Functional Outcomes Associated With Blood Pressure Decrease After Endovascular Thrombectomy.

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.

Long-term outcomes of patients with embolic stroke of undetermined source according to subtype.

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305-4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108-5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.

Fatal Femoral Pseudoaneurysm Rupture after Endovascular Intervention: A Case Report and Literature Review.

A rupture of a femoral pseudoaneurysm is an extremely rare complication of endovascular procedures, but its outcome can be life-threatening. In this report, we present a case of a femoral pseudoaneursym rupture in a patient in their early 90s following intra-arterial mechanical thrombectomy for acute ischemic stroke. Despite receiving medical and surgical interventions, the patient subsequently developed multiple organ failure, ultimately resulting in death. This case emphasizes the critical role of appropriate selection of vascular closure technique and careful post-procedural monitoring, particularly in high-risk patients.

Combined use of anticoagulant and antiplatelet on outcome after stroke in patients with nonvalvular atrial fibrillation and systemic atherosclerosis.

This study aimed to investigate whether there was a difference in one-year outcome after stroke between patients treated with antiplatelet and anticoagulation (OAC + antiplatelet) and those with anticoagulation only (OAC), when comorbid atherosclerotic disease was present with non-valvular atrial fibrillation (NVAF). This was a retrospective study using a prospective cohort of consecutive patients with ischemic stroke. Patients with NVAF and comorbid atherosclerotic disease were assigned to the OAC + antiplatelet or OAC group based on discharge medication. All-cause mortality, recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction, and bleeding events within 1 year after the index stroke were compared. Of the 445 patients included in this study, 149 (33.5%) were treated with OAC + antiplatelet. There were no significant differences in all outcomes between groups. After inverse probability of treatment weighting, OAC + antiplatelet was associated with a lower risk of all-cause mortality (hazard ratio 0.48; 95% confidence interval 0.23-0.98; P = 0.045) and myocardial infarction (0% vs. 3.0%, P < 0.001). The risk of hemorrhagic stroke was not significantly different (P = 0.123). OAC + antiplatelet was associated with a decreased risk of all-cause mortality and myocardial infarction but an increased risk of ischemic stroke among patients with NVAF and systemic atherosclerotic diseases.

Spontaneous transfer of small peripheral peptides between supported lipid bilayer and giant unilamellar vesicles.

Vesicular trafficking facilitates material transport between membrane-bound organelles. Membrane protein cargos are trafficked for relocation, recycling, and degradation during various physiological processes. In vitro fusion studies utilized synthetic lipid membranes to study the molecular mechanisms of vesicular trafficking and to develop synthetic materials mimicking the biological membrane trafficking. Various fusogenic conditions which can induce vesicular fusion have been used to establish synthetic systems that can mimic biological systems. Despite these efforts, the mechanisms underlying vesicular trafficking of membrane proteins remain limited and robust in vitro methods that can construct synthetic trafficking systems for membrane proteins between large membranes (>1 µm2) are unavailable. Here, we provide data to show the spontaneous transfer of small membrane-bound peptides (∼4 kD) between a supported lipid bilayer (SLB) and giant unilamellar vesicles (GUVs). We found that the contact between the SLB and GUVs led to the occasional but notable transfer of membrane-bound peptides in a physiological saline buffer condition (pH 7.4, 150 mM NaCl). Quantitative and dynamic time-lapse analyses suggested that the observed exchange occurred through the formation of hemi-fusion stalks between the SLB and GUVs. Larger protein cargos with a size of ∼77 kD could not be transferred between the SLB and GUVs, suggesting that the larger-sized cargos limited diffusion across the hemi-fusion stalk, which was predicted to have a highly curved structure. Compositional study showed Ni-chelated lipid head group was the essential component catalyzing the process. Our system serves as an example synthetic platform that enables the investigation of small-peptide trafficking between synthetic membranes and reveals hemi-fused lipid bridge formation as a mechanism of peptide transfer.

Association of clot ultrastructure with clot perviousness in stroke patients.

