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Article ; Online: Continue rare cancers collaboration with European Reference Networks after Brexit.

Blay, Jean-Yves / Fenaux, Pierre / Ladenstein, Ruth / Hoogerbrugge, Nicoline

2021 Volume 397, Issue 10276, Page(s) 793

MeSH term(s)	European Union ; Humans ; Neoplasms ; United Kingdom
Language	English
Publishing date	2021-02-25
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(21)00264-6
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Article ; Online: The impact of the EU General Data Protection Regulation on childhood cancer research in Europe.

Vassal, Gilles / Lazarov, Deyan / Rizzari, Carmelo / Szczepański, Tomasz / Ladenstein, Ruth / Kearns, Pamela R

The Lancet. Oncology

2022 Volume 23, Issue 8, Page(s) 974–975

MeSH term(s)	Child ; Computer Security ; Europe/epidemiology ; Humans ; Neoplasms/epidemiology ; Neoplasms/therapy ; Research
Language	English
Publishing date	2022-07-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(22)00287-X
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Zs.A 5696: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study.

Lode, Holger N / Ehlert, Karoline / Huber, Stephanie / Troschke-Meurer, Sascha / Siebert, Nikolai / Zumpe, Maxi / Loibner, Hans / Ladenstein, Ruth

British journal of cancer

2023 Volume 129, Issue 11, Page(s) 1780–1786

Abstract: Background: Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta ... ...

Abstract	Background: Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma. Methods: In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival. Results: Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108-290). Three-year progression-free and overall survival rates were 31% (95% CI 17-47) and 66% (95% CI 47-79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia. Conclusion: Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma. Clinical trial registration: The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).
MeSH term(s)	Humans ; Morphine Derivatives/therapeutic use ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/etiology ; Neuroblastoma/drug therapy ; Pain/drug therapy ; Pain/etiology
Chemical Substances	dinutuximab (7SQY4ZUD30) ; Morphine Derivatives
Language	English
Publishing date	2023-10-10
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02457-x
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Article ; Online: Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation.

Kirchberger, Stefanie / Shoeb, Mohamed R / Lazic, Daria / Wenninger-Weinzierl, Andrea / Fischer, Kristin / Shaw, Lisa E / Nogueira, Filomena / Rifatbegovic, Fikret / Bozsaky, Eva / Ladenstein, Ruth / Bodenmiller, Bernd / Lion, Thomas / Traver, David / Farlik, Matthias / Schöfer, Christian / Taschner-Mandl, Sabine / Halbritter, Florian / Distel, Martin

Nature communications

2024 Volume 15, Issue 1, Page(s) 1792

Abstract: Neutrophils are evolutionarily conserved innate immune cells playing pivotal roles in host defense. Zebrafish models have contributed substantially to our understanding of neutrophil functions but similarities to human neutrophil maturation have not been ...

Abstract	Neutrophils are evolutionarily conserved innate immune cells playing pivotal roles in host defense. Zebrafish models have contributed substantially to our understanding of neutrophil functions but similarities to human neutrophil maturation have not been systematically characterized, which limits their applicability to studying human disease. Here we show, by generating and analysing transgenic zebrafish strains representing distinct neutrophil differentiation stages, a high-resolution transcriptional profile of neutrophil maturation. We link gene expression at each stage to characteristic transcription factors, including C/ebp-β, which is important for late neutrophil maturation. Cross-species comparison of zebrafish, mouse, and human samples confirms high molecular similarity of immature stages and discriminates zebrafish-specific from pan-species gene signatures. Applying the pan-species neutrophil maturation signature to RNA-sequencing data from human neuroblastoma patients reveals association between metastatic tumor cell infiltration in the bone marrow and an overall increase in mature neutrophils. Our detailed neutrophil maturation atlas thus provides a valuable resource for studying neutrophil function at different stages across species in health and disease.
MeSH term(s)	Animals ; Humans ; Mice ; Neutrophils ; Zebrafish/genetics ; Zebrafish/metabolism ; Animals, Genetically Modified ; Bone Marrow/metabolism ; Gene Expression Profiling
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45802-1
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Article: Multimodal Therapy with Consolidating Haploidentical Stem Cell Transplantation and Dinutuximab Beta for Patients with High-Risk Neuroblastoma and Central Nervous System Relapse.

Flaadt, Tim / Ebinger, Martin / Schreiber, Malin / Ladenstein, Ruth L / Simon, Thorsten / Lode, Holger N / Hero, Barbara / Schuhmann, Martin U / Schäfer, Jürgen / Paulsen, Frank / Timmermann, Beate / Eggert, Angelika / Lang, Peter

Journal of clinical medicine

2023 Volume 12, Issue 19

Abstract: Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse ... ...

Abstract	Despite highly intensive multimodality treatment regimens, the prognosis of patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse remains poor. We retrospectively reviewed data from 13 patients with HRNB and CNS relapse who received multimodal therapy with consolidating haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta ± subcutaneous interleukin-2 (scIL-2). Following individual relapse treatment, patients aged 1-21 years underwent haplo-SCT with T/B-cell-depleted grafts followed by dinutuximab beta 20 mg/m
Language	English
Publishing date	2023-09-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12196196
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Article: Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy.

