University of Freiburg

About: University of Freiburg is a education organization based out in Freiburg, Baden-Württemberg, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 41992 authors who have published 77296 publications receiving 2896269 citations. The organization is also known as: alberto-ludoviciana & Albert-Ludwigs-Universität Freiburg.

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Abstract: Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Abstract: The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial

Abstract: Summary Background Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma. Methods Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m 2 temozolomide, given on days 1–7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6–7 weeks in 30 fractions of 1·8–2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. This trial is registered with ClinicalTrials.gov, number NCT01502241. Findings Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3–10·2) in the temozolomide group versus 9·6 months (8·2–10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84–1·42, p non-inferiority =0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2–4·1] vs 4·7 [4·2–5·2]; HR 1·15, 95% CI 0·92–1·43, p non-inferiority =0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0–10·0]; HR 0·62, 95% CI 0·42–0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5–11·7] vs 4·6 [4·2–5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0–3·5] vs 4·6 months [3·7–6·3]). The most frequent grade 3–4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight). Interpretation Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making. Funding Merck Sharp & Dohme.

Recent Developments in the Field of Inorganic Phosphors

Abstract: Because fossil fuels are becoming scarce and because of the expected climate change, our standard of living can only be maintained by a significant increase in energy efficiency. Large amounts of energy are consumed for lighting and during operation of displays. Thus, the targets are the development of economical light sources like white-light-emitting diodes and display panels with enhanced efficiency. Solar energy is converted into electricity by solar cells, and their efficiency must be improved considerably. A possible contribution might be delivered by phosphors which allow the conversion of thermal radiation into electrical energy. Although the target of energy efficiency is very important, we must not overlook that medical imaging diagnostic methods require efficient and sensitive detectors. For the solution of these central questions, inorganic solid-state materials doped with rare-earth ions are very promising and are therefore in the focus of current research activities.