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Article ; Online: Letermovir use may impact on the Cytomegalovirus DNA fragmentation profile in plasma from allogeneic hematopoietic stem cell transplant recipients.

Giménez, Estela / Gozalbo-Rovira, Roberto / Albert, Eliseo / Piñana, José Luis / Solano, Carlos / Navarro, David

2024 Volume 96, Issue 3, Page(s) e29564

Abstract: Cytomegalovirus (CMV) DNA in plasma is mainly unprotected and highly fragmented. The size of the amplicon largely explains the variation in CMV DNA loads quantified across PCR platforms. In this proof-of-concept study, we assessed whether the CMV DNA ... ...

Abstract	Cytomegalovirus (CMV) DNA in plasma is mainly unprotected and highly fragmented. The size of the amplicon largely explains the variation in CMV DNA loads quantified across PCR platforms. In this proof-of-concept study, we assessed whether the CMV DNA fragmentation profile may vary across allogeneic hematopoietic stem cell transplant recipients (allo-SCT), within the same patient over time, or is affected by letermovir (LMV) use. A total of 52 plasma specimens from 14 nonconsecutive allo-SCT recipients were included. The RealTime CMV PCR (Abbott Molecular), was used to monitor CMV DNA load in plasma, and fragmentation was assessed with a laboratory-designed PCR generating overlapping amplicons (around 90-110 bp) within the CMV UL34, UL80.5, and UL54 genes. Intrapatient, inter-patient, and LMV-associated qualitative and quantitative variations in seven amplicons were observed. These variations were seemingly unrelated to the CMV DNA loads measured by the Abbott PCR assay. CMV DNA loads quantified by UL34_4, UL54.5, and UL80.5_1 PCR assays discriminate between LMV and non-LMV patients. Our observations may have relevant implications in the management of active CMV infection in allo-SCT recipients, either treated or not with LMV, although the data need further validation.
MeSH term(s)	Humans ; Cytomegalovirus/genetics ; DNA Fragmentation ; Hematopoietic Stem Cell Transplantation/adverse effects ; Cytomegalovirus Infections/drug therapy ; Transplant Recipients ; DNA, Viral ; Antiviral Agents/therapeutic use ; Viral Proteins/genetics ; Acetates ; Quinazolines
Chemical Substances	letermovir (1H09Y5WO1F) ; DNA, Viral ; Antiviral Agents ; UL34 protein, Human herpesvirus 1 ; Viral Proteins ; Acetates ; Quinazolines
Language	English
Publishing date	2024-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29564
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Article ; Online: Torque Teno Virus DNA Load in Blood as an Immune Status Biomarker in Adult Hematological Patients: The State of the Art and Future Prospects.

Albert, Eliseo / Giménez, Estela / Hernani, Rafael / Piñana, José Luis / Solano, Carlos / Navarro, David

Viruses

2024 Volume 16, Issue 3

Abstract: A solid body of scientific evidence supports the assumption that Torque teno virus (TTV) DNA load in the blood compartment may behave as a biomarker of immunosuppression in solid organ transplant recipients; in this clinical setting, high or increasing ... ...

Abstract	A solid body of scientific evidence supports the assumption that Torque teno virus (TTV) DNA load in the blood compartment may behave as a biomarker of immunosuppression in solid organ transplant recipients; in this clinical setting, high or increasing TTV DNA levels precede the occurrence of infectious complications, whereas the opposite anticipates the development of acute rejection. The potential clinical value of the TTV DNA load in blood to infer the risk of opportunistic viral infection or immune-related (i.e., graft vs. host disease) clinical events in the hematological patient, if any, remains to be determined. In fact, contradictory data have been published on this matter in the allo-SCT setting. Studies addressing this topic, which we review and discuss herein, are highly heterogeneous as regards design, patient characteristics, time points selected for TTV DNA load monitoring, and PCR assays used for TTV DNA quantification. Moreover, clinical outcomes are often poorly defined. Prospective, ideally multicenter, and sufficiently powered studies with well-defined clinical outcomes are warranted to elucidate whether TTV DNA load monitoring in blood may be of any clinical value in the management of hematological patients.
MeSH term(s)	Adult ; Humans ; Torque teno virus/genetics ; Prospective Studies ; DNA, Viral ; Immunosuppression Therapy ; Biomarkers ; Viral Load ; DNA Virus Infections ; Multicenter Studies as Topic
Chemical Substances	DNA, Viral ; Biomarkers
Language	English
Publishing date	2024-03-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030459
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Article ; Online: SARS-CoV-2 Immunity in Hematopoietic Stem Cell Transplant and Cell Therapy Recipients

José Luis Piñana / Manuel Guerreiro / Carlos Solano

Hemato, Vol 4, Iss 14, Pp 170-

What Do We Know, and What Remains to Be Determined?

