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Background and Purpose: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD. Methods: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 at admission) and control (eGFR ≥60 mL/min/1.73 m2) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound. Results: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m2 at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85–1.57 vs. controls 0.84, IQR: 0.54–1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1–3 vs. controls median score 1, IQR: 0–2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051–20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038–1.114) as independent predictors of a high PI. Conclusions: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful. [ABSTRACT FROM AUTHOR]

In this technical report, we describe a challenging case concerning the retrieval of a distal embolic protection device (DEPD) post-carotid artery stenting. We propose a novel rescue retrieval technique for DEPD, employing a fabricated monorail-type HN5 diagnostic catheter. When integrated with existing strategies, this approach may optimize and streamline the process of DEPD removal. [ABSTRACT FROM AUTHOR]

In this technical report, we describe a challenging case concerning the retrieval of a distal embolic protection device (DEPD) post-carotid artery stenting. We propose a novel rescue retrieval technique for DEPD, employing a fabricated monorail-type HN5 diagnostic catheter. When integrated with existing strategies, this approach may optimize and streamline the process of DEPD removal. [ABSTRACT FROM AUTHOR]

Melanin pigments are the primary contributors for the skin color. They are produced in melanocytes and then transferred to keratinocytes, eventually giving various colors on skin surface. Although many depigmenting and/or skin-lightening agents have been developed, there is still a growing demand on materials for reducing pigmentation. We attempted to find materials for depigmentation and/or skin-lightening using the small molecule compounds commercially available, and found that 5-iodotubercidin had inhibitory potential on pigmentation. When HM3KO melanoma cells were treated with 5-iodotubercidin, pigmentation was dramatically reduced. The 5-iodotubercidin decreased the protein level for pigmentation-related molecules such as MITF, tyrosinase, and TRP1. In addition, 5-iodotubercidin decreased the phosphorylation of CREB, while increased the phosphorylation of AKT and ERK. These data suggest that 5-iodotubercidin inhibits melanogenesis via the regulation of intracellular signaling related with pigmentation. Finally, 5-iodotubercidin markedly inhibited the melanogenesis of zebrafish embryos, an in vivo evaluation model for pigmentation. Together, these data suggest that 5-iodotubercidin can be developed as a depigmenting and/or skin-lightening agent. [ABSTRACT FROM AUTHOR]

Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke. [ABSTRACT FROM AUTHOR]

Objective: Although blood pressure (BP) variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT.Methods: A total of 211 patients with acute ischemic stroke and successful recanalization (thrombolysis in cerebral infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP. sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale.Results: Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio = 1.71, 95% confidence interval = 1.013-2.886).Interpretation: Time-related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP levels. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT. Ann Neurol 2019;85:574-581. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of mechanical thrombectomy (MT) in cancer-related stroke (CRS) is largely unknown. This study aims to investigate the clinical and radiological outcomes of MT in CRS patients. We also explored the factors that independently affect functional outcomes of patients with CRS after MT.Methods: We retrospectively reviewed 341 patients who underwent MT after acute ischemic stroke onset between May 2014 and May 2020. We classified the patients into CRS (n = 34) and control (n = 307) groups and compared their clinical details. Among CRS patients, we analyzed the groups with and without good outcomes (3-months modified Rankin scale [mRS] score 0, 1, 2). Multivariate analysis was performed to investigate the independent predictors of unfavorable outcomes in patients with CRS after MT.Results: A total of 341 acute ischemic stroke patients received MT, of whom 34 (9.9%) had CRS. Although the baseline National institute of health stroke scale (NIHSS) score and the rate of successful recanalization was not significantly different between CRS patients and control group, CRS patients showed more any cerebral hemorrhage after MT (41.2% vs. controls 23.8%, p = 0.037) and unfavorable functional outcome at 3 months (CRS patients median 3-month mRS score 4, interquartile range [IQR] 2 to 5.25 vs. controls median 3-month mRS score 3, IQR 1 to 4, [p = 0.026]). In the patients with CRS, elevated serum D-dimer level and higher baseline NIHSS score were independently associated with unfavorable functional outcome at 3 months (adjusted odds ratio [aOR]: 1.524, 95% confidence interval [CI]: 1.043-2.226; aOR: 1.264, 95% CI: 1.010-1.582, respectively).Conclusions: MT is an appropriate therapeutic treatment for revascularization in CRS patients. However, elevated serum D-dimer levels and higher baseline NIHSS scores were independent predictors of unfavorable outcome. Further research is warranted to evaluate the significance of these predictors. [ABSTRACT FROM AUTHOR]

Background/Objective: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. Methods: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. Results: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. Conclusions: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients. [ABSTRACT FROM AUTHOR]

Background: The tendency of amyloid-β to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAβ and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity.Methods: The performance of EDTA-based MDS-OAβ in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAβ level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset.Results: The random forest model best-predicted amyloid PET positivity based on MDS-OAβ combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAβ, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAβ value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%.Conclusions: The Random Forest model using EDTA-based MDS-OAβ combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity. [ABSTRACT FROM AUTHOR]

