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1.
Eur J Clin Invest ; 45(8): 824-32, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26058473

RESUMEN

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected in patients with clinically suspicion. The aim of our study was to evaluate whether CRBSIs could be anticipated and detected in a subclinical stage by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) using universal hybridization probes or acridine orange leucocyte cytospin (AOLC) tests in haematooncological patients with central venous catheters (CVCs) in situ. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization and AOLC tests using blood samples from one CVC lumen/port chamber in haematooncological patients were continuously performed. These results were compared to those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred and eighty-two patients with 342 catheter periods were investigated. Seventeen CRBSI cases were detected in 6466 CVC days by routine measures resulting in a CRBSI rate of 2.6/1000 catheter days. Two of 17 showed positive PNA FISH tests, and five positive AOLC test results before the diagnosis were established with routine measures. The screening revealed further seven patients with positive universal PNA FISH tests and 10 positive AOLC tests without symptoms indicative for infection and were therefore considered not to have CRBSI. CONCLUSIONS: Sampling of only one CVC lumen/port chamber screening for CRBSI in haematooncological patients seems not to be a useful tool for anticipative diagnosis of CRBSI. Reasons for false-negative results might include origin of CRBSIs from the other CVC lumina not sampled for screening, and false-positive results might origin from catheter colonization without subsequent spread of micro-organisms into the peripheral bloodstream.


Asunto(s)
Bacteriemia/diagnóstico , Infecciones Relacionadas con Catéteres/diagnóstico , Catéteres Venosos Centrales , Fungemia/diagnóstico , Neoplasias Hematológicas/complicaciones , Naranja de Acridina , Adulto , Anciano , Bacteriemia/complicaciones , Candidiasis/complicaciones , Candidiasis/diagnóstico , Infecciones Relacionadas con Catéteres/complicaciones , Estudios de Cohortes , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/diagnóstico , Reacciones Falso Negativas , Femenino , Colorantes Fluorescentes , Fungemia/complicaciones , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Grampositivas/complicaciones , Infecciones por Bacterias Grampositivas/diagnóstico , Humanos , Hibridación Fluorescente in Situ , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico , Masculino , Persona de Mediana Edad , Ácidos Nucleicos de Péptidos , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/diagnóstico , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/diagnóstico , Stenotrophomonas maltophilia
2.
Eur J Clin Invest ; 43(9): 964-9, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23848936

RESUMEN

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected with a reactive diagnostic policy, that is, application of tests to patients with clinically suspected CRBSI. The aim of our study was to evaluate whether CRBSIs could be anticipated in an earlier stage by microbiological screening using peptide nucleic acid fluorescence in situ hybridization (PNA FISH) with universal hybridization probes or acridine-orange leucocyte cytospin (AOLC) tests in haemodialysis and haematological patients with CVCs in situ compared with routine test. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization (PNA FISH) and AOLC tests using blood samples from both CVC lines in patients undergoing haemodialysis were performed three times a week and from one CVC line in haematological patients were performed daily. Results were compared with those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred fifteen patients with 139 catheter periods were investigated. The mean observation time per catheter period was 25 days (IQR 13.5-43.5), resulting in 5615 CVC days with a total of 4839 tested blood samples. Five CRBSI cases were detected by routine measures resulting in a CRBSI rate of 0.9/1000 catheter days. Four of five CRBSIs could be anticipated by positive PNA FISH and AOLC tests 2-8 days before the diagnosis was established with routine measures. CONCLUSIONS: The proactive anticipative strategy using microscopic examination of CVC blood samples to anticipate CRBSI in an earlier stage compared with routine measures is a new diagnostic approach in patients with CVCs and a high risk of developing CRBSI.


Asunto(s)
Infecciones Relacionadas con Catéteres/diagnóstico , Catéteres Venosos Centrales , Naranja de Acridina , Adulto , Anciano , Diagnóstico Precoz , Colorantes Fluorescentes , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Humanos , Hibridación Fluorescente in Situ/métodos , Técnicas Microbiológicas , Persona de Mediana Edad , Ácidos Nucleicos de Péptidos/metabolismo , Estudios Prospectivos , Diálisis Renal , Adulto Joven
3.
J Med Genet ; 49(7): 422-8, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22652532

RESUMEN

BACKGROUND: Therapy related myeloid neoplasms (t-MNs) are complex diseases originating from an interplay between exogenous toxicities and a susceptible organism. It has been hypothesised that in a subset of cases t-MNs develop in the context of hereditary cancer predisposition syndromes. METHODS: The study systematically evaluated pedigrees of patients with t-MNs for cancer incidences and the possibility of a hereditary cancer predisposition syndrome. In addition, mutational analyses were performed using constitutional DNA from index patients, and deleterious heterozygous germline mutations were assessed for loss of heterozygosity in sorted leukaemic cells by single nucleotide polymorphism array. RESULTS: A nuclear pedigree was obtained in 51/53 patients with t-MNs resulting in a total of 828 individuals analysed. With a standardised incidence ratio of 1.03 (95% CI 0.74 to 1.39), the tumour incidence of first- degree relatives was not increased. However, six pedigrees were suggestive for a hereditary breast and ovarian cancer syndrome, three of a Li-Fraumeni like syndrome, and three index patients showed multiple primary neoplasms. Mutational analysis revealed two BRCA1 (c.3112G→T, c.5251C→T), one BRCA2 (c.4027A→G), two BARD1 (C557S) and four TP53 germline mutations (g.18508_18761delinsGCC, c.847C→T, c.845_848dupGGCG, c.1146delA) in nine of 53 (17%) index patients with t-MNs. Loss of heterozygosity in leukaemic cells was demonstrated for the BRCA1c.3112G→T and TP53c.845_848dupGGCG mutations, respectively. CONCLUSION: It is concluded that a proportion of patients with t-MNs carry cancer susceptibility mutations which are likely to contribute to therapy related leukaemogenesis.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación de Línea Germinal , Neoplasias Primarias Secundarias/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Niño , Preescolar , Daño del ADN , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Síndrome de Cáncer de Mama y Ovario Hereditario/patología , Síndrome de Cáncer de Mama y Ovario Hereditario/terapia , Heterocigoto , Humanos , Inmunohistoquímica , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/terapia , Linaje , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Adulto Joven
4.
J Antimicrob Chemother ; 67(8): 2029-33, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22566591