Clot perviousness on computerized tomography (CT) is predictive of response to reperfusion therapy. This study aimed to determine the association of clot perviousness with ultrastructural features of clot in stroke patients undergoing endovascular thrombectomy. We quantitatively analyzed the ultrastructural components identified using scanning electron microscopy. The clot components were determined in the inner portions of the clots. Clot perviousness was assessed as thrombus attenuation increase (TAI) using noncontrast CT and CT angiography. We compared the association between the identified ultrastructural components and clot perviousness. The proportion of pores consisted of 3.5% on scanning electron microscopy images. The proportion of porosity in the inner portion was 2.5%. Among the ultrastructural components, polyhedrocytes were most commonly observed. The mean TAI was 9.3 ± 10.0 (median 5.6, interquartile range 1.1-14.3) Hounsfield units. TAI correlated positively with inner porosity (r = 0.422, p = 0.020). Among the ultrastructural clot components, TAI was independently associated with polyhedrocytes (B = - 0.134, SE = 0.051, p = 0.008). Clot perviousness is associated with porosity and the proportion of polyhdrocytes of clots.

Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke: The OPTIMAL-BP Randomized Clinical Trial.

Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (-15.1% [95% CI, -26.2% to -3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P = .03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, -5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P = .82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, -3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P = .31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305.

Delayed Migration of Tapered Open-Cell Design Carotid Stent: A Case Report.

We present a case of delayed migration of an open-cell design carotid stent, which is a rare complication following carotid artery stenting (CAS). A 65-year-old patient with carotid artery stenosis underwent CAS with an open-cell stent, initially achieving successful deployment. However, 4 months later, the stent migrated and resulted in restenosis. The patient underwent balloon angioplasty and received an additional stent, leading to improved blood flow. The rarity of stent migration, particularly in the absence of risk factors, highlights the need for clinicians to be vigilant and consider early imaging follow-up for patients at risk of this complication after CAS.

Prognostic value of central blood pressure on the outcomes of embolic stroke of undetermined source.

We investigated the prognostic impact of central blood pressure (BP) on outcomes in patients with embolic stroke of undetermined source (ESUS). The prognostic value of central BP according to ESUS subtype was also evaluated. We recruited patients with ESUS and data on their central BP parameters (central systolic BP [SBP], central diastolic BP [DBP], central pulse pressure [PP], augmentation pressure [AP], and augmentation index [AIx]) during admission. ESUS subtype classification was arteriogenic embolism, minor cardioembolism, two or more causes, and no cause. Major adverse cardiovascular event (MACE) was defined as recurrent stroke, acute coronary syndrome, hospitalization for heart failure, or death. Over a median of 45.8 months, 746 patients with ESUS were enrolled and followed up. Patients had a mean age of 62.8 years, and 62.2% were male. Multivariable Cox regression analysis showed that central SBP and PP were associated with MACE. All-cause mortality was independently associated with AIx. In patients with no cause ESUS, central SBP and PP, AP, and AIx were independently associated with MACE. AP and AIx were independently associated with all-cause mortality (all p < 0.05). We demonstrated that central BP can predict poor long-term prognosis in patients with ESUS, especially those with the no cause ESUS subtype.

Impact of Left Atrial or Left Atrial Appendage Thrombus on Stroke Outcome: A Matched Control Analysis.

BACKGROUND AND PURPOSE: Left atrial or left atrial appendage (LA/LAA) thrombi are frequently observed during cardioembolic evaluation in patients with ischemic stroke. This study aimed to investigate stroke outcomes in patients with LA/LAA thrombus. METHODS: This retrospective study included patients admitted to a single tertiary center in Korea between January 2012 and December 2020. Patients with nonvalvular atrial fibrillation who underwent transesophageal echocardiography or multi-detector coronary computed tomography were included in the study. Poor outcome was defined as modified Rankin Scale score >3 at 90 days. The inverse probability of treatment weighting analysis was performed. RESULTS: Of the 631 patients included in this study, 68 (10.7%) had LA/LAA thrombi. Patients were likely to have a poor outcome when an LA/LAA thrombus was detected (42.6% vs. 17.4%, P<0.001). Inverse probability of treatment weighting analysis yielded a higher probability of poor outcomes in patients with LA/LAA thrombus than in those without LA/LAA thrombus (P<0.001). Patients with LA/LAA thrombus were more likely to have relevant arterial occlusion on angiography (36.3% vs. 22.4%, P=0.047) and a longer hospital stay (8 vs. 7 days, P<0.001) than those without LA/LAA thrombus. However, there was no difference in early neurological deterioration during hospitalization or major adverse cardiovascular events within 3 months between the two groups. CONCLUSIONS: Patients with ischemic stroke who had an LA/LAA thrombus were at risk of a worse functional outcome after 3 months, which was associated with relevant arterial occlusion and prolonged hospital stay.

