Prehospital Ultra-Early Neurological Deterioration in Intracerebral Hemorrhage: Definition, Prevalence, and Association with Outcomes.

INTRODUCTION: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months. RESULTS: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015). CONCLUSION: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH.

Relationship Between Non-contrast Computed Tomography Imaging Markers and Perihemorrhagic Edema Growth in Intracerebral Hemorrhage.

OBJECTIVES: Perihemorrhagic edema (PHE) growth has been gradually considered as predictor for outcome of Intracerebral hemorrhage (ICH) patients. The aim of our study was to investigate correlation between non-contrast computed tomography (CT) markers and early PHE growth. METHODS: ICH patients between July 2011 and March 2017 were included in this retrospective analysis. ICH and PHE volumes were measured by using a validated semiautomatic volumetric algorithm. Nonparametric test was used for comparing PHE volume at different time points of non-contrast computed tomography (NCCT) imaging markers. Multivariable linear regression was constructed to study the relationship between NCCT imaging markers and PHE growth over 36 h. RESULTS: A total of 214 patients were included. Nonparametric test showed that PHE volume was significantly different between patients with and without NCCT imaging markers. (all p < 0.05) In multivariable linear regression analysis adjusted for ICH characteristics, blend sign (p = 0.011), black hole sign (p = 0.002), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001) were correlated with PHE growth. Follow-up PHE volume within 36 h after baseline CT scan was associated with blend sign (p = 0.001), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001). CONCLUSION: NCCT imaging markers of hematoma expansion are associated with PHE growth. This suggests that early PHE growth can be predicted using radiology markers on admission CT scan.

Prediction of Early Perihematomal Edema Expansion Based on Noncontrast Computed Tomography Radiomics and Machine Learning in Intracerebral Hemorrhage.

OBJECTIVES: To investigate the predictive value of noncontrast computed tomography (NCCT) models based on radiomics features and machine learning for early perihematomal edema (PHE) expansion in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We retrospectively reviewed NCCT data from 214 patients with spontaneous ICH. All radiomics features were extracted from volume of interest of hematomas on admission scans. A total of 8 machine learning methods were applied for constructing models in the training and the test set. Receiver operating characteristic analysis and the areas under the curve were used to evaluate the predictive value. RESULTS: A total of 23 features were finally selected to establish models of early PHE expansion after feature screening. Patients were randomly assigned into training (n = 171) and test (n = 43) sets. The accuracy, sensitivity, and specificity in the test set were 72.1%, 90.0%, and 66.7% for the support vector machine model; 79.1%, 70.0%, and 84.4% for the k-nearest neighbor model; 88.4%, 90.0%, and 87.9% for the logistic regression model; 74.4%, 90.0%, and 69.7% for the extra tree model; 74.4%, 90.0%, and 69.7% for the extreme gradient boosting model; 83.7%, 100%, and 78.8% for the multilayer perceptron (MLP) model; 72.1%, 100%, and 65.6% for the light gradient boosting machine model; and 60.5%, 90.0%, and 53.1% for the random forest model, respectively. CONCLUSIONS: The MLP model seemed to be the best model for prediction of PHE expansion in patients with ICH. NCCT models based on radiomics features and machine learning could predict early PHE expansion and improve the discrimination of identify spontaneous intracerebral hemorrhage patients at risk of early PHE expansion.

Comparison of different noncontrast computed tomographic markers for predicting early perihematomal edema expansion in patients with intracerebral hemorrhage.

