@article{ProetelPletschLausekeretal.2014, author = {Proetel, Ulrike and Pletsch, Nadine and Lauseker, Michael and M{\"u}ller, Martin C. and Hanfstein, Benjamin and Krause, Stefan W. and Kalmanti, Lida and Schreiber, Annette and Heim, Dominik and Baerlocher, Gabriela M. and Hofmann, Wolf-Karsten and Lange, Elisabeth and Einsele, Hermann and Wernli, Martin and Kremers, Stephan and Schlag, Rudolf and M{\"u}ller, Lothar and H{\"a}nel, Mathias and Link, Hartmut and Hertenstein, Bernd and Pfirrmann, Markus and Hochhaus, Andreas and Hasford, Joerg and Hehlmann, R{\"u}diger and Saußele, Susanne}, title = {Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV}, series = {Annals of Hematology}, volume = {93}, journal = {Annals of Hematology}, number = {7}, issn = {0939-5555}, doi = {10.1007/s00277-014-2041-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121574}, pages = {1167-76}, year = {2014}, abstract = {The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 \%) on IM400 and 83 (21 \%) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874}, language = {en} } @article{BaeHeidrichLevicketal.2020, author = {Bae, Soyeon and Heidrich, Lea and Levick, Shaun R. and Gossner, Martin M. and Seibold, Sebastian and Weisser, Wolfgang W. and Magdon, Paul and Serebryanyk, Alla and B{\"a}ssler, Claus and Sch{\"a}fer, Deborah and Schulze, Ernst-Detlef and Doerfler, Inken and M{\"u}ller, J{\"o}rg and Jung, Kirsten and Heurich, Marco and Fischer, Markus and Roth, Nicolas and Schall, Peter and Boch, Steffen and W{\"o}llauer, Stephan and Renner, Swen C. and M{\"u}ller, J{\"o}rg}, title = {Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi-taxa and multi-scale approach}, series = {Diversity and Distribution}, volume = {27}, journal = {Diversity and Distribution}, number = {3}, doi = {10.1111/ddi.13204}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236117}, pages = {439-453}, year = {2020}, abstract = {Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size. Location: Temperate forests in five regions across Germany. Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined. Results: In the inter-region analysis, over half of the explained variation in community composition (23\% of the total explained 35\%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size. Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy.}, language = {en} } @article{KarimiFreundWageretal.2021, author = {Karimi, Sohail M. and Freund, Matthias and Wager, Brittney M. and Knoblauch, Michael and Fromm, J{\"o}rg and M. Mueller, Heike and Ache, Peter and Krischke, Markus and Mueller, Martin J. and M{\"u}ller, Tobias and Dittrich, Marcus and Geilfus, Christoph-Martin and Alfaran, Ahmed H. and Hedrich, Rainer and Deeken, Rosalia}, title = {Under salt stress guard cells rewire ion transport and abscisic acid signaling}, series = {New Phytologist}, volume = {231}, journal = {New Phytologist}, number = {3}, doi = {10.1111/nph.17376}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259635}, pages = {1040-1055}, year = {2021}, abstract = {Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.}, language = {en} } @article{FiedlerMuellenbachRolfesetal.2022, author = {Fiedler, Mascha O. and Muellenbach, Ralf M. and Rolfes, Caroline and Lotz, Christopher and Nickel, Felix and M{\"u}ller-Stich, Beat P. and Supady, Alexander and Lepper, Philipp M. and Weigand, Markus A. and Meybohm, Patrick and Kalenka, Armin and Reyher, Christian}, title = {Pumpless extracorporeal hemadsorption technique (pEHAT): a proof-of-concept animal study}, series = {Journal of Clinical Medicine}, volume = {11}, journal = {Journal of Clinical Medicine}, number = {22}, issn = {2077-0383}, doi = {10.3390/jcm11226815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297347}, year = {2022}, abstract = {Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb\(^®\) and four Oxiris\(^®\) hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45-85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb\(^®\) blood flow [mL/min] = 4.226 × MAP [mmHg] - 3.496 (R-square 0.8133) and Oxiris\(^®\) blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb\(^®\) and Oxiris\(^®\) devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.}, language = {en} } @article{MollMuellerGillitzeretal.1991, author = {Moll, Heidrun and M{\"u}ller, Christoph and Gillitzer, Reinhard and Fuchs, Harald and R{\"o}llinghoff, Martin and Simon, Markus M. and Kramer, Michael D.}, title = {Expression of T-cell-associated serine proteinase-1 during murine Leishmania major infection correlates with susceptibility to disease}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61311}, year = {1991}, abstract = {The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.}, subject = {Biologie}, language = {en} } @article{HanfsteinLausekerHehlmannetal.2014, author = {Hanfstein, Benjamin and Lauseker, Michael and Hehlmann, R{\"u}diger and Saussele, Susanne and Erben, Philipp and Dietz, Christian and Fabarius, Alice and Proetel, Ulrike and Schnittger, Susanne and Haferlach, Claudia and Krause, Stefan W. and Schubert, J{\"o}rg and Einsele, Hermann and H{\"a}nel, Mathias and Dengler, Jolanta and Falge, Christiane and Kanz, Lothar and Neubauer, Andreas and Kneba, Michael and Stengelmann, Frank and Pfreundschuh, Michael and Waller, Cornelius F. and Spiekerman, Karsten and Baerlocher, Gabriela M. and Pfirrmann, Markus and Hasford, Joerg and Hofmann, Wolf-Karsten and Hochhaus, Andreas and M{\"u}ller, Martin C.