Succinate activates UCP2 to suppress neuroinflammation and confer protection following intracerebral hemorrhage.

AIMS: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. RESULTS: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxide, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophage, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream AMP-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I or AMPK abolished the therapeutic effects of succinate following ICH. INNOVATION AND CONCLUSION: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate. KEY WORDS: succinate; uncoupling protein 2; microglia; neuroinflammation; intracerebral hemorrhage.

Cryptosporidium spp. in captive snakes from 26 provinces in China: Prevalence, molecular characterization, and symptoms.

Snakes are sometimes regarded as pets and are used in traditional Chinese medicine. Cryptosporidium spp. are frequently identified in snakes, representing an important pathogen and causing gastrointestinal diseases. Current data indicate that risk factors for infection and patterns of clinical symptom presentation may differ among Cryptosporidium spp. To better understand the infection status by Cryptosporidium spp., fecal samples were collected from 603 asymptomatic and 147 symptomatic snakes in 26 provinces of China. These samples came from Elaphe guttata, Elaphe obsoleta, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getulus, and Heterodon nasicus. The partial small subunit (SSU) rRNA gene was amplified using nested polymerase chain reaction (PCR) to investigate the infection rate of Cryptosporidium spp., and to assess evolutionary relationships and genetic characterization. A prevalence of 20% was recorded in asymptomatic snakes, with age identified as a significant risk factor. In contrast, 70% of symptomatic snakes were positive for Cryptosporidium spp., with Cryptosporidium serpentis and Cryptosporidium varanii (syn. C. saurophilum). Further analysis revealed a potential association between C. serpentis and regurgitation, and C. varanii and diarrhea, while neither species was linked to flatulence. To our knowledge, this is the first study to report Cryptosporidium spp. and associated clinical signs in symptomatic snakes in China. This study aims to enhance the understanding of Cryptosporidium infections, risk factors, and clinical manifestations in snakes, providing data crucial for the control and prevention of cryptosporidiosis.

Title: Cryptosporidium spp. chez les serpents captifs de 26 provinces de Chine : prévalence, caractérisation moléculaire et symptômes. Abstract: Les serpents sont parfois considérés comme animaux de compagnie et sont utilisés en médecine traditionnelle chinoise. Des Cryptosporidium spp. sont fréquemment identifiés chez les serpents, ont un rôle d'agent pathogène important et provoquent des maladies gastro-intestinales. Les données actuelles indiquent que les facteurs de risque d'infection et les schémas de présentation des symptômes cliniques peuvent varier en fonction des espèces de Cryptosporidium. Pour mieux comprendre l'état d'infection par Cryptosporidium spp., des échantillons fécaux ont été collectés auprès de 603 serpents asymptomatiques et 147 serpents symptomatiques dans 26 provinces de Chine. Ces échantillons provenaient d'Elaphe guttata, Elaphe obsoleta, Pituophis melanoleucus, Thamnophis sirtalis, Lampropeltis getulus et Heterodon nasicus. Le gène de l'ARNr de la petite sous-unité partielle (SSU) a été amplifié à l'aide d'une réaction en chaîne par polymérase (PCR) imbriquée pour étudier le taux d'infection par Cryptosporidium spp. et évaluer les relations évolutives et la caractérisation génétique. Une prévalence de 20 % a été trouvée chez les serpents asymptomatiques, l'âge étant identifié comme un facteur de risque important. En revanche, 70 % des serpents symptomatiques étaient positifs à Cryptosporidium spp. avec Cryptosporidium serpentis et Cryptosporidium varanii (syn. C. saurophilum). Une analyse plus approfondie a révélé une association potentielle entre C. serpentis et la régurgitation, et C. varanii et la diarrhée, alors qu'aucune des deux espèces n'était liée aux flatulences. À notre connaissance, il s'agit ici de la première étude à signaler la présence de Cryptosporidium spp. et les signes cliniques associés chez des serpents symptomatiques en Chine. Cette étude vise à améliorer la compréhension des infections à Cryptosporidium, des facteurs de risque et des manifestations cliniques chez les serpents, en fournissant des données cruciales pour le contrôle et la prévention de la cryptosporidiose.