Lode, Holger N / Ladenstein, Ruth / Troschke-Meurer, Sascha / Struppe, Linda / Siebert, Nikolai / Zumpe, Maxi / Ehlert, Karoline / Huber, Stefanie / Glogova, Evgenia / Hundsdoerfer, Patrick / Eggert, Angelika / Zaniewska-Tekieli, Anna / Balwierz, Walentyna / Wieczorek, Aleksandra

Cancers

2023 Volume 15, Issue 13

Abstract: The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. ...

Abstract	The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines. The treatment did not result in any unexpected severe toxicities or in any major treatment delays. Grade 3/4 pain was reported by 4/25 patients in cycle 1, decreasing to 0/9 patients in cycles 3 and 4. The median follow-up was 0.6 years. The best response in this group was 48% (12/25 patients), which included three patients with minor responses. At 1 year, the estimated event-free survival was 27% (95% confidence interval [CI] 8-47) and overall survival was 44% (95% CI 24-65). Combining long-term infusion of dinutuximab beta with N5 and N6 chemotherapy demonstrated an acceptable safety profile and encouraging objective response rates in heavily pretreated patients with high-risk neuroblastoma, warranting further evaluation in clinical trials.
Language	English
Publishing date	2023-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133364
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Article: Pediatric Patients with Stage IV Rhabdomyosarcoma Significantly Benefit from Long-Term Maintenance Therapy: Results of the CWS-IV 2002 and the CWS DOK IV 2004-Trials.

Tramsen, Lars / Bochennek, Konrad / Sparber-Sauer, Monika / Salzmann-Manrique, Emilia / Scheer, Monika / Dantonello, Tobias / Borkhardt, Arndt / Dirksen, Uta / Thorwarth, Anne / Greiner, Jeanette / Ebinger, Martin / Weclawek-Tompol, Jadwiga / Ladenstein, Ruth / Ljungman, Gustaf / Hallmen, Erika / Lehrnbecher, Thomas / Koscielniak, Ewa / Klingebiel, Thomas

Cancers

2023 Volume 15, Issue 7

Abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma (STS) in childhood. Whereas more than 90% of patients with localized low-risk RMS can be cured, metastatic RMS have a dismal outcome, with survival rates of less than 30%. The HD CWS-96 trial ... ...

Abstract	Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma (STS) in childhood. Whereas more than 90% of patients with localized low-risk RMS can be cured, metastatic RMS have a dismal outcome, with survival rates of less than 30%. The HD CWS-96 trial showed an improved outcome for patients receiving maintenance therapy after completing intensive chemotherapy. Consequently, the international clinical trials CWS-IV 2002 and CWS DOK IV 2004 on metastatic disease of STS of the Cooperative Weichteilsarkom Studiengruppe (CWS) were designed in addition to the CWS-2002P trial for localized RMS disease. All patients received a multimodal intensive treatment regimen. To maintain remission, three options were compared: long-term maintenance therapy (LTMT) versus allogeneic hematopoietic stem cell transplantation (alloHSCT) versus high-dose chemotherapy (HDCT). A total of 176 pediatric patients with a histologically confirmed diagnosis of metastatic RMS or RMS-like tumor were included. A total of 89 patients receiving LTML showed a significantly better outcome, with an event-free survival (EFS) of 41% and an overall survival (OS) of 53%, than alloHSCT (
Language	English
Publishing date	2023-03-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15072050
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Article ; Online: Radiotherapy quality assurance in paediatric clinical trials: first report from six QUARTET-affiliated trials.

Kelly, Sarah M / Turcas, Andrada / Corning, Coreen / Bailey, Simon / Cañete, Adela / Clementel, Enrico / di Cataldo, Andrea / Dieckmann, Karin / Gaze, Mark N / Horan, Gail / Jenney, Meriel / Ladenstein, Ruth / Padovani, Laetitia / Valteau-Couanet, Dominique / Boterberg, Tom / Mandeville, Henry

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

2023 Volume 182, Page(s) 109549

Abstract: Background and purpose: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of ... ...

