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Article ; Online: Clinical pharmacist interventions in an intensive care unit reduces ICU mortality at a tertiary hospital in Dubai, United Arab Emirates.

Ali Hussain Alsayed, Hawra / Saheb Sharif-Askari, Fatemeh / Saheb Sharif-Askari, Narjes / Halwani, Rabih

Exploratory research in clinical and social pharmacy

2024 Volume 14, Page(s) 100431

Abstract: Background: Drug-related problems (DRPs) are prevalent in critical care settings and can be life-threatening. Involving clinical pharmacists (CP) within the critical care team is recommended to optimize therapy and improve patient survival.: Objective! ...

Abstract	Background: Drug-related problems (DRPs) are prevalent in critical care settings and can be life-threatening. Involving clinical pharmacists (CP) within the critical care team is recommended to optimize therapy and improve patient survival. Objective: To classify DRPs identified by a CP in the Intensive Care Unit (ICU) and to assess the impact of CP interventions accepted by physicians on the length of ICU stay and in-hospital survival. Methods: This study was conducted prospectively at the Medical ICU of Rashid Hospital, a tertiary hospital in Dubai, over a 16-month period from September 2021 to December 2022. The study included patients admitted to ICU during the study period. CP interventions were documented, and DRPs were classified using the modified Pharmaceutical Care Network Europe V.9.1. Results: During the study period, 1004 interventions were recommended for 200 patients. The majority of these interventions, 92% ( Conclusion: The study emphasizes the critical role of CP in the ICU, addressing DRPs, and enhancing overall patient care. Furthermore, it highlights the potential impact of pharmacist interventions in improving patient survival outcomes. This underscores the importance of implementing CP services in ICUs across the UAE.
Language	English
Publishing date	2024-03-09
Publishing country	United States
Document type	Journal Article
ISSN	2667-2766
ISSN (online)	2667-2766
DOI	10.1016/j.rcsop.2024.100431
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Article ; Online: Hemizygous BTK Gene Variant Causing X-Linked Agammaglobulinemia in Two Siblings.

Saheb Sharif-Askari, Narjes / Hafezi, Shirin / Saheb Sharif-Askari, Fatemeh / Frommenwiler, Naomi / Halwani, Rabih

Journal of clinical immunology

2023 Volume 43, Issue 7, Page(s) 1533–1536

MeSH term(s)	Humans ; Siblings ; Protein-Tyrosine Kinases/genetics ; Agammaglobulinaemia Tyrosine Kinase/genetics ; Agammaglobulinemia/diagnosis ; Agammaglobulinemia/genetics ; Genetic Diseases, X-Linked/diagnosis ; Genetic Diseases, X-Linked/genetics ; Mutation/genetics
Chemical Substances	Protein-Tyrosine Kinases (EC 2.7.10.1) ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
Language	English
Publishing date	2023-06-21
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-023-01534-3
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Article: Unraveling the gut-Lung axis: Exploring complex mechanisms in disease interplay.

Eladham, Mariam Wed / Selvakumar, Balachandar / Saheb Sharif-Askari, Narjes / Saheb Sharif-Askari, Fatemeh / Ibrahim, Saleh Mohamed / Halwani, Rabih

Heliyon

2024 Volume 10, Issue 1, Page(s) e24032

Abstract: The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung ... ...

Abstract	The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung diseases via multifaceted mechanisms. Advancements in omics and metagenomics technologies revealed a potential link between gut and lung microbiota, adding further complexity to GLA. Despite substantial studies on GLA in various disease models, mechanisms beyond microbial dysbiosis regulating the interplay between gut and lung tissues during disease conditions are not thoroughly reviewed. This review outlines disease specific GLA mechanisms, emphasizing research gaps with a focus on gut-to-lung direction based on current GLA literature. Moreover, the review discusses potential gut microbiota and their products like metabolites, immune modulators, and non-bacterial contributions as a basis for developing treatment strategies for lung diseases. Advanced experimental methods, modern diagnostic tools, and technological advancements are also highlighted as crucial areas for improvement in developing novel therapeutic approaches for GLA-related diseases. In conclusion, this review underscores the importance of exploring additional mechanisms within the GLA to gain a deeper understanding that could aid in preventing and treating a wide spectrum of lung diseases.
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e24032
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Article ; Online: Risk factors and early preventive measures for long COVID in non-hospitalized patients: analysis of a large cohort in the United Arab Emirates.

Saheb Sharif-Askari, Fatemeh / Ali Hussain Alsayed, Hawra / Saheb Sharif-Askari, Narjes / Saddik, Basema / Al Sayed Hussain, Ali / Halwani, Rabih

Public health

2024 Volume 230, Page(s) 198–206

Abstract: Objectives: Long COVID is characterized by persistent symptoms lasting for 4 weeks or more following the acute infection with SARS-CoV-2. Risk factors for long COVID and the impact of pre-COVID vaccination and treatment during acute COVID-19 remain ... ...

