Ratiometric Fluorescence Aptasensor of Allergen Protein Based on Multivalent Aptamer-Encoded DNA Flowers as Fluorescence Resonance Energy Transfer Platform.

Life-threatening allergic reactions to food allergens, particularly peanut protein Ara h1, are a growing public health concern affecting millions of people worldwide. Thus, accurate and rapid detection is necessary for allergen labeling and dietary guidance and ultimately preventing allergic incidents. Herein, we present a novel ratiometric fluorescence aptasensor based on multivalent aptamer-encoded DNA flowers (Mul-DNFs) for the high-stability and sensitive detection of allergen Ara h1. The flower-shaped Mul-DNFs were spontaneously packaged using ultralong polymeric DNA amplicons driven by a rolling circle amplification reaction, which contains a large number of Ara h1 specific recognition units and has excellent binding properties. Furthermore, dual-color fluorescence-labeled Mul-DNFs probes were developed by hybridizing them with Cy3- and Cy5-labeled complementary DNA (cDNA) to serve as a ratiometric fluorescence aptasensor platform based on fluorescence resonance energy transfer. Benefiting from the combined merits of the extraordinary synergistic multivalent binding ability of Mul-DNFs, the excellent specificity of the aptamer, and the sensitivity of the ratiometric sensor to avoid exogenous interference. The developed ratiometric aptasensor showed excellent linearity (0.05-2000 ng mL-1) with a limit of detection of 0.02 ng mL-1. Additionally, the developed ratiometric fluorescence aptasensor was utilized for quantifying the presence of Ara h1 in milk, infant milk powder, cookies, bread, and chocolate with recoveries of 95.7-106.3%. The proposed ratiometric aptasensor is expected to be a prospective universal aptasensor platform for the rapid, sensitive, and accurate determination of food and environmental hazards.

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

BACKGROUND: Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. METHODS: From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50 ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48 h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. RESULTS: Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). CONCLUSIONS: Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.

A novel di-functional fluorescent probe for ONOO- and Zn2+ imaging in cells.

Peroxynitrite (ONOO-) is one of the most significant reactive oxygen species (ROS) in living cells. Zn2+ in living cells plays an essential part in different physiological processes. The abnormal concentration of ONOO- and Zn2+ in living cells are related to many kinds of diseases, such as anemia, epilepsy, diarrhea, Alzheimer's disease, and so on. The relationship of ONOO- and Zn2+ in living cells when the relative disease occurs remains unknown. So we develop the first probe H-1 for detecting ONOO- and Zn2+ at the same time. The probe H-1 shows high selectivity, good anti-interference capability, low detection limit and short response time to ONOO- and Zn2+. When the probe was applied to detect ONOO- and Zn2+ in HeLa cells, we could observe the fluorescence changing in the green and blue channels separately without interference in real time. It has the potential to employ the relation of ONOO- and Zn2+ in some disease mechanism research.

First pass effect in patients undergoing endovascular treatment for posterior circulation acute ischemic stroke.

OBJECTIVE: This study aims to investigate the impact of first pass effect (FPE) on outcomes in the posterior circulation acute ischemic stroke (PC-AIS) and the independent predictors of FPE. METHODS: This was a multicenter, retrospective study. PC-AIS patients who underwent endovascular treatment were reviewed. The cohort achieving complete or nearly complete reperfusion (defined as expanded treatment in cerebralischemia [eTICI] ≥ 2c) was categorized into the FPE and multiple pass effect (MPE) groups. FPE was defined as achieving eTICI ≥ 2c with a single pass and without the use of rescue therapy. Modified FPE (mFPE) was defined as meeting the criteria for FPE but with eTICI ≥ 2b. The association of FPE with 90-day clinical outcomes and predictors for FPE were both investigated. RESULTS: The study included a total of 328 patients, with 69 patients (21 %) in the FPE group. For primary outcome, FPE had a significant higher favorable outcome (mRS ≤ 3) rate than MPE (65.2 % vs. 44.8 %, p = 0.003). Similar outcomes were observed in the mFPE. Furthermore, FPE was significantly associated with favorable outcome (adjusted OR 2.23, 95 % CI 1.06-4.73, p = 0.036). Positive predictors for FPE included occlusion in the distal basilar artery, the first-line aspiration or combination, and cardioembolic etiology. Negative predictors for FPE included hypertension and general anesthesia. CONCLUSION: For PC-AIS patients due to large or medium vessel occlusion, FPE is associated with favorable clinical outcomes. The first-line techniques of aspiration or combination, as well as avoiding general anesthesia, contribute to a better realization of FPE.

