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1.
Ann Hematol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884787

RESUMO

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

2.
Cancer Med ; 12(16): 16788-16792, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37403747

RESUMO

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.


Assuntos
Síndromes Mielodisplásicas , Fator de Processamento U2AF , Humanos , Incidência , Mutação , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/genética , Prognóstico , Fator de Processamento U2AF/genética
3.
Clin Epigenetics ; 13(1): 9, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446256

RESUMO

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Metilação de DNA , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/fisiopatologia , Medição de Risco/métodos , Espanha
4.
Blood Cancer J ; 10(7): 75, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678078

RESUMO

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.


Assuntos
Suscetibilidade a Doenças , Variação Genética , Imunidade/genética , Leucemia Mieloide Aguda/etiologia , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Suscetibilidade a Doenças/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Imunomodulação/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Esteroides/metabolismo
5.
Ann Hematol ; 99(4): 765-772, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062741

RESUMO

Bone marrow WT1 mRNA levels assessed by the ELN method are useful to establish prognostic correlations in myeloid malignancies treated with chemotherapy or hematopoietic stem cell transplantation (HCT). Those patients with WT1 levels below ten copies have a good outcome. However, some of these patients relapse. To further characterize this group of cases, we applied a new and sensitive digital (ddPCR) WT1 method. A consecutive series of 49 patients with treated myeloid malignancies and with an ELN WT1 quantitation of < 10 copies were included in the study. All cases (47 AML and 2 MDS) have received intensive chemotherapy or HCT. One to four micrograms of total RNA were retrotranscribed to obtain ≥ 10,000 ABL1 copies using the ELN protocol. Only those cases with a good quality cDNA were used in the ddPCR WT1 test. The ddPCR Gene Expression WT1 Assay of Bio-Rad© was used to perform the PCR amplification, and the microdroplets were quantified in the Bio-Rad's QX200 droplet reader. Eighteen patients showed a negative WT1 ddPCR assay (0 copies/µl), whereas 31 cases were positive (results ranged from 1 to 15.2 copies/µl). Survival analysis showed statistically significant differences in terms of OS between both groups, 83 ± 8% vs. 46 ± 9% (p = 0.024). A statistically significant correlation was also found between ddPCRWT1 results and CD123+ cell number detected by flow cytometry (p = 0.024). Larger series of patients tested with the current ddPCRWT1 method will solve whether it could be used to stratify patients with myeloid malignancies achieving deep WT1 molecular response (< 10 copies).


Assuntos
Genes do Tumor de Wilms , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Reação em Cadeia da Polimerase/métodos , Adulto , Idoso , DNA Complementar/genética , Feminino , Citometria de Fluxo , Dosagem de Genes , Humanos , Imunofenotipagem , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
6.
J Hematol Oncol ; 11(1): 96, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041662

RESUMO

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.


Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteína Supressora de Tumor p14ARF/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico
7.
Artigo em Inglês | MEDLINE | ID: mdl-26729645

RESUMO

The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.


Assuntos
Anemia/fisiopatologia , Nível de Saúde , Síndromes Mielodisplásicas/fisiopatologia , Qualidade de Vida , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Transfusão de Sangue , Estudos de Coortes , Ecocardiografia , Feminino , Seguimentos , Coração/diagnóstico por imagem , Hemoglobinas/metabolismo , Humanos , Masculino , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Estudos Prospectivos , Inquéritos e Questionários , Velocidade de Caminhada/fisiologia
8.
Blood Cancer J ; 5: e352, 2015 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-26430723

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.


Assuntos
Biomarcadores Tumorais/genética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Análise Citogenética , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Transcriptoma , Adulto Jovem
9.
PLoS One ; 10(9): e0137293, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26394150