Association between blood viscosity and early neurological deterioration in lacunar infarction.

Background: Understanding the factors related to early neurologic deterioration (END) is crucial in the management of patients with lacunar infarction. Blood viscosity is a significant factor for microvascular perfusion. We investigated the association between blood viscosity and occurrence of END in lacunar infarction. Methods: We included consecutive patients admitted for lacunar infarction within 72 h from symptoms onset. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score ≥2 within 24 h of admission. Viscosity was measured within 24 h of hospitalization with a scanning capillary tube viscometer. Viscosity measured at a shear rate of 300 s-1 was defined as systolic blood viscosity (SBV), whereas that measured at a shear rate of 5 s-1 as diastolic blood viscosity (DBV). Results: Of the 178 patients included (median age, 65.5; interquartile range [IQR], 56.0, 76.0], END occurred in 33 (18.5%). DBV was significantly higher in patients with END than those without END (13.3 mPa·s [IQR 11.8, 16.0] vs. 12.3 mPa·s [IQR11.0, 13.5]; P = 0.023). In the multivariate analysis, DBV was independently associated with the occurrence of END (odds ratio 1.17; 95% confidence interval 1.01-1.36; P = 0.043). Subgroup analysis showed no heterogeneity in the effect of viscosity on the occurrence of END. Conclusions: Blood viscosity at a low shear rate (DBV) was associated with the occurrence of END in patients with lacunar infarction. Blood rheology may be important in pathophysiology of END in patients with lacunar infarction.

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

BACKGROUND: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. METHODS: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. RESULTS: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. CONCLUSIONS: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Early depression screening and short-term functional outcome in hospitalized patients for acute ischemic stroke.

Background: Patients with ischemic stroke are at high risk for post-stroke depression (PSD). There are limited data regarding the clinical impact of early PSD, assessed in hospitalized patients with acute ischemic stroke. Methods: This hospital-based observational cohort study included consecutive patients with acute ischemic stroke or transient ischemic attack between July 2019 and June 2021. In the study hospital, all admitted patients were systematically screened for depression. The depression was screened using the Patient Health Questionnaire-9 (PHQ-9), and PHQ-9 positivity indicated early PSD, which was defined as a score of >4. Logistic regression analyses were used to compare the rates of poor functional outcomes at 3 months in patients with and without PHQ-9 positivity. Results: Among 1339 patients admitted during the study period, 775 were included, with a median age of 68.0 years, and 316 (40.8%) were women. A total of 111 (14.3%) patients were PHQ-9 positive. History of cancer and early neurological deterioration were independently associated with PHQ-9 positivity. Poor functional outcomes at 3 months were observed in 147 patients (18.8%). PHQ-9 positivity independently showed a 2.2-fold increased risk of poor functional outcome at 3 months (Odds ratio 2.23; 95% confidence interval 1.05-4.73, P = 0.037). Conclusions: Patients with history of cancer and early neurological deterioration were at risk for early PSD. Early PSD was independently associated with poor functional outcomes at 3 months. The identification of early depression could offer opportunities for further questioning and exploration of symptoms, as well as interventions.

Association between Low Ankle-Brachial Index and Poor Outcomes in Patients with Embolic Stroke of Undetermined Source.

We investigated the association of low ankle-brachial index (ABI < 0.9) with major adverse cardiovascular events (MACE) and all-cause mortality in patients with embolic stroke of undetermined source (ESUS) as well as whether the association differed by ESUS subtype. This retrospective single-center study included ESUS patients who underwent transesophageal echocardiography and ABI during hospitalization. ESUS was classified as ESUS with minor cardioembolic source, arteriogenic embolism, two or more causes, or no cause. Arteriogenic embolism was defined and classified as complex aortic or non-stenotic relevant artery plaque. MACE was defined as stroke recurrence, acute coronary syndrome, hospitalization for heart failure, or death. Overall, 829 patients were included, with a median follow-up of 45.8 months. Of these, 42 (5.1%) and 370 (44.6%) had low ABI and arteriogenic embolism, respectively. ABI < 0.9 was independently associated with MACE (hazard ratio [HR]: 2.038, 95% confidence interval [CI]: 1.093−3.801) and all-cause mortality (HR: 3.608, 95% CI: 1.538−8.465) according to the multivariable Cox regression analysis. Between ESUS subtypes, low ABI was independently associated with MACE (HR: 2.513, 95% CI: 1.257−5.023) and all-cause mortality (HR: 5.681, 95% CI: 2.151−15.008) in arteriogenic embolism patients, especially in those with complex aortic plaque. However, in non-arteriogenic embolism patients, low ABI was not related to MACE and mortality. In ESUS patients, low ABI was linked to MACE and all-cause mortality, especially in those with arteriogenic embolisms from complex aortic plaque.