MS3 Imaging Enables the Simultaneous Analysis of Phospholipid C═C and sn-Position Isomers in Tissues.

Mass spectrometry (MS) imaging of lipids in tissues with high structure specificity is challenging in the effective fragmentation of position-selective structures and the sensitive detection of multiple lipid isomers. Herein, we develop an MS3 imaging method for the simultaneous analysis of phospholipid C═C and sn-position isomers by on-tissue photochemical derivatization, nanospray desorption electrospray ionization (nano-DESI), and a dual-linear ion trap MS system. A novel laser-based sensing probe is developed for the real-time adjustment of the probe-to-surface distance for nano-DESI. This method is validated in mouse brain and kidney sections, showing its capability of sensitive resolving and imaging of the fatty acyl chain composition, the sn-position, and the C═C location of phospholipids in an MS3 scan. MS3 imaging of phospholipids has shown the capability of differentiation of cancerous, fibrosis, and adjacent normal regions in liver cancer tissues.

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke.

BACKGROUND: This study aimed to investigate regional levels of TAT (thrombin-antithrombin complex), PIC (plasmin-α2 plasmin inhibitor complex), t-PAIC (tissue plasminogen activator-plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D-dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. METHODS AND RESULTS: We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self-control) arterial compartments. Levels of TAT, PIC, t-PAIC, and D-dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1-unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03-1.145]; P=0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087-1.644]; P=0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1-unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016-1.139]; P=0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194-2.022]; P=0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615-0.961]; P=0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90-day outcome (modified Rankin scale of 3-6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P<0.01). CONCLUSIONS: We observed a hyperactive state of the coagulation-fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra-arterial procedures may provide additional information for stroke risk stratification and therapeutic decision-making, and warrants further investigation.

Early venous filling after mechanical thrombectomy in acute ischemic stroke due to large vessel occlusion in anterior circulation.

BACKGROUND: The significance of early venous filling (EVF) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) is not fully understood. In this study, we aimed to investigate the impact of EVF after MT. METHODS: From January 2019 to May 2022, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score (mTICI) ≥2b) after MT were retrospectively reviewed. EVF was evaluated on final digital subtraction angiography runs after successful recanalization and was categorized into phase subgroups (arterial phase and capillary phase) and pathway subgroups (cortical veins subgroup and thalamostriate veins subgroup), respectively. The impact of EVF subgroups on functional outcomes after successful recanalization were both investigated. RESULTS: A total of 349 patients achieving successful recanalization after MT were included, including 45 patients in the EVF group and 304 patients in the non-EVF group. Multivariable logistic regression analysis showed the EVF group had a higher rate of intracranial hemorrhage (ICH; 66.7% vs 22%, adjusted odds ratio (aOR) 6.805, 95% CI 3.389 to 13.662, P<0.001), symptomatic ICH (sICH; 28.9% vs 4.9%, aOR 6.011, 95% CI 2.493 to 14.494, P<0.001) and malignant cerebral edema (MCE; 20% vs 6.9%, aOR 2.682, 95% CI 1.086 to 6.624, P=0.032) than the non-EVF group. Furthermore, the cortical veins subgroup of EVF had a higher rate of mortality than the thalamostriate veins subgroup (37.5% vs 10.3%, P=0.029). CONCLUSIONS: EVF is independently associated with ICH, sICH and MCE after successful recanalization of MT, but not with favorable outcome and mortality.

Parallel Planar Heterojunction Strategy Enables Sb2 S3 Solar Cells with Efficiency Exceeding 8 .

