Netzhautkomplikationen bei Diabetes

In September 2015 a revised version of the guideline “Prevention and therapy of diabetes-induced retinal complications” was released in Germany. It summarizes current recommendations for diagnosis and therapy of diabetic retinopathy with a special focus on practicability in daily routine. Newly included were the use of optical coherence tomography (OCT) for the diagnosis of diabetic macular edema and the evaluation of the therapeutic effect of anti-VEGF drugs (VEGF: vascular endothelial growth factor) or corticosteroids after intravitreal drug delivery. Screening intervals for diabetic retinopathy were extended to every 2 years for all diabetic patients with no retinopathy and limited systemic risk factors. Patients with known risk factors should be screened annually or in case of retinopathy, followed-up as recommended by the ophthalmologist.     

Antiangiogenic property of human thrombin

Using protein chromatography, we purified and identified human prothrombin from human plasma as antiangiogenic. Prothrombin significantly inhibited endothelial cell tube formation in vitro at 10 microg/ml. Importantly, it also inhibited bFGF-induced angiogenesis in Matrigel-plug assays performed in mice. The proteolytic activity of thrombin appeared to be critical for the antiangiogenic activity of prothrombin. For example, thrombin exhibited inhibitory effects on endothelial cell tube formation in vitro at 10 U/ml. Addition of lepirudin, a specific inhibitor of thrombin, completely blocked prothrombin's and thrombin's antiangiogenic effects in vitro. We also assessed the importance of thrombin receptors in angiogenesis. Using small peptides that activate different protease-activated receptors (PARs), we showed that activation of PAR-1 led to inhibition of endothelial cell tube formation in vitro and bFGF-induced angiogenesis in vivo. Collectively, our data suggest that thrombin's proteolytic activity can be antiangiogenic.     

PD-L1 – inhibitors in neuroendocrine neoplasia: Results from a real-life study

Immune check-point inhibitors (ICIs) have changed our view on how to treat cancer. Despite their approval in treatment of many different cancers, efficacy of immune check-point inhibitors (ICI) in neuroendocrine neoplasia is limited and poorly understood. Established treatment options of neuroendocrine tumors (NET) and neuroendocrine carcinomas (NECs) are based on surgery, tumor-targeted medical treatments, Peptide Receptor Radionuclide Therapy (PRRT), and locoregional therapies. However, in many patients these treatments lose efficacy over time, and novel therapies are urgently needed. We report on 8 patients diagnosed with neuroendocrine neoplasms (NEN) that were treated with ICI (pembrolizumab, avelumab, nivolumab plus ipilimumab) as salvage therapy. In this cohort, we observed tumor response with partial remission in 3 patients and stable disease in 1 patient. Four patients showed progressive disease. Of note, responses were observed both in PD-L1 positive and PD-L1 negative patients. Here, we discuss clinical courses of these patients in the context of available literature to highlight limitations and drawbacks currently preventing the use of ICI in routine management of patients with NEN.     

Brief Report: Educational attainment does not influence brain aging

Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.