Prediction of Hidden Coronary Artery Disease Using Machine Learning in Patients With Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: A machine learning technique for identifying hidden coronary artery disease (CAD) might be useful. We developed and validated machine learning models to predict patients with hidden CAD and to assess long-term outcomes in patients with acute ischemic stroke. METHODS: Multidetector coronary CT was performed for patients without a known history of CAD. Primary outcomes were defined as having any degree of CAD and having obstructive CAD (≥50% stenosis). Demographic variables, risk factors, laboratory results, Trial of ORG 10172 in Acute Stroke Treatment classification, NIH Stroke Scale score, blood pressure, and carotid artery stenosis were used to develop and validate machine learning models to predict CAD. Area under the receiver operating characteristic curves (AUC) was calculated for performance analysis, and Kaplan-Meier and Cox survival analyses of long-term outcomes were performed. Major adverse cardiovascular events (MACEs) were defined as ischemic stroke, myocardial infarction, unstable angina, urgent coronary revascularization, and cardiovascular mortality. RESULTS: Overall, 1,710 patients were included for the training dataset and 348 patients for the validation dataset. An extreme gradient boosting model was developed to predict any degree of CAD, which showed an AUC of 0.763 (95% CI 0.711-0.814) on validation. A logistic regression model was used to predict obstructive CAD and had an AUC of 0.714 (95% CI 0.692-0.799). During the first 5 years of follow-up, MACEs occurred more frequently with predictions of any CAD (p = 0.022) or obstructive CAD (p < 0.001). Cox proportional analysis showed that the hazard ratio of MACE was 1.5 (95% CI 1.1-2.2; p = 0.016) with prediction of any CAD, whereas it was 1.9 (95% CI 1.3-2.6; p < 0.001) for obstructive CAD. DISCUSSION: We demonstrated that machine learning may help identify hidden CAD in patients with acute ischemic stroke. Long-term outcomes were also associated with prediction results. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke with CAD risk factors but no known history of CAD, a machine learning model predicts CAD on multidetector coronary CT with an AUC of 0.763 (95% CI 0.711-0.814).

Impact of Sarcopenia on Functional Outcomes Among Patients With Mild Acute Ischemic Stroke and Transient Ischemic Attack: A Retrospective Study.

Introduction: Sarcopenia, a age-related disease characterized by loss of muscle mass accompanied by loss of function, is associated with nutrition imbalance, physical inactivity, insulin resistance, inflammation, metabolic syndrome, and atherosclerosis which are risk factors for cardiovascular disease. However, its association with outcomes after ischemic stroke has not been well-established. This study investigated whether functional outcomes of patients with acute ischemic stroke is associated with sarcopenia. Methods: Data were collected from 568 consecutive patients with acute ischemic stroke with National Institute of Health Stroke Scale 0-5 or transient ischemic attack who underwent bioelectrical impedance analysis between March 2018 and March 2021. Sarcopenia was defined, as low muscle mass, as measured by bioelectrical impedance analysis, and low muscle strength, as indicated by the Medical Research Council score. Unfavorable functional outcome was defined as mRS score of 2-6 at 90 days after discharge. The relationship between functional outcomes and the presence of sarcopenia or its components was determined. Results: Of the 568 patients included (mean age 65.5 ± 12.6 years, 64.6% male), sarcopenia was detected in 48 (8.5%). After adjusting for potential confounders, sarcopenia was independently and significantly associated with unfavorable functional outcome (odds ratio 2.37, 95% confidence interval 1.15-4.73 for unfavorable functional outcome, odds ratio 2.10, 95% confidence interval 1.18-3.71 for an increase in the mRS score). Each component of sarcopenia was also independently associated with unfavorable functional outcome (odds ratio 1.76, 95% confidence interval 1.05-2.95 with low muscle mass, odds ratio 2.64, 95% confidence interval 1.64-4.23 with low muscle strength). The impact of low muscle mass was larger in men than in women, and in patients with lower muscle mass of the lower extremities than in those with lower muscle mass of the upper extremities. Conclusions: In this study, the prevalence of sarcopenia in patients with stroke was lower than most of previous studies and patients with sarcopenia showed higher likelihood for unfavorable functional outcomes at 90 days after acute ischemic stroke or TIA. Further investigation of the interventions for treating sarcopenia and its impact on the outcome of ischemic stroke patients is needed.

