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Article: Advancing towards accurate phenotyping based on metabolic and fibrosis risk in metabolic-dysfunction associated steatotic liver disease: one step closer to personalized care.

Muñoz-Martínez, Sergio / Jiménez-Masip, Alba / Pericàs, Juan M

2024 Volume 13, Issue 1, Page(s) 128–131

Language	English
Publishing date	2024-01-18
Publishing country	China (Republic : 1949- )
Document type	Editorial ; Comment
ZDB-ID	2812398-0
ISSN	2304-389X ; 2304-3881
ISSN (online)	2304-389X
ISSN	2304-3881
DOI	10.21037/hbsn-23-563
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Article ; Online: The tireless search to improve the prognostic assessment of intrahepatic cholangiocarcinoma: An urgent need.

Muñoz-Martínez, Sergio / Forner, Alejandro

Liver international : official journal of the International Association for the Study of the Liver

2021 Volume 41, Issue 2, Page(s) 252–254

MeSH term(s)	Bile Duct Neoplasms/diagnosis ; C-Reactive Protein ; Cholangiocarcinoma/diagnosis ; Cohort Studies ; Humans ; Lymphocytes ; Prognosis
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.14768
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Zs.A 1632: Show issues

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Article ; Online: Current pharmacological treatment of hepatocellular carcinoma.

Muñoz-Martínez, Sergio / Iserte, Gemma / Sanduzzi-Zamparelli, Marco / Llarch, Neus / Reig, Maria

Current opinion in pharmacology

2021 Volume 60, Page(s) 141–148

Abstract: The landscape of hepatocellular carcinoma (HCC) has changed since the incorporation of sorafenib in 2007 as the first pharmacological treatment for HCC. The combination of atezolizumab plus bevacizumab is currently the first-line treatment for HCC ... ...

Abstract	The landscape of hepatocellular carcinoma (HCC) has changed since the incorporation of sorafenib in 2007 as the first pharmacological treatment for HCC. The combination of atezolizumab plus bevacizumab is currently the first-line treatment for HCC patients, and there are several second-line options approved for patients who had received sorafenib as the first-line treatment. The advantage of having multiple options of pharmacological treatment for HCC patients is associated to the need to redefine the clinical decision-making approach and considering new endpoints for the clinical trials design. The aim of this review was to share the Barcelona Clinic Liver Cancer approach and to summarize the ongoing clinical trials, which are testing pharmacological treatments.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/therapeutic use ; Carcinoma, Hepatocellular/drug therapy ; Humans ; Liver Neoplasms/drug therapy ; Sorafenib/therapeutic use
Chemical Substances	Bevacizumab (2S9ZZM9Q9V) ; Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2021-08-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2021.07.009
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Zs.A 5608: Show issues

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Article ; Online: Phenotypes of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatocellular Carcinoma.

Rivera-Esteban, Jesús / Muñoz-Martínez, Sergio / Higuera, Mónica / Sena, Elena / Bermúdez-Ramos, María / Bañares, Juan / Martínez-Gomez, María / Cusidó, M Serra / Jiménez-Masip, Alba / Francque, Sven M / Tacke, Frank / Minguez, Beatriz / Pericàs, Juan M

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2024

Abstract: Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction- ... ...

Abstract	Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2024.03.028
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Zs.A 5836: Show issues

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Article ; Online: Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis.

El Hajra, Ismael / Sanduzzi-Zamparelli, Marco / Sapena, Víctor / Muñoz-Martínez, Sergio / Mauro, Ezequiel / Llarch, Neus / Iserte, Gemma / Forner, Alejandro / Rios, José / Bruix, Jordi / Reig, María

Hepatology (Baltimore, Md.)

2023 Volume 77, Issue 4, Page(s) 1139–1149

Abstract: Background and aims: Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver ... ...

Abstract	Background and aims: Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens. Methods: Systematic review and meta-analysis of original articles or abstracts reporting survival of HCC patients treated with immunotherapy according to liver function between 2017 and 2022. Overal survival (OS) according to restricted mean survival time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment. Results: Of the 2218 articles considered, 15 articles recruiting 2311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95% CI, 6.15-10.57; I2 =93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI,1.45-1.84; I2 =0% heterogeneity; p = 0.45). Treatment line data were available for 47% of the patients and 3 studies included patients treated with atezolizumab-bevacizumab in the first line. Conclusions: The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular ; Liver Neoplasms ; Immunotherapy
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1097/HEP.0000000000000030
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Zs.A 1660: Show issues

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Article: Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study.

