The Influence of Erythropoietin on the axonal regeneration in the roden central vervous system in vitro and in vivo

Die Wirkung von EPO auf die axonale Regeneration im ZNS der Ratte wird in vitro (Retinastanzen-assay) und in vivo (Opticus-Crush-Modell)untersucht.The influence of EPO on the axonal regeneration in the roden CNS is examined in vitro (retinal-explant-assay) and in vivo (opticus-crush-model)

A Smart Device System to Identify New Phenotypical Characteristics in Movement Disorders

Parkinson's disease and Essential Tremor are two of the most common movement disorders and are still associated with high rates of misdiagnosis. Collected data by technology-based objective measures (TOMs) has the potential to provide new promising and highly accurate movement data for a better understanding of phenotypical characteristics and diagnostic support. A technology-based system called Smart Device System (SDS) is going to be implemented for multi-modal high-resolution acceleration measurement of patients with PD or ET within a clinical setting. The 2-year prospective observational study is conducted to identify new phenotypical biomarkers and train an Artificial Intelligence System. The SDS is going to be integrated and tested within a 20-min assessment including smartphone-based questionnaires, two smartwatches at both wrists and tablet-based Archimedean spirals drawing for deeper tremor-analyses. The electronic questionnaires will cover data on medication, family history and non-motor symptoms. In this paper, we describe the steps for this novel technology-utilizing examination, the principal steps for data analyses and the targeted performances of the system. Future work considers integration with Deep Brain Stimulation, dissemination into further sites and patient's home setting as well as integration with further data sources as neuroimaging and biobanks. Study Registration ID on ClinicalTrials.gov: NCT03638479

Validating a new generation filter system for visualizing 5-ALA-induced PpIX fluorescence in malignant glioma surgery: a proof of principle study

Background!#!The BLUE 400 filter system (Carl Zeiss Meditec, Oberkochen, Germany) has provided visualization of 5-ALA-induced fluorescence-guided surgery for more than 20 years. Nevertheless, constraints, e.g., limited background discrimination during hemostasis, obstruct fluency of surgery. A novel filter with improved background visualization was developed, requiring validation regarding fluorescence discrimination. The aim of this article is to determine diagnostic accuracy and perception of protoporphyrin IX (PpIX) discrimination of a novel filter system with higher background illumination (BLUE 400 AR) compared with the gold standard, BLUE 400.!##!Methods!#!A surgical microscope equipped with both BLUE 400 and BLUE 400 AR was used. Comparisons were performed on a biological basis and on the visual perception of margins. High-resolution images were compared during and after surgery by senior neurosurgeons. In a predefined biopsy algorithm, four biopsies per patient at tumor margins of PpIX fluorescence and adjacent brain were acquired using BLUE 400 AR only from regions intended for resection and assessed for cell count and density.!##!Results!#!Thirty-two patients with malignant gliomas were included in this study. BLUE 400 AR markedly enhanced the brightness of the surgical field, allowing superior discrimination of brain anatomy. A total of 128 biopsies from fluorescence margins were collected. Positive predictive value (PPV) was 98.44% (95% CI, 90.06-99.77%) for malignant glioma. Residual median cell density in non-fluorescent tissue was 13% (IQR 13 to 31). Perception of the location of fluorescent margins on HD images was equivalent for both filter combinations.!##!Conclusions!#!BLUE 400 AR demonstrated superior background compared with conventional BLUE 400 in malignant glioma surgery but comparable fluorescence margins and PPV. Therefore, BLUE 400 AR can be considered safe and effective in supporting malignant glioma surgery