RESUMEN

OBJECTIVES: Fulfilment of host factors defined by the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria is required for establishing the diagnosis of possible or probable invasive fungal infection (IFI). This case-control study evaluates EORTC/MSG host factors among patients with haematological malignancies. METHODS: Fifty-eight patients with haematological malignancies who developed probable (n = 38) or proven (n = 20) IFI over a 5 year period were retrospectively evaluated regarding EORTC/MSG host factors. Results were compared with those obtained from patients with haematological malignancies who did not develop IFI (116 patients who received systemic antifungal prophylaxis or empirical therapy and 116 patients who did not; all data collected in 2010). RESULTS: Fourteen patients had invasive yeast infection and 44 patients had invasive mould infection (IMI). Prolonged neutropenia (35/58, 60% versus 29/116, 25%), prolonged systemic corticosteroid (cut-off 21 days: 13/58, 22% versus 6/116, 5%; cut-off 14 days: 18/58, 31% versus 9/116, 8%) and T cell suppressive therapy (35/44, 80% versus 69/116, 59%) were significantly associated with development of IFI/IMI in our cohort. Previous allogeneic stem cell transplantation (SCT; >6 months prior to episode) was not significantly associated with development of IMI (8/44, 18% versus 22/116, 19%), while recent SCT (<6 months prior to episode) was (11/44, 25% versus 12/116, 10%). CONCLUSIONS: We conclude that host factors according to revised EORTC/MSG criteria were significantly associated with the development of IFI/IMI in our patients. Previous allogeneic SCT was not a predisposing host factor for the development of IMI. Concerning prolonged corticosteroid treatment, a cut-off of 14 days seems preferable to the proposed cut-off.


Asunto(s)
Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Micosis/tratamiento farmacológico , Micosis/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/administración & dosificación , Quimioprevención/métodos , Europa (Continente) , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
5.
Leuk Lymphoma ; 55(8): 1739-42, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24138308

RESUMEN

Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/secundario , Citarabina/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Citarabina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Espinales , Liposomas , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Resultado del Tratamiento , Adulto Joven
6.
Blood Rev ; 26(1): 33-42, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21996651

RESUMEN

Although blood donation is generally safe, a variety of risks and complications exist, the most common being iron deficiency, vasovagal reactions and citrate-related events. In the last decades, extensive efforts have significantly improved recipient and product safety, but there is still great potential to optimise donor care. Many therapies in modern medicine depend on the prompt availability of blood products, therefore it is crucial to maintain a motivated and healthy donor pool in view of a limited number of healthy volunteers willing and able to give blood or blood components. We present a comprehensive review on adverse events addressing all types of blood donation including whole blood, plasma, platelet, peripheral blood stem cell, leucocyte and bone marrow donation. In addition, we outline strategies for the prevention and treatment of these events and give a blueprint for future research in this field.


Asunto(s)
Donantes de Sangre , Recolección de Muestras de Sangre/efectos adversos , Adolescente , Adulto , Femenino , Humanos , Masculino , Seguridad , Adulto Joven
7.
Int J Antimicrob Agents ; 39(6): 510-3, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22481057

RESUMEN

Posaconazole (PCZ) is a triazole antifungal agent that has broad activity against pathogenic fungi and is increasingly used for prophylaxis and treatment of invasive mould infections (IMIs). PCZ is only available as an oral formulation, with varying absorption from the gastrointestinal tract. However, reports correlating PCZ plasma concentrations (PPCs) with breakthrough IMIs are rare. In this study, PPCs were analysed in a prospective, observational, single-centre study and the correlation of PPCs with breakthrough IMIs in patients with haematological malignancies was evaluated. Risk factors associated with low PPCs were further evaluated. A total of 109 PPCs were measured in 34 cases receiving PCZ prophylaxis (n=31) or treatment (n=3). Levels below the target of 0.5 µg/mL were detected in 24 (71%) of the 34 cases; in 15 (63%) of these 24 cases concentrations were found to be <0.20 µg/mL. Three patients receiving PCZ prophylaxis met the criteria of breakthrough infection. Notably, prior to development of IMI, PPCs were below the target in all three individuals. Associated risk factors for insufficient PPCs varied from previous reports. In conclusion, these data demonstrate that therapeutic drug monitoring of PCZ is mandatory in all patients with haematological malignancies as low PPCs are common and may be associated with development of IMIs.


Asunto(s)
Antifúngicos/sangre , Quimioprevención , Monitoreo de Drogas , Neoplasias Hematológicas/complicaciones , Micosis/prevención & control , Triazoles/sangre , Adulto , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis/sangre , Micosis/tratamiento farmacológico , Factores de Riesgo , Triazoles/farmacocinética , Triazoles/uso terapéutico , Adulto Joven
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