Upadacitinib counteracts hepatic lipid deposition via the repression of JAK1/STAT3 signaling and AMPK/autophagy-mediated suppression of ER stress.

Upadacitinib (UPA) has been utilized to treat conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis by modulating inflammation via the JAK pathway. However, its impact on hepatic lipogenesis remains insufficiently studied. This research evaluated protein expression through Western blotting, lipid accumulation with oil red O staining, autophagosomes in hepatocytes via MDC staining, and hepatic apoptosis via cell viability and caspase 3 activity assays. This study aimed to explore the effects of UPA on hepatic lipogenesis and the underlying molecular mechanisms in in vitro models of hepatic steatosis. These findings demonstrated that UPA reduced lipid deposition, apoptosis, and ER stress in palmitate-treated hepatocytes. UPA treatment inhibited phosphorylated JAK1 and STAT3 while promoting the expression of phosphorylated AMPK and autophagy markers. AMPK siRNA negated the effects of UPA on lipogenic lipid deposition, apoptosis, JAK1/STAT3 phosphorylation, and ER stress. These results reveal that UPAmitigates ER stress through the JAK1/STAT3/AMPK pathway, thereby reducing lipid deposition and apoptosis in hyperlipidemic hepatocytes, supporting its potential as a therapeutic strategy for treating hepatic steatosis in obese individuals.

Dilated perivascular spaces and steno-occlusive changes in children and adults with moyamoya disease.

BACKGROUND: Dilated perivascular spaces (DPVS), known as one of imaging markers in cerebral small vessel disease, may be found in patients with moyamoya disease (MMD). However, little is known about DPVS in MMD. The purpose of this study was to investigate the distribution pattern of dPVS in children and adults with MMD and determine whether it is related to steno-occlusive changes of MMD. METHODS: DPVS was scored in basal ganglia (BG) and white matter (WM) on T2-weighted imaging, using a validated 4-point semi-quantitative score. The degree of dPVS was classified as high (score > 2) or low (score ≤ 2) grade. The steno-occlusive changes on MR angiography (MRA) was scored using a validated MRA grading. Asymmetry of DPVS and MRA grading was defined as a difference of 1 grade or higher between hemispheres. RESULTS: Fifty-one patients with MMD (mean age 24.9 ± 21.1 years) were included. Forty-five (88.2%) patients had high WM-DPVS grade (degree 3 or 4). BG-DPVS was found in 72.5% of all patients and all were low grade (degree 1 or 2). The distribution patterns of DPVS degree in BG (P = 1.000) and WM (P = 0.767) were not different between child and adult groups. The asymmetry of WM-DPVS (26%) and MRA grade (42%) were significantly correlated to each other (Kendall's tau-b = 0.604, P < 0.001). CONCLUSIONS: DPVS of high grade in MMD is predominantly found in WM, which was not different between children and adults. The correlation between asymmetry of WM-DPVS degree and MRA grade suggests that weak cerebral artery pulsation due to steno-occlusive changes may affect WM-DPVS in MMD.

Papilledema and venous stasis in patients with cerebral venous and sinus thrombosis.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) can cause increased intracranial pressure, often leading to papilledema. In this study, we investigated the association between papilledema and venous stasis on susceptibility weighted imaging (SWI) in CVST. METHODS: Patients with CVST between 2008 and 2020 were reviewed. Patients without fundoscopic examination or SWI were excluded in this study. Venous stasis was evaluated and scored for each cerebral hemisphere: each hemisphere was divided into 5 regions according to the venous drainage territories (superior sagittal sinus, Sylvian veins, transverse sinus and vein of Labbé, deep cerebral veins, and medullary veins) and 1 point was added if venous prominence was confirmed in one territory on SWI. The venous stasis score on SWI between cerebral hemispheres with and without papilledema was compared. RESULTS: Eight of 19 patients with CVST were excluded because of the absence of fundoscopic examination or SWI. Eleven patients (26.5 ± 2.1 years) were included in this study. Papilledema was identified in 6 patients: bilateral papilledema in 4 patients and unilateral papilledema in 2 patients. The venous stasis score on SWI was significantly higher (P = 0.013) in the hemispheres with papilledema (median, 4.0; 95% CI, 3.038-4.562) than in the hemispheres without papilledema (median, 2.5; 95% CI, 0.695-2.805). CONCLUSIONS: This study shows that higher score of venous stasis on SWI is associated with papilledema. Therefore, the venous stasis on SWI may be an imaging surrogate marker of increased intracranial pressure in patients with CVST.

