U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Indoor particulate matter induces epigenetic changes in companion atopic dogs.

The prevalence of atopic dermatitis (AD) is increasing and environmental factors are receiving attention as contributing causes. Indoor air pollutants (IAPs), especially particulate matter (PM) can alter epigenetic markers, DNA methylation (DNAm). Although DNAm-mediated epigenetic changes have been reported to modulate the pathogenesis of AD, their role at high risk of exposure to PM is still unclear. The study investigated the effects of exposure to IAPs in the development of AD and epigenetic changes through DNAm in companion atopic dogs that share indoor environment with their owners. Dogs were divided into two groups: AD (n = 47) and controls (n = 21). The IAPs concentration in each household was measured for 48 h, and a questionnaire on the residential environment was completed in all dogs. Eighteen dogs with AD and 12 healthy dogs were selected for DNAm analysis. In addition, clinical and immunological evaluations were conducted. The concentrations of PM2.5, PM10, and volatile organic compounds (VOCs) were significantly higher in the AD group. Moreover, there were more significant methylation differences in the LDLRAD4, KHSRP, and CTDSP2 genes in connection with PM10 in AD group compared to the controls. The degree of methylation of the LDLRAD4 and CTDSP2 genes was also correlated with related protein productions. The present study revealed that exposure to high indoor PM can cause epigenetic development of AD by methylation of the LDLRAD4, KHSRP, and CTDSP2 genes in dogs. Under the concept of "One Health," improving indoor environments should be considered to prevent the development of AD.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

BACKGROUND: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. METHODS: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. RESULTS: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). CONCLUSION: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Dynamic change of neutrophil-to-lymphocyte ratio and symptomatic intracerebral hemorrhage after endovascular recanalization therapy.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a known marker of systemic inflammation. Recent studies demonstrated its applicability as a marker of poor prognosis for stroke patients. In this study, we evaluated the relationship between dynamic changes in the NLR and sICH in patients with successful recanalization following ERT. MATERIALS AND METHODS: This study included 128 patients with acute ischemic stroke who underwent successful ERT between January 2013 and November 2019. We evaluated the NLR pre-ERT (at admission) and post-ERT (at 24-36 h after ERT). The symptomatic ICH and miserable outcomes at 3 months after ERT were analyzed as outcomes. sICH was defined as type-2 parenchymal hematoma with neurological deterioration (defined as National Institute of Health Stroke Scale score ≥4). Moreover, a modified Rankin Scale score of 5-6 at 3 months was considered a miserable outcome. RESULTS: Among the included patients, sICH occurred in 12 (9.4%). The sICH group had significantly higher post-ERT NLR (P < 0.001) and ∆NLR (calculated as the difference between pre-ERT NLR and post-ERT NLR) (P = 0.004). In the multivariate analysis, the post-ERT NLR was independently associated with sICH (odds ratio [OR], 1.166; 95% confidence interval [CI], 1.041-1.306; P = 0.008) and miserable outcome at 3 months (OR, 1.101; 95% CI, 1.002-1.210; P = 0.045). CONCLUSIONS: This study demonstrated that temporal elevation of the NLR is associated with sICH events after successful ERT in patients with acute ischemic stroke. The temporal variation in NLR may help to identify high-risk patients with sICH after ERT.

Decoding 'Maximum Entropy' Deconvolution.

For over five decades, the mathematical procedure termed "maximum entropy" (M-E) has been used to deconvolve structure in spectra, optical and otherwise, although quantitative measures of performance remain unknown. Here, we examine this procedure analytically for the lowest two orders for a Lorentzian feature, obtaining expressions for the amount of sharpening and identifying how spurious structures appear. Illustrative examples are provided. These results enhance the utility of this widely used deconvolution approach to spectral analysis.

Role of the A-Site Cation in Low-Temperature Optical Behaviors of APbBr3 (A = Cs, CH3NH3).

APbBr3 (A = Cs, CH3NH3) are prototype halide perovskites having bandgaps of 2.30-2.35 eV at room temperature, rendering their apparent color nearly identical (bright orange but opaque). Upon optical excitation, they emit bright photoluminescence (PL) arising from carrier recombination whose spectral features are also similar. At 10 K, however, the apparent color of CsPbBr3 becomes transparent yellow, whereas that of CH3NH3PbBr3 does not change significantly due to the presence of an indirect Rashba gap. With increasing the excitation level, evolution of the PL spectra, which are excitonic at 10 K, reveals the emergence of P-band emission arising from inelastic exciton-exciton scattering. Based on the spectral location of the P-band, exciton binding energies are determined to be 21.6 ± 2.0 and 38.3 ± 3.0 meV for CsPbBr3 and CH3NH3PbBr3, respectively. Intriguingly, upon further increase in the exciton density, electron-hole plasma appears in CsPbBr3 as evidenced by both red-shift and broadening of the PL. This phase, however, does not occur in CH3NH3PbBr3 presumably due to polaronic effects. Although the A-site cation is believed not to directly impact optical properties of APbBr3, our results underscore its critical role, which destines different high-density phases and apparent color at low temperatures.

