RepoMed (Medizinische Hochschule Hannover)
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Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis
No full textPreemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI "navigated" by hs-chimerism ("navigated DLI"). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution ("controls"). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT
Charakterisierung der Funktion von IgG- und IgE-Rezeptoren auf basophilen Granulozyten bei gesunden Individuen und Patienten mit systemischem Lupus erythematodes
No full textThe antipyretic effectiveness of dipyrone in the intensive care unit: a retrospective cohort study
No full textIntroduction Dipyrone (metamizol) is regularly used in critical care for pain and fever treatment, especially in Germany and Spain. However, indication for antipyretic therapy in critically ill patients is currently unclear and data for both the risk and benefit of dipyrone treatment in the intensive care environment are scarce. We hypothesized that antipyretic efficiency of dipyrone would not exceed antipyretic efficiency of acetaminophen. We therefore aimed to compare temperature courses in critically ill patients receiving either intravenous dipyrone, acetaminophen or no antipyretic medication. Material and methods We included 937 intensive care unit (ICU) patients with body temperature recordings of at least 37.5°C. We investigated temperature decrease associated with dipyrone or acetaminophen and additionally compared it to an untreated control group. Results Within the eight-hour study interval, maximum body temperature decrease in patients without antipyretic medication was -0.6°C (IQR: -1.0 to -0.4°C; n = 315). Maximal decrease in body temperature was higher both with dipyrone (-0.8°C (IQR: -1.2 to -0.4°C); p = 0.016; n = 341) and acetaminophen (-0.9°C (IQR: -1.6 to -0.6°C); p<0.001; n = 71), but did not differ between dipyrone and acetaminophen (p = 0.066). As compared to untreated patients, dipyrone only led to a marginal additional decrease in body temperature of only -0.1°C. Maximum of antipyretic effectiveness was reached four hours after administration. Conclusion Antipyretic effectiveness of dipyrone in ICU patients may be overestimated. Given the lack of prospective data, clinical evidence for antipyretic dipyrone therapy in the ICU is insufficient and warrants further critical evaluation
DRD2- Messung in einem Post Mortem Alkoholkollektiv
No full textDer Datensatz besteht aus Messungen von Methylierungsdaten des Dopamin Rezeptor 2- Gens bei einem Post Mortem- Kollektiv in Gehirn (6 Regionen) und Blut. Die Daten wurden an einem 3750XL Kapillaren-Sequencer von ABI (ABI Life Technologies, Grand Island, USA) durch Mathias Rhein am 14.-16. Juli 2020 im Labor für molekulare Neurowissenschaften (OE7110, Feodor-Lynen-Str.35, 30625 Hannover) erhoben. Die Messungen wurden als Fluoreszenz-Emissionsdaten im proprietären Format des Herstellers gespeichert (.ab1)
News and Views on Polysialic Acid: from Tumor Progression and Brain Development to Psychiatric Disorders, Neurodegeneration, Myelin Repair and Immunomodulation.
