Particokinetic models are important to predict the effective cellular dose, which is key to understanding the interactions of particles with biological systems. For the reliable establishment of ...dose-response curves in, e.g., the field of pharmacology and toxicology, mostly the In vitro Sedimentation, Diffusion and Dosimetry (ISDD) and Distorted Grid (DG) models have been employed. Here, we used high resolution scanning electron microscopy to quantify deposited numbers of particles on cellular and intercellular surfaces and compare experimental findings with results predicted by the ISDD and DG models.
Exposure of human lung epithelial A549 cells to various concentrations of differently sized silica particles (100, 200 and 500 nm) revealed a remarkably higher dose deposited on intercellular regions compared to cellular surfaces. The ISDD and DG models correctly predicted the areal densities of particles in the intercellular space when a high adsorption ("stickiness") to the surface was emulated. In contrast, the lower dose on cells was accurately inferred by the DG model in the case of "non-sticky" boundary conditions. Finally, the presence of cells seemed to enhance particle deposition, as aerial densities on cell-free substrates were clearly reduced.
Our results further validate the use of particokinetic models but also demonstrate their limitations, specifically, with respect to the spatial distribution of particles on heterogeneous surfaces. Consideration of surface properties with respect to adhesion and desorption should advance modelling approaches to ultimately predict the cellular dose with higher precision.
This study is concerned with backscattered electron scanning electron microscopy (BSE SEM) contrast of complex nanoscaled samples which consist of SiO2 nanoparticles (NPs) deposited on ...indium-tin-oxide covered bulk SiO2 and glassy carbon substrates. BSE SEM contrast of NPs is studied as function of the primary electron energy and working distance. Contrast inversions are observed which prevent intuitive interpretation of NP contrast in terms of material contrast. Experimental data is quantitatively compared with Monte-Carlo- (MC-) simulations. Quantitative agreement between experimental data and MC-simulations is obtained if the transmission characteristics of the annular semiconductor detector are taken into account. MC-simulations facilitate the understanding of NP contrast inversions and are helpful to derive conditions for optimum material and topography contrast.
Spreading depolarizations are waves of mass neuronal and glial depolarization that propagate across the injured human cortex. They can occur with depression of neuronal activity as spreading ...depressions or isoelectric spreading depolarizations on a background of absent or minimal electroencephalogram activity. Spreading depolarizations are characterized by the loss of neuronal ion homeostasis and are believed to damage functional neurons, leading to neuronal necrosis or neurological degeneration and poor outcome. Analgesics and sedatives influence activity-dependent neuronal ion homeostasis and therefore represent potential modulators of spreading depolarizations. In this exploratory retrospective international multicentre analysis, we investigated the influence of midazolam, propofol, fentanyl, sufentanil, ketamine and morphine on the occurrence of spreading depolarizations in 115 brain-injured patients. A surface electrode strip was placed on the cortex, and continuous electrocorticographical recordings were obtained. We used multivariable binary logistic regression to quantify associations between the investigated drugs and the hours of electrocorticographical recordings with and without spreading depolarizations or clusters of spreading depolarizations. We found that administration of ketamine was associated with a reduction of spreading depolarizations and spreading depolarization clusters (P < 0.05). Midazolam anaesthesia, in contrast, was associated with an increased number of spreading depolarization clusters (P < 0.05). By using a univariate odds ratio analysis, we also found a significant association between ketamine administration and reduced occurrence of isoelectric spreading depolarizations in patients suffering from traumatic brain injury, subarachnoid haemorrhage and malignant hemispheric stroke (P < 0.05). Our findings suggest that ketamine-or another N-methyl-d-aspartate receptor antagonist-may represent a viable treatment for patients at risk for spreading depolarizations. This hypothesis will be tested in a prospective study.
Aim Several factors influence the outcome after acute ischemic stroke secondary to proximal occlusions of cerebral vessels. Among others, noneligibility for intravenous thrombolysis (IVT) and ...incomplete revascularization have been identified as predictors of unfavorable outcome. The aim of this study was to investigate whether concomitant IVT influences the revascularization efficacy in mechanical thrombectomy (MT). Methods This study conducted a retrospective analysis of all consecutive patients presenting with an anterior circulation stroke due to large-artery occlusion with imaging evidence who were treated with MT between July 2012 and December 2013 at 2 high-volume stroke centers. Imaging data were regraded and re-evaluated according to the modified Treatment in Cerebral Ischemia scale and its respective vessel occlusion site definitions. Clinical end points included National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale; imaging and procedural measures were technical end points. Results We identified 93 patients who presented with an occlusion of the middle cerebral artery (MCA): of these patients, 66 (71%) received IVT. We did not find statistically significant differences in the baseline NIHSS score, time from symptom onset to groin puncture, and age when comparing the IVT group with the non-IVT group. The rate of successful recanalizations (modified Treatment in Cerebral Ischemia score ≥ 2b) was significantly higher in patients with MCA occlusion and concomitant IVT ( P = .01). Stepwise logistic regression identified IVT and thrombus length as predictive factors for successful mechanical recanalization ( P = .004, P = .002). Conclusion IVT and thrombus length are predictive factors for a successful recanalization in MT for acute ischemic stroke with underlying MCA occlusion.
The focus of this study was to determine ease of deployment, safety and effectiveness of the LVIS Jr device.
A retrospective analysis was performed of 32 cases comprising 34 aneurysms in which the ...LVIS Jr device was used for stent-assisted coil embolization of intracranial aneurysms from February to October 2012, including all clinical and angiographic data as well as mid-term follow-up (1-12 months of treatment).
The median age of the patients was 54 years (range 21-76) and 19 (59%) were women. The aneurysms were ruptured in 12/34 cases (35.3%); 26 (76.4%) were located within the anterior circulation and the remaining 8 (23.5%) were located in the posterior circulation. Eleven of the 34 aneurysms (32.3%) were treated with a Y-stent configuration. Immediate total occlusion was observed in 16/34 (47%), near total occlusion (90-95%) in 5/34 (14.7%) and a 'dog ear' or subtotal occlusion in 12/34 (35.2%). A single aneurysm was treated without coil embolization. Complications occurred in 5/34 cases (15%), including two cases of in-stent thrombosis.
Implantation of the LVIS Jr device as a support device for stent-assisted coil embolization seems to be safe and effective. The LVIS Jr device can also be implanted in a Y-stent configuration, offering a novel technique with a potentially lower risk of thromboembolic complications compared with other devices.
Background
Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically.
...Methods
Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale ≤9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up.
Results
114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale ≥3 after admission odds ratio (OR) 6.7, bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1).
Conclusion
The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care.
To determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a ...very long-term follow-up of nearly 20 years.
Sixty-five patients (median age 62 years, range 27-75; median Karnofsky performance score 70, range 20-90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation.
Median follow-up for surviving patients was 19.6 years (17.5-23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval CI 2.9-5.9); for patients ≤60 years, 11.0 years (95% CI 4.8-17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years.
At a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL.
This work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.
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