Early prediction of need for invasive mechanical ventilation in the neonatal intensive care unit using artificial intelligence and electronic health records: a clinical study.

BACKGROUND: Respiratory support is crucial for newborns with underdeveloped lung. The clinical outcomes of patients depend on the clinician's ability to recognize the status underlying the presented symptoms and signs. With the increasing number of high-risk infants, artificial intelligence (AI) should be considered as a tool for personalized neonatal care. Continuous monitoring of vital signs is essential in cardiorespiratory care. In this study, we developed deep learning (DL) prediction models for rapid and accurate detection of mechanical ventilation requirements in neonates using electronic health records (EHR). METHODS: We utilized data from the neonatal intensive care unit in a single center, collected between March 3, 2012, and March 4, 2022, including 1,394 patient records used for model development, consisting of 505 and 889 patients with and without invasive mechanical ventilation (IMV) support, respectively. The proposed model architecture includes feature embedding using feature-wise fully connected (FC) layers, followed by three bidirectional long short-term memory (LSTM) layers. RESULTS: A mean gestational age (GA) was 36.61 ± 3.25 weeks, and the mean birth weight was 2,734.01 ± 784.98 g. The IMV group had lower GA, birth weight, and longer hospitalization duration than the non-IMV group (P < 0.05). Our proposed model, tested on a dataset from March 4, 2019, to March 4, 2022. The mean AUROC of our proposed model for IMV support prediction performance demonstrated 0.861 (95%CI, 0.853-0.869). It is superior to conventional approaches, such as newborn early warning score systems (NEWS), Random Forest, and eXtreme gradient boosting (XGBoost) with 0.611 (95%CI, 0.600-0.622), 0.837 (95%CI, 0.828-0.845), and 0.0.831 (95%CI, 0.821-0.845), respectively. The highest AUPRC value is shown in the proposed model at 0.327 (95%CI, 0.308-0.347). The proposed model performed more accurate predictions as gestational age decreased. Additionally, the model exhibited the lowest alarm rate while maintaining the same sensitivity level. CONCLUSION: Deep learning approaches can help accurately standardize the prediction of invasive mechanical ventilation for neonatal patients and facilitate advanced neonatal care. The results of predictive, recall, and alarm performances of the proposed model outperformed the other models.

Systemic inflammatory markers of persistent cerebral edema after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH. METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early brain edema score' (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3-5 days [T3] and 6-8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2). RESULTS: Of the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002-1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE. CONCLUSIONS: We identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH.

The Spot Sign and Intraventricular Hemorrhage are Associated with Baseline Coagulopathy and Outcome in Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is the second most prevalent subtype of stroke and has high mortality and morbidity. The utility of radiographic features to predict secondary brain injury related to hematoma expansion (HE) or increased intracranial pressure has been highlighted in patients with ICH, including the computed tomographic angiography (CTA) spot sign and intraventricular hemorrhage (IVH). Understanding the pathophysiology of spot sign and IVH may help identify optimal therapeutic strategies. We examined factors related to the spot sign and IVH, including coagulation status, hematoma size, and location, and evaluated their prognostic value in patients with ICH. METHODS: Prospectively collected data from a single center between 2012 and 2015 were analyzed. Patients who underwent thromboelastography within 24 h of symptom onset and completed follow-up brain imaging and CTA within 48 h after onset were included for analysis. Multivariate logistic regression analyses were performed to identify determinants of the spot sign and IVH and their predictive value for HE, early neurological deterioration (END), in-hospital mortality, and functional outcome at discharge. RESULTS: Of 161 patients, 50 (31.1%) had a spot sign and 93 (57.8%) had IVH. In multivariable analysis, the spot sign was associated with greater hematoma volume (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), decreased white blood cell count (OR 0.88; 95% CI 0.79-0.98), and prolonged activated partial thromboplastin time (OR 1.14; 95% CI 1.06-1.23). IVH was associated with greater hematoma volume (OR 1.02; 95% CI 1.01-1.04) and nonlobar location of hematoma (OR 0.23; 95% CI 0.09-0.61). The spot sign was associated with greater risk of all adverse outcomes. IVH was associated with an increased risk of END and reduced HE, without significant impact on mortality or functional outcome. CONCLUSIONS: The spot sign and IVH are associated with specific hematoma characteristics, such as size and location, but are related differently to coagulation status and clinical course. A combined analysis of the spot sign and IVH can improve the understanding of pathophysiology and risk stratification after ICH.