RESUMO

BACKGROUND: To describe the lifetime and 12-month prevalence, severity and age of onset distribution of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) disorders and to explore the association between socio-demographic variables and economic stressors with mental disorders during the economic crisis in the general population of Murcia (Spain). METHODS AND FINDINGS: The PEGASUS-Murcia Project is a cross-sectional face-to-face interview survey of a representative sample of non-institutionalized adults in Murcia administered between June 2010 and May 2012. DSM-IV disorders were assessed by the Composite International Diagnostic Interview (CIDI 3.0). Main outcome measures were lifetime and 12-month prevalence of Anxiety, Mood, Impulse and Substance Disorders, Severity and Age of Onset. Sociodemographic variables and stressful economic life events during the preceding 12 months were entered as independent variables in a logistic regression analysis. A total of 2,621 participants (67.4% response rate) were interviewed, 54.5% female, mean age 48.6 years. Twelve-month prevalence (95%CI) of disorders: anxiety 9.7% (7.6-12.2), mood 6.6% (5.5-8.1), impulse 0.3% (0.1-1.2) and substance use 1.0% (0.4-2.4) disorders. Lifetime prevalence: anxiety 15.0% (12.3-18.1), mood 15.6% (13.5-18.1), impulse 2.4% (1.4-4.0) and substance use 8.3% (6.2-11.0) disorders. Severity among 12-month cases: serious 29.2% (20.8-39.4), moderate 35.6% (24.0-49.1) and mild severity 35.2% (29.5-41.5). Women were 3.7 and 2.5 times more likely than men to suffer 12-month anxiety and mood disorders, respectively. Substance use was more frequent among men. Younger age and lower income were associated with higher prevalence. Respondents exposed to multiple and recent economic stressors had the highest risk of anxiety disorders. CONCLUSIONS: Mental disorders in the adult population of Murcia during the economic crisis were more prevalent and serious than those in previous estimates for Spain. Prevalence was strongly associated with exposure to stressors related to the economic crisis.


Assuntos
Recessão Econômica , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/patologia , Estudos Transversais , Demografia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Nível de Saúde , Humanos , Entrevistas como Assunto , Masculino , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologia , Transtornos do Humor/patologia , Prevalência , Índice de Gravidade de Doença , Fatores Socioeconômicos , Espanha/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Inquéritos e Questionários , Adulto Jovem
10.
Leukemia ; 29(9): 1875-81, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25943181

RESUMO

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Masculino , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Sistema de Registros , Espanha/epidemiologia , Resultado do Tratamento
11.
Rev. esp. cardiol. (Ed. impr.) ; 68(3): 205-215, mar. 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-134067

RESUMO

Introducción y objetivos En España no existen unas cohortes poblacionales suficientemente grandes para hacer predicciones precisas del riesgo cardiovascular. Las ecuaciones de Framingham y EuroSCORE calibradas son las más utilizadas en España. El objetivo es desarrollar la primera ecuación de predicción autóctona para estimar con precisión el riesgo cardiovascular individual en España. Métodos Análisis conjunto de siete cohortes españolas de población de mediana edad y anciana. La población del estudio -11.800 personas (6.387 mujeres)- aportó un total de 107.915 personas-año de seguimiento y 1.214 eventos cardiovasculares (633 de ellos, mortales). Se efectuó un análisis de regresión de Cox para examinar la contribución de los diferentes factores al riesgo de cualquier evento cardiovascular (mortal y no mortal). Resultados La edad fue el principal factor de riesgo de eventos cardiovasculares. La presión arterial sistólica, la diabetes mellitus, el tabaquismo y el tratamiento antihipertensivo fueron factores predictivos fuertemente asociados con el riesgo cardiovascular. En cambio, la contribución del colesterol total sérico fue pequeña, especialmente en los mayores de 70 años. El modelo final de riesgo mostró un buen poder discriminatorio (estadístico C = 0,789 en varones y C = 0,816 en mujeres). Conclusiones ERICE es una nueva ecuación de riesgo cardiovascular genuinamente española obtenida a partir del riesgo concurrente individual de los participantes en varias cohortes. La ecuación ERICE ofrece una estimación directa y fiable del riesgo cardiovascular total teniendo en cuenta factores como la diabetes mellitus y el tratamiento farmacológico de los factores de riesgo cardiovascular, habitualmente no incluidos en otras ecuaciones (AU)


Introduction and objectives In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. Methods Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11 800 people (6387 women) representing 107 915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. Results Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic = 0.789 in men and C = 0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. Conclusions The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/prevenção & controle , Envelhecimento , Diabetes Mellitus/epidemiologia , Fumar/epidemiologia , Hipertensão/epidemiologia , Risco Ajustado/métodos , Fatores de Risco
12.
Rev Esp Cardiol (Engl Ed) ; 68(3): 205-15, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25155342

RESUMO

INTRODUCTION AND OBJECTIVES: In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. METHODS: Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11800 people (6387 women) representing 107915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. RESULTS: Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic=0.789 in men and C=0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. CONCLUSIONS: The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain.