Refining the optimal CAF cluster marker for predicting TME-dependent survival expectancy and treatment benefits in NSCLC patients.

The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.

BACKGROUND: High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. OBJECTIVE: The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model. METHODS: Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. RESULTS: We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1ß in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. CONCLUSIONS: Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Effect of heart rate on poor outcome in stroke patients treated with intra-arterial thrombectomy.

BACKGROUND AND PURPOSE: The relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy. METHODS: Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome. RESULTS: Among 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio [aHR] with 95% CI: 1.29 [1.09-1.51], 1.19 [1.07-1.32], 1.14 [1.03-1.27]; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio [aOR] with 95% CI: 1.35 [1.11-1.64], 1.27 [1.05-1.53], 1.19 [1.02-1.40]; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome. CONCLUSIONS: Higher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients.

Nomogram to Predict 90-Day All-Cause Mortality in Acute Ischemic Stroke Patients after Endovascular Thrombectomy.

OBJECTIVE: Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT. METHODS: AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance. RESULTS: Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5. CONCLUSION: Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.

Prevalence and molecular characterization of Trichomonas gallinae from pigeons in Anhui, China.

Trichomonas gallinae, a protozoan parasite causing avian trichomonosis, exhibits a widespread global prevalence. It primarily affects the upper digestive tract of birds and has resulted in significant ecological problems worldwide. This study aimed to investigate the prevalence and genotypes of T. gallinae in Anhui Province, China. A total of 1612 oropharyngeal swab samples were collected from pigeon farms in Anhui Province to determine the prevalence of T. gallinae infection. The results revealed 565 (35.1%) positive samples of T. gallinae. Significant differences in infection rates were observed among different regions and age groups. Furthermore, the ITS1/5.8 S/ITS2 region was amplified, sequenced, and subjected to phylogenetic analysis. Genotypes A and B of T. gallinae were identified, and genotype B was the dominant genotype in Anhui Province. This is the first report on the prevalence and molecular characterization of T. gallinae in Anhui Province, China. Additionally, we integrated reports on the prevalence and genotype of T. gallinae in relevant provinces in China.

Trajectory Groups of 72-Hour Heart Rate After Mechanical Thrombectomy and Outcomes.

Background and Purpose: Elevated heart rate (HR) after mechanical thrombectomy (MT) was associated with an increased risk of adverse outcomes. However, optimal HR management after MT remains unclear. This study aimed to identify patient subgroups with distinct HR trajectories after MT and explore their association with outcomes. Methods: Acute ischemic stroke patients undergoing MT therapy were prospectively recruited from July 2020 to December 2022. Their heart rate indicators were collected every hour for 72 hours after MT procedure. Latent variable mixture modeling was used to separate subjects into five groups with distinct HR trajectories. The primary outcome was poor functional outcome (mRS score >2) at 3 months. Additional outcome was all-cause mortality (mRS score = 6) at 3 months. Results: A total of 224 patients with large vessel occlusion were enrolled, with a mean age of 65.2+14.0 years. Eighty-seven patients had a good functional outcome, and 137 patients had a poor functional outcome. Five distinct HR trajectories were observed: low (19.2%), moderate (33.0%), rapidly stabilized HR group (20.5%), persistently high HR group (21.0%), and very high HR group (6.3%). After adjusting for potential confounders, the HR trajectory group was independently associated with poor functional outcome at 3 months (P for interaction = 0.022). The risk of having poor functional outcome was increased in the rapidly stabilized HR group (odds ratio, 3.18 [95% confidence interval, 1.10-9.19]), the persistently high HR group (odds ratio, 5.55 [95% confidence interval, 1.72-17.87]) and very high HR group (odds ratio, 18.32 [95% confidence interval, 2.20-95.52]) but not in the moderate group (odds ratio, 1.50 [95% confidence interval, 0.61-3.69]), when compared with the low HR group. No significant association was found between trajectory group and 3-month all-cause mortality. Conclusion: HR during the first 72 hours after MT may be categorized into distinct trajectory groups, which differ in relation to poor functional outcome event risks. The findings may help to recognize potential candidates for future HR control trials.