Capmatinib attenuates lipogenesis in 3T3-L1 adipocytes through an adenosine monophosphate-activated protein kinase-dependent pathway.

Recently, there is a rapid increase in the incidence of obesity, a condition for which there are no effective therapeutic agents. Capmatinib (CAP), a novel mesenchymal-to-epithelial transition inhibitor, is reported to attenuate pro-inflammatory mediators and oxidative stress. In this study, the effects of CAP on lipogenesis in the adipocytes were examined. Treatment with CAP dose-dependently suppressed lipid accumulation in, and differentiation of, and increased lipolysis in, 3T3-L1 adipocytes. Additionally, CAP treatment augmented adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and FNDC5 expression in the adipocytes. Transfection with si-AMPK or si-FNDC5 mitigated the CAP-induced suppression of lipogenesis and enhanced lipolysis. Furthermore, transfection with si-FNDC5 mitigated the CAP-induced phosphorylation of AMPK. These results suggest that the anti-obesity effect of CAP is mediated through the irisin/AMPK pathway and that CAP is a novel therapeutic agent for obesity.

Inverse association between triglyceride glucose index and muscle mass in Korean adults: 2008-2011 KNHANES.

BACKGROUND: Since sarcopenia is an important risk factor for falls or cardiovascular disease, early detection and prevention of sarcopenia are being increasingly emphasized. Emerging evidence has indicated relationships between sarcopenia, insulin resistance, and inflammation. The triglyceride glucose (TyG) index, a novel surrogate marker of insulin resistance and systemic inflammation, has not yet been shown to be associated with sarcopenia. This study aimed to examine the relationship between the TyG index and muscle mass in Korean adults. METHODS: This study included 15,741 non-diabetic adults over 19 years old using data from the 2008-2011 Korea National Health and Nutrition Examination Survey. Participants were divided into three groups according to tertiles of the TyG index. A low skeletal muscle mass index (LSMI) was defined by the Foundation for the National Institutes of Health Sarcopenia Project criteria. A weighted multivariate logistic regression model was used to analyze relationships between TyG index tertiles and LSMI. RESULTS: The ORs (95% CIs) for LSMI in the second and third TyG tertiles, compared to the first tertile, were 1.463 (1.131-1.892) and 1.816 (1.394-2.366), respectively, after adjusting for confounding factors. Higher TyG index values were also associated with increased odds of LSMI in adults under 65 years who did not exercise regularly, who consumed less than 30 g of alcohol per day, who did not currently smoke, and who ate less than 1.5 g of protein/kg/day. CONCLUSION: The TyG index was significantly and positively associated with LSMI in Korean adults.

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates.

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

BACKGROUND: Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions. METHODS: Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (< 24 h, 24-48 h, 3-5 days, and 6-8 days after SAH) and concentration levels of 41 cytokines were measured by multiplex immunoassay. Logistic regression analysis was used to identify cytokines associated with DCI and poor functional outcomes. Correlation networks were constructed to identify cytokine clusters. RESULTS: Of the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3 months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1α. Poor functional outcome was associated with increased levels of IL-6 and MCP-1α. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes. CONCLUSIONS: Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.