Effectiveness of radiologist training in improving reader agreement for Lung-RADS 4X categorization.

OBJECTIVES: To identify the agreement on Lung CT Screening Reporting and Data System 4X categorization between radiologists and an expert-adjudicated reference standard and to investigate whether training led to improvement of the agreement measures and diagnostic potential for lung cancer. METHODS: Category 4 nodules in the Korean Lung Cancer Screening Project were identified retrospectively, and each 4X nodule was matched with one 4A or 4B nodule. An expert panel re-evaluated the categories and determined the reference standard. Nineteen radiologists were asked to determine the presence of CT features of malignancy and 4X categorization for each nodule. A review was performed in two sessions, and training material was given after session 1. Agreement on 4X categorization between radiologists and the expert-adjudicated reference standard and agreement between radiologist-assessed 4X categorization and lung cancer diagnosis were evaluated. RESULTS: The 48 expert-adjudicated 4X nodules and 64 non-4X nodules were evenly distributed in each session. The proportion of category 4X decreased after training (56.4% ± 16.9% vs. 33.4% ± 8.0%; p < 0.001). Cohen's κ indicated poor agreement (0.39 ± 0.16) in session 1, but agreement improved in session 2 (0.47 ± 0.09; p = 0.03). The increase in agreement in session 2 was observed among inexperienced radiologists (p < 0.05), and experienced and inexperienced reviewers exhibited comparable agreement performance in session 2 (p > 0.05). All agreement measures between radiologist-assessed 4X categorization and lung cancer diagnosis increased in session 2 (p < 0.05). CONCLUSION: Radiologist training can improve reader agreement on 4X categorization, leading to enhanced diagnostic performance for lung cancer. KEY POINTS: • Agreement on 4X categorization between radiologists and an expert-adjudicated reference standard was initially poor, but improved significantly after training. • The mean proportion of 4X categorization by 19 radiologists decreased from 56.4% ± 16.9% in session 1 to 33.4% ± 8.0% in session 2. • All agreement measures between the 4X categorization and lung cancer diagnosis increased significantly in session 2, implying that appropriate training and guidance increased the diagnostic potential of category 4X.

NUT Midline Carcinoma of the Lung: Computed Tomography Findings in 10 Patients.

OBJECTIVE: The aim of the study was to evaluate computed tomography (CT) findings of pulmonary NUT midline carcinoma. METHODS: We assessed clinical and CT features of pulmonary NUT carcinoma in 10 consecutive patients (M:F, 7:3; mean, 39 years). RESULTS: The primary tumors (size range, 15-65 mm) manifested as either a peripheral tumor (5/10) or a central tumor (5/10). All tumors showed relatively low-attenuation at contrast-enhanced CT (mean net enhancement, 26 HU). Associated CT findings were metastatic hilar or mediastinal lymphadenopathy (8/10), ipsilateral pleural seeding with malignant pleural effusion (2/10), and distant metastasis (2/10). Five patients with low tumor-node-metastasis stages after optimal treatment showed no evidence of disease (50%) for 6 to 35 months. CONCLUSIONS: Pulmonary NUT carcinoma presented as a peripheral or a central lung mass showing mild degree of contrast enhancement, frequent metastatic regional lymphadenopathy, affecting relatively young adults. Although known to be highly aggressive, an early diagnosis in low TNM stages can lead to a favorable prognosis.

Classification of Diffuse Glioma Subtype from Clinical-Grade Pathological Images Using Deep Transfer Learning.

Diffuse gliomas are the most common primary brain tumors and they vary considerably in their morphology, location, genetic alterations, and response to therapy. In 2016, the World Health Organization (WHO) provided new guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features to diffuse gliomas. In this study, we demonstrate how deep learning approaches can be used for an automatic classification of glioma subtypes and grading using whole-slide images that were obtained from routine clinical practice. A deep transfer learning method using the ResNet50V2 model was trained to classify subtypes and grades of diffuse gliomas according to the WHO's new 2016 classification. The balanced accuracy of the diffuse glioma subtype classification model with majority voting was 0.8727. These results highlight an emerging role of deep learning in the future practice of pathologic diagnosis.