Fbxw7 suppresses carcinogenesis and stemness in triple-negative breast cancer through CHD4 degradation and Wnt/ß-catenin pathway inhibition.

BACKGROUND: Cancer stem cells (CSCs) are a small population of cells in tumor tissues that can drive tumor initiation and promote tumor progression. A small number of previous studies indirectly mentioned the role of F-box and WD repeat domain-containing 7 (FBXW7) as a tumor suppressor in Triple-negative breast cancer (TNBC). However, few studies have focused on the function of FBXW7 in cancer stemness in TNBC and the related mechanism. METHODS: We detected FBXW7 by immunohistochemistry (IHC) in 80 TNBC patients. FBXW7 knockdown and overexpression in MD-MBA-231 and HCC1937 cell models were constructed. The effect of FBXW7 on malignant phenotype and stemness was assessed by colony assays, flow cytometry, transwell assays, western blot, and sphere formation assays. Immunoprecipitation-Mass Spectrometry (IP-MS) and ubiquitination experiments were used to find and verify potential downstream substrate proteins of FBXW7. Animal experiments were constructed to examine the effect of FBXW7 on tumorigenic potential and cancer stemness of TNBC cells in vivo. RESULTS: The results showed that FBXW7 was expressed at low levels in TNBC tissues and positively correlated with prognosis of TNBC patients. In vitro, FBXW7 significantly inhibited colony formation, cell cycle progression, cell migration, EMT process, cancer stemness and promotes apoptosis. Further experiments confirmed that chromodomain-helicase-DNA-binding protein 4 (CHD4) is a novel downstream target of FBXW7 and is downregulated by FBXW7 via proteasomal degradation. Moreover, CHD4 could promote the nuclear translocation of ß-catenin and reverse the inhibitory effect of FBXW7 on ß-catenin, and ultimately activate the Wnt/ß-catenin pathway. Rescue experiments confirmed that the FBXW7-CHD4-Wnt/ß-catenin axis was involved in regulating the maintenance of CSC in TNBC cells. In animal experiments, FBXW7 reduced CSC marker expression and suppressed TNBC cell tumorigenesis in vivo. CONCLUSIONS: Taken together, these results highlight that FBXW7 degrades CHD4 protein through ubiquitination, thereby blocking the activation of the Wnt/ß-catenin pathway to inhibit the stemness of TNBC cells. Thus, targeting FBXW7 may be a promising strategy for therapeutic intervention against TNBC.

A prospective, multicentre, registry study of RECO in the endovascular treatment of acute ischaemic stroke.

The RECO is a novel endovascular treatment (EVT) device that adjusts the distance between two mesh segments to axially hold the thrombus. We organized this postmarket study to assess the safety and performance of RECO in acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO). This was a single-arm prospective multicentre study that enrolled patients as first-line patients treated with RECO at 9 stroke centres. The primary outcome measures included functional independence at 90 days (mRS 0-2), symptomatic intracranial haemorrhage (sICH), time from puncture to recanalization and time from symptom onset to recanalization. The secondary outcome measures were a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3 after the first attempt and at the end of the procedure and the all-cause mortality rate within 90 days. From May 22, 2020, to July 30, 2022, a total of 268 consecutive patients were enrolled in the registry. The median puncture-to-recanalization time was 64 (IQR, 45-92), and the symptom onset-to-recanalization time was 328 min (IQR, 228-469). RECO achieved successful reperfusion (mTICI 2b-3) after the first pass in 133 of 268 patients (49.6%). At the end of the operation, 96.6% of the patients reached mTICI 2b-3, and 97.4% of the patients ultimately achieved successful reperfusion. Sixteen (7.2%) patients had sICH. A total of 132 (49.3%) patients achieved functional independence at 90 days, and the all-cause mortality rate within 90 days was 17.5%. In this clinical experience, the RECO device achieved a high rate of complete recanalization with a good safety profile and favourable 90-day clinical outcomes.Clinical trial registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT04840719.