}, title = {Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib}, series = {Haematologica}, volume = {99}, journal = {Haematologica}, number = {9}, issn = {1592-8721}, doi = {10.3324/haematol.2013.096537}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115476}, pages = {1441-1447}, year = {2014}, abstract = {The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874)}, language = {en} } @article{GrausLiRathjeetal.2023, author = {Graus, Dorothea and Li, Kunkun and Rathje, Jan M. and Ding, Meiqi and Krischke, Markus and M{\"u}ller, Martin J. and Cuin, Tracey Ann and Al-Rasheid, Khaled A. S. and Scherzer, S{\"o}nke and Marten, Irene and Konrad, Kai R. and Hedrich, Rainer}, title = {Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling}, series = {New Phytologist}, volume = {237}, journal = {New Phytologist}, number = {1}, doi = {10.1111/nph.18501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312152}, pages = {217 -- 231}, year = {2023}, abstract = {Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically-driven leaf movements. Leaf downward movement caused by hydro-passive turgor loss reached a maximum within 2 h. Salt-driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca\(^{2+}\)) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H\(^{+}\)) pumping, a salt uptake-dependent cytosolic alkalization, and a return of the apoplast osmolality to pre-stress levels. Although, transcript numbers of abscisic acid- and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H\(^{+}\)/Na\(^{+}\)-exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na\(^{+}\)) rapidly even under massive salt loads, based on pre-established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca\(^{2+}\) signaling.}, language = {en} } @article{McLaughlinSchmulensonTeplytskaetal.2021, author = {Mc Laughlin, Anna M. and Schmulenson, Eduard and Teplytska, Olga and Zimmermann, Sebastian and Opitz, Patrick and Groenland, Stefanie L. and Huitema, Alwin D. R. and Steeghs, Neeltje and M{\"u}ller, Lothar and Fuxius, Stefan and Illerhaus, Gerald and Joerger, Markus and Mayer, Frank and Fuhr, Uwe and Holdenrieder, Stefan and Hempel, Georg and Scherf-Clavel, Oliver and Jaehde, Ulrich and Kloft, Charlotte}, title = {Developing a nationwide infrastructure for therapeutic drug monitoring of targeted oral anticancer drugs: the ON-TARGET study protocol}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {24}, issn = {2072-6694}, doi = {10.3390/cancers13246281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252196}, year = {2021}, abstract = {Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80\% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.}, language = {en} } @article{SchulzRuppertHermsetal.2017, author = {Schulz, Herbert and Ruppert, Ann-Kathrin and Herms, Stefan and Wolf, Christiane and Mirza-Schreiber, Nazanin and Stegle, Oliver and Czamara, Darina and Forstner, Andreas J. and Sivalingam, Sugirthan and Schoch, Susanne and Moebus, Susanne and P{\"u}tz, Benno and Hillmer, Axel and Fricker, Nadine and Vatter, Hartmut and M{\"u}ller-Myhsok, Bertram and N{\"o}then, Markus M. and Becker, Albert J. and Hoffmann, Per and Sander, Thomas and Cichon, Sven}, title = {Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-01818-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173168}, year = {2017}, abstract = {Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.}, language = {en} } @article{RothDoerflerBaessleretal.2019, author = {Roth, Nicolas and Doerfler, Inken and B{\"a}ssler, Claus and Blaschke, Markus and Bussler, Heinz and Gossner, Martin M. and Heideroth, Antje and Thorn, Simon and Weisser, Wolfgang W. and M{\"u}ller, J{\"o}rg}, title = {Decadal effects of landscape-wide enrichment of dead wood on saproxylic organisms in beech forests of different historic management intensity}, series = {Diversity and Distributions}, volume = {25}, journal = {Diversity and Distributions}, number = {3}, doi = {10.1111/ddi.12870}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227061}, pages = {430-441}, year = {2019}, abstract = {Aim: European temperate forests have lost dead wood and the associated biodiversity owing to intensive management over centuries. Nowadays, some of these forests are being restored by enrichment with dead wood, but mostly only at stand scales. Here, we investigated effects of a seminal dead-wood enrichment strategy on saproxylic organisms at the landscape scale. Location: Temperate European beech forest in southern Germany. Methods: In a before-after control-impact design, we compared assemblages and gamma diversities of saproxylic organisms in strictly protected old-growth forest areas (reserves) and historically moderately and intensively managed forest areas before and a decade after starting a landscape-wide strategy of dead-wood enrichment. Results: Before enrichment with dead wood, the gamma diversity of saproxylic organisms in historically intensively managed forest stands was