Abstract	Background and purpose: SIOP Europe's QUARTET project launched in 2016; aiming to improve access to high-quality radiotherapy for children and adolescents treated within clinical trials across Europe. The aim of this report is to present the profile of institutions participating in six QUARTET-affiliated trials and a description of the initial individual case review (ICR) outcomes. Methods: This is a two-part analysis. Firstly, using facility questionnaires, beam output audit certificates, and advanced technique credentialing records to create a profile of approved institutions, and secondly, collating trial records for ICRs submitted prior to 31/10/2022. Trials included are: SIOPEN HR-NBL1, SIOPEN-LINES, SIOPEN- VERITAS, SIOP-BTG HRMB, EpSSG-FaR-RMS, and SIOPEN HR-NBL2. Results: By 31/10/2022, a total of 103 institutions had commenced QUARTET site approval procedures to participate in QUARTET-affiliated trials; 66 sites across 20 countries were approved. These participating institutions were often paediatric referral sites with intensity modulated radiotherapy or proton beam therapy, designated paediatric radiation oncologists, and paediatric adapted facilities and imaging protocols available. In total, 263 patient plans were submitted for ICR, 254 ICRs from 15 countries were completed. ICRs had a rejection rate of 39.8%, taking an average of 1.4 submissions until approval was achieved. Target delineation was the most frequent reason for rejection. Conclusion: The QUARTET facility questionnaire is a valuable tool for mapping resources, personnel, and technology available to children and adolescents receiving radiotherapy. Prospective ICR is essential for paediatric oncology clinical trials and should be prioritised to reduce protocol violations.
MeSH term(s)	Adolescent ; Child ; Humans ; Prospective Studies ; Quality Assurance, Health Care ; Radiation Oncology ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated
Language	English
Publishing date	2023-02-23
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605646-5
ISSN	1879-0887 ; 0167-8140
ISSN (online)	1879-0887
ISSN	0167-8140
DOI	10.1016/j.radonc.2023.109549
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Article ; Online: Which Patients With Rhabdomyosarcoma Need Radiotherapy? Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry.

Koscielniak, Ewa / Timmermann, Beate / Münter, Marc / Weclawek-Tompol, Jadwiga / Ladenstein, Ruth / Niggli, Felix / Ljungman, Gustaf / Brecht, Ines B / Blank, Bernd / Hallmen, Erika / Scheer, Monika / Fuchs, Joerg / Seitz, Guido / Blattmann, Claudia / Sparber-Sauer, Monika / Klingebiel, Thomas

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2023 Volume 41, Issue 31, Page(s) 4916–4926

Abstract: Purpose: To analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS).: Methods: One thousand four hundred seventy patients with ... ...

Abstract	Purpose: To analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). Methods: One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5). Results: The 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% ( Conclusion: RT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.
MeSH term(s)	Humans ; Protons ; Rhabdomyosarcoma/drug therapy ; Prognosis ; Rhabdomyosarcoma, Embryonal/radiotherapy ; Progression-Free Survival ; Combined Modality Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Chemical Substances	Protons
Language	English
Publishing date	2023-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.22.02673
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Radiotherapy and long-term sequelae in pediatric patients with parameningeal rhabdomyosarcoma: Results of two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry.

Sparber-Sauer, Monika / Dietzschold, Maximilian / Schönstein, Anton / Heinz, Amadeus / Vokuhl, Christian / Pajtler, Kristian W / Harrabi, Semi / Lin, Yi-Lan / Kalle, Thekla von / Hagen, Rudolf / Ladenstein, Ruth / Kazanowska, Bernarda / Ljungman, Gustaf / Klingebiel, Thomas / Ebinger, Martin / Koscielniak, Ewa / Münter, Marc / Timmermann, Beate

Pediatric blood & cancer

2023 Volume 71, Issue 1, Page(s) e30742

Abstract: Background: Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome.: Methods: Treatment and outcome of 395 children with PM ... ...

Abstract	Background: Parameningeal location of rhabdomyosarcoma (PM RMS) is known to be an unfavorable prognostic factor. Scarce data are available on radiotherapy (RT) concepts with regard to outcome. Methods: Treatment and outcome of 395 children with PM RMS registered within two Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1995-2021) were evaluated. Results: Patients were IRS group II (n = 15) and III (n = 380) and received systemic treatment according to the enrolled protocols: I2VA (n = 172), VAIA/CEVAIE (n = 223). Delayed resection was performed in 88/395 (22%) patients, and RT was additionally given in 79/88 (90%) resected patients. RT was the predominant local treatment in 355/395 (90%) patients: hyperfractionated accelerated photon (HART; n = 77), conventionally fractionated photon (n = 91) or proton beam (n = 126), brachytherapy (n = 4), heavy ions (n = 1), not available (n = 56). In the subgroup of RT as only local treatment (n = 278), no intracranial tumor extension and complete remission at end of treatment were significant positive prognostic factors. No significant difference on tumor outcome was seen between different radiotherapy concepts. Long-term toxicity with mostly endocrinological and visual deficiencies was reported in 161/279 (58%) surviving patients with a lower trend after proton beam RT (48%) when compared to HART or conventionally fractionated photon RT (71% and 72%, respectively). Ten-year event-free and overall survival in the overall group were 62% (±5, 95% confidence interval [CI]) and 67% (±5, 95% CI); in the RT-only group 67% (±6, 95% CI) and 71% (±6, 95% CI), respectively. Conclusion: CWS data confirm the recent RT concept in PM RMS. Long-term sequelae as endocrinological and visual deficiencies need to be addressed.
MeSH term(s)	Child ; Humans ; Infant ; Protons ; Rhabdomyosarcoma/radiotherapy ; Rhabdomyosarcoma/drug therapy ; Combined Modality Therapy ; Remission Induction ; Disease Progression ; Registries ; Antineoplastic Combined Chemotherapy Protocols
Chemical Substances	Protons
Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30742
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