Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Endovascular thrombectomy versus medical management for patients with large vessel stroke and infective endocarditis.

BACKGROUND: The safety and efficacy of endovascular thrombectomy (EVT) for large vessel occlusion (LVO) strokes associated with infective endocarditis (IE) compared with medical management (MM) is unclear. METHODS: In this nationwide analysis of hospitalizations in the United States, we assessed the outcomes of EVT versus medical management (MM) for patients with LVO and IE. Primary outcome was routine home discharge with self-care. Secondary outcomes include home discharge, in-hospital mortality, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Propensity score matching (PSM) was performed to adjust for confounders. Additional multivariable adjustments were performed for doubly robust analyses. RESULTS: 2574 patients were identified; 656 (25.5%) received EVT. After PSM, the rate of routine discharge was significantly higher for patients with EVT compared with MM (14.6% vs 8.5%, p=0.021), and patients with EVT had significantly higher rate of home discharge (34.5% vs 26.5%, p=0.041), lower rate of in-hospital death (14.8% vs 25.2%, p=0.002), and lower rate of ICH (15.8% vs 23.1%, p=0.039). EVT was not associated with a different rate of SAH compared with MM (11.2% vs 7.9%, p=0.17). These associations remained unchanged with additional multivariable adjustments. CONCLUSION: For patients with LVO stroke and IE, EVT was associated with significantly higher odds of favorable hospitalization outcomes and lower odds of ICH compared with MM.

Ambient catalyst-free oxidation reactions of aromatic amines using water radical cations.

Water radical cations play a pivotal role in various scientific and industrial fields due to their unique reactivity and capacity to drive complex chemical transformations. Here we explored the formation of quaternary ammonium cations through the direct oxidation reaction of aromatic amines, facilitated by water radical cations within water microdroplets. This process was monitored via in situ mass spectrometry and occurs under ambient conditions, negating the need for traditional chemical catalysts or oxidants and achieving an impressive yield of approximately 80%. Additionally, we employed a multi-channel spray system and enhanced both the reactant concentration and flow rate, thereby enabling gram-scale synthesis. These findings not only demonstrate the effectiveness and eco-friendliness of microdroplet chemistry but also provide a new understanding of heterogeneous ˙OH generation channels, thereby boosting the synthetic efficiency and sustainability of chemical processes.

Post-Thrombectomy Subarachnoid Hemorrhage: Incidence, Predictors, Clinical Relevance, and Effect Modulators.

BACKGROUND: Subarachnoid hemorrhage (SAH) following endovascular thrombectomy (EVT) is a poorly understood phenomenon, and whether it is associated with clinical detriment is unclear. METHODS: This was an explorative analysis of a national database of real-world hospitalizations in the United States. Patients who underwent EVT were included. Patients were divided into SAH and non-SAH groups, and hospitalization outcomes were compared using multivariable logistic regression models. Regression models were also used to identify significant predictors for post-EVT SAH, and significant modulators of SAH's association with hospitalization outcomes were also assessed. RESULTS: A total of 99,219 EVT patients were identified; 6174 (6.2%) had SAH. Overall, SAH was independently associated with increased odds of in-hospital mortality (21.5% vs. 10.6%, adjusted OR 2.53 [95%CI 2.23-2.87], p < 0.001) and lower odds of routine discharge to home with self-care (18.2% vs. 28.0%, aOR 0.58 [95%CI 0.52-0.65], p < 0.001). Distal/medium vessel occlusion (DMVO), coagulopathy, angioplasty or stenting, concurrent intraparenchymal hemorrhage (IPH), and female sex were associated with higher odds of SAH. DMVO was associated with particularly heightened risk of death (31.8% vs. 7.9%, aOR 6.99 [95%CI 2.99 to 16.3], p < 0.001), which was an effect size significantly larger than other sites of vascular occlusion (interaction p > 0.05). CONCLUSION: SAH is an uncommon but likely clinically detrimental post-EVT complication. DMVO, coagulopathy, angioplasty or stenting, concurrent IPH, and female sex were independently associated with higher odds of post-EVT SAH. SAH associated with DMVO-EVT may be particularly harmful.

MR Imaging-Guided Focused Ultrasound-Clinical Applications in Managing Malignant Gliomas.

Malignant gliomas (MGs) are the most common primary brain tumors in adults. Despite recent advances in understanding the biology and potential therapeutic vulnerabilities of MGs, treatment options remain limited as the delivery of drugs is often impeded by the blood-brain barrier (BBB), and safe, complete surgical resection may not always be possible, especially for deep-seated tumors. In this review, the authors highlight emerging applications for MR imaging-guided focused ultrasound (MRgFUS) as a noninvasive treatment modality for MGs. Specifically, the authors discuss MRgFUS's potential role in direct tumor cell killing, opening the BBB, and modulating antitumor immunity.

