Glial cell line-derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia-mediated glioma progression.

Glial cell line-derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF-induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen-activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll-like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro-tumorigenic phenotype of microglia.

Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma.

Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment. The impact of host-derived GPNMB on tumor growth was confirmed in two distinct murine glioma cell lines in organotypic brain slices from GPNMB-KO and control mice. Using published data bases of human glioma, the elevated levels in TAMs could be confirmed and the GPNMB expression correlated with a poorer survival.

Changes in Health-Related Quality of Life in Patients with Therapy-Resistant Migraine during Treatment with Erenumab in an Ambulatory Care Setting.

Migraine preventive treatment with the CGRP-receptor monoclonal antibody Erenumab can positively impact health-related quality of life (HRQoL) and disease-associated disability. Patient-reported outcome measures (PROMs) are a valuable additional datapoint to real-world evidence covering how treatment affects physical, mental, and social domains of patients' lives. In this real-world, single-center retrospective observational cohort study, we analyzed clinical performance indicators and PROMs for migraine patients who failed at least four other preventive medications and received Erenumab over the course of one year. Endpoints were the average monthly migraine days as well as PROMs including the MIDAS, EQ-5D-VAS and PROMIS-29. Data were collected digitally via the software heartbeat ONE in an ambulatory care setting as part of the clinical routine. A total of 145 patients treated with Erenumab provided data for 12 months. After 12 months, the median number of monthly migraine days decreased from 9 to 7 days. A clinically relevant reduction in migraine days by ≥30% was reported by 40% of the patients. The migraine-specific MIDAS score, the EQ-5D-VAS measuring the overall health status and all PROMIS domains, except sleep disturbance, changed significantly, reflecting a positive disease progression. This study highlights how patients with a treatment-resistant migraine in an outpatient setting benefit from a preventive treatment with Erenumab. A decrease in migraine days and an increase in HRQoL was maintained over one year. It also underscores the significance of collecting real-world evidence, including PROMs, as an integral component of the healthcare cycle, as such data can reveal additional factors relevant to treatment.

Integration of mobile sensors in a telemedicine hospital system: remote-monitoring in COVID-19 patients.

Aim: The goal is to design and, in a next step, establish a scalable, multi-center telemonitoring platform based on existing systems for monitoring COVID-19 patients in home quarantine. In particular, the focus will be on raw data acquisition, integration of sensor data into the hospital system, structured data storage, and interoperability. Subject and methods: Data necessary for monitoring, otherwise provided in various portals, will be continuously queried and integrated into the hospital system via a new interface in this proof-of-concept work. Results: Based on extensive preliminary work at Klinikum rechts der Isar with a structured clinical database, we extend our system's integration of raw data and visualization in dashboards, as well as scientific provision of data from mobile sensors for monitoring patients in home quarantine. Conclusion: Based on existing integrated telemonitoring systems supporting semantic and syntactic interoperability, short-term provision of scientific databases is possible. The integration of different mobile sensors into a clinical system for remote monitoring of patients around the clock is still new and to our knowledge unique.