2023 Volume 183

Abstract: Hematopoietic stem cell transplantation (HSCT) results in profound immunosuppression for the first few months after the procedure, requiring patients to be revaccinated against childhood vaccine-preventable infectious diseases. Patients who undergo allo- ... ...

Abstract	Hematopoietic stem cell transplantation (HSCT) results in profound immunosuppression for the first few months after the procedure, requiring patients to be revaccinated against childhood vaccine-preventable infectious diseases. Patients who undergo allo-HSCT are at high risk of bacterial, fungal, and viral infections, with infectious complications responsible for at least one third of deaths. Even before the COVID-19 pandemic, respiratory virus infections were known to be more severe in HSCT recipients. The pandemic has highlighted the vulnerability of HSCT recipients, who experience an increased risk of morbidity and mortality after COVID-19 compared with healthy populations due to their severe immunodeficiency status. However, the current pandemic has also provided an exceptional scenario to better understand the immune response to SARS-CoV-2 cases and mRNA vaccines in HSCT recipients, including those receiving CD19-directed chimeric antigen receptor T cell (CAR-T) therapy. Researchers have focused on the role of the immune system in protecting against severe SARS-CoV-2 in patients with hematologic malignancies, including HSCT recipients. Insights gained during the pandemic will likely soon be used to improve preventive strategies in this population against viral infections in the near future. This narrative review summarizes the current knowledge on SARS-CoV-2 immunity in HSCT and cell therapy recipients following SARS-CoV-2 cases or vaccination.
Keywords	mRNA vaccine ; SARS-CoV-2 vaccines ; allogeneic stem cell transplantation ; autologous stem cell transplantation ; CAR-T cell ; COVID-19 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: A machine learning approach to identify groups of patients with hematological malignant disorders.

Rodríguez-Belenguer, Pablo / Piñana, José Luis / Sánchez-Montañés, Manuel / Soria-Olivas, Emilio / Martínez-Sober, Marcelino / Serrano-López, Antonio J

Computer methods and programs in biomedicine

2024 Volume 246, Page(s) 108011

Abstract: Background and objective: Vaccination against SARS-CoV-2 in immunocompromised patients with hematologic malignancies (HM) is crucial to reduce the severity of COVID-19. Despite vaccination efforts, over a third of HM patients remain unresponsive, ... ...

Abstract	Background and objective: Vaccination against SARS-CoV-2 in immunocompromised patients with hematologic malignancies (HM) is crucial to reduce the severity of COVID-19. Despite vaccination efforts, over a third of HM patients remain unresponsive, increasing their risk of severe breakthrough infections. This study aims to leverage machine learning's adaptability to COVID-19 dynamics, efficiently selecting patient-specific features to enhance predictions and improve healthcare strategies. Highlighting the complex COVID-hematology connection, the focus is on interpretable machine learning to provide valuable insights to clinicians and biologists. Methods: The study evaluated a dataset with 1166 patients with hematological diseases. The output was the achievement or non-achievement of a serological response after full COVID-19 vaccination. Various machine learning methods were applied, with the best model selected based on metrics such as the Area Under the Curve (AUC), Sensitivity, Specificity, and Matthew Correlation Coefficient (MCC). Individual SHAP values were obtained for the best model, and Principal Component Analysis (PCA) was applied to these values. The patient profiles were then analyzed within identified clusters. Results: Support vector machine (SVM) emerged as the best-performing model. PCA applied to SVM-derived SHAP values resulted in four perfectly separated clusters. These clusters are characterized by the proportion of patients that generate antibodies (PPGA). Cluster 1, with the second-highest PPGA (69.91%), included patients with aggressive diseases and factors contributing to increased immunodeficiency. Cluster 2 had the lowest PPGA (33.3%), but the small sample size limited conclusive findings. Cluster 3, representing the majority of the population, exhibited a high rate of antibody generation (84.39%) and a better prognosis compared to cluster 1. Cluster 4, with a PPGA of 66.33%, included patients with B-cell non-Hodgkin's lymphoma on corticosteroid therapy. Conclusions: The methodology successfully identified four separate patient clusters using Machine Learning and Explainable AI (XAI). We then analyzed each cluster based on the percentage of HM patients who generated antibodies after COVID-19 vaccination. The study suggests the methodology's potential applicability to other diseases, highlighting the importance of interpretable ML in healthcare research and decision-making.
MeSH term(s)	Humans ; COVID-19 Vaccines ; Hematologic Diseases ; Area Under Curve ; COVID-19 ; Machine Learning
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2024-01-09
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632564-6
ISSN	1872-7565 ; 0169-2607
ISSN (online)	1872-7565
ISSN	0169-2607
DOI	10.1016/j.cmpb.2024.108011
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Article ; Online: Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

