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Article ; Online: Comparison of two reduced intensity conditioning regimens: Flu-Bu2 versus RIC-TBF in allogeneic hematopoietic stem cell transplantation.

Verstraete, Emma / Baumann, Cédric / Rousseau, Hélène / Campidelli, Arnaud / Rubio, Marie-Thérèse / D'Aveni, Maud

2024 Volume 65, Issue 2, Page(s) 283–286

MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Transplantation Conditioning ; Graft vs Host Disease ; Retrospective Studies
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2281269
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Article: A Serious Game About Hematology for Health Care Workers (SUPER HEMO): Development and Validation Study.

Perrin, Julien / Meeus, Amélie / Broseus, Julien / Morieux, Pierre-Jean / Di Ceglie, Valentine / Gravoulet, Julien / D'Aveni, Maud

JMIR serious games

2023 Volume 11, Page(s) e40350

Abstract: Background: Complete blood count (CBC) and hemostatic screening tests are among the most commonly prescribed blood tests worldwide. All health care workers (nurse practitioners, pharmacists, dentists, midwives, and physicians) are expected to correctly ... ...

Abstract	Background: Complete blood count (CBC) and hemostatic screening tests are among the most commonly prescribed blood tests worldwide. All health care workers (nurse practitioners, pharmacists, dentists, midwives, and physicians) are expected to correctly interpret the results in their daily practice. Currently, the undergraduate hematology curriculum consists predominantly of lecture-based teaching. Because hematology combines basic science (blood cells and hemostasis physiology) and clinical skills, students report that they do not easily master hematology with only lecture-based teaching. Having interviewed students at the University of Lorraine, we considered it necessary to develop new teaching approaches and methods. Objective: We aimed to develop and validate a serious game about CBC analysis for health care students. Our primary objective was to help students perceive hematology as being a playful and easy topic and for them to feel truly involved in taking care of their patients by analyzing blood tests. We considered that this game-based approach would be attractive to students as an addition to the classic lecture-based approach and improve their knowledge and skills in hematology. Methods: We developed an adventure game called SUPER HEMO, a video game in which the player assumes the role of a protagonist in an interactive story driven by exploration and problem-solving tests. Following validation with beta testing by a panel of volunteer students, we used a novel, integrated teaching approach. We added 1.5 hours of gaming to the standard curriculum for a small group of volunteer students. Physician and pharmacy students in their third year at a single French university were invited to attend this extracurricular course. Pregame and postgame tests and satisfaction surveys were immediately recorded. Final hematology exam results were analyzed. Results: A total of 86 of 324 physician students (26.5%) and 67 of 115 pharmacy students (58%) opted to participate. Median scores on the pre- and posttests were 6 out of 10 versus 7 out of 10, respectively, for the physician students, (P<.001) and 7.5 out of 10 versus 8 out of 10, respectively, for the pharmacy students (P<.001). At the final hematology evaluation, physician students who played SUPER HEMO had a slightly better median score than those who did not: 13 out of 20 versus 12 out of 20, respectively (P=.002). Pharmacy students who played SUPER HEMO had a median score of 21.75 out of 30; this was not significantly different from pharmacy students who did not play SUPER HEMO (20/30; P=.12). Among the participants who answered the survey (n=143), more than 86% (123/143) believed they had strengthened their knowledge and nearly 80% (114/143) of them had fun. Conclusions: Feedback from this game session provided evidence to support the integration of interactive teaching methods in undergraduate hematology teaching. The development of SUPER HEMO is intended to be completed so that it can become a support tool for continuing education.
Language	English
Publishing date	2023-02-13
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2798265-8
ISSN	2291-9279
ISSN	2291-9279
DOI	10.2196/40350
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Article ; Online: Wharton's jelly-derived stromal cells and their cell therapy applications in allogeneic haematopoietic stem cell transplantation.

Pochon, Cécile / Notarantonio, Anne-Béatrice / Laroye, Caroline / Reppel, Loic / Bensoussan, Danièle / Bertrand, Allan / Rubio, Marie-Thérèse / D'Aveni, Maud

Journal of cellular and molecular medicine

2022 Volume 26, Issue 5, Page(s) 1339–1350

Abstract: For decades, mesenchymal stromal cells (MSCs) have been of great interest in the fields of regenerative medicine, tissue engineering and immunomodulation. Their tremendous potential makes it desirable to cryopreserve and bank MSCs to increase their ... ...