Solution-processed solar cells based on inorganic heterojunctions provide a potential approach to the efficient, stable and low-cost solar cells required for the terrestrial generation of photovoltaic energy. Antimony trisulfide (Sb2 S3 ) is a promising photovoltaic absorber. Here, an easily solution-processed parallel planar heterojunction (PPHJ) strategy and related principle are developed to prepare efficient multiple planar heterojunction (PHJ) solar cells, and the PPHJ strategy boosts the efficiency of solution-processed Sb2 S3 solar cells up to 8.32 % that is the highest amongst Sb2 S3 devices. The Sb2 S3 -based PPHJ device consists of two kinds of conventional planar heterojunction (PHJ) subcells in a parallel connection: Sb2 S3 -based PHJ subcells dominating the absorption and charge generation and CH3 NH3 PbI3 -based PHJ subcells governing the electron transport towards collection electrode, but it belongs to an Sb2 S3 device in nature. The resulting PPHJ device combines together the distinctive structural features of Sb2 S3 absorbing layer as a main absorber and the duplexity of well-crystallized/oriented CH3 NH3 PbI3 layer in charge transportation as an additional absorber, while the presence of perovskite does not affect device stability. The PPHJ strategy maintains the facile preparation by the conventional sequential depositions of multiple layers, but eliminates the normal complexity in both tandem and parallel tandem PHJ systems.

Clinical evidence in ischemic stroke: Where we have gone so far and hopes for the future.

OBJECTIVE: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions. METHODS: Ischemic stroke-related RCT articles were identified in six high-impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted. RESULTS: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972-1982) to 208 (53.5%; 2013-2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke-related RCT articles. CONCLUSIONS: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions.

PHGDH promotes esophageal squamous cell carcinoma progression via Wnt/ß-catenin pathway.

PURPOSE: Esophageal squamous carcinoma (ESCC) with a high incidence in China, lacks effective therapeutic targets. Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in serine biosynthesis. However, the biological role of PHGDH in ESCC has not been revealed. METHODS: The expression of PHGDH in ESCC was investigated by UALCAN. The relationship between PHGDH expression and its prognostic value was analyzed by Kaplan-Meier and univariate Cox regression. Further, the potential functions of PHGDH involved in ESCC were explored through DAVID database and GSEA software. In addition, the expression of PHGDH was verified in ESCC. Then, the effects of PHGDH knockdown on ESCC were evaluated in vitro and in vivo by cell proliferation, clone formation, cell cycle, apoptosis, tube formation assays and ESCC cells derived xenograft model. In addition, western blotting and immunohistochemistry were used to detect the expression of Wnt/ß-catenin pathway which was associated with PHGDH. RESULTS: Bioinformatics analysis found that PHGDH was highly expressed in ESCC, and meaningfully, patients with high PHGDH expression had a poor prognosis. Moreover, the overexpression of PHGDH was verified in ESCC. Afterwards, PHGDH knockdown inhibited the cell proliferation, induced cell cycle arrest and apoptosis in ESCC cells, and inhibited the angiogenesis of HUVECs induced by ESCC conditioned medium, as well as inhibited the growth of xenograft tumor. Mechanistically, PHGDH knockdown inhibited Wnt/ß-catenin signaling pathway in ESCC. CONCLUSION: High expression of PHGDH predicts a poor prognosis for ESCC. PHGDH knockdown inhibits ESCC progression by suppressing Wnt/ß-catenin signaling pathway, indicating that PHGDH might be a potential target for ESCC therapy.

Diosmetin suppresses the progression of ESCC by CDK2/Rb/E2F2/RRM2 pathway and synergies with cisplatin.

Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.

Outcome after endovascular treatment for acute ischemic stroke by underlying etiology: Tertiary experience and meta-analysis.