Pérez, Ariadna / Montoro, Juan / Chorão, Pedro / Gómez, Dolores / Guerreiro, Manuel / Giménez, Estela / Villalba, Marta / Sanz, Jaime / Hernani, Rafael / Hernández-Boluda, Juan Carlos / Lorenzo, Ignacio / Navarro, David / Solano, Carlos / Ljungman, Per / Piñana, José Luis

Infection

2024

Abstract: Background: This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess ... ...

Abstract	Background: This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. Patients and methods: The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). Results: Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 10 Conclusion: ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.
Language	English
Publishing date	2024-04-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	185104-4
ISSN	1439-0973 ; 0300-8126 ; 0173-2129
ISSN (online)	1439-0973
ISSN	0300-8126 ; 0173-2129
DOI	10.1007/s15010-024-02213-0
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Zs.A 881: 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: Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir.

Giménez, Estela / Guerreiro, Manuel / Torres, Ignacio / Aguilar, Cristobal / Albert, Eliseo / Hernández-Boluda, Juan Carlos / Hernani, Rafael / Pérez, Ariadna / Amat, Paula / Piñana, José Luis / Montoro, Juan / Solano, Carlos / Navarro, David

Transplant infectious disease : an official journal of the Transplantation Society

2023 Volume 25, Issue 2, Page(s) e14021

Abstract: Background: There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis.: ...

Abstract	Background: There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis. Methods: Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of ≥1500 IU/ml. CMV-specific interferon-gamma (IFN-γ)-producing CD8 Results: Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4 Conclusions: In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.
MeSH term(s)	Adult ; Male ; Female ; Humans ; Middle Aged ; Cytomegalovirus ; Cytomegalovirus Infections/drug therapy ; CD8-Positive T-Lymphocytes ; Transplant Recipients ; Hematopoietic Stem Cell Transplantation/adverse effects ; Transplantation, Homologous/adverse effects ; Antiviral Agents/therapeutic use
Chemical Substances	letermovir (1H09Y5WO1F) ; Antiviral Agents
Language	English
Publishing date	2023-02-07
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1476094-0
ISSN	1399-3062 ; 1398-2273
ISSN (online)	1399-3062
ISSN	1398-2273
DOI	10.1111/tid.14021
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Article ; Online: Impact of cytomegalovirus immunodominant HLA-I donor-recipient matching on the incidence and features of virus DNAemia and virus-specific T-cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation.

Huntley, Dixie / Giménez, Estela / Vázquez, Lourdes / Pascual, María Jesús / Amat, Paula / Remigia, María José / Hernández-Boluda, Juan Carlos / García, Magdalena / Gago, Beatriz / Torres, Ignacio / de la Asunción, Carlos Solano / Hernani, Rafael / Pérez, Ariadna / Albert, Eliseo / Piñana, José Luis / Solano, Carlos / Navarro, David

Transplant infectious disease : an official journal of the Transplantation Society

2023 Volume 25, Issue 3, Page(s) e14065

Abstract: Background: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and ... ...

Abstract	Background: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo). Methods: Multicenter observational study including 106 consecutive adult PT/Cy-haplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation. Results: The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8 Conclusion: CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8
MeSH term(s)	Adult ; Humans ; Cytomegalovirus ; Incidence ; Cytomegalovirus Infections ; Immune Reconstitution ; Transplantation, Homologous ; Hematopoietic Stem Cell Transplantation/adverse effects
Language	English
Publishing date	2023-04-30
Publishing country	Denmark
Document type	Observational Study ; Multicenter Study ; Journal Article
ZDB-ID	1476094-0
ISSN	1399-3062 ; 1398-2273
ISSN (online)	1399-3062
ISSN	1398-2273
DOI	10.1111/tid.14065
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Article ; Online: Multi-body-site colonization screening cultures for predicting multi-drug resistant Gram-negative and Gram-positive bacteremia in hematological patients.

