjuvant radiotherapy remains the most commonly used strategy. Here, we report a 71-year-old woman presented with progressive right medial canthal swellings for six months. A transnasal endoscopic biopsy revealed NKSCC of the lacrimal sac. She then underwent a combination of magnetic resonance images (MRI) and 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging purposes. Following cisplatin-based concurrent chemo-radiotherapy (CCRT), the post-treatment PET/CT illustrated the absence of an abnormal metabolic accumulation over the suspicious region as observed in post-treatment CT. A further trans-ostia re-biopsy confirmed complete tumor remission. This case demonstrates the remarkable ability of 18F-FDG PET/CT to differentiate between a persistent malignancy and post-treatment changes. Furthermore, a definite CCRT might provide comparable outcomes to traditional surgery.

Elevated Neutrophil to Lymphocyte Ratio Associated With Increased Risk of Recurrent Vascular Events in Older Minor Stroke or TIA Patients.

BACKGROUND: The risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA. METHODS: Consecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients). RESULTS: Overall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96-4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; p = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07-3.75; p = 0.031) was independently associated with the composite outcome in older patients. CONCLUSION: In older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events.

Evaluating the Velocity and Extent of Cortical Venous Filling in Patients With Severe Middle Cerebral Artery Stenosis or Occlusion.

Objective: To investigate the velocity and extent of cortical venous filling (CVF) and its association with clinical manifestations in patients with severe stenosis or occlusion of the middle cerebral artery (MCA) using dynamic computed tomography angiography (CTA). Methods: Fifty-eight patients (36 symptomatic and 22 asymptomatic) with severe unilateral stenosis (≥70%) or occlusion of the MCA M1 segment who underwent dynamic CTA were included. Collateral status, antegrade flow, and CVF of each patient were observed using dynamic CTA. Three types of cortical veins were selected to observe the extent of CVF, and the absence of CVF (CVF-) was recorded. Based on the appearance of CVF in the superior sagittal sinus, instances of CVF, including early (CVF1), peak (CVF2), and late (CVF3) venous phases, were recorded. The differences in CVF times between the affected and contralateral hemispheres were represented as rCVFs, and CVF velocity was defined compared to the median time of each rCVF. Results: All CVF times in the affected hemisphere were longer than those in the contralateral hemisphere (p < 0.05). Patients with symptomatic MCA stenosis had more ipsilateral CVF- (p = 0.02) and more delayed CVF at rCVF2 and rCVF21 (rCVF2-rCVF1) (p = 0.03 and 0.001, respectively) compared to those with asymptomatic MCA stenosis. For symptomatic patients, fast CVF at rCVF21 was associated with poor collateral status (odds ratio [OR] 6.42, 95% confidence interval [CI] 1.37-30.05, p = 0.02), and ipsilateral CVF- in two cortical veins was associated with poor 3-month outcomes (adjusted OR 0.025, 95% CI 0.002-0.33, p = 0.005). Conclusions: Complete and fast CVF is essential for patients with symptomatic MCA stenosis or occlusion. The clinical value of additional CVF assessment should be explored in future studies to identify patients with severe MCA stenosis or occlusion at a higher risk of stroke occurrence and poor recovery.