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PURPOSE: Glioma patients face a limited life expectancy and at the same time, they suffer from afflicting symptoms and undesired effects of tumor treatment. Apart from bone marrow suppression, standard chemotherapy with temozolomide causes nausea, emesis and loss of appetite. In this pilot study, we investigated how chemotherapy-induced nausea and vomiting (CINV) affects the patients' levels of depression and their quality of life. METHODS: In this prospective observational multicentre study (n = 87), nausea, emesis and loss of appetite were evaluated with an expanded MASCC questionnaire, covering 10 days during the first and the second cycle of chemotherapy. Quality of life was assessed with the EORTC QLQ-C30 and BN 20 questionnaire and levels of depression with the PHQ-9 inventory before and after the first and second cycle of chemotherapy. RESULTS: CINV affected a minor part of patients. If present, it reached its maximum at day 3 and decreased to baseline level not before day 8. Levels of depression increased significantly after the first cycle of chemotherapy, but decreased during the further course of treatment. Patients with higher levels of depression were more severely affected by CINV and showed a lower quality of life through all time-points. CONCLUSION: We conclude that symptoms of depression should be perceived in advance and treated in order to avoid more severe side effects of tumor treatment. Additionally, in affected patients, delayed nausea was most prominent, pointing toward an activation of the NK1 receptor. We conclude that long acting antiemetics are necessary totreat temozolomide-induced nausea.

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Blinatumomab, the first-in-class CD3/CD19 bispecific T-cell engager antibody construct, has recently been approved for treating patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia. However, the clinical proof of concept of blinatumomab efficacy was initially demonstrated in patients with R/R B-cell non-Hodgkin lymphoma (B-NHL) in the MT103-104 phase 1 dose-escalation and expansion trial (NCT00274742), which defined 60 µg/m2 per day as the maximum tolerated dose (MTD). The clinically most relevant adverse effects were neurologic symptoms and cytokine release syndrome. Currently, there are no data on long-term outcomes and toxicity for B-NHL patients receiving blinatumomab treatment, so we performed a single-center, long-term follow-up analysis of 38 patients who participated in the MT103-104 phase 1 trial. We found no evidence for long-term toxicities, especially no blinatumomab-induced neurocognitive impairments. For the entire study population, the median overall survival (OS) was 4.6 years. Remarkably, patients who had received ≥60 µg/m2 per day and responded to blinatumomab achieved a median OS of 7.7 years. Of note, 6 of the surviving patients treated at the MTD have been treatment-free for more than 7 years. In contrast, patients who were treated at dose levels below the MTD had a median OS of only 1.1 years. These results indicate that 60 µg/m2 per day seems to represent the targeted dose level of blinatumomab required for durable remission in R/R B-NHL. Here, we provide the first clinical evidence that blinatumomab lacks long-term toxicity and has the potential to induce sustained remissions in patients with R/R B-NHL.

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BACKGROUND: Public funding for medical research in Germany is primarily provided by the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). The aim of this study was to analyze the amount of national public funding for medical research on predominant causes of death in Germany, cardiovascular diseases and neoplasms, in relation to the burden of these diseases in Germany. METHODS: Three evaluators categorized medical research projects funded by the DFG or BMBF between 2010 and 2012 into the categories "Diseases of the circulatory system" (with subgroups "Ischemic heart diseases", "Heart failure" and "Cerebrovascular diseases") and "Neoplasms". The total amount of public funding by the national agencies was analyzed in relation to the burden of disease for the respective disease condition. RESULTS: Information on national public funding for medical research of 2091 million euros was available; of those, 246.8 million euros (11.8%) were categorized being spent for research on "Neoplasms", 118.4 million euros (5.7%) for research on "Diseases of the circulatory system". This results in 362.08 euros per case of death, 16.58 euros per year of life lost (YLL) and 16.04 euros per disability-adjusted life year (DALY) for "Neoplasms" and in 113.44 euros per case of death, 8.05 euros per YLL and 7.17 euros per DALY for "Diseases of the circulatory system". CONCLUSIONS: In Germany, research on cardiovascular diseases receives a lower share of national public funding for medical research compared to oncological research. These results are comparable to other European countries.

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High-resolution magic angle spinning (HRMAS) MRS is a powerful method for gaining insight into the physiological and pathological processes of cellular metabolism. Given its ability to obtain high-resolution spectra of non-liquid biological samples, while preserving tissue architecture for subsequent histopathological analysis, the technique has become invaluable for biochemical and biomedical studies. Using HRMAS MRS, alterations in measured metabolites, metabolic ratios, and metabolomic profiles present the possibility to improve identification and prognostication of various diseases and decipher the metabolomic impact of drug therapies. In this review, we evaluate HRMAS MRS results on human tissue specimens from malignancies and non-localized diseases reported in the literature since the inception of the technique in 1996. We present the diverse applications of the technique in understanding pathological processes of different anatomical origins, correlations with in vivo imaging, effectiveness of therapies, and progress in the HRMAS methodology.

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