Cerebral paragonimiasis (CP), caused by aberrant migration of Paragonimus worms, frequently invokes serious illness. The causal relationship between the lesion characteristics and patients' symptoms has poorly been understood. CP serodiagnosis has not been properly evaluated to date. A total of 111 CP cases were diagnosed in our laboratory between 1982 and 2003. This study retrospectively assessed the clinical and imaging characteristics of the 105 patients along with the evaluation of diagnostic potentials of recombinant P. westermani yolk ferritin (rPwYF) by enzyme-linked immunosorbent assay (ELISA) employing patients' sera and cerebrospinal fluids (CSFs). We analyzed 60 male and 45 female patients; 50 early-stage patients with non-calcified enhancing nodule(s) (median age, 38 years; interquartile range [IQR], 24.75–52; median symptom duration, 0.75 years; IQR, 0.2–2) and 54 chronic cases having calcified lesion(s) (median age, 33 years; IQR, 25–41; median symptom duration, 10 years; IQR, 5–20). One patient showed a normal neuroimage. The patients were largely diagnosed in their 30s. The parietal lobe was most commonly affected, followed by occipital, frontal, and temporal lobes. Twenty-six patients had lesions encompassing ≥ two lobes. The patients complained mainly of seizures, headaches, hemiparesis, and focal neurologic deficits (P < 0.001). Seizures and visual defect were predominant in patients with calcified lesion(s) (P < 0.001). The diagnostic sensitivity and specificity of rPwYF against serum/CSF were 100%/97% and 97.2%/92.5%, respectively. The specific IgG antibody levels against rPwYF in sera and CSFs showed a positive correlation (r = 0.59). The clinical manifestations of the early-stage patients might be associated with cortical lesions or meningeal irritation, while those in the chronic stage were caused by conglomerated space-occupying lesions. rPwYF would be useful for the serodiagnosis of both early and chronic CP cases. Author summary: Paragonimiasis, caused by the lung fluke Paragonimus spp., is a global foodborne zoonosis of great public health concern. Paragonimiasis is primarily a pleuropulmonary disease. However, the worms sometimes migrate aberrantly to other parts of the body, thereby causing the granulomatous lesion(s). The most serious condition elicited by ectopic migration is cerebral paragonimiasis. This study retrospectively analyzed the clinical and imaging features of the largest number of 105 cases diagnosed between 1982 and 2003 in our laboratory. We also evaluated diagnostic feasibility of recombinant P. westermani yolk ferritin by ELISA. The patients were largely diagnosed in their 30s with the chief complaints of seizures, headaches, hemiparesis, and focal neurologic deficits. Seizures and visual defect were significant in the chronic stage patients having calcified lesion(s). The diagnostic sensitivity and specificity of recombinant P. westermani yolk ferritin by ELISA against patients' sera or CSFs were 100% or 97%, and 97.2% or 92.5%, respectively. The diverse neurological manifestations of patients might be related to the nature and/or location of the lesions. P. westermani yolk ferritin is a promising antigen for serodiagnosis of both early-stage patients with non-calcified lesion(s) and chronic calcified cerebral paragonimiasis cases. [ABSTRACT FROM AUTHOR]

The microstructure, pole figure and r-value of the frictionally rolled and subsequently heat treated AA 5052 Al sheets were investigated by optical microscopy, x-ray diffractometer and tensile tester, respectively. Frictionally rolled AA 5052 Al specimens showed a fine grain size. After subsequently heat treated specimens, the ND//<111> texture component was increased. The r-values of the frictionally rolled and subsequently heat treated Al alloy sheets were about two times higher than those of the original Al sheets. These could be related to the formation of ND//<111> texture components through frictional rolling in and subsequent heat treatment of AA 5052 Al sheet. [ABSTRACT FROM AUTHOR]

The physical, mechanical properties and formability of sheet metal depend on preferred crystallographic orientations (texture). In this research work, we investigated texture development and formability of AA 3003 aluminum alloy sheets after asymmetry rolling and subsequent heat treatment. After asymmetry rolling, the specimens showed fine grain size. We also investigated the change of the plastic strain ratios after asymmetry rolling and subsequent heat-treating condition. The plastic strain ratios of asymmetrically rolled and subsequent heat treated samples are 1.5 times higher than the initial AA 3003 Al alloy sheets. These could be attributed to the formation of ND//<111> texture component through asymmetry rolling in Al sheet. [ABSTRACT FROM AUTHOR]