Objective: To investigate the effect of two major etiologies [intracranial atherosclerotic stenosis (ICAS) and cardioembolism (CE])] on outcomes of acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO) after endovascular thrombectomy (EVT). Methods: Anterior circulation AIS patients receiving EVT were retrospectively analyzed. Clinical and laboratory data were collected. Clinical outcomes including favorable outcome (90-day modified Rankin Scale 0-2), mortality, intracranial hemorrhage (ICH) and symptomatic ICH (sICH) were compared. A systematic review and meta-analysis was also performed. Results: A total of 302 AIS patients were included and divided into the ICAS group (86 patients) and the CE group (216 patients). Patients in the ICAS group were younger (62[18.0] vs. 68[19.0] years, p < 0.001), more likely to have smoking (52.3% vs. 26.9%, p < 0.001) and drinking (52.3% vs. 23.1%, p < 0.001) history, and more frequently required rescue therapy (80.2% vs. 4.6%, p < 0.001) compared to the CE group. However, favorable outcome (aOR 0.722, 95%CI 0.372-1.402, p = 0.336) and mortality (aOR 1.522, 95%CI 0.606-3.831, p = 0.371) were not significantly different between the two groups before and after adjustment. The incidence of sICH and ICH were comparable between the two groups before and after adjustment. Systematic review and meta-analysis consisted of 8 eligible studies (7 previous studies and this current study), incorporating 552 ICAS patients and 1,402 CE patients. Favorable outcome was slightly more likely in the ICAS group compared to the CE group (54.2% vs. 46.3%, OR 1.40, 95%CI 1.00-1.96, I 2 = 53.2%). Moreover, the ICAS group had a lower rate of mortality (14.3% vs. 22.2%, OR 0.63, 95%CI 0.46-0.87, I 2 = 0.0%) and ICH (19.5% vs. 31.9%, OR 0.60, 95%CI 0.42-0.84, I 2 = 0.0%) than the CE group, while the two groups were similar in sICH rate (5.9% vs. 6.7%, OR 0.94, 95%CI 0.55-1.60, I 2 = 6.3%). Conclusion: Etiology was not considered as an important factor in functional outcome, despite the differences in baseline characteristics and technical EVT approach. The current study of anterior circulation AIS-LVO patients supports that outcomes for those with ICAS are not significantly different from those with CE.

Perspectives on miRNAs directly targeting BDNF for cancer diagnosis and treatment (Review).

MicroRNA (miRNA), a non­coding single­stranded RNA molecule with a length of 21­25 nucleotides transcripts, has been identified to play important roles in tumorigenesis and shows great potential applications in cancer diagnosis, prognosis and therapy. Brain derived neurotrophic factor (BDNF) is a member of the nerve growth factor family and usually serves as a biomarker in neurological and neuropsychiatric diseases for diagnosis and treatment by regulating its high­affinity receptor TrkB (Tyrosine Kinase Receptor B). Abnormal expression of BDNF is also closely related to the development of cancer, cancer­related pain and depression. However, little significant progress has been made in the application of BDNF in cancers. Recent studies have shown that the expression of BDNF is directly regulated by a cluster of miRNAs. This review concluded and discussed the role and mechanism of miRNAs targeting BDNF in cancers, and provided novel insights into the diagnosis and therapy of cancer in the future.

Tandem Mass Spectrometry Imaging Enables High Definition for Mapping Lipids in Tissues.

Mass spectrometry imaging (MSI) of lipids in biological tissues is useful for correlating molecular distribution with pathological results, which could provide useful information for both biological research and disease diagnosis. It is well understood that the lipidome could not be clearly deciphered without tandem mass spectrometry analysis, but this is challenging to achieve in MSI due to the limitation in sample amount at each image spot. Here we develop a multiplexed MS2 imaging (MS2 I) method that can provide MS2 images for 10 lipid species or more for each sampling spot, providing spatial structural lipidomic information. Coupling with on-tissue photochemical derivatization, imaging of 20 phospholipid C=C location isomers is also realized, showing enhanced molecular images with high definition in structure for mouse brain and human liver cancer tissue sections. Spatially mapped t-distributed stochastic neighbor embedding has also been adopted to visualize the tumor margin with enhancement by structural lipidomic information.

Clinical Significance and Influencing Factors of Microvascular Tissue Reperfusion After Macrovascular Recanalization.

The relevance of impaired microvascular tissue reperfusion despite successful macrovascular angiographic reperfusion (no-reflow) in acute ischemic stroke (AIS) remains controversial. In this study, we aimed to investigate the impact of tissue optimal reperfusion (TOR) and its influencing factors. From December 1, 2020 to December 1, 2021, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score [mTICI] ≥ 2b) after mechanical thrombectomy (MT) were retrospectively reviewed. Computed tomography perfusion was performed before and after MT. Successful reperfusion was assessed by TOR, defined as > 90% reduction of the Tmax > 6 s lesion volumes between baseline and early follow-up perfusion profiles. The impact of TOR on functional outcomes after successful recanalization and influencing factors for TOR were both investigated. Sixty-three patients were included, including 44 cases in the TOR group and 19 cases in the non-TOR group. The TOR group had a higher rate of favorable outcome (aOR 4.366, 95%CI 1.159-16.445, p = 0.030) and NIHSS improvement (aOR 5.089, 95%CI 1.340-19.322, p = 0.017) than the non-TOR group. Multivariable logistic regression showed baseline glucose (OR 0.648, 95%CI 0.492-0.854, p = 0.002) and mTICI 2c/3 (OR 10.984, 95%CI 2.220-54.343, p = 0.003) predicted TOR in model 1; in model 2, postoperative glucose (OR 0.468, 95%CI 0.278-0.787, p = 0.004) and mTICI 2c/3 (OR 9.436, 95%CI 1.889-47.144, p = 0.006) were predictive. TOR was strongly associated with good functional outcomes after successful recanalization of MT. Higher mTICI grade and lower perioperative glucose level may predict microvascular tissue reperfusion.