Mediators of sex-specific differences in rates of stroke mimics among patients treated with intravenous thrombolysis: A nationwide analysis of 174,995 patients.

INTRODUCTION: Women are at higher risk of stroke mimics; however, the underlying reasons are unclear. METHODS: In this retrospective cohort study of the 2016-2020 National Inpatient Sample database, we identified patients treated with intravenous thrombolysis (IVT). Demographic information, vascular risk factors, comorbidities, and presence of known risk factors for stroke mimics (seizures, migraines, demyelinating diseases, psychiatric illnesses, and functional neurological disorders [FND]) were identified using ICD-10 codes. Rates of no cerebral infarction (NCI) were compared between men and women. Mediation analyses were conducted to identify significant drivers of sex-specific differences in the rate of NCI. RESULTS: 174,995 IVT-treated patients were identified; 41,605 (23.8 %) had NCI. Female patients had significantly higher rates of NCI compared to men (26.2 % vs. 20.9 %, p < 0.001). Women had significantly higher rates of stroke mimic risk factors (seizures, migraines, demyelinating disease, anxiety, depression, FND, and electrolyte derangements; all p < 0.001). Mediation analyses revealed that 39.8 %, 19.1 % of female sex's association with higher rates of NCI were mediated by higher rates of migraines and FND among women, respectively (both p < 0.001). CONCLUSIONS: IVT-treated women were more likely to have NCI than men. This relationship was largely mediated by higher rates of migraine and FND among women.

Endovascular Stroke Thrombectomy for Patients With Large Ischemic Core: A Review.

Importance: Recently, 6 randomized clinical trials-RESCUE-Japan-LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial), ANGEL-ASPECT (Trial of Endovascular Therapy for Acute Ischemic Stroke With Large Infarct), SELECT2 (Trial of Endovascular Thrombectomy for Large Ischemic Strokes), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke), TENSION (Endovascular Thrombectomy for Acute Ischemic Stroke With Established Large Infarct), and LASTE (Large Stroke Therapy Evaluation)-have concluded their investigations on the efficacy and safety of endovascular thrombectomy (EVT) for the treatment of patients with ischemic stroke, anterior-circulation large vessel occlusions, and large areas of ischemic changes defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 5 or less. Overall, the results appeared to be positive, with 5 of the 6 trials meeting their primary efficacy end point, and 1 trial that was a near miss. However, questions remain regarding how these trial results should be interpreted and incorporated into routine clinical practice. Observations: In this narrative review and analysis of published trials, important nuances of the available clinical data were identified, and important areas of lingering uncertainty were highlighted, including the efficacy and safety of EVT for patients with a low ASPECTS score in late treatment windows and those with large core volumes. Also emphasized was the possibly important role of advanced neuroimaging modalities such as perfusion and magnetic resonance imaging when making EVT treatment decisions for select patients with low ASPECTS scores. Conclusions and Relevance: Recent trial data provide strong evidence that EVT is safe and effective for patients with anterior, large vessel-occlusion stroke and low ASPECTS scores who present within 6 hours from stroke onset. However, patient outcomes often remain poor despite EVT treatment. The efficacy and safety of EVT for patients with low ASPECTS scores who present beyond 6 hours of stroke onset remain uncertain, and the current trial data seem too scarce to justify forgoing advanced stroke imaging during this extended time window. Furthermore, the efficacy and safety of EVT for patients with large core volumes (100 mL or greater) or M2 occlusions (ie, occlusions of the second segment of the middle cerebral artery) remain uncertain. Future research to better identify patients likely to meaningfully respond to EVT is needed to further optimize the stroke triage process and health care resource utilization.

Endovascular thrombectomy versus medical management for acute basilar artery occlusion stroke in the elderly.

