TY - JOUR A1 - El-Helou, Sabine M. A1 - Biegner, Anika-Kerstin A1 - Bode, Sebastian A1 - Ehl, Stephan R. A1 - Heeg, Maximilian A1 - Maccari, Maria E. A1 - Ritterbusch, Henrike A1 - Speckmann, Carsten A1 - Rusch, Stephan A1 - Scheible, Raphael A1 - Warnatz, Klaus A1 - Atschekzei, Faranaz A1 - Beider, Renata A1 - Ernst, Diana A1 - Gerschmann, Stev A1 - Jablonka, Alexandra A1 - Mielke, Gudrun A1 - Schmidt, Reinhold E. A1 - Schürmann, Gesine A1 - Sogkas, Georgios A1 - Baumann, Ulrich H. A1 - Klemann, Christian A1 - Viemann, Dorothee A1 - Bernuth, Horst von A1 - Krüger, Renate A1 - Hanitsch, Leif G. A1 - Scheibenbogen, Carmen M. A1 - Wittke, Kirsten A1 - Albert, Michael H. A1 - Eichinger, Anna A1 - Hauck, Fabian A1 - Klein, Christoph A1 - Rack-Hoch, Anita A1 - Sollinger, Franz M. A1 - Avila, Anne A1 - Borte, Michael A1 - Borte, Stephan A1 - Fasshauer, Maria A1 - Hauenherm, Anja A1 - Kellner, Nils A1 - Müller, Anna H. A1 - Ülzen, Anett A1 - Bader, Peter A1 - Bakhtiar, Shahrzad A1 - Lee, Jae-Yun A1 - Heß, Ursula A1 - Schubert, Ralf A1 - Wölke, Sandra A1 - Zielen, Stefan A1 - Ghosh, Sujal A1 - Laws, Hans-Juergen A1 - Neubert, Jennifer A1 - Oommen, Prasad T. A1 - Hönig, Manfred A1 - Schulz, Ansgar A1 - Steinmann, Sandra A1 - Klaus, Schwarz A1 - Dückers, Gregor A1 - Lamers, Beate A1 - Langemeyer, Vanessa A1 - Niehues, Tim A1 - Shai, Sonu A1 - Graf, Dagmar A1 - Müglich, Carmen A1 - Schmalzing, Marc T. A1 - Schwaneck, Eva C. A1 - Tony, Hans-Peter A1 - Dirks, Johannes A1 - Haase, Gabriele A1 - Liese, Johannes G. A1 - Morbach, Henner A1 - Foell, Dirk A1 - Hellige, Antje A1 - Wittkowski, Helmut A1 - Masjosthusmann, Katja A1 - Mohr, Michael A1 - Geberzahn, Linda A1 - Hedrich, Christian M. A1 - Müller, Christiane A1 - Rösen-Wolff, Angela A1 - Roesler, Joachim A1 - Zimmermann, Antje A1 - Behrends, Uta A1 - Rieber, Nikolaus A1 - Schauer, Uwe A1 - Handgretinger, Rupert A1 - Holzer, Ursula A1 - Henes, Jörg A1 - Kanz, Lothar A1 - Boesecke, Christoph A1 - Rockstroh, Jürgen K. A1 - Schwarze-Zander, Carolynne A1 - Wasmuth, Jan-Christian A1 - Dilloo, Dagmar A1 - Hülsmann, Brigitte A1 - Schönberger, Stefan A1 - Schreiber, Stefan A1 - Zeuner, Rainald A1 - Ankermann, Tobias A1 - Bismarck, Philipp von A1 - Huppertz, Hans-Iko A1 - Kaiser-Labusch, Petra A1 - Greil, Johann A1 - Jakoby, Donate A1 - Kulozik, Andreas E. A1 - Metzler, Markus A1 - Naumann-Bartsch, Nora A1 - Sobik, Bettina A1 - Graf, Norbert A1 - Heine, Sabine A1 - Kobbe, Robin A1 - Lehmberg, Kai A1 - Müller, Ingo A1 - Herrmann, Friedrich A1 - Horneff, Gerd A1 - Klein, Ariane A1 - Peitz, Joachim A1 - Schmidt, Nadine A1 - Bielack, Stefan A1 - Groß-Wieltsch, Ute A1 - Classen, Carl F. A1 - Klasen, Jessica A1 - Deutz, Peter A1 - Kamitz, Dirk A1 - Lassy, Lisa A1 - Tenbrock, Klaus A1 - Wagner, Norbert A1 - Bernbeck, Benedikt A1 - Brummel, Bastian A1 - Lara-Villacanas, Eusebia A1 - Münstermann, Esther A1 - Schneider, Dominik T. A1 - Tietsch, Nadine A1 - Westkemper, Marco A1 - Weiß, Michael A1 - Kramm, Christof A1 - Kühnle, Ingrid A1 - Kullmann, Silke A1 - Girschick, Hermann A1 - Specker, Christof A1 - Vinnemeier-Laubenthal, Elisabeth A1 - Haenicke, Henriette A1 - Schulz, Claudia A1 - Schweigerer, Lothar A1 - Müller, Thomas G. A1 - Stiefel, Martina A1 - Belohradsky, Bernd H. A1 - Soetedjo, Veronika A1 - Kindle, Gerhard A1 - Grimbacher, Bodo T1 - The German national registry of primary immunodeficiencies (2012-2017) JF - Frontiers in Immunology N2 - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment. KW - registry for primary immunodeficiency KW - primary immunodeficiency (PID) KW - German PID-NET registry KW - PID prevalence KW - European Society for Immunodeficiencies (ESID) KW - IgG substitution therapy KW - CVID Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629 VL - 10 ER - TY - THES A1 - Schmidt, Philipp T1 - Vanadium(V)-katalysierte Oxidationen substituierter Bishomoallylalkohole zur stereoselektiven O-Heterocyclen-Synthese T1 - Vanadium(V)-catalyzed Oxidations of Substituted Bishomoallylic Alcohols for the Stereoselective Synthesis of O-Heterocycles N2 - In der vorligenden Arbeit wurden Vanadium-abhängige Bromidperoxidase- (VBPO-) Modelle zur stereoselektiven Synthese funktionalisierter O-Heterocyclen entwickelt, die durch Vanadium-katalysierte Oxygenierung von Bishomoallylalkoholen mechanistisch untersucht wurden. Weiterhin wurden Bromcyclisierungen von Bishomoallylalkoholen auf enzymatischem (VBPO), oxidativem und radikalischem Weg für Referenzprodukte einer neuen Variante der Bromcyclisierung durch Vanadium-katalysierte Bromidoxidation durchgeführt. Die Selektivitätsmuster aus den Synthesen ß-hydroxylierter und ß-bromierter Tetrahydrofurane wurden anschließend innerhalb einfacher Naturstoffsynthesen genutzt. Anhand eigener Vorarbeiten wurden neue Vanadium(V)-Komplexe aus Triethoxyvanadat mit tridentaten Schiffbaseliganden, basierend auf Salicylaldehyd und Aminoalkoholen mit strukturell unterschiedlichen Seitenketten in quantitativen Ausbeuten synthetisiert und charakterisiert (51V-NMR, UV und IR). In Test-Cyclisierungen unterschiedlicher Bishomoallylalkohole eignete sich VO(salin)(OEt) mit hohen Umsätzen und guten Regio- wie Stereoselektivitäten am besten. Die relative Geschwindigkeitskonstante (krel = 120±20) der Vanadium-katalysierten Oxidation des Testsystems konnte über Konkurrenzkinetik (Alkenol versus Alken) ermittelt werden und weist deutlich auf eine Bindung des Alkenols an Vanadium während der Oxidation hin. Um die Regio- und Stereoselektivitäten Vanadium-Schiffbase-katalysierter Oxidationen von Bishomoallylalkoholen verstehen zu können, wurden stereochemische Studien anhand des Testsystems durchgeführt. Dessen Oxidation wird demnach im selektivitätsbestimmenden Schritt dem Metallzentrum abgewandt in like-Position bevorzugt gebildet und führt zu dem cis-konfigurierten Tetrahydrofuran als Hauptprodukt. Im Folgenden wurden Vanadium-katalysierte Oxidationen unterschiedlich substituierter bishomoallylischer Alkohole durchgeführt, sämtliche Oxidationen führten regioselektiv zu Tetrahydrofuranen als Hauptprodukte, die Oxygenierung Dimethyl-substituierter Pentenole lieferte durch Substitution an C-1 selektiv cis-konfigurierte Tetrahydrofurane, 2-Substitution führte ebenso wie 3-Substitution zu trans-konfigurierte Oxolanen. Alkohole nicht aktivierter Olefine wurden in der Reihenfolge C-1 ? C-3 mit höherer Selektivität zu trans-konfigurierten Tetrahydrofuranen gebildet. Die Regio- und Stereoselektivitäten der radikalischen Bromcyclisierungen folgen den schon in früheren Arbeiten unserer Arbeitsgruppe aufgestellten Richtlinien (5-exo-trig; 2,5-trans, 2,4-cis und 2,3-trans). Die ionischen Bromcyclisierungen 5,5-dimethylierter Bishomoallyl-alkohole mittels NBS verliefen komplementär zu den Radikal-Cyclisierungen regioselektiv und in Abhängigkeit der Phenylsubstituenten an C-1 - C-3 stereoselektiv zu den 2,5-trans-, 3,5-cis- und 4,5-trans-konfigurierten Tetrahydropyranen. Aus der Bromcyclisierung prochiraler Pentenole in Gegenwart eines Acetonpulvers aus Ascophyllum nodosum (A.n.A.P.) konnte das b-bromierte Tetrahydrofuran racemisch in 87proz. Ausbeute erhalten werden. Ebensowenig führte der Einsatz chiraler Liganden in der Vanadium-katalysierten Oxygenierung prochiraler Penten-1-ole bei guten Ausbeuten (>80%) zu Enantiomeren-angereicherten Tatrahydrofuranen. Innerhalb einfacher Naturstoffsynthesen wurden cis-Pityol, Linalooloxid sowie (-)-epi-Bisabololoxid selektiv unter Standardbedingungen der Vanadium-Schiffbase-katalysierten Oxidationen mit VO(salin)(OEt) und TBHP dargestellt. Die Stereoselektivitäten steigen proportional zu dem Größenunterschied der Substituenten an Position 1 der Bishomoallylalkohole. Abschließend wurde durch Vanadium-katalysierte Bromidoxiadtion mit TBHP eine neue dreistufige Totalsynthese der vier "natürlichen" Muscarin-Isomere ausgearbeitet. Die Gesamtausbeuten dieser Synthesen liegen zwischen 3.0 und 19.9%. N2 - In the present work vanadium dependent bromoperoxidase- (VBPO-) models have been developed for the stereoselective synthesis of functionalized O-heterocycles, that were examined mechanistically by vanadium catalyzed oxygenation of bishomoallylic alcohols. Furthermore bromine cyclizations of pentenols were carried out in an enzymatic (VBPO), oxidative and radical version for reference products of a new variant of the bromine cyclization by vanadium catalyzed bromide oxidation. The selectivity models from these syntheses of ß-hydroxylated and ß-brominated tetrahydrofurans were then used within simple natural product syntheses. By means of own preleminary works new vanadium(V)-complexes were synthesized in quantitative yields from triethyl vanadate and tridentate Schiff-base ligands generated from salicylic aldehyde and amino alcohols with structurally differing side chains, and were characterized spectroscopically (51V-NMR, UV and IR). Cyclizations of different bishomoallylic alcohols indicated that VO(salin)(OEt) was the best among the catalysts tested since it afforded high yields and good regio- and stereoselectivities of oxidation products. The relative rate constant (krel = 120±20) for the vanadium catalyzed oxidation of a test system was determined by competition kinetics (alkenol vs. alkene) and is a clear indication for the coordination of the alkenol at vanadium within the oxidation step. In order to understand the regio- and stereoselectivities of the vanadium Schiff-base catalyzed oxidation of bishomoallylic alcohols stereochemical studies were carried out with the test pentenol. The oxidation of the alkenol double bond has to be the selectivity determining step, proceeding in like-fashion and leading to the cis-configured tetrahydrofuran as main product. Next, vanadium catalyzed oxidations of differently substituted bishomoallylic alcohols were performed, which all led regioselectively to tetrahydrofurans as main products. Oxygenation of 1-substituted pentenols resulted in cis-configured tetrahydrofurans, 2- and 3-substitution led to trans-configured oxolanes. Alcohols with non-activated olefins were converted into trans-substituted tetrahydrofurans with increasing selectivity in the order of C-1- ? C-3-substitution. The regio- and stereoselectivities of the radical bromine cyclization follow the guidelines already set up in former works of our group (5-exo-trig; 2,5-trans, 2,4-cis and 2,3-trans). The ionic bromine cyclizations of 5,5-dimethylated bishomoallylic alcohols by means of NBS ran regioselective complementarily to the radical cyclizations and stereoselective in dependence of the phenyl substituents at C-1 - C-3 to the 2,5-trans-, 3,5-cis- and 4,5-trans-configured tetrahydropyrans. Bromine cyclization of a prochiral pentenol in presence of A.n.A.P. gave rise to the ß-brominated tetrahydrofuran racemically in 87% yield. Even the use of chiral ligands in vanadium catalyzed oxygenation of prochiral pentenols led to no enantiomeric enriched tatrahydrofurans. Within simple natural product syntheses cis-pityol, linalool oxide as well as (-)-epi-bisabololoxid was synthesized selectively under standard conditions of the vanadium Schiff-base catalyzed oxidation with VO(salin)(OEt) and TBHP. The stereoselectivities increased proportionally with the size difference of the substituents in position 1 of bishomoallylic alcohols. Finally a new three-step total synthesis of the four "natural" muscarine isomers was developed by vanadium catalyzed bromide oxiadtion with TBHP. The overall yields of these syntheses range between 3.0 and 19.9%. KW - Vanadium KW - Tetrahydrofuran KW - Schiffsche Basen KW - Pentenole KW - Vanadium KW - Tetrahydrofuran KW - Schiffbase KW - Pentenol KW - Oxidation KW - vanadium KW - tetrahydrofuran KW - Schiff-base KW - pentenol KW - oxidation Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-3296 ER - TY - JOUR A1 - Schmidt, Sven A1 - Alt, Yvonne A1 - Deoghare, Nikita A1 - Krüger, Sarah A1 - Kern, Anna A1 - Rockel, Anna Frederike A1 - Wagner, Nicole A1 - Ergün, Süleyman A1 - Wörsdörfer, Philipp T1 - A blood vessel organoid model recapitulating aspects of vasculogenesis, angiogenesis and vessel wall maturation JF - Organoids N2 - Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5–6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation. KW - organoid KW - blood vessel KW - vasculogenesis KW - angiogenesis KW - induced pluripotent stem cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284043 SN - 2674-1172 VL - 1 IS - 1 SP - 41 EP - 53 ER - TY - JOUR A1 - Herrmann, Johannes A1 - Lotz, Christopher A1 - Karagiannidis, Christian A1 - Weber-Carstens, Steffen A1 - Kluge, Stefan A1 - Putensen, Christian A1 - Wehrfritz, Andreas A1 - Schmidt, Karsten A1 - Ellerkmann, Richard K. A1 - Oswald, Daniel A1 - Lotz, Gösta A1 - Zotzmann, Viviane A1 - Moerer, Onnen A1 - Kühn, Christian A1 - Kochanek, Matthias A1 - Muellenbach, Ralf A1 - Gaertner, Matthias A1 - Fichtner, Falk A1 - Brettner, Florian A1 - Findeisen, Michael A1 - Heim, Markus A1 - Lahmer, Tobias A1 - Rosenow, Felix A1 - Haake, Nils A1 - Lepper, Philipp M. A1 - Rosenberger, Peter A1 - Braune, Stephan A1 - Kohls, Mirjam A1 - Heuschmann, Peter A1 - Meybohm, Patrick T1 - Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation JF - Critical Care N2 - Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO\(_{2}\)/FiO\(_{2}\) ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. KW - Covid-19 KW - extracorporeal membrane oxygenation (ECMO) KW - intensive care unit Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299686 VL - 26 IS - 1 ER - TY - JOUR A1 - Dogan, Leyla A1 - Scheuring, Ruben A1 - Wagner, Nicole A1 - Ueda, Yuichiro A1 - Schmidt, Sven A1 - Wörsdörfer, Philipp A1 - Groll, Jürgen A1 - Ergün, Süleyman T1 - Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels JF - Biofabrication N2 - Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type I bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimics the embryonic steps of vessel formation during vasculogenesis. Histological evaluations at different time points of extrusion revealed the initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, endothelial cells in capillary-like vessel structures deposited a basement membrane-like matrix at the basal side between the vessel wall and the alginate-collagen matrix. After transplantation of the printed constructs into the chicken chorioallantoic membrane (CAM) the printed vessels connected to the CAM blood vessels and get perfused in vivo. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis. KW - vascular biofabrication KW - human iPSC-derived mesodermal cells (hiMPCs) KW - extrusion of hiMPC-containing bioinks alginate + collagen type I KW - multilayered vessel wall with intimate, media and adventitia KW - vascular network and hierarchical organized vessels KW - electron microscopy KW - serial block face EM Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254046 VL - 13 IS - 4 ER - TY - JOUR A1 - Janjetovic, Snjezana A1 - Lohneis, Philipp A1 - Nogai, Axel A1 - Balci, Derya A1 - Rasche, Leo A1 - Jähne, Doris A1 - Bokemeyer, Carsten A1 - Schilling, Georgia A1 - Blau, Igor Wolfgang A1 - Schmidt-Hieber, Martin T1 - Clinical and biological characteristics of medullary and extramedullary plasma cell dyscrasias JF - Biology N2 - Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP. KW - plasma cell disorder KW - multiple myeloma KW - extramedullary KW - immunohistochemistry KW - cytogenetics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242592 SN - 2079-7737 VL - 10 IS - 7 ER - TY - JOUR A1 - Jakuscheit, Axel A1 - Schaefer, Nina A1 - Roedig, Johannes A1 - Luedemann, Martin A1 - Hertzberg-Boelch, Sebastian Philipp von A1 - Weissenberger, Manuel A1 - Schmidt, Karsten A1 - Holzapfel, Boris Michael A1 - Rudert, Maximilian T1 - Modifiable individual risks of perioperative blood transfusions and acute postoperative complications in total hip and knee arthroplasty JF - Journal of Personalized Medicine N2 - Background: The primary aim of this study was to identify modifiable patient-related predictors of blood transfusions and perioperative complications in total hip and knee arthroplasty. Individual predictor-adjusted risks can be used to define preoperative treatment thresholds. Methods: We performed this retrospective monocentric study in orthopaedic patients who underwent primary total knee or hip arthroplasty. Multivariate logistic regression models were used to assess the predictive value of patient-related characteristics. Predictor-adjusted individual risks of blood transfusions and the occurrence of any perioperative adverse event were calculated for potentially modifiable risk factors. Results: 3754 patients were included in this study. The overall blood transfusion and complication rates were 4.8% and 6.4%, respectively. Haemoglobin concentration (Hb, p < 0.001), low body mass index (BMI, p < 0.001) and estimated glomerular filtration rate (eGFR, p = 0.004) were the strongest potentially modifiable predictors of a blood transfusion. EGFR (p = 0.001) was the strongest potentially modifiable predictor of a complication. Predictor-adjusted risks of blood transfusions and acute postoperative complications were calculated for Hb and eGFR. Hb = 12.5 g/dL, BMI = 17.6 kg/m\(^2\), and eGFR = 54 min/mL were associated, respectively, with a 10% risk of a blood transfusion, eGFR = 59 mL/min was associated with a 10% risk of a complication. Conclusion: The individual risks for blood transfusions and acute postoperative complications are strongly increased in patients with a low preoperative Hb, low BMI or low eGFR. We recommend aiming at a preoperative Hb ≥ 13g/dL, an eGFR ≥ 60 mL/min and to avoid a low BMI. Future studies must show if a preoperative increase of eGFR and BMI is feasible and truly beneficial. KW - patient blood management KW - total joint arthroplasty KW - haemoglobin KW - perioperative management Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250290 SN - 2075-4426 VL - 11 IS - 11 ER - TY - JOUR A1 - Summa, Michela A1 - Klein, Martin A1 - Schmidt, Philipp T1 - Introduction: Double Intentionality JF - Topoi N2 - No abstract available. KW - double intentionality KW - intentional directions KW - experiences Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269865 SN - 1572-8749 VL - 41 IS - 1 ER -