Senolytic Therapy for Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.

A Comparative Analysis of In Vitro Toxicity of Synthetic Zeolites on IMR-90 Human Lung Fibroblast Cells.

Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different types and compositions of zeolite on cytotoxicity is still unknown. Four types of synthetic zeolites have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D), ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity-related gene expressions were evaluated by PCR array. The result showed significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.

Static Rashba Effect by Surface Reconstruction and Photon Recycling in the Dynamic Indirect Gap of APbBr3 (A = Cs, CH3NH3) Single Crystals.

Recently, halide perovskites have gained significant attention from the perspective of efficient spintronics owing to the Rashba effect. This effect occurs as a consequence of strong spin-orbit coupling under a noncentrosymmetric environment, which can be dynamic and/or static. However, there exist intense debates on the origin of broken inversion symmetry since the halide perovskites typically crystallize into a centrosymmetric structure. In order to clarify the issue, we examine both dynamic and static effects in the all-inorganic CsPbBr3 and organic-inorganic CH3NH3PbBr3 (MAPbBr3) perovskite single crystals by employing temperature- and polarization-dependent photoluminescence excitation spectroscopy. The perovskite single crystals manifest the dynamic effect by photon recycling in the indirect Rashba gap, causing dual peaks in the photoluminescence. However, the effect vanishes in CsPbBr3 at low temperatures (<50 K) accompanied by a striking color change of the crystal, arising presumably from lower degrees of freedom for inversion symmetry breaking associated with the thermal motion of the spherical Cs cation compared with the polar MA cation in MAPbBr3. We also show that the static Rashba effect occurs only in MAPbBr3 below 90 K, presumably due to surface reconstruction via MA-cation ordering, which likely extends across a few layers from the crystal surface to the interior. We further demonstrate that this static Rashba effect can be completely suppressed upon surface treatment with polymethyl methacrylate (PMMA) coating. We believe that our results provide a rationale for the Rashba effects in halide perovskites.

Blood pressure variability and hemorrhagic transformation in patients with successful recanalization after endovascular recanalization therapy: A retrospective observational study.

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.

Focal hyperemia in Wernicke's encephalopathy: a preliminary arterial spin labeling MRI study.

Although a perturbed cerebral blood flow (CBF) has been reported in patients with Wernicke's encephalopathy (WE), its clinical meaning is still elusive. A retrospective analysis of 10 patients (male, 6; mean age, 57.7 years) with WE between October 2012 and May 2018 was performed. Brain imaging was performed using fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), arterial spin labeling (ASL) perfusion-weighted imaging (PWI), and contrasted enhanced T1-weighted imaging. All patients had symmetric high signal intensity lesions in the vulnerable areas on FLAIR or DWI with focal hyperintensity on ASL-PWI (100% sensitivity). CBFlesion was variable (from 70 mL/100 g/min to 190.0 mL/100 g/min). CBFlesion/CBFwhite matter was elevated, ranging from 2.5 to 5.5. Focal hyperintensity on ASL in the vulnerable areas can be a diagnostic clue for WE.

Parameterized optical properties of InxAl1-xP alloys.

We report values of parametric-model (PM) parameters that can be used to obtain dielectric functions (refractive indices) from 1.5 to 6.0 eV for ${{\rm In}_x}{{\rm Al}_{1 - x}}{\rm P}$InxAl1-xP alloys of arbitrary compositions $x$x. Using reported pseudo-dielectric data for several In compositions, we extract their dielectric functions by multilayer calculations, then parameterize them with PM lineshapes that well describe the asymmetric nature of their critical point (CP) contributions. We follow the ${E_0}$E0 fundamental bandgap as a function of $x$x, and determine the composition of the indirect-to-direct crossover.

Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes.

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.

Lack of Association between Low Cumulative Dose of Hydroxyethyl Starch and Acute Kidney Injury in Patients with Acute Ischemic Stroke.