Protectin DX ameliorates palmitate-induced hepatic insulin resistance through AMPK/SIRT1-mediated modulation of fetuin-A and SeP expression.

The role as well as the molecular mechanisms of protectin DX (PDX) in the prevention of hepatic insulin resistance, a hallmark of type 2 diabetes, remains unknown. Therefore, the present study was designed to explore the direct impact of PDX on insulin resistance and to investigate the expression of fetuin-A and selenoprotein P (SeP), hepatokines that are involved in insulin signalling, in hepatocytes. Human serum levels of PDX as well as fetuin-A and SeP were determined by high-performance liquid chromatography (HPLC). Human primary hepatocytes were treated with palmitate and PDX. NF-κB phosphorylation as well as expression of insulin signalling associated genes and hepatokines were determined by Western blotting analysis. FOXO1 binding levels were measured by quantitative real-time PCR. Selected genes from candidate pathways were evaluated by small interfering (si) RNA-mediated gene suppression. Serum PDX levels were significantly (P < 0.05) downregulated, whereas serum fetuin-A and SeP levels were increased (P < 0.05) in obese subjects compared with healthy subjects. In in vitro experiments, PDX treatment increased AMP-activated protein kinase (AMPK) phosphorylation and SIRT1 expression and attenuated palmitate-induced fetuin-A and SeP expression and insulin resistance in hepatocytes. AMPK or SIRT1 siRNA mitigated the suppressive effects of PDX on palmitate-induced fetuin-A through NF-κB and SeP expression linked to FOXO1 and insulin resistance. Recombinant fetuin-A and SeP reversed the suppressive effects of fetuin-A and SeP expression on palmitate-mediated impairment of insulin signalling. The current finding provides novel insight into the underlying mechanism linking hepatokines to the pathogenesis of hepatic insulin resistance.

Maresin 1 attenuates pro-inflammatory reactions and ER stress in HUVECs via PPARα-mediated pathway.

The current study was designed to investigate the therapeutic effects of Maresin 1 (MAR1) on atherosclerotic response. Human monocytes THP-1 and human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of MAR1 on lipopolysaccharide (LPS)-induced inflammation and apoptosis. In this study, we found that MAR1 induces peroxisome proliferator-activated receptor alpha (PPARα) expression. We also demonstrated that MAR1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARα-dependent pathway. MAR1 treatment inhibited LPS-induced phosphorylation of nuclear factor kappa B (NF-κB) and secretion of pro-inflammatory cytokines in HUVECs and THP-1 cells. In HUVEC cells, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after MAR1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis was significantly decreased after MAR1 treatment of HUVECs. MAR1 also led to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression which is responsible for the inhibition of ER stress. Notably, all of the pro-atherosclerotic effects were completely abrogated by treatment with small interfering (si) RNA targeting PPARα. In conclusion, MAR1 ameliorates LPS-induced atherosclerotic reactions via PPARα-mediated suppression of inflammation and ER stress.

Patterns and Outcomes of the Top of the Basilar Artery Syndrome: The Role of the Posterior Communicating Artery.

