https://hdl.handle.net/20.500.11811/884 2026-04-10T21:49:24Z 2026-04-10T21:49:24Z Büttner, Thomas Hartmann, Gunther Coenen, Martin https://hdl.handle.net/20.500.11811/13674 2025-11-13T10:46:28Z 2025-05-27T00:00:00Z

Case Report: Practical approach to unmask unspecific adverse effects under lipid-lowering medication Büttner, Thomas; Hartmann, Gunther; Coenen, Martin The nocebo effect, driven by negative expectations rather than pharmacological mechanisms, contributes significantly to medication non-adherence, particularly in lipid-lowering therapy. Up to 50% of reported statin-related adverse effects may result from nocebo responses, leading to unnecessary discontinuation and increased cardiovascular risk. Blinded provocation tests may offer a solution for the differentiation of true drug intolerance from nocebo-driven symptoms. Although this methodology is well-established in experimental studies, it has not been transferred to routine clinical practice so far. We present a 65-year-old female with hypercholesterolemia and cardiovascular risk factors who experienced recurrent, dose-dependent leftsided lower abdominal pain with different lipid-lowering drugs. These symptoms prompted repeated and ultimately continuous treatment discontinuations, each followed by resolution of complaints. Despite extensive evaluations, no organic cause was found. To assess the role of nocebo effects, a six-week single-blinded, placebo-controlled crossover provocation test with a commercially available placebo preparation and atorvastatin placed in neutral pill containers was conducted. Upon initiation of the provocation phase, the patient experienced similar intermittent symptoms under both treatments. The pain ratings on a numeric rating scale did not significantly differ during placebo (mean: 2.75) and atorvastatin administration (mean: 3.26), suggesting that these symptoms were not pharmacologically induced. Following information of the patient, atorvastatin therapy could be continued. During continued intake over several weeks, symptoms further diminished, reinforcing the therapeutic value of addressing nocebo effects. This case report provides for the first time the structured and detailed step-by-step description of a pragmatic approach for a prospective blinded, placebo-controlled provocation testing that can directly be implemented in routine clinical practice. This method enables the distinction of true drug intolerance from nocebo effects, thereby enabling necessary therapies and highlighting its diagnostic and therapeutic potential.

2025-05-27T00:00:00Z Fandrey, Caroline I. Jentzsch, Marius Konopka, Peter Hoch, Alexander Blumenstock, Katja Zackria, Afraa Maasewerd, Salie Lovotti, Marta Lapp, Dorothee J. Gohr, Florian N. Suwara, Piotr Świeżewski, Jędrzej Rossnagel, Lukas Gobs, Fabienne Cristodaro, Maia Muhandes, Lina Behrendt, Rayk Lam, Martin C. Walgenbach, Klaus J. Bald, Tobias Schmidt, Florian I. Latz, Eicke Schmid-Burg, Jonathan L. https://hdl.handle.net/20.500.11811/13338 2025-08-08T12:06:17Z 2024-12-19T00:00:00Z

NIS-Seq enables cell-type-agnostic optical perturbation screening Fandrey, Caroline I.; Jentzsch, Marius; Konopka, Peter; Hoch, Alexander; Blumenstock, Katja; Zackria, Afraa; Maasewerd, Salie; Lovotti, Marta; Lapp, Dorothee J.; Gohr, Florian N.; Suwara, Piotr; Świeżewski, Jędrzej; Rossnagel, Lukas; Gobs, Fabienne; Cristodaro, Maia; Muhandes, Lina; Behrendt, Rayk; Lam, Martin C.; Walgenbach, Klaus J.; Bald, Tobias; Schmidt, Florian I.; Latz, Eicke; Schmid-Burg, Jonathan L. Optical pooled screening offers a broader-scale alternative to enrichment-based perturbation screening, using fluorescence microscopy to correlate phenotypes and perturbations across single cells. Previous methods work well in large, transcriptionally active cell lines, because they rely on cytosolic detection of endogenously expressed barcoded transcripts; however, they are limited by reliable cell segmentation, cytosol size, transcriptional activity and cell density. Nuclear In-Situ Sequencing (NIS-Seq) expands this technology by creating bright sequencing signals directly from nuclear genomic DNA to screen nucleated cells at high density and high library complexity. By inserting an inverted phage promoter downstream of the single guide RNA (sgRNA), many RNA copies of the sgRNA can be generated and sequenced independently of cellular transcription. In this study, we benchmarked NIS-Seq across eight cell types from two species and performed four genome-scale optical perturbation screens, identifying key players of inflammation-related cellular pathways. Finally, we performed a small-scale pooled optical screen in primary human macrophages from blood of healthy donors and demonstrated barcode identification in lentivirally transduced human skin tissue.

2024-12-19T00:00:00Z Wilhelm, Christoph Surendar, Jayagopi Karagiannis, Fotios https://hdl.handle.net/20.500.11811/11507 2024-04-22T10:01:45Z 2021-04-14T00:00:00Z

Enemy or ally? Fasting as an essential regulator of immune responses Wilhelm, Christoph; Surendar, Jayagopi; Karagiannis, Fotios Nutrition is essential for supplying an organism with sufficient energy to maintain its bodily functions. Apart from serving as an energy supply, the immunomodulatory effects of diet are emerging as a central aspect of human health. The latest evidence suggests that dietary restriction may play an important regulatory role by influencing the activation and effector functions of immune cells. However, depending on the context, nutrient restriction may have both pathogenic and beneficial effects. Here, we discuss the diverse roles of fasting programs, including ketogenesis in infection and chronic inflammation, aiming to clarify their detrimental and/or beneficial effects. Understanding these differences may help identify conditions under which dietary interventions might serve as putative effective approaches to treat various diseases.

2021-04-14T00:00:00Z Karagiannis, Fotios Wilhelm, Christoph https://hdl.handle.net/20.500.11811/11506 2024-04-22T09:46:46Z 2018-06-04T00:00:00Z

Innate lymphoid cells - key immune integrators of overall body homeostasis Karagiannis, Fotios; Wilhelm, Christoph The maintenance of the tissue barrier is essential to protect the host from external pathogens, thus ensuring the survival of the organism. This process requires the integration of various physiological signals originating from the digestive, immune, endocrine and the nervous system as indicators of overall body fitness. Innate lymphoid cells (ILC) are a group of immune cells equipped for the guarding and maintenance of the tissue barrier against invading pathogens. Extensive research has focused on the regulation of ILC by cytokines derived from immune or non-immune cells, such as the epithelium. However, recent findings suggest that ILC may play an additional role in the monitoring of the overall health status of the host. This requires the combined sensing of cytokines, metabolites, hormones and neuropeptides. ILC appear to be essential in this process functioning as hubs for the integration of different physiological signals to facilitate barrier immunity. Here we discuss the emerging literature revealing dietary, metabolic, hormonal and neuronal signals as important controllers and modulators of ILC function in health and disease.

2018-06-04T00:00:00Z