Abstract	For decades, mesenchymal stromal cells (MSCs) have been of great interest in the fields of regenerative medicine, tissue engineering and immunomodulation. Their tremendous potential makes it desirable to cryopreserve and bank MSCs to increase their accessibility and availability. Postnatally derived MSCs seem to be of particular interest because they are harvested after delivery without ethical controversy, they have the capacity to expand at a higher rate than adult-derived MSCs, in which expansion decreases with ageing, and they have demonstrated immunological and haematological supportive properties similar to those of adult-derived MSCs. In this review, we focus on MSCs obtained from Wharton's jelly (the mucous connective tissue of the umbilical cord between the amniotic epithelium and the umbilical vessels). Wharton's jelly MSCs (WJ-MSCs) are a good candidate for cellular therapy in haematology, with accumulating data supporting their potential to sustain haematopoietic stem cell engraftment and to modulate alloreactivity such as Graft Versus Host Disease (GVHD). We first present an overview of their in-vitro properties and the results of preclinical murine models confirming the suitability of WJ-MSCs for cellular therapy in haematology. Next, we focus on clinical trials and discuss tolerance, efficacy and infusion protocols reported in haematology for GVHD and engraftment.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Mice ; Umbilical Cord ; Wharton Jelly
Language	English
Publishing date	2022-01-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.17105
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Article ; Online: Efficacy of eculizumab in transplantation-associated thrombotic microangiopathy: results of the French nationwide study on behalf of the SFGM-TC and the CNR-MAT.

Peyre, Marion / Sicre de Fontbrune, Flore / Berceanu, Ana / Benjemia, Lise / Castelle, Martin / D'Aveni, Maud / Marçais, Ambroise / Kaphan, Eleonore / Bulabois, Claude-Eric / Sirvent, Anne / Rohrlich, Pierre-Simon / Coiteux, Valerie / Chantepie, Sylvain / Nguyen-Quoc, Stéphanie / Peffault de Latour, Régis / Coppo, Paul

Bone marrow transplantation

2024

Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Letter
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-024-02279-2
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Article ; Online: Myeloid-Derived Suppressor Cells in the Context of Allogeneic Hematopoietic Stem Cell Transplantation.

D'Aveni, Maud / Notarantonio, Anne B / Bertrand, Allan / Boulangé, Laura / Pochon, Cécile / Rubio, Marie T

Frontiers in immunology

2020 Volume 11, Page(s) 989

Abstract: Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the ... ...

Abstract	Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses. In the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), MDSCs (in the donor graft and in the recipient, after allo-HSCT) might mediate immune suppression through multiple mechanisms. However, it remains unclear how MDSCs can be distinguished from their normal myeloid counterparts in the hematopoietic stem cell donor graft and during immune reconstitution after allo-HSCT in the recipient. Our ability to understand their exact role in allo-HSCT is limited by the absence of a specific gene signature or surface markers for identifying MDSCs among myeloid cells and by their plasticity in different microenvironments. According to various studies, MDSCs might induce transplant tolerance and control graft vs. host disease (GVHD), but their impact on the graft vs. tumor effect (GVT) is not fully understood. In fact, we know that MDSCs commonly expand in patients with cancer, and they are thought to promote hematological malignancy progression. However, little is known about whether depleting them might be an effective strategy for enhancing GVT effects. Here, we review data published over the past 40 years on allo-HSCT to delineate the different MDSC subsets, and their abilities to induce transplant tolerance and preserve the GVT effect. This review will provide a basis for determining whether one MDSC subset might be proposed as the most appropriate candidate for cellular therapies, due to its ability to modulate GVHD.
MeSH term(s)	Animals ; Graft Rejection/immunology ; Graft Rejection/metabolism ; Graft Rejection/prevention & control ; Graft Survival ; Graft vs Host Disease/immunology ; Graft vs Host Disease/metabolism ; Graft vs Host Disease/prevention & control ; Graft vs Tumor Effect ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Phenotype ; Risk Factors ; Transplantation Tolerance ; Transplantation, Homologous ; Treatment Outcome
Keywords	covid19
Language	English
Publishing date	2020-05-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00989
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Article ; Online: A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

Laroye, Caroline / Thilly, Nathalie / Gauthier, M / Luc, Amandine / Latger-Cannard, Véronique / Eschwege, Valérie / Bensoussan, Danièle / Pochon, Cécile / Campidelli, Arnaud / Rubio, Marie-Thérèse / D'Aveni, Maud / Decot, Véronique

Cytotherapy

2023 Volume 25, Issue 8, Page(s) 877–884

Abstract: Background aims: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies ... ...