BACKGROUND: Clinical syndromes secondary to infarcts in the distal basilar artery (BA) area have been described as "top of the basilar" (TOB) syndrome. However, in the era of advanced imaging technology, it has been realized that the clinical and imaging features are quite diverse in patients with distal BA occlusion. The aim of the present study was to investigate the patterns and clinical outcomes of TOB assessed with modern images and categorize TOBs accordingly. Additionally, we examined the possible influence of the posterior communicating artery (PcoA) on the patterns of TOB. METHODS: Patients with distal BA occlusion on magnetic resonance angiography were categorized as TOB-A, and those with multiple lesions in the distal BA territory on diffusion-weighted magnetic resonance imaging as TOB-L. Patients with angiographically and lesion distribution-defined TOB were classified as having TOB-A&L; those with angiographically defined TOB as having TOB-A without TOB-L; and those with lesion distribution-defined TOB as having TOB-L without TOB-A. The PcoA was categorized as "textbook-type" (good P1) and "fetal-type" (absent P1). Factors associated with unfavorable short-term outcomes (modified Rankin Scale 5-6 at discharge), and 1-year and long-term mortalities, were assessed. RESULTS: Of 1,466 patients with ischemic stroke in the posterior circulation who were admitted to Asan Medical Center within 24 h of symptom onset, 124 (8.5%) had TOB, including 45 with TOB-A&L, 44 with TOB-A, and 35 with TOB-L. NIHSS scores (21 [9.5-26] vs. 6 [3-11.5] vs. 6 [3-9]; p < 0.01) and rates of motor deficit (75.6 vs. 54.5 vs. 34.4%; p < 0.01), concomitant pontine lesions (17.8 vs. 25.0 vs. 2.9%; p < 0.01), PcoA presence (44.4 vs. 68.2 vs. 25.7%; p < 0.01), and unfavorable short-term outcomes (62.2 vs. 25.0 vs. 14.3%; p < 0.01) differed significantly in the 3 patient groups. Multivariate analysis showed that textbook-type PcoA was independently associated with a lower frequency of unfavorable short-term outcomes (OR 0.15, 95% CI 0.03-0.70). Reperfusion therapy (hazard ratio [HR] 0.25, 95% CI 0.07-0.89) and the presence of textbook-type PcoA (HR 0.20, 95% CI 0.05-0.90) were associated with a lower 1-year mortality rate after stroke. CONCLUSION: Patterns and clinical outcomes of TOB vary and are affected by the hemodynamic status of the arterial system, such as BA recanalization and the presence of textbook-type PcoA.

Fluid-Attenuated Inversion Recovery Hyperintensity Is Associated with Hemorrhagic Transformation following Reperfusion Therapy.

BACKGROUND: It is still controversial whether early fluid-attenuated inversion recovery (FLAIR) hyperintensity within acute ischemic lesions carries the risk of hemorrhagic transformation (HT) after reperfusion therapy. Furthermore, the association between the location of FLAIR hyperintensity and HT has not been investigated. METHODS: We retrospectively reviewed patients who underwent reperfusion therapy within 6 hours of stroke onset and magnetic resonance imaging including a FLAIR sequence before completing reperfusion therapy. FLAIR hyperintensity within the diffusion-weighted imaging (DWI) lesion was rated qualitatively, and HT was assessed on follow-up gradient echo imaging. The location of the FLAIR change and HT was classified as subcortical, cortical, or cortico-subcortical. RESULTS: Of 134 patients with acute ischemic stroke included in this study, early FLAIR changes within DWI lesions were identified in 56 (41.8%) patients, and HT was noted in 51 (38.1%) patients. FLAIR change was independently associated with HT (odds ratio: 4.37, 95% confidence interval: 1.72-11.12). Geographically, 48.2% of the patients with a FLAIR change developed a matched HT (restricted to the region with the FLAIR change), and the risk of HT was further increased in patients with a FLAIR change in the cortico-subcortical region (68.8%). CONCLUSIONS: In patients in the acute stage of stroke, an early FLAIR change is associated with the risk of HT following reperfusion therapy with a highly matched geographic relationship and common risk factors. Thus, identification of FLAIR change may be a useful surrogate marker to assess the likelihood of subsequent HT in patients treated with reperfusion therapy.

Nonatheroscleotic Isolated Middle Cerebral Artery Disease May Be Early Manifestation of Moyamoya Disease.