OBJECTIVES: Noncontrast computed tomography (NCCT) imaging markers are associated with early perihematomal edema (PHE) growth. The aim of this study was to compare the predictive value of different NCCT markers in predicting early PHE expansion. METHODS: ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan within 36 h between July 2011 and March 2017 were included in this study. The predictive value of hypodensity, satellite sign, heterogeneous density, irregular shape, blend sign, black hole sign, island sign and expansion-prone hematoma for early perihematomal edema expansion were assessed, separately. RESULTS: 214 patients were included in our final analysis. After adjusting for ICH characteristics, hypodensity, blend sign, island sign and expansion-prone hematoma are still predictors of early perihematomal edema expansion in multivariable logistics regression analysis (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of expansion-prone hematoma was significantly larger than the area under the ROC curve of hypodensity, blend sign and island sign in predicting PHE expansion (P = 0.003, P < 0.001 and P = 0.002, respectively). CONCLUSION: Compared with single NCCT imaging markers, expansion-prone hematoma seems to be optimal predictor for early PHE expansion than any single NCCT imaging marker.

Beam dynamics optimization design of Rhodotron electron accelerator based on genetic algorithm and sensitivity analysis.

The beam dynamics optimization study of Rhodotron electron accelerator for irradiation sterilization is introduced in this paper. The Rhodotron accelerator acceleration principle and the RF field distribution in the coaxial resonant cavity are described in detail. Beam dynamics in the Rhodotron accelerator are analyzed from both transverse and longitudinal directions. Beam dynamics of two kinds of Rhodotron electron accelerators with maximum beam energy of 10 MeV and 40 MeV were optimized based on multi-objective genetic algorithm. The key parameters of Rhodotron accelerators are determined, and the influence of some parameters on the overall acceleration effect is quantitatively analyzed. This paper provides some references for the research, manufacture, installation, and commissioning of this type of accelerator.

Near-Infrared Light-Remote Localized Drug Delivery Systems Based on Zwitterionic Polymer Nanofibers for Combination Therapy.

Localized drug delivery systems (LDDS) have gained great interests because they can directly treat the tumors and minimize systematic toxicity, and maximize drug action by controlling release precisely at the tumor site. However, the resistance of the non-specific adsorption of biomolecules is also important to alleviate the inflammatory reactions and avoid the decrease in performance of LDDS. In this study, we develop a near infrared (NIR) light-triggered nanofibrous delivery system consisting of zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(ε-caprolactone) (PMPC-b-PCL) encapsulated with indocyanine green (ICG) and doxorubicin (DOX) for dual photothermal therapy and chemotherapy. The nanofibrous mat shows hydrophilic characteristics and good antifouling performance. Under mild NIR irradiation, ICG could convert NIR light into thermal energy that elevates the surrounding temperature above 45 °C. This thermal energy also markedly accelerates the DOX release from the nanofibrous mat due to softening of the nanofibers, indicating the drug release could be controlled and switched on/off by light-triggering. Moreover, this light-triggered thermal energy and releasing behavior contribute to enhancing the cell lethality. Intracellular DOX distribution confirms the more drugs release upon light irradiation. All results demonstrate the developed light-triggered drug release nanofibers as LDDS are biocompatible and antifouling as well as has the superior combinational chemotherapy/photothermal therapy.

3D island sign on computed tomography predicts early perihematomal edema expansion and poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To determine the prognostics significance of the computed tomography (CT) 3D island sign for predicting early perihematomal edema (PHE) expansion and poor functional outcome in patients presenting with intracerebral hemorrhage (ICH). METHODS: Between July 2011 and March 2017, patients with intracerebral hemorrhage who had undergone baseline CT within 6 h after ICH symptom onsets and follow-up CT in our hospital were included. Two different readers independently assessed the presence of 3D island sign on admission CT scan of each patient. Multivariable logistic regression analysis was used to analyze association between 3D island sign and early perihematomal edema expansion and poor functional outcome, separately. RESULTS: A total of 214 patients who met the inclusion criteria were included in our study, 3D island sign was observed in 60 patients (28.0 %) on admission CT scan. The multivariate logistic regression analysis demonstrated that baseline hematoma volume, time to baseline and follow-up CT scans and the presence of 3D island sign were predictors of early PHE expansion. After adjusting for age, baseline hematoma and edema volume, time to baseline and follow-up CT scans, GCS on admission, presence of intraventricular hemorrhage (IVH) and systolic blood pressure, the 3D island sign was an independently imaging marker for poor outcome (OR, 2.803; 95 % confidence interval, 1.189-6.609; P = 0.018). CONCLUSION: The 3D island sign in patients with intracerebral hemorrhage was a reliable predictor for early perihematomal edema expansion and poor functional outcome. It may serve as a potential therapeutic target for intervention.