Mechanical thrombectomy first versus direct angioplasty or stenting for the treatment of intracranial atherosclerotic stenosis-related large vessel occlusion: protocol for a systematic review and meta-analysis.

INTRODUCTION: Mechanical thrombectomy (MT) using stent retrievers or a direct aspiration first-pass technique has proven to yield better results over intravenous thrombolysis in treating acute ischaemic stroke caused by large vessel occlusion (LVO). However, the treatment of intracranial atherosclerotic stenosis-related LVO remains unclear and has been a critical problem in daily clinical practice, as it can cause a relatively high failure rate for MT. Whether direct angioplasty and/or stenting is clinically feasible and shows advantage in reducing delay to revascularisation with better functional outcome compared with MT with rescue angioplasty and/or stenting remains unclear. This study seeks to provide direct and practical clinical evidence for clinicians. METHODS AND ANALYSIS: The main databases of PubMed, the Cochrane library, Embase and Web of Science will be screened for related studies published after1 January 2015. Primary outcomes include successful recanalisation and 90-day favourable outcome. Secondary outcomes include puncture to revascularisation time, vascular complication (perforation, dissection and vasospasm), intracerebral haemorrhage, hospital-related complications and 90-day mortality. The Newcastle-Ottawa Scale will be adopted to assess risk bias of observational studies. The I 2 statistic will be used to assess heterogeneity. ETHICS AND DISSEMINATION: No primary data of patients are needed. Therefore, ethics approval is unnecessary. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021268061.

Influence of pre-stroke dependency on safety and efficacy of endovascular therapy: A systematic review and meta-analysis.

Background and purpose: In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients. Methods: We searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality. Results: A total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSImRS≤2, PSDmRS>2 had a lower favorable outcome (OR 0.51; 95% CI, 0.33-0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77-3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58-2.49) remained significantly higher in PSDmRS>2. Compared with PSImRS≤1, PSDmRS>1 had lower 90-day mortality (OR, 3.10; 95% CI, 1.84-5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66-2.72) remained in PSDmRS>1. Conclusions: PSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.

Postoperative neutrophil-lymphocyte ratio predicts unfavorable outcome of acute ischemic stroke patients who achieve complete reperfusion after thrombectomy.

Purpose: Only approximately half of anterior circulation large vessel occlusion (LVO) patients receiving endovascular treatment (EVT) have a favorable outcome. The aim of this study was to explore the association of dynamic inflammatory markers (i.e., neutrophil to lymphocyte ratios, NLR, measured at different times after EVT) as well as other potential influencing factors with unfavorable outcome among acute ischemic stroke (AIS) patients who achieved complete reperfusion after EVT. Methods: Patients treated with EVT for LVO between January 2019 to December 2021 were prospectively enrolled. Complete reperfusion was defined as modified thrombolysis in cerebral infarction (mTICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as unfavorable outcome (i.e., futile reperfusion). A logistic regression analysis was performed with unfavorable outcome as a dependent variable. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were then used to determine the diagnostic values of NLR and other relevant factors. Results: 170 patients with complete reperfusion (mTICI 3) were included in this study. Unfavorable outcome was observed in 70 (41.2%). Higher NLR within 24h (p=0.017) and at 3-7d (p=0.008) after EVT were an independent risk factors for unfavorable outcome at 3 months. In addition, older age, higher NIHSS scores, poor collaterals, and general anesthesia were independent predictors of unfavorable outcomes. When accounting for NLR, the diagnostic efficiency improved compared to conventional characteristics. Conclusion: Our findings suggest that advanced age, increased stroke severity, poor collaterals, general anesthesia, and NLR are independent predictors for an unfavorable clinical outcome following complete reperfusion after EVT. Neuroinflammation may merit particular attention in future studies.