BACKGROUND AND PURPOSE: Middle cerebral artery steno-occlusive disease (MCAD) is not an uncommon cause of ischemic stroke in young Asians. Aside from atherosclerosis, the pathogenesis of MCAD include various nonatherosclerotic vasculopathies, most of which are yet to be defined. This study investigated the pathogenesis of symptomatic isolated MCAD in young Asian patients using high-resolution magnetic resonance imaging (HR-MRI) and mutation analysis of RNF213. METHODS: Patients aged <60 years with stroke or transient ischemic attack caused by MCAD were prospectively enrolled. Patients with a confirmed diagnosis of moyamoya disease, dissection, and vasculitis; with significant steno-occlusion in cerebral arteries other than the MCA; or with high-risk cardioembolic source were excluded. Using high-resolution MRI, patients were classified into an atherosclerosis group and a nonatherosclerosis group. RESULTS: Eighty-one patients were enrolled, 45 (56.6%) in the atherosclerosis and 36 (44.4%) in the nonatherosclerosis group. The nonatherosclerosis group was significantly younger (P=0.013), had a smaller number of vascular risk factors (P=0.001), showed a lower homocysteine level (P<0.001), thinner intima-media thickness (P=0.006), and had more frequent heterozygotes at RNF213 (P=0.045) than the atherosclerosis group. Diffusion-weighted image lesion pattern showed no significant differences in assumed stroke mechanisms between the 2 groups. CONCLUSIONS: Nonatherosclerotic pathogenesis are common in young Asians with symptomatic isolated MCAD. Clinical findings, high-resolution MRI features, and results of RNF213 mutation analysis suggest that moyamoya disease is responsible etiologically for a significant portion of nonatherosclerotic lesions. Symptomatic isolated MCAD may be an early manifestation of moyamoya disease in young Asian adults.

Lateral Thalamic Infarction and the Vascular Geometry of the Posterior Cerebral Artery.

BACKGROUND: The geometric properties of the parental artery affect the development of local atherosclerosis and perforator infarction. In this study, we aimed at investigating the association between vascular geometry of the posterior cerebral artery (PCA) and the development of isolated lateral thalamic infarction (LTI), the most frequent type of thalamic infarction. METHODS: The geometric properties of the corresponding PCA in LTI patients were assessed and they include the diameters of the distal basilar artery (BA) and proximal PCA, distal BA - PCA angle, first PCA angle (angle between P1 and P2), and the presence of the posterior communicating artery (Pcom). These parameters obtained from the ipsilesional PCA were compared with the contralesional PCA and the corresponding PCA in age- and sex-matched controls. RESULTS: Forty-five LTI patients were enrolled. The ipsilesional PCA in LTI patients demonstrated a greater ipsilesional P1 - P2 angle (81.4 ± 22.6 vs. 71.3 ± 23.2°, respectively; p = 0.04) and a higher prevalence of Pcom (42.2 vs. 13.3%; p = 0.002) when compared to control subjects. In comparison with the contralesional PCA, ipsilesional PCA demonstrated a smaller diameter, larger angle between P1 and P2 segment, and a higher prevalence of Pcom. The presence of hyperlipidemia (OR 3.548 (1.283-9.811); p = 0.02) and Pcom (OR 3.507 (1.104-11.135); p = 0.03) was a factor that was independently associated with LTI. CONCLUSIONS: Local hemodynamics in the PCA may be influenced by the P1 - P2 angle and the presence of Pcom, which are associated with the development of LTI.

Isolated MCA disease in patients without significant atherosclerotic risk factors: a high-resolution magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diagnosis of intracranial artery atherosclerosis remains often uncertain. The high-resolution magnetic resonance imaging (HR-MRI) enables vessel wall assessment for more precise diagnoses. The aim of the present study was to investigate the etiologies of middle cerebral artery steno-occlusive disease in young adult patients with few atherosclerotic risk factors using HR-MRI. METHODS: We prospectively studied patients who visited a tertiary hospital in Seoul, Korea, and had (1) unilateral middle cerebral artery disease (≥50% stenosis or occlusion), (2) were ≤55 years old and had no or minimal (≤1) atherosclerotic risk factors. We excluded patients with a confirmed diagnosis of Moyamoya disease, vasculitis, or dissection and those having emboligenic sources. A presumptive diagnosis was made based on HR-MRI findings, and patients were categorized as HR-athero (atherosclerotic disease), HR-MMD (Moyamoya disease), HR-dissection, or HR-vasculitis. RESULTS: Among 95 patients analyzed, 26 (27.4%) had HR-athero who were more often male (P=0.004), smokers (P=0.018), and had focal stenosis (P=0.003) than others.As compared with the HR-athero patients, 29 HR-MMD patients were more often female (P<0.001) and more often had occlusive lesions (P=0.001) and nonfocal stenosis (P<0.001). The 22 HR-dissection patients tended to have hypertension less often, and the 13 HR-vasculitis patients were younger (P=0.004) and tended to have nonfocal stenosis. [corrected]. CONCLUSIONS: In our cohort of young patients with minimal risk factors, atherosclerosis seems to be an uncommon pathology of middle cerebral artery stenosis. HR-MRI aids us to make a more reliable diagnosis.