Assuntos
Doenças Cardiovasculares/etnologia , Medição de Risco , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Humanos , Masculino , Região do Mediterrâneo/etnologia , Pessoa de Meia-Idade , Morbidade/tendências , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Adulto Jovem
13.
Leuk Res ; 38(10): 1199-206, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25139847

RESUMO

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Resultado do Tratamento , Adulto Jovem
14.
Leukemia ; 28(4): 804-12, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24072101

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.


Assuntos
Leucemia Mieloide Aguda/genética , MicroRNAs/análise , Adolescente , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Risco
15.
Gac. sanit. (Barc., Ed. impr.) ; 27(4): 325-331, jul.-ago. 2013. tab
Artigo em Inglês | IBECS | ID: ibc-115271

RESUMO

Objective: To develop a Spanish version of the WHO-Composite International Diagnostic Interview (WHO-CIDI) applicable to Spain, through cultural adaptation of its most recent Latin American (LA v 20.0) version. Methods: A 1-week training course on the WHO-CIDI was provided by certified trainers. An expert panel reviewed the LA version, identified words or expressions that needed to be adapted to the cultural or linguistic norms for Spain, and proposed alternative expressions that were agreed on through consensus. The entire process was supervised and approved by a member of the WHO-CIDI Editorial Committee. The changes were incorporated into a Computer Assisted Personal Interview (CAPI) format and the feasibility and administration time were pilot tested in a convenience sample of 32 volunteers. Results: A total of 372 questions were slightly modified (almost 7% of approximately 5000 questions in the survey) and incorporated into the CAPI version of the WHO-CIDI. Most of the changes were minor - but important - linguistic adaptations, and others were related to specific Spanish institutions and currency. In the pilot study, the instrument's mean completion administration time was 2h and 10min, with an interquartile range from 1.5 to nearly 3h. All the changes made were tested and officially approved. Conclusions: The Latin American version of the WHO-CIDI was successfully adapted and pilot-tested in its computerized format and is now ready for use in Spain (AU)


Objetivo: Desarrollar la versión española de la WHO-Composite International Diagnostic Interview (WHO-CIDI) para su uso en España mediante la adaptación cultural de la versión latinoamericana más reciente disponible (LA; v 20.0). Métodos: Se realizó un curso de una semana impartido por entrenadores certificados. Un panel de expertos revisó la versión latinoamericana e identificó las palabras o expresiones que requerían ser adaptadas a las normas culturales o linguísticas de España y se propusieron, por consenso, palabras o expresiones alternativas. El proceso fue supervisado y aprobado por un miembro del Comité Editorial de la WHO-CIDI. Los cambios fueron implementados en el formato informatizado CAPI (Computer Assisted Personal Interview). Un estudio piloto en una muestra de conveniencia de 32 voluntarios permitió calcular los tiempos de administración y viabilidad. Resultados: 372 preguntas fueron modificadas (alrededor de un 7% del total de 5000 preguntas del instrumento completo) e implementadas en la versión CAPI de la WHO-CIDI. La mayoría de las modificaciones fueron adaptaciones lingüísticas menores, pero importantes, y otras se relacionaron con los recursos específicos de España y adaptaciones a la moneda utilizada. En el estudio piloto, la mediana del tiempo de duración de la WHO-CIDI completa fue de 2 horas y 10 minutos, con un rango intercuartil entre 1 hora y 25 minutos y casi 3 horas. Todos los cambios implementados fueron comprobados y aprobados oficialmente. Conclusiones: La version latinoamericana de la WHO-CIDI ha sido adaptada y el formato informático ha sido pilotado con éxito, estando disponible para su utilización en España (AU)


Assuntos
Humanos , Entrevista Psicológica , Psicometria/instrumentação , Transtornos Mentais/diagnóstico , Estudos Epidemiológicos , Comparação Transcultural
16.
Ann Oncol ; 24(9): 2449-55, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23720454

RESUMO

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.


Assuntos
Neoplasias do Sistema Biliar/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Insulina/uso terapêutico , Neoplasias Hepáticas/epidemiologia , Neoplasias do Sistema Biliar/complicações , Composição Corporal , Índice de Massa Corporal , Carcinoma Hepatocelular/complicações , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/epidemiologia , Estudos Prospectivos , Fatores de Risco , Autorrelato
17.
Diabetologia ; 56(7): 1520-30, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23620057

RESUMO

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.