Rivera-Esteban, Jesús / Jiménez-Masip, Alba / Muñoz-Martínez, Sergio / Augustin, Salvador / Guerrero, Rafael A / Gabriel-Medina, Pablo / Ferrer-Costa, Roser / Rodríguez-Frías, Francisco / Turu, Elisabet / Marco, Andrés / Pericàs, Juan M / On Behalf Of The Prisonafld Study Group Collaborators

Journal of clinical medicine

2023 Volume 12, Issue 23

Abstract: Background and aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease ( ... ...

Abstract	Background and aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. Method: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. Results: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. Conclusions: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.
Language	English
Publishing date	2023-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12237276
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Article: Risk of Treatment Failure and Death after Ablation in Hepatocellular Carcinoma Patients-A Multiparametric Prediction.

Muñoz-Martínez, Sergio / Sapena, Victor / García-Criado, Ángeles / Darnell, Anna / Forner, Alejandro / Belmonte, Ernest / Sanduzzi-Zamparelli, Marco / Rimola, Jordi / Soler, Alexandre / Llarch, Neus / Iserte, Gemma / Mauro, Ezequiel / Ayuso, Carmen / Rios, Jose / Bruix, Jordi / Vilana, Ramon / Reig, María

Cancers

2023 Volume 15, Issue 13

Abstract: Background: Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and ... ...

Abstract	Background: Ablation is a first-line treatment for Barcelona Clinic Liver Cancer (BCLC)-0/A hepatocellular carcinoma (HCC). However, there are scarce data about patients' outcomes after recurrence. The present study evaluates the impact of patient and tumor characteristics at baseline and at recurrence on the Clinical Decision-Making process. Methods: We evaluated BCLC-0/A patients treated with percutaneous ablation from January 2010 to November 2018. Clinical and radiological data such as age, tumor location at ablation, pattern of recurrence/progression, and comorbidities during follow-up were registered. Tumor location was divided into 'suboptimal' vs. 'optimal' locations for ablation. The Clinical Decision-Making was based on tumor burden, liver dysfunction, or comorbidities. The statistical analysis included the time-to-recurrence/progression, censoring at time of death, date of last follow-up or liver transplantation, and time-to-event was estimated by the Kaplan-Meier method and Cox regression models to evaluate the risk of an event of death and change of treatment strategy. Results: A total of 225 patients [39.1% BCLC-0 and 60.9% BCLC-A] were included, 190 had unifocal HCC and 82.6% were ≤3 cm. The complete response rate and median overall survival were 96% and 60.7 months. The HCC nodules number (Hazard Ratio-HR 3.1), Child-Pugh (HR 2.4), and Albumin-Bilirubin score (HR 3.2) were associated with increased risk of death during follow-up. HCC in 'suboptimal location' presented a shorter time to recurrence. When comorbidities prevented further loco-regional or systemic treatment, the risk of death was significantly increased (HR 2.0, Conclusions: These results expose the impact of non-liver comorbidities when considering treatment for recurrence after ablation in the real-world setting and in research trials. Ultimately, we identified an orphan population for which effective interventions are needed.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133269
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Article: Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma.

Corominas, Josep / Sapena, Victor / Sanduzzi-Zamparelli, Marco / Millán, Cristina / Samper, Esther / Llarch, Neus / Iserte, Gemma / Torres, Ferràn / Da Fonseca, Leonardo G / Muñoz-Martínez, Sergio / Forner, Alejandro / Bruix, Jordi / Boix, Loreto / Reig, María

Cancers

2021 Volume 13, Issue 3

Abstract: Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between ... ...

Abstract	Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1
Language	English
Publishing date	2021-01-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13030426
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Article: Survival and adverse events of elderly patients treated with sorafenib for hepatocellular carcinoma.

Soria, Anna / Calvo, Mariona / Casas, Meritxell / Vidales, Zara / Muñoz-Martínez, Sergio / Sapena, Victor / Puigvehi, Marc / Canillas, Lidia / Guardeño, Raquel / Gallego, Adolfo / Mínguez, Beatriz / Horta, Diana / Clos, Ariadna / Montoliu, Silvia / Roget, Mercè / Reig, Maria / Vergara, Mercedes

Frontiers in oncology

2022 Volume 12, Page(s) 829483

Abstract: Introduction: The first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy ...