Color-coded fluid-attenuated inversion recovery images improve inter-rater reliability of fluid-attenuated inversion recovery signal changes within acute diffusion-weighted image lesions.

BACKGROUND AND PURPOSE: Diffusion-weighted image fluid-attenuated inversion recovery (FLAIR) mismatch has been considered to represent ischemic lesion age. However, the inter-rater agreement of diffusion-weighted image FLAIR mismatch is low. We hypothesized that color-coded images would increase its inter-rater agreement. METHODS: Patients with ischemic stroke <24 hours of a clear onset were retrospectively studied. FLAIR signal change was rated as negative, subtle, or obvious on conventional and color-coded FLAIR images based on visual inspection. Inter-rater agreement was evaluated using κ and percent agreement. The predictive value of diffusion-weighted image FLAIR mismatch for identification of patients <4.5 hours of symptom onset was evaluated. RESULTS: One hundred and thirteen patients were enrolled. The inter-rater agreement of FLAIR signal change improved from 69.9% (k=0.538) with conventional images to 85.8% (k=0.754) with color-coded images (P=0.004). Discrepantly rated patients on conventional, but not on color-coded images, had a higher prevalence of cardioembolic stroke (P=0.02) and cortical infarction (P=0.04). The positive predictive value for patients <4.5 hours of onset was 85.3% and 71.9% with conventional and 95.7% and 82.1% with color-coded images, by each rater. CONCLUSIONS: Color-coded FLAIR images increased the inter-rater agreement of diffusion-weighted image FLAIR recovery mismatch and may ultimately help identify unknown-onset stroke patients appropriate for thrombolysis.

The second elevation of neuron-specific enolase peak after ischemic stroke is associated with hemorrhagic transformation.

BACKGROUND: Neuron-specific enolase (NSE) is a surrogate marker for the extent of brain damage after ischemic stroke and affords a good predictor of stroke prognosis. We hypothesized that the pattern of NSE level changes in the peripheral blood during the acute period of ischemic stroke is dependent on stroke mechanism and is associated with hemorrhagic transformation. METHODS: Acute ischemic stroke patients visiting our center within 24 hours of symptom onset were recruited into the study. NSE levels were obtained serially at various time points after stroke, and the pattern of change was categorized into no significant change, continuously increasing, continuously decreasing, with 1 peak and with 2 peaks. Clinical, laboratory, and imaging variables were compared among the patient groups. Multivariate analysis was performed to verify the independent association between the second NSE peak and hemorrhagic transformation after adjusting for potential confounders. RESULTS: Among 83 patients, NSE levels were stationary in 22 (26.5%) of the patients, increased in 9 (10.8%), decreased in 18 (21.7%), and showed 1 peak in 17 (20.5%) and 2 peaks in 17 (20.5%) patients. The incidence of atrial fibrillation and hemorrhagic transformation was significantly elevated (P = .02) in patients with 2 NSE peaks. Furthermore, the second NSE peak and the initial lesion volume were associated independently with hemorrhagic transformation after we adjusted for potential confounders (odds ratio = 6.844 and 1.024, P = .04 and .02, respectively). CONCLUSIONS: Serial NSE analysis during the acute period of ischemic stroke is useful for monitoring hemorrhagic transformation and the blood-brain barrier disruption status.

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.