Basilar artery occlusion location and clinical outcome: data from the ATTENTION multicenter registry.

BACKGROUND: Acute basilar artery occlusion is a disabling and life-threatening condition. The purpose of this study was to evaluate the impact of occluded vessel location on the prognostic outcomes of patients who underwent endovascular treatment for acute basilar artery occlusion. METHODS: Patient data for this study were obtained from the ATTENTION registry. Baseline data of the patients were described and compared across different occlusion locations. Univariable and multivariable regression analyses were performed to assess the effect of occluded vessel location on associated prognostic outcomes. RESULTS: A total of 1672 patients were included in the analysis, with 583 having distal occlusion, 540 having middle occlusion, and 549 having proximal occlusion. Unlike distal occlusion, both proximal and middle occlusions were significantly and negatively associated with favorable clinical outcomes (for modified Rankin Scale score 0-3: adjusted odds ratio (aOR) 0.634, 95% confidence interval (95% CI) 0.493 to 0.816, P<0.001 in middle occlusion, and aOR 0.620, 95% CI 0.479 to 0.802, P<0.001 in proximal occlusion). Mortality was higher in patients with proximal and middle occlusions (aOR 1.461, 95% CI 1.123 to 1.902, P=0.005 in middle occlusion, and aOR 1.648, 95% CI 1.265 to 2.147, P<0.001 in proximal occlusion). The occluded vessel location was not associated with symptomatic intracranial hemorrhage. CONCLUSIONS: Proximal and middle basilar artery occlusions were predominantly associated with poor clinical outcomes and increased risk of death following endovascular treatment.

Regulators of phagocytosis as pharmacologic targets for stroke treatment.

Stroke, including ischemic and hemorrhagic stroke, causes massive cell death in the brain, which is followed by secondary inflammatory injury initiated by disease-associated molecular patterns released from dead cells. Phagocytosis, a cellular process of engulfment and digestion of dead cells, promotes the resolution of inflammation and repair following stroke. However, professional or non-professional phagocytes also phagocytose stressed but viable cells in the brain or excessively phagocytose myelin sheaths or prune synapses, consequently exacerbating brain injury and impairing repair following stroke. Phagocytosis includes the smell, eating and digestion phases. Notably, efficient phagocytosis critically depends on phagocyte capacity to take up dead cells continually due to the limited number of phagocytes vs. dead cells after injury. Moreover, phenotypic polarization of phagocytes occurring after phagocytosis is also essential to the proresolving and prorepair properties of phagocytosis. Much has been learned about the molecular signals and regulatory mechanisms governing the sense and recognition of dead cells by phagocytes during the smell and eating phase following stroke. However, some key areas remain extremely understudied, including the mechanisms involved in digestion regulation, continual phagocytosis and phagocytosis-induced phenotypic switching following stroke. Here, we summarize new discoveries related to the molecular mechanisms and multifaceted effects of phagocytosis on brain injury and repair following stroke and highlight the knowledge gaps in poststroke phagocytosis. We suggest that advancing the understanding of poststroke phagocytosis will help identify more biological targets for stroke treatment.

Revascularization of acute stent thrombosis caused by diarrhea after carotid artery stenting in an intermediate clopidogrel metabolizer.

Carotid artery stenting (CAS) is an alternative treatment to carotid endarterectomy for carotid artery stenosis. Acute stent thrombosis (ACST) is an extremely rare complication but can have devastating consequences. Although many cases have been reported, the best treatment is still uncertain. In this study, we report the treatment of ACST caused by diarrhea in an intermediate clopidogrel metabolizer. We also review the literature and discuss appropriate treatment strategies for this rare event.

Eosinophil: A New Circulating Biomarker for Risk of Poor Outcome in Stroke Patients Undergoing Mechanical Thrombectomy.