Abstract	Background aims: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. Methods: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 Results: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 10 Conclusions: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.
MeSH term(s)	Humans ; SARS-CoV-2 ; Pandemics ; COVID-19 ; Hematopoietic Stem Cell Transplantation/methods ; Antigens, CD34 ; Cryopreservation/methods
Chemical Substances	Antigens, CD34
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2023.04.006
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Article ; Online: Haemolytic paroxysmal nocturnal haemoglobinuria in patients with myeloid neoplasms: A rare association with specific therapeutic implications.

Sutra Del Galy, Aurélien / Willems, Lise / D'Aveni, Maud / Pautas, Cécile / Chantepie, Sylvain / Carpentier, Benjamin / Barraco, Fiorenza / Banos, Anne / Garidi, Reda / Forcade, Edouard / Sicre de Fontbrune, Flore / Peffault de Latour, Régis

British journal of haematology

2023 Volume 201, Issue 2, Page(s) e16–e20

MeSH term(s)	Humans ; Hemoglobinuria, Paroxysmal/therapy ; Hemoglobinuria, Paroxysmal/drug therapy ; Neoplasms/complications ; Myeloproliferative Disorders/complications ; Hemolysis
Language	English
Publishing date	2023-02-17
Publishing country	England
Document type	Letter
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18693
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Article ; Online: Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.

Pagliuca, Simona / Gurnari, Carmelo / Hercus, Colin / Hergalant, Sébastien / Hong, Sanghee / Dhuyser, Adele / D'Aveni, Maud / Aarnink, Alice / Rubio, Marie Thérèse / Feugier, Pierre / Ferraro, Francesca / Carraway, Hetty E / Sobecks, Ronald / Hamilton, Betty K / Majhail, Navneet S / Visconte, Valeria / Maciejewski, Jaroslaw P

Nature communications

2023 Volume 14, Issue 1, Page(s) 3153

Abstract: Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a ... ...

Abstract	Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experiences relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.
MeSH term(s)	Humans ; Graft vs Host Disease ; Leukemia/genetics ; Leukemia/therapy ; HLA Antigens/genetics ; Chronic Disease ; Hematopoietic Stem Cell Transplantation/adverse effects ; Recurrence
Chemical Substances	HLA Antigens
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38113-4
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Article: Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.

Research square

2023

Abstract	Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experience relapses because of the failure of the immunological responses to control leukemic outgrowth. Here, through a broad immunogenetic study, we demonstrate that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune reactions and response to immunomodulatory strategies. These findings define key molecular modes of post-transplant leukemia escape contributing to relapse.
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2773498/v1
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Article ; Online: Age-related immune cell dynamics influence outcomes after allogeneic haematopoietic cell transplantation.

Jandin, Alizée / Pochon, Cécile / Campidelli, Arnaud / D'Aveni, Maud / Kicki, Céline / Notarantonio, Anne-Béatrice / Roth Guepin, Gabrielle / Mbuyi, Tshinguta Anita / Feugier, Pierre / Chastagner, Pascal / Schweitzer, Cyril / de Carvalho Bittencourt, Marcelo / Rubio, Marie Thérèse / Pagliuca, Simona

British journal of haematology

2023 Volume 202, Issue 1, Page(s) 122–134

Abstract: An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post-transplant immune recovery have been largely investigated across ... ...

Abstract	An efficient immunological reconstitution construes the pillar for the success of allogeneic haematopoietic cell transplantation (HCT) in haematological disorders. Factors influencing post-transplant immune recovery have been largely investigated across multiple cohorts issuing heterogeneous results. Differences in outcomes in adult and paediatric populations suggest an age-related contribution to post-transplant immune reconstitution; however, it is unclear how recipient and donor age may affect the dynamics of single immune cells. Here, we retrospectively collected and analysed immunological data of 174 patients (58 children and 116 adults) consecutively transplanted for haematological disorders in our centre. We show that trajectories of specific immune cells were strictly dependent on recipient age and pretransplant virus exposure, with the strongest effect seen on T CD4+ and B-cell counterparts, while donor age and transplant platforms had a minimal impact. This mirrored different kinetics of immune reconstitution in adult and paediatric patients, with major divergences in immune cell composition in late post-transplant phases, featuring better survival, relapse-free survival and cumulative incidence of pathogen-specific infections in younger patients. Altogether, these findings underpin the importance of recipient age on post-transplant immune cell recovery and define the basic dynamics of the immune reconstitution in paediatric and adult populations as a benchmark for future studies.
MeSH term(s)	Adult ; Humans ; Child ; Retrospective Studies ; Transplantation, Homologous/adverse effects ; Hematopoietic Stem Cell Transplantation/adverse effects ; B-Lymphocytes ; Graft vs Host Disease/etiology
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18822
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