A prospective study of immune responses in patients with lung metastases treated with stereotactic body radiotherapy with or without concurrent systemic treatment.

We prospectively evaluated the effects of stereotactic body radiotherapy (SBRT) on circulating immune cells. Patients with oligo-metastatic and oligo-progressive pulmonary lesions were treated with SBRT with (cSBRT) or without (SBRT group) concurrent systemic treatment (chemotherapy or immune checkpoint blockade) using different fractionation regimes. Immunoprofiling of peripheral blood cells was performed at baseline, during, at the end of SBRT, and at the first and second follow-ups. The study accrued 100 patients (80 with evaluable samples). The proportion of proliferating CD8+ T-cells significantly increased after treatment. This increase remained significant at follow-up in the SBRT group, but not in the cSBRT group and was not detected with doses of >10Gy per fraction indicating that lower doses are necessary to increase proliferating T-cells' frequency. We detected no favorable impact of concurrent systemic treatment on systemic immune responses. The optimal timing of systemic treatment may be post-SBRT to leverage the immune-modulating effects of SBRT.

Low Dietary Fiber Intake Links Development of Obesity and Lupus Pathogenesis.

Changed dietary habits in Western countries such as reduced fiber intake represent an important lifestyle factor contributing to the increase in inflammatory immune-mediated diseases. The mode of action of beneficial fiber effects is not fully elucidated, but short-chain fatty acids (SCFA) and gut microbiota have been implicated. The aim of this study was to explore the impact of dietary fiber on lupus pathology and to understand underlying mechanisms. Here, we show that in lupus-prone NZB/WF1 mice low fiber intake deteriorates disease progression reflected in accelerated mortality, autoantibody production and immune dysregulation. In contrast to our original assumption, microbiota suppression by antibiotics or direct SCFA feeding did not influence the course of lupus-like disease. Mechanistically, our data rather indicate that in low fiber-fed mice, an increase in white adipose tissue mass, fat-inflammation and a disrupted intestinal homeostasis go along with systemic, low-grade inflammation driving autoimmunity. The links between obesity, intestinal leakage and low-grade inflammation were confirmed in human samples, while adaptive immune activation predominantly correlated with lupus activity. We further propose that an accelerated gastro-intestinal passage along with energy dilution underlies fiber-mediated weight regulation. Thus, our data highlight the often-overlooked effects of dietary fiber on energy homeostasis and obesity prevention. Further, they provide insight into how intricately the pathologies of inflammatory immune-mediated conditions, such as obesity and autoimmunity, might be interlinked, possibly sharing common pathways.

"Assistant physician light?" - Feedback from graduates on the practical year.

Background: As the final and longest practical phase of undergraduate medical study in Germany, the final year is essential for the acquisition and development of core medical competencies. However, studies show that the educational conditions are often not optimal. The aim of this study was to learn more about the educational conditions connected with the final year and to find out how it can be improved. To do this, written comments from graduate evaluation surveys were analyzed. Methods: Using the data from the survey of Freiburg medical students in the graduating classes of 2015/16 and 2016/17, we investigated which potential improvements were identified by students who had completed the final year and which aspects these students felt they especially benefited from in terms of beginning their medical careers. The written responses by the Freiburg graduating classes of 2015/16 (n=88; response rate: 28%) and 2016/17 (n=112; response rate: 36%) to the questions about beneficial aspects of the final year and potential improvements were qualitatively analyzed for content. As a comparison condition, the written comments of medical students graduating in the same years from the other medical schools in Baden-Württemberg were analyzed. Results: The written responses of the Freiburg graduates to these two questions could be classified according to five main categories. Comments were most frequently assigned either to the category "(more) autonomous work, like an assistant physician" or "(increased) mentoring of the final-year students as learners". In hindsight, the Freiburg medical graduates felt that they had already benefited in terms of beginning their careers from working independently under supervision during the final year, but they also saw room for improvement and wished that they had been perceived more strongly as learners and encouraged as such. The analysis of the written comments made by students in the same graduating classes at other medical schools in Baden-Württemberg showed corroborating results. Conclusion: The results of this study show how the educational conditions of final year can be optimized. For instance, more opportunities should be created for final-year students to work independently and care for patients, and the course offerings should be expanded and adjusted, if needed, to match the needs of the students. Furthermore, those teaching final year students should be better trained and released from other duties so that they can focus on teaching.

Relevance of Receptor for Advanced Glycation end Products (RAGE) in Murine Antibody-Mediated Autoimmune Diseases.

It is incompletely understood how self-antigens become targets of humoral immunity in antibody-mediated autoimmune diseases. In this context, alarmins are discussed as an important level of regulation. Alarmins are recognized by various receptors, such as receptor for advanced glycation end products (RAGE). As RAGE is upregulated under inflammatory conditions, strongly binds nucleic acids and mediates pro-inflammatory responses upon alarmin recognition, our aim was to examine its contribution to immune complex-mediated autoimmune diseases. This question was addressed employing RAGE-/- animals in murine models of pristane-induced lupus, collagen-induced, and serum-transfer arthritis. Autoantibodies were assessed by enzyme-linked immunosorbent assay, renal disease by quantification of proteinuria and histology, arthritis by scoring joint inflammation. The associated immune status was determined by flow cytometry. In both disease entities, we detected tendentiously decreased autoantibody levels in RAGE-/- mice, however no differences in clinical outcome. In accordance with autoantibody levels, a subgroup of the RAGE-/- animals showed a decrease in plasma cells, and germinal center B cells and an increase in follicular B cells. Based on our results, we suggest that RAGE deficiency alone does not significantly affect antibody-mediated autoimmunity. RAGE may rather exert its effects along with other receptors linking environmental factors to auto-reactive immune responses.