Torres, Ignacio / Huntley, Dixie / Tormo, Mar / Calabuig, Marisa / Hernández-Boluda, Juan Carlos / Terol, María José / Carretero, Carlos / de Michelena, Paula / Pérez, Ariadna / Piñana, José Luis / Colomina, Javier / Solano, Carlos / Navarro, David

BMC infectious diseases

2022 Volume 22, Issue 1, Page(s) 172

Abstract: Background: To investigate the multi-drug resistant bacteria (MDRB) colonization rate in hematological patients hospitalized for any cause using a multi-body-site surveillance approach, and determine the extent to which this screening strategy helped ... ...

Abstract	Background: To investigate the multi-drug resistant bacteria (MDRB) colonization rate in hematological patients hospitalized for any cause using a multi-body-site surveillance approach, and determine the extent to which this screening strategy helped anticipate MDRB bloodstream infections (BSI). Methods: Single-center retrospective observational study including 361 admissions documented in 250 adult patients. Surveillance cultures of nasal, pharyngeal, axillary and rectal specimens (the latter two combined) were performed at admission and subsequently on a weekly basis. Blood culture samples were incubated in an automated continuous monitoring blood culturing instrument (BACTEC FX). Results: In total, 3463 surveillance cultures were performed (pharyngeal, n = 1201; axillary-rectal, n = 1200; nasal, n = 1062). MDRB colonization was documented in 122 out of 361 (33.7%) admissions corresponding to 86 patients (34.4%). A total of 149 MDRB were isolated from one or more body sites, of which most were Gram-negative bacteria, most frequently non-fermenting (n = 83) followed by Enterobacterales (n = 51). BSI were documented in 102 admissions (28%) involving 87 patients. Overall, the rate of BSI caused by MDRB was significantly higher (p = 0.04) in the presence of colonizing MDRB (16 out of 47 admissions in 14 patients) than in its absence (9 out of 55 admissions in 9 patients). Colonization by any MDRB was independently associated with increased risk of MDRB-BSI (HR, 3.70; 95% CI, 1.38-9.90; p = 0.009). Conclusion: MDRB colonization is a frequent event in hematological patients hospitalized for any reason and is associated with an increased risk of MDRB BSI. The data lend support to the use of MDRB colonization surveillance cultures for predicting the occurrence of MDRB BSI in this cohort.
MeSH term(s)	Adult ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteremia/drug therapy ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; Humans ; Pharmaceutical Preparations ; Retrospective Studies ; Sepsis/drug therapy
Chemical Substances	Anti-Bacterial Agents ; Pharmaceutical Preparations
Language	English
Publishing date	2022-02-21
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-022-07154-3
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Article ; Online: Disseminated toxoplasma infection after hematopoietic stem cell transplantation with myositis and encephalitis.

Asensi Cantó, Pedro / Mayordomo, Empar / Dorado, Andrea / Villalba, Marta / Mañez, Rosana Blanco / González, Eva / Salavert, Miguel / Facal, Ana / Chorão, Pedro / Balaguer, Aitana / Sivera, Rafael / Montoro, Juan / Vilchez, Juan J / Piñana, José Luis / Sanz, Miguel / Sanz, Jaime / Muelas, Nuria / Guerreiro, Manuel

Transplant infectious disease : an official journal of the Transplantation Society

2023 Volume 25, Issue 4, Page(s) e14067

MeSH term(s)	Humans ; Toxoplasma ; Encephalitis/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Myositis/etiology
Language	English
Publishing date	2023-05-13
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1476094-0
ISSN	1399-3062 ; 1398-2273
ISSN (online)	1399-3062
ISSN	1398-2273
DOI	10.1111/tid.14067
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Article ; Online: Cytomegalovirus DNAemia in haematological patients undergoing CD19-directed chimeric antigen receptor T-cell therapy: should it be systematically monitored?

Solano de la Asunción, Carlos / Hernani, Rafael / Albert, Eliseo / Gómez, María Dolores / Giménez, Estela / Benzaquén, Ana / González-Barberá, Eva María / Hernández-Boluda, Juan Carlos / Pérez, Ariadna / Piñana, José Luis / Chorao, Pedro / Guerreiro, Manuel / Montoro, Juan / Sanz, Jaime / Solano, Carlos / Navarro, David

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2023 Volume 29, Issue 8, Page(s) 1093–1095

MeSH term(s)	Humans ; Cytomegalovirus/genetics ; Receptors, Chimeric Antigen ; Cytomegalovirus Infections ; Stem Cell Transplantation
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2023-05-13
Publishing country	England
Document type	Letter
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2023.05.010
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