BACKGROUND AND PURPOSE: The efficacy and safety of endovascular thrombectomy (EVT) for elderly basilar artery occlusion (BAO) stroke patients is unclear. MATERIALS AND METHODS: This was an explorative retrospective analysis of the 2016-21 National Inpatient Sample in the United States. Elderly BAO stroke patients (80 years or older) with NIH stroke scale of at least 5 were included. Primary outcome was discharge to home. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Outcomes were compared between patients treated with EVT and those treated with medical management (MM) alone. Propensity score matching (PSM) was performed to control for confounders. Subgroup analyses were conducted for patients who did and did not receive intravenous thrombolysis (IVT). RESULTS: 2,520 elderly BAO patients were identified; 830 received EVT, and 1,690 received MM alone. After PSM, 1,115 patients and 715 patients remained in the MM and EVT groups, respectively. Compared to PSM controls, EVT was not significantly associated with different rates of home discharge (17.5% vs. 12.2%, OR 1.36 [95%CI 0.76-2.44], p=0.30) or in-hospital mortality (31.5% vs. 32.9%, OR 1.00 [95%CI 0.63-1.60], p=0.99), but it was significantly associated with higher rates of ICH (18.2% vs. 7.3%, OR 2.69 [95%CI 1.41- 5.15], p=0.003). Among patients who did not receive IVT, EVT was significantly associated with higher rates of home discharge (21.5% vs. 11.5%, OR 1.93 [95%CI 1.02-3.66], p=0.044), whereas EVT was not significantly associated with the same among those treated with IVT (5.6% vs. 15.0%, OR 0.28 [95%CI 0.05-1.46], p=0.13). Interaction analysis revealed that IVT was a negative modulator of EVT's positive association with home discharge (interaction p=0.031). CONCLUSIONS: EVT was not significantly associated with more favorable hospitalization outcomes for elderly BAO stroke patients, and it was significantly associated with increased risk of ICH. EVT may be an effective treatment for patients who did not receive IVT. ABBREVIATIONS: EVT = endovascular thrombectomy; BAO = basilar artery occlusion; ICH = intracranial hemorrhage; MM = medical management; PSM = propensity score matching; IVT = intravenous thrombolysis.

Endovascular thrombectomy versus medical management for moderate-to-severe anterior cerebral artery occlusion stroke.

BACKGROUND: There are no established patient selection criteria for endovascular thrombectomy (EVT) for anterior cerebral artery (ACA) stroke. METHODS: This was a retrospective cohort study of the 2016-2020 National Inpatient Sample in the United States. Isolated ACA-occlusion stroke patients with moderate-to-severe stroke symptoms (NIH stroke scale [NIHSS] ≥ 6) were included. Primary outcome was hospital discharge to home with self-care. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Confounders were accounted for by multivariable logistic regression. RESULTS: 6685 patients were included; 335 received EVT. Compared to medical management (MM), EVT patients were younger (mean 67.2 versus 72.2 years; p = 0.014) and had higher NIHSS (mean 16.0 versus 12.5; p < 0.001). EVT was numerically but not statistically significantly associated with higher odds of home discharge compared to MM (aOR 2.26 [95%CI 0.99-5.17], p = 0.053). EVT was significantly associated with higher odds of home discharge among patients with NIHSS 10 or greater (aOR 3.35 [95%CI 1.06-10.58], p = 0.039), those who did not receive prior thrombolysis (aOR 3.96 [95%CI 1.53-10.23], p = 0.005), and those with embolic stroke etiology (aOR 4.03 [95%CI 1.21-13.47], p = 0.024). EVT was not significantly associated with higher rates of mortality (aOR 1.93 [95%CI 0.80-4.63], p = 0.14); however, it was significantly associated with higher rates of ICH (22.4% vs. 8.5%, p < 0.001). CONCLUSION: EVT was associated with higher odds of favorable short-term outcomes for moderate-to-severe ACA-occlusion stroke in select patients. Future studies are needed to confirm the efficacy of EVT in terms of longer term neurological outcomes.

Demethylation C-C coupling reaction facilitated by the repulsive Coulomb force between two cations.

Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C-C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C-C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

Rapid in situ identification of honey authenticity based on RP-Nano-ESI-MS using online desalting.

High-content sugar in honey frequently results in severe matrix effects and requires complex pretreatment prior to analysis, posing significant challenges for the rapid analysis of honey. In this study, the reversal polarity nano-electrospray ionization mass spectrometry (RP-Nano-ESI-MS) analysis was developed for the direct evaluation of honey samples. The results indicated that RP-Nano-ESI-MS significantly mitigated the matrix effects induced by high-content sugar through the implementation of online desalting. Furthermore, RP-Nano-ESI-MS has been proven capable of not only differentiating acacia honey adulterated with 10% rape honey, but also effectively distinguishing six types of honey and exhibiting remarkable proficiency in detecting honey adulteration and botanical traceability. Additionally, RP-Nano-ESI-MS exhibited strong quantitative abilities, effectively characterizing variations in amino acid composition among six types of honey with high stability and reproducibility. Our studies underscore the significant potential of RP-Nano-ESI-MS for its rapid in situ analysis of sugar-rich foods like honey, especially in their authenticity verification.