BACKGROUND: Hydroxyethyl starch (HES, 6% 130/0.4) has been used as a volume expander for the treatment of cerebral hypoperfusion in acute ischemic stroke. Although HES use was associated with renal failure in sepsis or critical illness, it still remains to be elucidated whether HES is linked to renal adverse events in patients with acute ischemic stroke. METHODS: A total of 524 patients with acute ischemic stroke within 7 days of onset were included between January 2012 and May 2016. Renal function on admission and follow-up on day 7 ± 2 was assessed using serum creatinine (SCr) and estimated glomerular filtration rate (eGFR). Propensity score matching (PSM) was used to perform a 1:1 matched-pair analysis to minimize the group differences caused by covariates. The percentage of patients with new-onset acute renal injury (AKI) using the Kidney Disease: Improving Global Outcomes or good functional outcome (modified Rankin Scale 0-2) at 90 days were compared between HES cohort and controls. RESULTS: Among the included patients (mean age, 68.6 years; male, 56.5%), 81 patients (15.5%) were HES cohort (median cumulative dose, 1,450 mL). Baseline renal function was better in HES cohort compared to that in the controls (SCr, 0.87 ± 0.43 mg/dL vs. 1.15 ± 1.15 mg/dL, P < 0.001; eGFR, 86.91 ± 24.27 mL/min vs. 74.55 ± 29.58 mL/min, P < 0.001), which became not significant in PSM cohort (72 pairs). The percentage of new-onset AKI did not differ between the HES cohort and controls (1.4% vs. 1.4%, P = 1.000). In addition, new-onset AKI was not related to HES (odds ratio, 1.422; 95% confidence interval, 0.072-28.068; P = 0.817) after adjusting for confounders. HES cohort tended to have higher percentage of good functional outcome at 90 days compared to controls, which failed to reach statistical significance (68.1% vs. 54.2%, P = 0.087). CONCLUSION: A low cumulative dose of HES was not associated with renal adverse events in patients with acute ischemic stroke.

Impact of the Dedicated Neurointensivists on the Outcome in Patients with Ischemic Stroke Based on the Linked Big Data for Stroke in Korea.

BACKGROUND: Neurocritical care by dedicated neurointensivists may improve outcomes of critically ill patients with severe brain injury. In this study, we aimed to validate whether neurointensive care could improve the outcome in patients with critically ill acute ischemic stroke using the linked big dataset on stroke in Korea. METHODS: We included 1,405 acute ischemic stroke patients with mechanical ventilator support in the intensive care unit after an index stroke. Patients were retrieved from linking the Clinical Research Center for Stroke Registry and the Health Insurance Review and Assessment Service data from the period between January 2007 and December 2014. The outcomes were mortality at discharge and at 3 months after an index stroke. The main outcomes were compared between the centers with and without dedicated neurointensivists. RESULTS: Among the included patients, 303 (21.6%) were admitted to the centers with dedicated neurointensivists. The patients treated by dedicated neurointensivists had significantly lower in-hospital mortality (18.3% vs. 26.8%, P = 0.002) as well as lower mortality at 3-month (38.0% vs. 49.1%, P < 0.001) than those who were treated without neurointensivists. After adjusting for confounders, a treatment without neurointensivists was independently associated with higher in-hospital mortality (odds ratio [OR], 1.59; 95% confidence intervals [CIs], 1.13-2.25; P = 0.008) and 3-month mortality (OR, 1.48; 95% CIs, 1.12-1.95; P = 0.005). CONCLUSION: Treatment by dedicated neurointensivists is associated with lower in-hospital and 3-month mortality using the linked big datasets for stroke in Korea. This finding stresses the importance of neurointensivists in treating patients with severe ischemic stroke.

Non-Thermal Plasma Couples Oxidative Stress to TRAIL Sensitization through DR5 Upregulation.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells without affecting most normal cells. Despite being in clinical testing, novel strategies to induce TRAIL-mediated apoptosis are in need to overcome cancer cell unresponsiveness and resistance. Plasma-activated medium (PAM) markedly stimulates reactive oxygen/nitrogen species (ROS/RNS)-dependent apoptosis in cancer cells. We investigate the capability of PAM and TRAIL (PAM/TRAIL) combination therapy to overcome TRAIL resistance and improve the anticancer efficacy of TRAIL. The combinatorial treatment of PAM and TRAIL shows synergistic effects on growth inhibition in TRAIL-resistant cancer cells via augmented apoptosis by two attributes. DR5 (TRAIL-R2) transcription by CHOP is upregulated in a PAM-generated ROS/RNS-dependent manner, and PAM itself upregulates PTEN expression mediated by suppression of miR-425 which is involved in Akt inactivation, leading to increased apoptosis induction. Treatment of cancer cell lines with the antioxidant N-acetylcysteine reduces the extent of membrane dysfunction and the expression of both CHOP-DR5 and miR-425-PTEN axes, attenuating PAM/TRAIL-induced cancer cell apoptosis. These data suggest that PAM/TRAIL treatment is a novel approach to sensitizing cancer cells to TRAIL-induced apoptosis and overcoming TRAIL resistance. PAM is a promising candidate for further investigations as a chemotherapeutic sensitizer in the treatment of cancer.