significantly lower than in reserves and historically moderately managed forest stands; this difference disappeared after 10 years of dead-wood enrichment. The species composition of beetles in forest stands of the three historical management intensities differed before the enrichment strategy, but a decade thereafter, the species compositions of previously intensively logged and forest reserve plots were similar. However, the differences in fungal species composition between historical management categories before and after 10 years of enrichment persisted. Main conclusions: Our results demonstrate that intentional enrichment of dead wood at the landscape scale is a powerful tool for rapidly restoring saproxylic beetle communities and for restoring wood-inhabiting fungal communities, which need longer than a decade for complete restoration. We propose that a strategy of area-wide active restoration combined with some permanent strict refuges is a promising means of promoting the biodiversity of age-long intensively managed Central European beech forests.}, language = {en} } @article{SeiboldHothornGossneretal.2021, author = {Seibold, Sebastian and Hothorn, Torsten and Gossner, Martin M. and Simons, Nadja K. and Bl{\"u}thgen, Nico and M{\"u}ller, J{\"o}rg and Ambarl{\i}, Didem and Ammer, Christian and Bauhus, J{\"u}rgen and Fischer, Markus and Habel, Jan C. and Penone, Caterina and Schall, Peter and Schulze, Ernst-Detlef and Weisser, Wolfgang W.}, title = {Insights from regional and short-term biodiversity monitoring datasets are valuable: a reply to Daskalova et al. 2021}, series = {Insect Conservation and Diversity}, volume = {14}, journal = {Insect Conservation and Diversity}, number = {1}, doi = {10.1111/icad.12467}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228309}, pages = {144 -- 148}, year = {2021}, abstract = {Reports of major losses in insect biodiversity have stimulated an increasing interest in temporal population changes. Existing datasets are often limited to a small number of study sites, few points in time, a narrow range of land-use intensities and only some taxonomic groups, or they lack standardised sampling. While new monitoring programs have been initiated, they still cover rather short time periods. Daskalova et al. 2021 (Insect Conservation and Diversity, 14, 1-18) argue that temporal trends of insect populations derived from short time series are biased towards extreme trends, while their own analysis of an assembly of shorter- and longer-term time series does not support an overall insect decline. With respect to the results of Seibold et al. 2019 (Nature, 574, 671-674) based on a 10-year multi-site time series, they claim that the analysis suffers from not accounting for temporal pseudoreplication. Here, we explain why the criticism of missing statistical rigour in the analysis of Seibold et al. (2019) is not warranted. Models that include 'year' as random effect, as suggested by Daskalova et al. (2021), fail to detect non-linear trends and assume that consecutive years are independent samples which is questionable for insect time-series data. We agree with Daskalova et al. (2021) that the assembly and analysis of larger datasets is urgently needed, but it will take time until such datasets are available. Thus, short-term datasets are highly valuable, should be extended and analysed continually to provide a more detailed understanding of insect population changes under the influence of global change, and to trigger immediate conservation actions.}, language = {en} } @article{Jung‐KoenigFuellenbachMurphyetal.2020, author = {Jung-K{\"o}nig, Mona and F{\"u}llenbach, Christoph and Murphy, Michael F. and Manzini, Paola and Laspina, Stefan and Pendry, Kate and M{\"u}hling, J{\"o}rg and Wikman, Agneta and Humbrecht, Catherine and Rigal, Jean-Christophe and Lasocki, Sigismond and Foll{\´e}a, Gilles and Seifried, Erhard and M{\"u}ller, Markus M. and Geisen, Christof and Aranko, Kari and Zacharowski, Kai and Meybohm, Patrick}, title = {Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) working group}, series = {Vox Sanguinis}, volume = {115}, journal = {Vox Sanguinis}, number = {3}, doi = {10.1111/vox.12872}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214049}, pages = {182 -- 191}, year = {2020}, abstract = {Background and objectives Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. Materials and methods To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. Results Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. Conclusion Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.}, language = {en} } @article{FischerThiesAwadetal.2022, author = {Fischer, Dania and Thies, Fabian and Awad, Omar and Brat, Camilla and Meybohm, Patrick and Baer, Patrick C. and M{\"u}ller, Markus M. and Urbschat, Anja and Maier, Thorsten J. and Zacharowski, Kai and Roos, Jessica}, title = {Red blood cell-derived microparticles exert no cancer promoting effects on colorectal cancer cells in vitro}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms23169323}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286018}, year = {2022}, abstract = {The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage.}, language = {en} }