Abstract	Objectives: Long COVID is characterized by persistent symptoms lasting for 4 weeks or more following the acute infection with SARS-CoV-2. Risk factors for long COVID and the impact of pre-COVID vaccination and treatment during acute COVID-19 remain uncertain. This study aimed to investigate patient-specific factors associated with long COVID in a large cohort of non-hospitalized adult patients with mild to moderate COVID-19 in Dubai. Study design: Cohort study. Methods: The study included 28,375 non-hospitalized adult patients diagnosed with mild to moderate COVID-19 between January 1, 2021, and September 31, 2022, in Dubai, who were followed up for 90 days. The presence of long COVID symptoms was documented by physicians during patient visits to the family medicine department. Furthermore, long COVID-related risk factors were collected and analyzed, including patient demographics, comorbidities, pre-COVID vaccination status, and the COVID-related treatments received during the acute phase of the illness. Cox proportional hazard models were applied for the statistical analysis. Results: Among the cohort, 2.8% of patients experienced long COVID symptoms during the 90-day follow-up. Patients with long COVID tended to be younger, female, and of Caucasian race. Common symptoms included fatigue, muscle pain, respiratory symptoms, abdominal and neurological symptoms, allergic reactions, skin rashes, and hair loss. Risk factors for long COVID were identified as diabetes mellitus, asthma, and Vitamin D deficiency. Females and Caucasians had a higher risk of long COVID during the pre-Omicron period compared to the Omicron period. Pre-COVID vaccination was associated with a reduced risk of long COVID in all patient subgroups. Treatment with favipiravir or sotrovimab during the acute phase of COVID-19 was linked to a decreased risk of long COVID, although favipiravir showed limited effectiveness in the high-risk group. Conclusion: This study contributes to the existing knowledge by identifying risk factors for long COVID among non-hospitalized patients and emphasizing the potential benefits of pre-COVID vaccination and timely treatment.
MeSH term(s)	Adult ; Humans ; Female ; Post-Acute COVID-19 Syndrome ; COVID-19/epidemiology ; COVID-19/prevention & control ; United Arab Emirates/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Risk Factors ; Amides ; Pyrazines
Chemical Substances	favipiravir (EW5GL2X7E0) ; Amides ; Pyrazines
Language	English
Publishing date	2024-04-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	427333-3
ISSN	1476-5616 ; 0033-3506
ISSN (online)	1476-5616
ISSN	0033-3506
DOI	10.1016/j.puhe.2024.02.031
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Article ; Online: Role of inflammasome in severe, steroid-resistant asthma.

Khalil, Bariaa A / Sharif-Askari, Narjes Saheb / Halwani, Rabih

Current research in immunology

2023 Volume 4, Page(s) 100061

Abstract: Purpose of review: Asthma is a common heterogeneous group of chronic inflammatory diseases with different pathological phenotypes classified based on the various clinical, physiological and immunobiological profiles of patients. Despite similar clinical ...

Abstract	Purpose of review: Asthma is a common heterogeneous group of chronic inflammatory diseases with different pathological phenotypes classified based on the various clinical, physiological and immunobiological profiles of patients. Despite similar clinical symptoms, asthmatic patients may respond differently to treatment. Hence, asthma research is becoming more focused on deciphering the molecular and cellular pathways driving the different asthma endotypes. This review focuses on the role of inflammasome activation as one important mechanism reported in the pathogenesis of severe steroid resistant asthma (SSRA), a Th2-low asthma endotype. Although SSRA represents around 5-10% of asthmatic patients, it is responsible for the majority of asthma morbidity and more than 50% of asthma associated healthcare costs with clear unmet need. Therefore, deciphering the role of the inflammasome in SSRA pathogenesis, particularly in relation to neutrophil chemotaxis to the lungs, provides a novel target for therapy. Recent findings: The literature highlighted several activators of inflammasomes that are elevated during SSRA and result in the release of proinflammatory mediators, mainly IL-1β and IL-18, through different signaling pathways. Consequently, the expression of NLRP3 and IL-1β is shown to be positively correlated with neutrophil recruitment and negatively correlated with airflow obstruction. Furthermore, exaggerated NLRP3 inflammasome/IL-1β activation is reported to be associated with glucocorticoid resistance. Summary: In this review, we summarized the reported literature on the activators of the inflammasome during SSRA, the role of IL-1β and IL-18 in SSRA pathogenesis, and the pathways by which inflammasome activation contributes to steroid resistance. Finally, our review shed light on the different levels to target inflammasome involvement in an attempt to ameliorate the serious outcomes of SSRA.
Language	English
Publishing date	2023-06-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-2555
ISSN (online)	2590-2555
DOI	10.1016/j.crimmu.2023.100061
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Article ; Online: Unraveling the gut-Lung axis