SOFIA Aspiration System as first-line Technique (SOFAST): a prospective, multicenter study to assess the efficacy and safety of the 6 French SOFIA Flow Plus aspiration catheter for endovascular stroke thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). The SOFAST study collected clinical evidence on the safety and efficacy of the 6 French SOFIA Flow Plus aspiration catheter (SOFIA 6F) when used as first-line treatment. METHODS: This was a prospective, multicenter investigation to assess the safety and efficacy of SOFIA 6F used for first-line aspiration. Anterior circulation LVO stroke patients were enrolled. The primary endpoint was the final modified Thrombolysis in Cerebral Infarction (mTICI)≥2b rate. Secondary endpoints included first-pass and first-line mTICI≥2b rates, times from arteriotomy to clot contact and mTICI≥2b, and 90-day modified Rankin Scale (mRS)≤2. First-line and final mTICI scores were adjudicated by an independent imaging core lab. Safety events were assessed by an independent clinical events adjudicator. RESULTS: A total of 108 patients were enrolled across 12 centers from July 2020 to June 2022. Median age was 67 years, median National Institutes of Health Stroke Scale (NIHSS) was 15.5, and 56.5% of patients received intravenous thrombolytics. At the end of the procedure, 97.2%, 85.2%, and 55.6% of patients achieved mTICI≥2b, ≥2c, and 3, respectively. With SOFIA 6F first-line aspiration, 87.0%, 79.6%, and 52.8% achieved mTICI≥2b, ≥2c, and 3, respectively. After the first pass, 75.0%, 70.4%, and 50.9% achieved mTICI≥2b, ≥2c, and 3, respectively. Median times from arteriotomy to clot contact and successful revascularization were 12 and 17 min, respectively. At 90 days, 66.7% of patients achieved mRS≤2. CONCLUSIONS: First-line aspiration with SOFIA 6F is safe and effective with high revascularization rates and short procedure times.

Gold nanoclusters cure implant infections by targeting biofilm.

The biofilm-mediated implant infections pose a huge threat to human health. It is urgent to explore strategies to reverse this situation. Herein, we design 3-amino-1,2,4-triazole-5-thiol (ATT)-modified gold nanoclusters (AGNCs) to realize biofilm-targeting and near-infrared (NIR)-II light-responsive antibiofilm therapy. The AGNCs can interact with the bacterial extracellular DNA through the formation of hydrogen bonds between the amine groups on the ATT and the hydroxyl groups on the DNA. The AGNCs show photothermal properties even at a low power density (0.5 W/cm2) for a short-time (5 min) irradiation, making them highly effective in eradicating the biofilm with a dispersion rate up to 90 %. In vivo infected catheter implantation model demonstrates an exceptional high ability of the AGNCs to eradicate approximately 90 % of the bacteria encased within the biofilms. Moreover, the AGNCs show no detectable toxicity or systemic effects in mice. Our study suggests the great potential of the AGNCs for long-term prevention and elimination of the biofilm-mediated infections.

Focal Status Epilepticus and Extreme Delta Brush Associated With Thrombotic Thrombocytopenic Purpura.

Acute focal neurological deficits demand immediate evaluation. In this report, we present the case of a woman 20-some years of age with a history of hemolytic anemia and thrombocytopenia who presented with altered mental status and focal neurological deficits including aphasia, acute left gaze preference, right homonymous hemianopsia, right lower facial weakness, and right arm and leg weakness. Extensive neurological and hematological workup revealed that the patient suffered from focal status epilepticus associated with an extreme delta brush patten on electroencephalogram, likely secondary to thrombotic thrombocytopenic purpura. This case underscores the connection between hematological disorders and the neurological axis, emphasizing the critical role of integrating the neurological examination and neuroimaging findings to formulate an effective management plan.

Machine Learning-Based Integrated Multiomics Characterization of Colorectal Cancer Reveals Distinctive Metabolic Signatures.

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.

Advances in chronic subdural hematoma and membrane imaging.

Chronic subdural hematoma (cSDH) is projected to become the most common cranial neurosurgical disease by 2030. Despite medical and surgical management, recurrence rates remain high. Recently, middle meningeal artery embolization (MMAE) has emerged as a promising treatment; however, determinants of disease recurrence are not well understood, and developing novel radiographic biomarkers to assess hematomas and cSDH membranes remains an active area of research. In this narrative review, we summarize the current state-of-the-art for subdural hematoma and membrane imaging and discuss the potential role of MR and dual-energy CT imaging in predicting cSDH recurrence, surgical planning, and selecting patients for embolization treatment.

Predicting effect of anti-PD-1/PD-L1 inhibitors therapy for hepatocellular carcinoma by detecting plasma metabolite based on UHPLC-MS.

Introduction: Anti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy. Methods: Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS. Results: A partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy. Discussion: This study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.