Background and purpose: Previous studies have reported that early hospital arrival improves clinical outcomes in patients with acute ischemic stroke; however, whether early arrival is associated with favorable outcomes regardless of reperfusion therapy and the type of stroke onset time is unclear. Thus, we investigated the impact of onset-to-door time on outcomes and evaluated the predictors of pre-hospital delay after ischemic stroke. Methods: Consecutive acute ischemic stroke patients who arrived at the hospital within five days of onset from September 2019 to May 2020 were selected from the prospective stroke registries of Seoul National University Hospital and Chung-Ang University Hospital of Seoul, Korea. Patients were divided into early (onset-to-door time, ≤4.5 h) and late (>4.5 h) arrivers. Multivariate analyses were performed to assess the effect of early arrival on clinical outcomes and predictors of late arrival. Results: Among the 539 patients, 28.4% arrived early and 71.6% arrived late. Early hospital arrival was significantly associated with favorable outcomes (three-month modified Rankin Scale [mRS]: 0−2, adjusted odds ratio [aOR]: 2.03, 95% confidence interval: [CI] 1.04–3.96) regardless of various confounders, including receiving reperfusion therapy and type of stroke onset time. Furthermore, a lower initial National Institute of Health Stroke Scale (NIHSS) score (aOR: 0.94, 95% CI: 0.90–0.97), greater pre-stroke mRS score (aOR: 1.58, 95% CI: 1.18–2.13), female sex (aOR: 1.71, 95% CI: 1.14–2.58), unclear onset time, and ≤6 years of schooling (aOR: 1.76, 95% CI: 1.03–3.00 compared to >12 years of schooling) were independent predictors of late arrival. Conclusions: Thus, the onset-to-door time of≤4.5 h is crucial for better clinical outcome, and lower NIHSS score, greater pre-stroke mRS score, female sex, unclear onset times, and ≤6 years of schooling were independent predictors of late arrival. Therefore, educating about the importance of early hospital arrival after acute ischemic stroke should be emphasized. More strategic efforts are needed to reduce the prehospital delay by understanding the predictors of late arrival. [ABSTRACT FROM AUTHOR]

Background: The prognosis for cardiac arrest (CA) is associated with the degree of cerebral ischemia. We investigated the relationship between the wavelet coherence of cerebral oxyhemoglobin (HbO2) among different channels and outcomes after CA. Moreover, we aimed to develop a prognostication method after CA.Methods: Eighty-three post-resuscitation patients were included. The HbO2 data were collected during the post-resuscitation period (median day, 1) using functional near-infrared spectroscopy. The coherence between sections of prefrontal HbO2 oscillations in five frequency intervals (I, 0.6-2 Hz; II, 0.15-0.6 Hz; III, 0.05-0.15 Hz; IV, 0.02-0.05 Hz; and V, 0.0095-0.02 Hz) were analyzed. We evaluated the outcomes using cerebral performance category (CPC) scores (good outcome, CPC ≤ 2 and poor outcome, CPC ≥ 3) at 3 months after CA. Additionally, the predictive method was developed using the biomarker and coherence value after CA.Results: Among the included patients, 19 patients (22.9%) had a good outcome. Poor outcome group had significantly lower phase coherence in the myogenic frequency interval III compared to good outcome group (0.36 ± 0.14 vs. 0.54 ± 0.18, P < 0.001). The predictive method using neuron-specific enolase (NSE) and interval III value demonstrated good discrimination (area under the curve 0.919; 95% confidence interval, 0.850-0.989).Conclusions: The predictive method using NSE and phase coherence of HbO2 in the interval III from the vascular smooth muscle cells could be a useful tool for prognosticating after CA. This suggests that evaluating cerebral ischemia using phase coherence of HbO2 might be a helpful outcome predictor following CA. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays an important role in atherosclerosis and its complications. Since a dysregulated inflammatory response is associated with early neurological deterioration (END), serum neutrophil-to-lymphocyte ratio (NLR) could be a marker of END as well. Aim: In this study, we evaluated the relationship between the serum NLR and END in patients with ischemic stroke due to large-artery atherosclerosis (LAA). Methods: We evaluated consecutive patients with ischemic stroke due to LAA between January 2010 and December 2015. END was defined as an increase ≥ 2 on the total NIHSS score or ≥ 1 on the motor NIHSS score within the first 72 hours of admission. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Results: Of the 349 included patients, 18.1% (n = 63) had END events. In multivariate analysis, serum NLR was independently associated with END (adjusted odds ratio, 1.08; 95% confidence interval [1.00–1.16], P = 0.043). Time to admission, and in-situ thrombosis and artery-to-artery embolization mechanisms were also significantly associated with END events. In an analysis of the relationship between serum NLR and vascular lesion burden, serum NLR was positively correlated with both the degree of stenotic lesions (P for trend = 0.006) and the number of vessel stenosis (P for trend = 0.038) in a dose-response manner. We also compared serum NLR by the stroke mechanisms: patients with hypoperfusion or in-situ thrombosis had the highest levels of NLR: however, only those with in-situ thrombosis had significantly higher NLR in the END group compared to the non-END group (P = 0.005). Conclusions: Serum NLR levels were associated with END events in patients with ischemic stroke due to LAA. Since NLR was also closely correlated with the underlying vascular lesions, our results indicated clues for mechanisms of END events. [ABSTRACT FROM AUTHOR]