Mariam Wed Eladham / Balachandar Selvakumar / Narjes Saheb Sharif-Askari / Fatemeh Saheb Sharif-Askari / Saleh Mohamed Ibrahim / Rabih Halwani

Heliyon, Vol 10, Iss 1, Pp e24032- (2024)

Exploring complex mechanisms in disease interplay

2024

Abstract	The link between gut and lung starts as early as during organogenesis. Even though they are anatomically distinct, essential bidirectional crosstalk via complex mechanisms supports GLA. Emerging studies have demonstrated the association of gut and lung diseases via multifaceted mechanisms. Advancements in omics and metagenomics technologies revealed a potential link between gut and lung microbiota, adding further complexity to GLA. Despite substantial studies on GLA in various disease models, mechanisms beyond microbial dysbiosis regulating the interplay between gut and lung tissues during disease conditions are not thoroughly reviewed. This review outlines disease specific GLA mechanisms, emphasizing research gaps with a focus on gut-to-lung direction based on current GLA literature. Moreover, the review discusses potential gut microbiota and their products like metabolites, immune modulators, and non-bacterial contributions as a basis for developing treatment strategies for lung diseases. Advanced experimental methods, modern diagnostic tools, and technological advancements are also highlighted as crucial areas for improvement in developing novel therapeutic approaches for GLA-related diseases. In conclusion, this review underscores the importance of exploring additional mechanisms within the GLA to gain a deeper understanding that could aid in preventing and treating a wide spectrum of lung diseases.
Keywords	GLA ; Microbiota ; Gut ; Lung ; Dysbiosis ; Metabolites ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article: Multiple inborn errors of type I IFN immunity in a 33-year-old male with a fatal case of COVID-19.

Saheb Sharif-Askari, Narjes / Hafezi, Shirin / Saheb Sharif-Askari, Fatemeh / Ali Hussain Alsayed, Hawra / B M Ahmed, Samrein / Alsafar, Habiba S / Halwani, Rabih

Heliyon

2024 Volume 10, Issue 8, Page(s) e29338

Abstract: The host genetic inborn errors of immunity (IEIs) have been shown to contribute to susceptibility to life-threatening coronavirus disease 2019 (COVID-19), as it had been associated previously with other viral infections. Most genetic association studies ... ...

Abstract	The host genetic inborn errors of immunity (IEIs) have been shown to contribute to susceptibility to life-threatening coronavirus disease 2019 (COVID-19), as it had been associated previously with other viral infections. Most genetic association studies have described IEIs as a monogenic defect, while there have been no reports of patients with multiple inherited immune deficiencies. This is a complex case of IEIs predisposing to severe viral infections in an unvaccinated 33-year-old male patient. The patient was admitted with no respiratory symptoms, showed a SARS-CoV-2 PCR positive test on the second day of admission, started developing progressive lung consolidation within three days of hospitalization, and was moved from non-invasive to mechanical ventilation within 12 days of hospitalization. Impaired production of type I IFN was detected in patient PBMCs treated with poly(I:C), at both mRNA and protein levels. Whole exome sequencing revealed three mutations across type I IFN production pathway, which were predicted to be loss-of-function (pLOF). The three mutations were predicted to predispose to severe viral infections: monoallelic R488X TLR3, monoallelic His684Arg TLR3, and biallelic Val363Met IRF3. Functional analysis confirmed that all these mutations dysregulated the type I IFN pathway. Evaluation of TLR3 and IRF3 IFN-β1 luciferase reporter activity showed a hypomorphic suppression of function. TOPO TA cloning was used to ascertain the positioning of both TLR3 variants, indicating that both variants were on the same allele. We have described a unique complex IEI patient with multiple mutations, particularly along type I IFN production pathway.
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e29338
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Article ; Online: Salivary autoantibodies to type I IFNs: Mirror plasma levels, predispose to severe COVID-19, and enhance feasibility for clinical screening.

Saheb Sharif-Askari, Narjes / Saheb Sharif-Askari, Fatemeh / Bayram, Ola Salam / Hafezi, Shirin / Alsayed, Hawra Ali Hussain / Kasim, Fathima / Mdkhana, Bushra / Selvakumar, Balachandar / Alsafar, Habiba S / Halwani, Rabih

Heart & lung : the journal of critical care

2024 Volume 66, Page(s) 31–36

Abstract: Background: Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections.!## ...