No full textPolysialic acid (polySia) is a sugar homopolymer consisting of at least eight glycosidically linked sialic acid units. It is a posttranslational modification of a limited number of proteins with the neural cell adhesion molecule NCAM being the most prominent. As extensively reviewed before, polySia-NCAM is crucial for brain development and synaptic plasticity but also modulates tumor growth and malignancy. Functions of polySia have been attributed to its polyanionic character, its spatial expansion into the extracellular space, and its modulation of NCAM interactions. In this mini-review, we first summarize briefly, how the modulation of NCAM functions by polySia impacts tumor cell growth and leads to malformations during brain development of polySia-deficient mice, with a focus on how the latter may be linked to altered behaviors in the mouse model and to neurodevelopmental predispositions to psychiatric disorders. We then elaborate on the implications of polySia functions in hippocampal plasticity, learning and memory of mice in light of recently described polySia changes related to altered neurogenesis in the aging human brain and in neurodegenerative disease. Furthermore, we highlight recent progress that extends the range of polySia functions across diverse fields of neurobiology such as cortical interneuron development and connectivity, myelination and myelin repair, or the regulation of microglia activity. We discuss possible common and distinct mechanisms that may underlie these seemingly divergent roles of polySia, and provide prospects for new therapeutic approaches building on our improved understanding of polySia functions
The transcription factor PAX6 is involved in the negative regulation of the irritant receptor TRPA1
No full textEs handelt sich um Sequenzdaten aus Zellkulturexperimenten, sowie aus Blut gesunder Probandinnen einer vorherigen Publikation (Gombert, S., Rhein, M., Eberhardt, M., Munster, T., Bleich, S., Leffler, A., Frieling, H. (2017). Epigenetic divergence in the TRPA1 promoter correlates with pressure pain thresholds in healthy individuals. Pain 158(4), 698-704. doi: 10.1097/j.pain.0000000000000815.). Erhoben wurden sie mittels Sanger Bisulfit Sequenzierung im Labor für Molekulare Neurowissenschaften der Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie (MHH) am 11./12.02.2020 (im Fall der Zellkulturexperimente) und am 18./19.11.2014 (im Fall der Blutproben). Verwendet wurde ein 3500XL genetic analyzer (ABI life technologies), Datenformat: ab1, sowie PDF
Three Layers of Intestinal γδ T Cells Talk Different Languages With the Microbiota
No full textThe mucosal surfaces of our body are the main contact site where the immune system encounters non-self molecules from food-derived antigens, pathogens, and symbiotic bacteria. γδ T cells are one of the most abundant populations in the gut. Firstly, they include intestinal intraepithelial lymphocytes, which screen and maintain the intestinal barrier integrity in close contact with the epithelium. A second layer of intestinal γδ T cells is found among lamina propria lymphocytes (LPL)s. These γδ LPLs are able to produce IL-17 and likely have functional overlap with local Th17 cells and innate lymphoid cells. In addition, a third population of γδ T cells resides within the Peyer´s patches, where it is probably involved in antigen presentation and supports the mucosal humoral immunity. Current obstacles in understanding γδ T cells in the gut include the lack of information on cognate ligands of the γδ TCR and an incomplete understanding of their physiological role. In this review, we summarize and discuss what is known about different subpopulations of γδ T cells in the murine and human gut and we discuss their interactions with the gut microbiota in the context of homeostasis and pathogenic infections
Major traumatic amputations and replantations of the upper extremity in Germany - National quality reports 2014-2018
No full textThe treatment of traumatic major upper limb amputation is complex and of great urgency. Loss of time often represents a majorrestriction for replantation. Thus, logistical and infrastructural developments, such as the expansion of specialised hand trauma centres, are crucial for optimizing delivery of care. Surveillance represents the fundament for a proper, demand-adapted implementation of such therapeutical improvements. However, a comprehensive database for surveillance of these injuries does currently not exist in Germany or Europe. In this study quality reports of German hospitals from 2014 to 2018 were screened retrospectively for traumatic major upper extremity amputations and replantations. A total of 329 amputations and 87 replantations were recorded, accounting for an overall replantation rate (RR) of 26%. Most of the injuries affected the level of the wrist and forearm. Treatment of these injuries experienced an increasing centralisation to medical teaching facilities, which accounted for higher RRs compared with non-teaching facilities. The cumulatively most populous federal states handled most of the amputation injures in this five-year study period. Ratio calculations on the basis of population counts, however, revealed great discrepancies to these results, with Hamburg, Rhineland-Palatinate and Saarland accounting for the highest per capita incidences. In 2018 Germany was provided with 46 specialised hand trauma and replantation centres, which performed 45% of the replantations in that year, revealing a RR of 17%, compared to an overall RR of 14% in that year. Nevertheless, there might be potential for improvement in the geographical distribution of these specialised centres. The provision of highly specialised therapy in highly specialised centres for highly complex injuries is a future challenge in replantation surgery. This data is contributing to logistical improvements for a need-adapted expansion of these specialised hand trauma centres. The study demonstrates an approach of a standardised and comprehensive injury surveillance program based on national quality reports, while underlining the importance of such a national or rather European database for optimisations in medical care. Level of evidence IV