Synthesis of Short-Chain-Fatty-Acid Resveratrol Esters and Their Antioxidant Properties.

To expand the applications and enhance the stability and bioactivity of resveratrol (RE), and to simultaneously include the potential health benefits of short chain fatty acids (SCFA) esters of RE were prepared by Steglich reactions with acetic, propionic, and butyric acids, respectively. RE and the esterified RE-SCFA products (including RAE, RPE, and RBE) were analyzed using nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential thermal analysis (DTA), and liquid chromatography-mass spectrometry (LC-MS). The FTIR and 13C NMR spectra of the esterified products included ester-characteristic peaks at 1751 cm-1 and 171 ppm, respectively. Moreover, the peaks in the range of 1700 to 1600 cm-1 in the FTIR spectra of the esterified products indicated that the esterification of RE-SCFA was successful. The TGA results revealed that the RE-SCFA esters decomposed at lower temperatures than RE. The peaks in the LC-MS profiles of the esterified products indicated the formation of mono- and diesters, and the calculated monoester synthesis rates ranged between 45.81 and 49.64%. The RE esters inhibited the Cu2+-induced low-density lipoprotein oxidation reaction, exhibited antioxidant activity in bulk oil, and effectively inhibited the hydroxyl radical-induced DNA scission. Moreover, the RE-SCFA esters had better hydrogen peroxide scavenging activity than RE. Our results are the first in the literature to successfully including short chain fatty acids in the esters of resveratrol, and the products could be used as a functional food ingredient in processed foods or can be used as dietary supplements to promote health.

Early Perihematomal Edema Expansion: Definition, Significance, and Association with Outcomes after Intracerebral Hemorrhage.

OBJECTIVE: To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. RESULTS: In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70-10.60; p = 0.002). CONCLUSIONS: The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

Comparison of Satellite Sign and Island Sign in Predicting Hematoma Growth and Poor Outcome in Patients with Primary Intracerebral Hemorrhage.

OBJECTIVE: Satellite sign (SS) and island sign (IS) are novel noncontrast computed tomography (CT) predictors of hematoma growth. The aim of this study was to compare diagnostic performance of IS and SS in predicting hematoma growth and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: The study included patients with ICH who underwent baseline CT scan within 6 hours of symptom onset and follow-up CT scan within 36 hours after initial CT between July 2012 and April 2017. Sensitivity, specificity, positive predictive value, and negative predictive value of IS and SS in predicting hematoma growth and functional outcome were assessed. Accuracy of the 2 signs in predicting hematoma growth and functional outcome was analyzed using receiver operating characteristic analysis. Association between the presence of IS and SS and ICH growth was assessed using multivariate logistic regression. RESULTS: Of 307 patients with ICH, IS was observed in 46 patients (15.0%), and SS was observed in 151 patients (49.2%). Rates of hematoma growth were 40.4% in SS+ patients, 91.3% in IS+ patients, 18.4% in SS-IS- patients, 21.1% in SS+IS- patients, 100% in SS-IS+ patients, and 90.5% in SS+IS+ patients. After adjusting for potential confounders, IS remained an independent predictor for hematoma growth and poor functional outcome. The area under the curve of IS was significantly larger than the area under the curve of SS in predicting hematoma growth (P = 0.001). CONCLUSIONS: IS seems to be an optimal shape irregularity imaging marker for predicting hematoma growth and functional outcome in patients with ICH.

Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer.

The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε­caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG­COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.