Abstract	Background: Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections. Objectives: This study aimed to evaluate the prevalence of type I IFN aAbs in both plasma and saliva from COVID-19 patients, analyze their neutralizing activity, and examine their associations with clinical outcomes, including the need for mechanical ventilation and in-hospital mortality. Methods: Prospective analyses of patients admitted to intensive care units in three UAE hospitals from June 2020 to March 2021 were performed to measure aAbs using enzyme-linked immunosorbent assay (ELISA), assess aAbs activity via neutralization assays, and correlate aAbs with clinical outcomes. Results: Type I IFN aAbs (α2 and/or ω) were measured in plasma samples from 213 ICU patients, and positive results were obtained for 20 % (n = 42) of the patients, with half exhibiting neutralizing activity. Saliva samples from a subgroup of 24 patients reflected plasma levels. In multivariate regression analyses, presence of type I IFN aAbs was associated with a higher need for mechanical ventilation (OR 2.58; 95 % CI 1.07-6.22) and greater in-hospital mortality (OR 2.40; 95 % CI 1.13 - 5.07; P = 0.022). Similarly, positive neutralizing aAbs (naAbs) were associated with a greater need for mechanical ventilation (OR 4.96; 95 % CI 1.12-22.07; P = 0.035) and greater odds of in-hospital mortality (OR 2.87; 95 % CI 1.05-7.89; P = 0.041). Conclusions: Type I IFN autoantibodies can be detected in noninvasive saliva samples, alongside conventional plasma samples, from COVID-19 patients and are associated with worse outcomes, such as greater mechanical ventilation needs and in-hospital mortality.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	193129-5
ISSN	1527-3288 ; 0147-9563
ISSN (online)	1527-3288
ISSN	0147-9563
DOI	10.1016/j.hrtlng.2024.03.005
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Article ; Online: Investigating the Association between Diabetic Neuropathy and Vitamin D in Emirati Patients with Type 2 Diabetes Mellitus.

Al Ali, Tahra / Ashfaq, Alizeh / Saheb Sharif-Askari, Narjes / Abusnana, Salah / Mussa, Bashair M

Cells

2023 Volume 12, Issue 1

Abstract: 1) Background: Vitamin D deficiency is a common public health problem in the United Arab Emirates (UAE) and globally, and interestingly, improvements in diabetic neuropathy after taking Vitamin D supplementation for a short time have been reported. ... ...

Abstract	(1) Background: Vitamin D deficiency is a common public health problem in the United Arab Emirates (UAE) and globally, and interestingly, improvements in diabetic neuropathy after taking Vitamin D supplementation for a short time have been reported. Despite living in a country that is sunny all year round, hypovitaminosis D, indicated by an obvious low serum vitamin D level, has been recurrently noted in the UAE, as well as in the surrounding Arabian Gulf countries. This problem is receiving much attention and attracting clinical and academic interest. Therefore, the main objective of the present study is to identify the association, if any, between vitamin D deficiency and the development of diabetic neuropathy in the UAE population with T2DM. (2) Methods: a total of 600 Emirati patients (male and female) with T2DM, aged between 20 and 80, were recruited from University Hospital Sharjah (UHS). The medical records of the patients were reviewed and analyzed. (3) Results: The results of the present study showed that among the 600 patients, 50% were affected with diabetic neuropathy. Vitamin D level in patients with neuropathy were estimated to be around 20 ng/mL (IQR 14-25), and vitamin D levels were significantly higher (33 ng/mL (IQR 20-42)) among patients without neuropathy, with
MeSH term(s)	Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Neuropathies/drug therapy ; United Arab Emirates/epidemiology ; Vitamin D ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/drug therapy ; Vitamins
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins
Language	English
Publishing date	2023-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12010198
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Article ; Online: Increased blood immune regulatory cells in severe COVID-19 with autoantibodies to type I interferons.

Saheb Sharif-Askari, Fatemeh / Saheb Sharif-Askari, Narjes / Hafezi, Shirin / Alsayed, Hawra Ali Hussain / Selvakumar, Balachandar / Eladham, Mariam Wed Abdelaziz / Mdkhana, Bushra / Bayram, Ola Salam / Temsah, Mohamad-Hani / Halwani, Rabih

Scientific reports

2023 Volume 13, Issue 1, Page(s) 17344

Abstract: The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of ... ...

Abstract	The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. While regulatory T (Treg) and B (Breg) cells, as the main elements of immune homeostasis, contribute to the control of hyperinflammation during COVID-19 infection, we hypothesized change in their levels in relation to disease severity and the presence of autoantibodies (auto-Abs) to type I IFNs. Cytometric analysis of blood of 62 COVID-19 patients with different severities revealed an increased proportion of conventional (cTreg; CD25
MeSH term(s)	Humans ; Interleukin-10 ; T-Lymphocytes, Regulatory ; Autoantibodies ; COVID-19 ; Cytokines ; B-Lymphocytes, Regulatory ; Forkhead Transcription Factors
Chemical Substances	Interleukin-10 (130068-27-8) ; Autoantibodies ; Cytokines ; Forkhead Transcription Factors
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-43675-w
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