Abstract	Introduction: The first-line treatment for advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab, but its availability is not universal and elderly patients are underrepresented in clinical trials. There is little evidence of efficacy and tolerability in elderly patients under systemic treatment. The aims of this study were to characterize the profile of elderly patients treated with sorafenib, assess their survival and safety profile in order to extrapolate their eligibility for systemic treatment. Methods: Retrospective multicentre study of HCC patients aged ≥75 years old treated with sorafenib from January 2008 to December 2019. Demographic data, baseline characteristics, and variables related to HCC and sorafenib were recorded. Overall survival (OS) and safety were analyzed. Results: The study included 206 patients from 11 hospitals, median age 77.9 years; 71.4% men and 62.6% stage Barcelona Clinic Liver Cancer- C (BCLC-C). The main causes of cirrhosis were hepatitis C (60.7%) and alcohol (14.7%). Most patients (84.5%) started with sorafenib 800mg and 15.5% at lower dosage. Arterial hypertension (AHT) (74.2 vs 62.2%; standardized mean differences (STD): 26) and baseline ECOG-PS>0 (45.3 vs 34.7%; STD: 38.2) differed significantly between patients receiving low and full doses. Median OS was 15.4 months (18.2 in BCLC-B vs 13.6 in BCLC-C). OS was not modified by comorbidities, age or period with more expertise. Conclusions: Sorafenib appears to be safe in elderly patients with HCC. This is the first study to characterize the profile of elderly patients to be considered for systemic treatment. These findings could be used as the reference profile for elderly candidates for atezolizumab-bevacizumab.
Language	English
Publishing date	2022-08-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.829483
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Article ; Online: Early diarrhoea under sorafenib as a marker to consider the early migration to second-line drugs.

Díaz-González, Álvaro / Sapena, Víctor / Boix, Loreto / Torres, Ferrán / Sanduzzi-Zamparelli, Marco / Da Fonseca, Leonardo G / LLarch, Neus / Iserte, Gemma / Guedes, Cassia / Muñoz-Martínez, Sergio / Darnell, Anna / Belmonte, Ernest / Rimola, Jordi / Forner, Alejandro / Ayuso, Carmen / Bruix, Jordi / Reig, María

United European gastroenterology journal

2021 Volume 9, Issue 6, Page(s) 655–661

Abstract: Background: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have ... ...

Abstract	Background: Despite atezolizumab and bevacizumab (A + B) is currently the first-line treatment for hepatocellular carcinoma (HCC) patients, some patients will not be adequate for this combination. In the setting of sorafenib some adverse events have been proposed as prognostic factors. Objective: To characterize the early diarrhoea development as prognostic factor in 344 HCC patients. Methods: The development of early diarrhoea in sorafenib treatment defined as patients who developed diarrhoea and needed dose modification within the first 60 days of treatment (e-diarrhoea) and 3-grouping variables were analysed: Patients with e-diarrhoea, patients who developed diarrhoea after the first 60 days of treatment (L-diarrhoea) and patients that never developed diarrhoea (never diarrhoea). Results: The median overall survival in sorafenib treated patients was significantly different across groups (6.8 months for e-diarrhoea, 26.7 months for L-diarrhoea and 13.3 months for never-diarrhoea). The emergence of e-diarrhoea was associated with poor outcomes (hazard ratio [HR] 1.84 [95%CI 1.15-2.95]), while there was no increased/decreased risk of dismal evolution in patients with L-diarrhoea (HR 0.66 [95%CI 0.42-1.03]). Conclusion: The emergence of e-diarrhoea in HCC patients treated with sorafenib is an early predictor of dismal evolution under this therapy. Thus, prompt identification of these non-responders may be useful for an early switch to second-line therapies.
MeSH term(s)	Aged ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/mortality ; Diarrhea/chemically induced ; Drug Resistance, Neoplasm ; Female ; Humans ; Liver Neoplasms/complications ; Liver Neoplasms/drug therapy ; Liver Neoplasms/mortality ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Sorafenib ; Survival Rate ; Time Factors ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2021-07-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2728585-6
ISSN	2050-6414 ; 2050-6406
ISSN (online)	2050-6414
ISSN	2050-6406
DOI	10.1002/ueg2.12111
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