Objective: Acute ischemic stroke (AIS), caused by occlusion of large vessel, is a serious life-threatening disease. This study aimed to comprehensively investigate the association of 14 common and readily available circulating biomarkers with the 90-day modified Rankin Scale (mRS) score in patients undergoing mechanical thrombectomy (MT). Methods: This study included patients with anterior circulation large vessel occlusive stroke treated with MT from 05/2017 to 12/2021. Baseline comparisons of poor outcome were performed among enrolled patients. Factors that may be associated with the mRS score were assessed using correlation analysis. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of circulating biomarkers and poor outcome. Results: The mRS score has a strong correlation with neutrophil to lymphocyte ratio (NLR) and eosinophil levels (all rs>0.4 in absolute value and all P<0.001) in addition to a high correlation with National Institute of Health Stroke Scale (NIHSS) score (rs=0.40, P<0.001). There was also a high correlation between NLR and eosinophil (rs=-0.58, P<0.001). In the multivariate regression analysis, only neutrophil (adjusted OR=1.301, 95% CI: 1.155-1.465, P<0.001), eosinophil (adjusted OR<0.001, 95% CI: <0.001-0.016, P<0.001), and NLR (adjusted OR=1.158, 95% CI: 1.082-1.241, P<0.001) were independently associated with poor outcome. Conclusion: This study evaluated a series of circulating biomarkers and found that neutrophil, eosinophil, and NLR independently predicted poor outcome after MT in AIS patients. There was a significant negative correlation between eosinophil and NLR levels.

Comparing a novel Catfish flow restoration device and the Solitaire stent retriever for thrombectomy revascularisation in emergent largevessel occlusion stroke: a prospective randomised controlled study.

BACKGROUND: The Catfish stent retriever is a newly developed mechanical thrombectomy device for rapid recanalisation in emergent large vessel occlusion (ELVO) stroke. The current trial aimed to assess whether the Catfish stent retriever is non-inferior to the Solitaire stent retriever in terms of outcomes in ELVO stroke. METHODS: This was a randomised, prospective, parallel-group, multicentre, open-label, non-inferiority study conducted at 18 sites in China. The primary outcome was the proportion of cases with successful recanalisation (modified thrombolysis in cerebral infarction score of 2b or 3) following the procedure. Secondary efficacy outcomes included the National Institutes of Health Stroke Scale scores at 24 hours and 7 days or discharge if earlier, time from artery puncture to successful recanalisation and good clinical outcome (modified Rankin scale score ≤2) at 90 days. Safety outcomes included symptomatic intracranial haemorrhage, all cause-death and severe adverse events at 90 days. RESULTS: Between 3 March 2019 and 5 June 2021, 118 and 120 patients were randomly allocated to the Catfish and Solitaire groups, respectively. The primary endpoint after all endovascular procedures was non-inferior in the Catfish group (88.5%, 100/113) than in the Solitaire group (87.7%, 100/114), with a rate difference (RD) of 0.78% (95% CI -7.64 to -9.20; p=0.001). Sensitivity analysis only considering the per-protocol set also yielded similar results, with an RD of 0.83% (95% CI -7.03 to -8.70; p<0.001). Additionally, the proportions of cases with good clinical outcomes (47.8% vs 50.0%, p=0.739) and all-cause death rates (17.7% vs 18.8%, p=0.700) were similar in both groups at 90 days. CONCLUSIONS: The Catfish stent retriever is an effective and safe device for endovascular recanalisation in ELVO stroke. TRIAL REGISTRATION NUMBER: NCT03820882.

Prognostic significance of blood pressure parameters after mechanical thrombectomy according to collateral status.