Membrane Cargo Density-Dependent Interaction between Protein and Lipid Domains on the Giant Unilamellar Vesicles.

Protein cargos anchored on the lipid membrane can be segregated by fluidic domain phase separation. Lipid membranes at certain compositions may separate into lipid domains to segregate cargos, and protein cargos themselves may be involved in protein condensate domain formation with multivalent binding proteins to segregate cargos. Recent studies suggest that these two driving forces of phase separation closely interact on the lipid membranes to promote codomain formation. In this report, we studied the effect of cargo density on the outcome of the cargo phase separation on giant unilamellar vesicles. Proteins and lipids are connected only by the anchored cargos, so it was originally hypothesized that higher cargo density would increase the degree of interaction between the lipid and protein domains, promoting more phase separation. However, fluorescence image analysis on different cargo densities showed that the cooperative domain formation and steric pressure are at a tug of war opposing each other. Cooperative domain formation is dominant under lower anchor density conditions, and above a threshold density, steric pressure was dominant opposing the domain formation. The result suggests that the cargo density is a key parameter affecting the outcome of cargo organization on the lipid membranes by phase separation.

Intelligent fluorescence image analysis of giant unilamellar vesicles using convolutional neural network.

BACKGROUND: Fluorescence image analysis in biochemical science often involves the complex tasks of identifying samples for analysis and calculating the desired information from the intensity traces. Analyzing giant unilamellar vesicles (GUVs) is one of these tasks. Researchers need to identify many vesicles to statistically analyze the degree of molecular interaction or state of molecular organization on the membranes. This analysis is complicated, requiring a careful manual examination by researchers, so automating the analysis can significantly aid in improving its efficiency and reliability. RESULTS: We developed a convolutional neural network (CNN) assisted intelligent analysis routine based on the whole 3D z-stack images. The programs identify the vesicles with desired morphology and analyzes the data automatically. The programs can perform protein binding analysis on the membranes or state decision analysis of domain phase separation. We also show that the method can easily be applied to similar problems, such as intensity analysis of phase-separated protein droplets. CNN-based classification approach enables the identification of vesicles even from relatively complex samples. We demonstrate that the proposed artificial intelligence-assisted classification can further enhance the accuracy of the analysis close to the performance of manual examination in vesicle selection and vesicle state determination analysis. CONCLUSIONS: We developed a MATLAB based software capable of efficiently analyzing confocal fluorescence image data of giant unilamellar vesicles. The program can automatically identify GUVs with desired morphology and perform intensity-based calculation and state decision for each vesicle. We expect our method of CNN implementation can be expanded and applied to many similar problems in image data analysis.

Lipid Raft Phase Modulation by Membrane-Anchored Proteins with Inherent Phase Separation Properties.

Cell plasma membranes are a heterogeneous mixture of lipids and membrane proteins. The importance of heterogeneous lipid domains (also called lipid rafts) as a molecular sorting platform has been implicated in many physiological processes. Cell plasma membranes that are detached from the cytoskeletal structure spontaneously phase separate into distinct domains at equilibrium, which show their inherent demixing properties. Recently, researchers have discovered that proteins with strong interprotein interactions also spontaneously phase separate into distinct protein domains, thus enabling the maintenance of many membraneless organelles. Protein phase separation may also take place on the lipid membranes via lipid-anchored proteins, which suggests another potential molecular sorting platform for physiological processes on the cell membrane. When two-phase separation properties coexist physiologically, they may change the resulting phase behavior or serve as independent sorting platforms. In this paper, we used in vitro reconstitution and fluorescence imaging to systematically quantify the phase behavior that arises when proteins with inherent phase separation properties interact with raft mixture lipid membranes. Our observations and simulations show both that the proteins may enhance lipid phase separation and that this is a general property of phase-separating protein systems with a diverse number of components involved. This suggests that we should consider the overall effect of the properties of both membrane-anchored proteins and lipids when interpreting molecular sorting phenomena on the membranes.