Assuntos
Bebidas/estatística & dados numéricos , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Bebidas Gaseificadas/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Edulcorantes
18.
Leukemia ; 27(11): 2157-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23584566

RESUMO

We retrospectively assessed whether normalized bone marrow WT1 levels could be used for risk stratification in a consecutive series of 584 acute myeloid leukemia (AML) patients. A cutoff value of 5065 copies at diagnosis identified two prognostic groups (overall survival (OS): 44 ± 3 vs 36 ± 3%, P=0.023; leukemia-free survival (LFS): 47 ± 3 vs 36 ± 4%, P=0.038; and cumulative incidence of relapse (CIR): 37 ± 3 vs 47 ± 4%, P=:0.043). Three groups were identified on the basis of WT1 levels post-induction: Group 0 (WT1 between 0 and 17.5 copies, 134 patients, OS: 59 ± 4%, LFS:59 ± 4% and CIR: 26 ± 4%); Group 1 (WT1 between 17.6 and 170.5 copies, 160 patients, OS: 48 ± 5%, LFS:41 ± 4% and CIR: 45 ± 4%); and Group 2 (WT1 >170.5 copies, 71 patients, OS: 23 ± 6%, LFS: 19 ± 7% and CIR: 68 ± 8%) (P<0.001). Post-intensification samples distinguished three groups: patients with WT1 >100 copies (47 patients, 16%); an intermediate group of patients with WT1 between 10 and 100 copies (148 patients, 52%); and a third group with WT1 <10 copies (92 patients, 32%). Outcomes differed significantly in terms of OS (30 ± 7%, 59 ± 4%, 72 ± 5%), LFS (24 ± 7%, 46 ± 4%, 65 ± 5%) and relapse probability (CIR 72 ± 7%, 45 ± 4%, 25 ± 5%), all P<0.001. WT1 levels in bone marrow assayed using the standardized ELN method provide relevant prognostic information in de novo AML.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Medula Óssea/metabolismo , Recidiva Local de Neoplasia/genética , Neoplasia Residual/genética , Proteínas WT1/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Quimioterapia de Consolidação , Feminino , Seguimentos , Dosagem de Genes , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/mortalidade , Reação em Cadeia da Polimerase , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Proteínas WT1/metabolismo , Adulto Jovem
19.
Med Mycol ; 51(2): 150-4, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22712457

RESUMO

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Candidemia/tratamento farmacológico , Candidíase Invasiva/tratamento farmacológico , Equinocandinas/uso terapêutico , Adulto , Idoso , Aspergilose/complicações , Aspergilose/microbiologia , Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidemia/complicações , Candidemia/microbiologia , Candidíase Invasiva/complicações , Candidíase Invasiva/microbiologia , Caspofungina , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/complicações , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Segurança , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
20.
J Interpers Violence ; 27(16): 3322-40, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22809817

RESUMO

Immigrants constitute a population vulnerable to the problem of violence. This study sought to ascertain the prevalence of violence reported by the immigrant population in the Murcian Region of Spain and characterize the related factors, taking the country population as reference. A cross-sectional study was carried out based on a representative population sample of Latin American (n = 672; 48% women), Moroccan (n = 361; 25% women), and Spanish origin (n = 1,303; 66% women), aged 16 to 64 years. Using a specific questionnaire, the prevalence of violence in the preceding year was assessed. The results were compared with the Spaniards using the 2006 National Health Survey (NHS). Multivariate logistic regression models were used to study the factors associated with violence having been reported in each group, both separately and in immigrants versus Spaniards. Finally, the cause and place of last aggression were studied. The prevalence of violence was 6.5% in Latin Americans, 12.0% in Moroccans, and 2.7% in Spaniards. Discrimination was the principal violence-related factor in all three groups. Among Latin Americans, low educational level was also associated with violence. Among Moroccans, those who had perceived discrimination showed the greatest differences in prevalence of violence compared with natives. Intimate partner violence (IPV) registered a prevalence of below 2%. As a conclusion, in this study, violence was little reported and higher among immigrants. The principal violence-related factor was discrimination. More studies of this type are called for to characterize the problem in other population-representative samples.


Assuntos
Emigrantes e Imigrantes , Violência/etnologia , Violência/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Coleta de Dados , Escolaridade , Feminino , Humanos , América Latina/etnologia , Masculino , Pessoa de Meia-Idade , Marrocos/etnologia , Prevalência , Análise de Regressão , Espanha/epidemiologia , Adulto Jovem
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