BACKGROUND: Mechanical thrombectomy (MT) has been proven as an effective and safe therapy for patients with acute ischemic stroke from large vessel occlusion. However, there is still a controversial topic about post-procedural management including blood pressure (BP). METHODS: A total of 294 patients who received MT in Second Affiliated Hospital of Soochow University from April 2017 to September 2021 were included consecutively. The association of blood pressure parameters (BPV and hypotension time) with poor functional outcome was evaluated using logistic regression models. Meanwhile, the effects of BP parameters on mortality was analyzed using cox proportional hazards regression models. Furthermore, the corresponding multiplicative term was added to the above models to study the interaction between BP parameters and CS. RESULTS: Two hundred ninety four patients were included finally. The mean age was 65.5 years. At the 3-month follow-up, 187(61.5%) had poor functional outcome and 70(23.0%) died. Regardless of the CS, BP CV is positively associated with poor outcome. Hypotension time was negatively associated with poor outcome. We conducted a subgroup analysis according to CS. BPV was significantly associated with mortality at 3-month and displayed a trend toward poor outcome for patients with poor CS only. The interaction between SBP CV and CS with respect to mortality after adjusting for confounding factors was statistically significant (P for interaction = 0.025) and the interaction between MAP CV and CS with respect to mortality after multivariate adjustment was also statistically significant (P for interaction = 0.005). CONCLUSION: In MT-treated stroke patients, higher BPV in the first 72 h is significantly associated with poor functional outcome and mortality at 3-month regardless of CS. This association was also found for hypotension time. Further analysis showed CS modified the association between BPV and clinical prognosis. BPV displayed a trend toward poor outcome for patients with poor CS.

Effects of Different Etiologies of Anterior Circulation Tandem Lesions on Short-term Prognosis of Acute Ischemic Stroke.

INTRODUCTION: The prognosis of anterior circulation tandem lesions caused by carotid artery dissection (CAD) and large artery atherosclerosis (LAA) after mechanical thrombectomy is controversial. By analyzing the clinical data of different etiologies, we explored the best treatment plan. METHODS: Clinical data of patients with anterior circulation tandem lesions admitted to the Second Affiliated Hospital of Soochow University from April 2018 to October 2021 were retrospectively collected. The Modified Rankin Scale was used as the standard to evaluate the functional prognosis of patients at 3 months. Safety assessment included symptomatic intracranial hemorrhage (sICH) and mortality. The technical evaluation of interventional procedures included operation time, successful recanalization, and times of pass. RESULTS: 74 patients were enrolled, 59 in the LAA group and 15 in the CAD group. The two groups were similar regarding the proportion of successful recanalization, the bridge treatment and the choice of surgical instruments. The puncture to recanalization time and the onset of symptoms to successful recanalization time had no significant difference (p > 0.05). There were no significant differences in hemorrhage transformation (p = 0.26), sICH (p > 0.999), good functional prognosis (p = 0.054), and mortality (p = 0.181) between the two groups. We found a trend toward a better functional outcome at 3 months in the CAD group (p = 0.054). CONCLUSION: The tandem lesions of anterior circulation caused by CAD tend to have a good functional prognosis in 3 months. The proportion of successful recanalization and surgical safety was similar between the two groups.

Value of angiographic regional circulation signs in predicting hemorrhagic transformation after endovascular thrombectomy.

OBJECTIVE: The aim of this study was to evaluate the predictive value of the early venous filling (EVF) sign, the basal ganglia blush (BGB) sign and both the EVF and BGB signs for the hemorrhagic transformation (HT) and parenchymal hematoma (PH) in patients after endovascular thrombectomy. METHODS: This study included patients with anterior circulation large vessel occlusive stroke treated with endovascular thrombectomy from May 2017 to December 2021. The predictive value of regional circulation signs for HT and PH were assessed using logistic regression models adjusted for confounders, and further a multiplicative interaction term was added to investigate the effect of different stroke severity on its predictive value. RESULTS: Among the 350 patients included and after adjusting for confounders, those with the EVF sign (adjusted OR=3.934, 95% CI:2.326-6.655), the BGB sign (adjusted OR=3.776, 95% CI:2.341-6.089), and both the EVF and BGB signs (adjusted OR=3.250, 95% CI: 1.886-5.600) were more likely to have HT. The EVF sign (adjusted OR=3.545, 95% CI:2.036-6.170), the BGB sign (adjusted OR=3.742, 95% CI:2.110-6.639), and both the EVF and BGB signs (adjusted OR=3.139, 95% CI: 1.776-5.549) were also significantly correlated with PH. When stratified according to stroke severity, we further found there were significant interactions between regional circulation signs and stroke severity on postoperative HT and PH (all P for interaction < 0.001). CONCLUSIONS: Regional circulation signs were independently associated with HT and PH after endovascular thrombectomy and had a higher predictive value in patients with severe stroke compared with mild to moderate stroke.