Diagnosing Mixing Properties in Model Simulations for CH4 in the Stratosphere

International audienceIsentropic mixing properties in the stratosphere modeled by the forward calculation of an inverse model (TM5-4DVAR) are evaluated against Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and Microwave Limb Sounder (MLS) observations. The isentropic mixing processes are separated into large-scale stirring described by the “equivalent length” and small-scale diffusion described by the diffusivity. Compared to the measurements, we find that the modeled stirring is not strong enough and that the small-scale diffusivity is too large. TM5-4DVAR produces excessive mixing-induced poleward flux for stratospheric CH4. The flux convergence presents negative biases in the tropics and positive biases in the polar regions. The biases cannot be reduced by improving the horizontal resolution only. Modeled isentropic mixing depends on the horizontal as well as the vertical resolution of the model. An increase in vertical resolution reduces numerical diffusion of the model in the vertical. The decreased vertical diffusion leads to reduction in the modeled isentropic diffusivity. Biases in modeled total column-averaged mixing ratios of CH4 are significant for both models with a coarse vertical resolution of 4° × 6° × 25 (and 2° × 3° × 25, 1° × 1° × 25) and an improved one of 1° × 1° × 40. They are estimated to be 7–14 and 3–7 ppb in the winter extratropics under the assumption that isentropic mixing is dominant over vertical transport on a time scale of 3 days. Correspondingly, resulted biases in inverted CH4 surface emissions are estimated to be 0.5–1 and 0.2–0.5 mg/m2/hr, respectively, in the extratropics

Evaluation of 311 contemporary cases of stereotactic biopsies in patients with neoplastic and non-neoplastic lesions—diagnostic yield and management of non-diagnostic cases

Stereotactic biopsies are an established tool for obtaining diagnosis of unclear brain lesions. However, non-diagnostic biopsies still occur. We aimed to analyze the contemporary diagnostic yield of stereotactic biopsies, predictors for non-diagnostic biopsies, outcome, and follow-up strategy after non-diagnostic biopsy. We conducted a single-center retrospective study of 311 adult patients undergoing stereotactic biopsies due to a newly diagnosed lesion at our department between 2012 and 2018. Patient data regarding comorbidities, presenting symptoms, imaging features, and non-invasive diagnostic procedures were obtained. The overall diagnostic yield was 86.2% and differed significantly between the various suspected diagnosis groups and was the highest when suspecting primary brain tumor compared with non-neoplastic lesions (91.2% vs. 73.3%, p > 0.001). Predicators for non-diagnostic biopsies were small lesion size, lack of contrast-enhancement, presence of sepsis, or underlying hemato-oncological disease. In case of non-diagnostic biopsy, a re-biopsy was performed in 12 cases, revealing a final diagnosis in 75%. In 16 cases, empiric therapy was started based on the suspected underlying disease. Close follow-up was performed in the remaining 15 cases. We showed that stereotactic biopsy is a safe procedure with reasonable diagnostic yield even for non-neoplastic lesions, when non-invasive diagnostic was inconclusive. In addition, we developed treatment recommendations for cases of non-diagnostic biopsies

Combined Fluorescence-Guided Resection and Intracavitary Thermotherapy with Superparamagnetic Iron-Oxide Nanoparticles for Recurrent High-Grade Glioma: Case Series with Emphasis on Complication Management

Background: Concepts improving local tumor control in high-grade glioma (HGG) are desperately needed. The aim of this study is to report an extended series of cases treated with a combination of 5-ALA-fluorescence-guided resection (FGR) and intracavitary thermotherapy with superparamagnetic iron oxide nanoparticles (SPION). Methods: We conducted a single-center retrospective review of all recurrent HGG treated with FGR and intracavitary thermotherapy (n = 18). Patients underwent six hyperthermia sessions in an alternating magnetic field and received additional adjuvant therapies on a case-by-case basis. Results: Nine patients were treated for first tumor recurrence; all other patients had suffered at least two recurrences. Nine patients received combined radiotherapy and thermotherapy. The median progression-free survival was 5.5 (95% CI: 4.67–6.13) months and median overall survival was 9.5 (95% CI: 7.12–11.79) months. No major side effects were observed during active treatment. Thirteen patients (72%) developed cerebral edema and more clinical symptoms during follow-up and were initially treated with dexamethasone. Six (33%) of these patients underwent surgical removal of nanoparticles due to refractory edema. Conclusions: The combination of FGR and intracavitary thermotherapy with SPION provides a new treatment option for improving local tumor control in recurrent HGG. The development of cerebral edema is a major issue requiring further refinements of the treatment protocol

First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study

Abstract Background Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. Methods Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. Results All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. Conclusions In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting