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Lehrnbecher, Thomas ; Rath, Peter ; Attarbaschi, Andishe ; Cario, Gunnar ; Döring, Michaela ; Moser, Olga ; Mücke, Urs ; Poyer, Fiona ; Rieken, Sarah ; Temme, Christian ; Voigt, Sebastian ; Groll, Andreas Hermann ; Lauten, Melchior Johannes
Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, but early microbiological diagnosis is difficult. As data on the value of biomarkers in the CNS are scarce, in particular in children, we retrospectively analyzed the performance of galactomannan (GM) and PCR assays in CNS samples of 15 children with proven and probable CNS IMD and of 32 immunocompromised children without fungal infection. Galactomannan in the cerebrospinal fluid (CSF) was assessed in nine of the 15 pediatric patients and was positive in five of them. Polymerase chain reaction (PCR) was performed in eight of the 15 patients and detected nucleic acids from molds in six patients. Galactomannan and PCR in CNS samples were the only positive microbiologic parameter in the CNS in three and two patients, respectively. In four patients, PCR specified the pathogen detected in microscopy. Galactomannan and PCR results remained negative in the CSF of all immunocompromised children without evidence for CNS IMD. Our data suggest that GM and PCR in CNS specimens are valuable additional tools in diagnosing CNS IMD and should be included in the work up of all pediatric patients with suspected mold disease of the CNS.
Wernicke, Caroline M. ; Grunewald, Thomas G. P. ; Juenger, Hendrik ; Kuçi, Selim ; Kuçi, Zyrafete ; Köhl, Ulrike ; Mueller, Ingo ; Döring, Michaela ; Peters, Christina ; Lawitschka, Anita ; Kolb, Hans-Jochem ; Bader, Peter ; Burdach, Stefan ; Teichert- von Lüttichau, Irene
Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B.
Ifversen, Marianne ; Meisel, Roland ; Sedlacek, Petr ; Kalwak, Krzysztof ; Sisinni, Luisa ; Hutt, Daphna ; Lehrnbecher, Thomas ; Balduzzi, Adriana ; Diesch, Tamara ; Jarisch, Andrea ; Güngör, Tayfun ; Stein, Jerry ; Yaniv, Isaac ; Bönig, Halvard-Björn ; Kuhlen, Michaela ; Ansari, Marc ; Nava, Tiago ; Dalle, Jean-Hugues ; Diaz-de-Heredia, Cristina ; Trigoso, Eugenia ; Falkenberg, Ulrike ; Hartmann, Mihaela ; Deiana, Marco ; Canesi, Marta ; Broggi, Chiara ; Bertaina, Alice ; Gibson, Brenda ; Krivan, Gergely ; Vettenranta, Kim ; Matic, Toni ; Büchner, Jochen ; Lawitschka, Anita ; Peters, Christina ; Yesilipek, Akif ; Yalçin, Koray ; Lucchini, Giovanna ; Bakhtiar, Shahrzad ; Turkiewicz, Dominik ; Niinimäki, Riitta ; Wachowiak, Jacek ; Cesaro, Simone ; Dalissier, Arnaud ; Corbacioglu, Selim ; Willasch, Andre Manfred ; Bader, Peter
Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
Bakhtiar, Shahrzad ; Salzmann-Manrique, Emilia ; Donath, Helena ; Wölke, Sandra ; Dücker, Ruth Pia ; Fritzemeyer, Stefanie ; Schubert, Ralf ; Hünecke, Sabine ; Kieslich, Matthias ; Klingebiel, Thomas ; Bader, Peter ; Zielen, Stefan
Ataxia-telangiectasia (A-T) is a hereditary immune system disorder with neurodegeneration. Its first neurologic symptoms include ataxic gait in early childhood, with slowly progressive cerebellar ataxia, oculomotor apraxia, oculocutaneous telangiectasia, and progressive muscle weakness. Neonatal screening for severe T-cell deficiency was recently found to diagnose A-T patients with a significantly reduced naïve T-cell pool. Our study includes 69 A-T patients between 8 January 2002 and 1 December 2019. Nineteen cases of cancer were diagnosed in 17 patients (25%), with a median overall survival [OS; 95% cumulative indcidence (CI)] of 26·9 years for the entire cohort. The 15-year OS of 82·5% (72–95%) was significantly decreased among A-T patients with malignancies, who had a median OS of 2·11 years, with a two-year-estimated OS of 50·7% (31–82%). Haematological malignancies were the major causes of death within the initial years of life with a 15 times increased risk for death [HR (95% CI): 6·9 (3·1–15.2), P < 0·001] upon malignancy diagnosis. Male patients with A-T are at a higher cancer risk than their female counterparts. This manuscript highlights the need for cancer surveillance and prevention, as well as optimal treatment in this cohort.
Hünecke, Sabine ; Cappel, Claudia ; Esser, Ruth ; Pfirrmann, Verena ; Salzmann-Manrique, Emilia ; Betz, Sibille ; Keitl, Eileen ; Banisharif-Dehkordi, Julia ; Bakhtiar, Shahrzad ; Königs, Christoph ; Jarisch, Andrea ; Sörensen, Jan ; Ullrich, Evelyn ; Klingebiel, Thomas ; Bader, Peter ; Bremm, Melanie
Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16− (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56bright NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56bright NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise analysis of the reconstitution of NK cell subpopulations post-HSCT might indicate the occurrence of undesired events post-HSCT such as severe aGvHD.values
Rodríguez Ramos, Pablo ; Chlad, Lukáš ; Epple, Eliane ; Fabbietti, Laura ; Galatyuk, Tetyana ; Golubeva, Marina ; Guber, Fedor ; Hlaváč, Stanislav ; Ivashkin, Alexander ; Kajetanowic, Marcin ; Kardan, Behruz ; Koenig, Wolfgang ; Korcyl, Grzegorz ; Kugler, Andrej ; Lapidus, Kirill ; Linev, Serguei ; Lisowski, Edward ; Neiser, Andreas ; Ott, Herwig ; Otte, Peter-Bernd ; Petukhov, Oleg ; Pietraszko, Jerzy ; Reshetin, Andrey ; Rost, Adrian ; Salabura, Piotr ; Sobolev, Yuri G. ; Svoboda, Ondřej ; Thomas, Andreas ; Tlustý, Pavel ; Traxler, Michael
Electromagnetic calorimeter (ECAL) is being developed to complement dilepton spectrometer HADES. ECAL will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 AGeV on the beam of future accelerator SIS100@FAIR. We will report results of the last beam test with quasi-monoenergetic photons carried out in MAMI facility at Johannes Gutenberg Universität Mainz.
Ramstein, Béatrice ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
Przygoda, Witold ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Epple, Eliane ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
Epple, Eliane ; Adamczewski-Musch, Jörn ; Arnold, Oliver Werner ; Atomssa, Ermias T. ; Behnke, Claudia ; Berger-Chen, Jia-Chii ; Biernat, Jacek ; Blanco, Alberto ; Blume, Christoph ; Böhmer, Michael ; Bordalo, Paula ; Chernenko, Sergey P. ; Deveaux, Christina Anna ; Dybczak, Adrian ; Fabbietti, Laura ; Fateev, Oleg ; Fonte, Paulo ; Franco, Celso ; Friese, Jürgen ; Fröhlich, Ingo ; Galatyuk, Tetyana ; Garzón, Juan A. ; Gill, Katharina ; Golubeva, Marina ; Guber, Fedor ; Gumberidze, Malgorzata ; Harabasz, Szymon ; Hennino, Thierry ; Hlaváč, Stanislav ; Höhne, Claudia ; Holzmann, Romain ; Ierusalimov, Alexander P. ; Ivashkin, Alexander ; Jurkovič, Martin ; Kämpfer, Burkhard ; Karavicheva, Tatiana L. ; Kardan, Behruz ; Koenig, Ilse ; Koenig, Wolfgang ; Kolb, Burkhard W. ; Korcyl, Grzegorz ; Kornakov, Georgy ; Kotte, Roland ; Krása, Antonin ; Krebs, Erik ; Kuc, Hubert ; Kugler, Andrej ; Kunz, Tobias ; Kurepin, Alexander ; Kurilkin, Aleksey K. ; Kurilkin, Pavel ; Ladygin, Vladimir P. ; Lalik, Rafał Tomasz ; Lapidus, Kirill ; Lebedev, Alexei ; Lopes, Luis Alberto Vieira ; Lorenz, Manuel ; Mahmoud, Tariq ; Maier, Ludwig W. ; Mangiarotti, Alessio ; Markert, Jochen ; Metag, Volker ; Michel, Jan ; Müntz, Christian ; Münzer, Robert Helmut ; Naumann, Lothar ; Palka, Marek ; Parpottas, Yannis ; Pechenov, Vladimir ; Pechenova, Olga ; Petousis, Vlasios ; Pietraszko, Jerzy ; Przygoda, Witold ; Ramstein, Béatrice ; Rehnisch, Laura ; Reshetin, Andrey ; Rost, Adrian ; Rustamov, Anar ; Sadovsky, Alexander ; Salabura, Piotr ; Scheib, Timo ; Schmidt-Sommerfeld, Korbinian ; Schuldes, Heidi ; Sellheim, Patrick ; Siebenson, Johannes Stephan ; Silva, Luis ; Sobolev, Yuri G. ; Spataro, Stefano ; Ströbele, Herbert ; Stroth, Joachim ; Strzempek, Paweł ; Sturm, Christian Thomas ; Svoboda, Ondřej ; Tarantola Peloni, Attilio ; Teilab, Khaled ; Tlustý, Pavel ; Traxler, Michael ; Tsertos, Haralabos ; Vasiliev, Taras A. ; Wagner, Vladimir ; Wendisch, Christian ; Wirth, Joana ; Wüstenfeld, Jörn ; Zanevsky, Yuri V. ; Zumbruch, Peter W.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
Schulz, Jörg B. ; Berlit, Peter ; Diener, Hans-Christoph ; Gerloff, Christian ; Greinacher, Andreas ; Klein, Christine ; Petzold, Gabor ; Piccininni, Marco ; Poli, Sven ; Röhrig, Rainer ; Steinmetz, Helmuth ; Thiele, Thomas ; Kurth, Tobias
Objective: We aimed to estimate the incidence of cerebral sinus and venous thrombosis (CVT) within 1 month from first dose administration and the frequency of vaccine-induced immune thrombotic thrombocytopenia (VITT) as the underlying mechanism after vaccination with BNT162b2, ChAdOx1, and mRNA-1273, in Germany. Methods: A web-based questionnaire was e-mailed to all departments of neurology. We requested a report of cases of CVT occurring within 1 month of a COVID-19 vaccination. Other cerebral events could also be reported. Incidence rates of CVT were calculated by using official statistics of 9 German states. Results: A total of 45 CVT cases were reported. In addition, 9 primary ischemic strokes, 4 primary intracerebral hemorrhages, and 4 other neurological events were recorded. Of the CVT patients, 35 (77.8%) were female, and 36 (80.0%) were younger than 60 years. Fifty-three events were observed after vaccination with ChAdOx1 (85.5%), 9 after BNT162b2 (14.5%) vaccination, and none after mRNA-1273 vaccination. After 7,126,434 first vaccine doses, the incidence rate of CVT within 1 month from first dose administration was 0.55 (95% confidence interval [CI] = 0.38–0.78) per 100,000 person-months (which corresponds to a risk of CVT within the first 31 days of 0.55 per 100,000 individuals) for all vaccines and 1.52 (95% CI = 1.00–2.21) for ChAdOx1 (after 2,320,535 ChAdOx1 first doses). The adjusted incidence rate ratio was 9.68 (95% CI = 3.46–34.98) for ChAdOx1 compared to mRNA-based vaccines and 3.14 (95% CI = 1.22–10.65) for females compared to non-females. In 26 of 45 patients with CVT (57.8%), VITT was graded highly probable. Interpretation: Given an incidence of 0.02 to 0.15 per 100,000 person-months for CVT in the general population, these findings point toward a higher risk for CVT after ChAdOx1 vaccination, especially for women.