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1.
Blood Cancer J ; 14(1): 74, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684670

RESUMO

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.


Assuntos
Biomarcadores Tumorais , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Mutação , Mieloma Múltiplo Latente , Humanos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Mieloma Múltiplo Latente/genética , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Cir. Esp. (Ed. impr.) ; 100(8): 504-510, ago. 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-207751

RESUMO

Introduction Outcomes after the introduction of surgical innovations can be impaired by learning periods. The aim of this study is to compare the short-term outcomes of a recently implemented RATS approach to a standard VATS program for anatomical lung resections. Methods Retrospective review of consecutive patients undergoing pulmonary anatomical resection through a minimally invasive approach since RATS approach was applied in our department (June 01, 2018, to November 30, 2019). Propensity score matching was performed according to patients’ age, gender, ppoFEV1, cardiac comorbidity, type of malignancy, and type of resection. Outcome evaluation includes: overall morbidity, significant complications (cardiac arrhythmia, pneumonia, prolonged air leak, and reoperation), 30-day mortality, and length of hospital stay. Data were compared by two-sided chi-square or Fisher's exact test for categorical and Mann–Whitney U test for continuous variables. Results A total of 273 patients (206 VATS, 67 RATS) were included in the study. After propensity score matching, data of 132 patients were analyzed. The thirty-days mortality was nil. Overall morbidity (RATS: 22.4%, VATS: 29.2%; p=0.369), major complications (RATS: 9% vs VATS: 9.2%; p=0.956) and the rates of specific major complications (cardiac arrhythmia RATS: 4.5%, VATS: 4.6%, p=1; pneumonia RATS:0%, VATS:4.6%, p=0.117; prolonged air leak RATS: 7.5%; VATS: 4.6%, p=0.718) and reoperation (RATS: 3%, VATS: 1.5%, p=1) were comparable between both groups. The median length of stay was 3 days in both groups (p=0.101) (AU)


Introducción La introducción de innovaciones quirúrgicas se asocia con períodos de aprendizaje que pueden afectar a los resultados. El objetivo de este estudio es comparar los resultados postoperatorios de un abordaje RATS para resecciones pulmonares anatómicas implementado recientemente frente a los de un abordaje VATS convencional. Métodos Revisión retrospectiva de los pacientes sometidos a resección pulmonar anatómica mediante un abordaje mínimamente invasivo en nuestro centro desde el inicio del programa de cirugía RATS (junio de 2018) hasta noviembre de 2019. Los pacientes fueron emparejados por puntuación de propensión según variables de riesgo. Los resultados analizados fueron: morbilidad global, complicaciones (mayores, arritmia, neumonía, fuga aérea prolongada y reintervención), mortalidad a los 30 días y estancia hospitalaria. Los datos se compararon mediante la prueba de chi-cuadrado o la exacta de Fisher para variables categóricas y la prueba de U de Mann-Whitney para variables continuas. Resultados Se incluyeron en el estudio 273 pacientes (206 VATS, 67 RATS). Tras el emparejamiento, se analizaron los datos de 132 pacientes. La mortalidad a los 30 días fue nula. La morbilidad global (RATS: 22,4%, VATS: 29,2%; p=0,369), complicaciones mayores (RATS: 9%, VATS: 9,2%; p=0,956), arritmia (RATS: 4,5%, VATS: 4,6%, p=1); neumonía (RATS: 0%, VATS: 4,6%, p=0,117); fuga aérea prolongada (RATS: 7,5%; VATS: 4,6%, p=0,718) y reintervención (RATS: 3%, VATS: 1,5%, p=1) fueron comparables entre ambos grupos. La mediana de la estancia hospitalaria fue de 3 días en ambos grupos (p=0,101). Conclusiones Un programa RATS para resecciones pulmonares anatómicas puede implementarse de manera segura por cirujanos experimentados en VATS sin aumentar los índices de morbilidad (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Cirurgia Torácica Vídeoassistida , Procedimentos Cirúrgicos Robóticos , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos
4.
Cir. Esp. (Ed. impr.) ; 100(6): 345-351, jun. 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-207441

RESUMO

Introducción Analizar los factores predictores de respuesta patológica completa (RCp) en pacientes con cáncer de pulmón no microcítico (CPNM) sometidos a resección pulmonar anatómica tras terapia de inducción y evaluar los resultados postoperatorios de estos pacientes. Métodos Se incluyeron en el estudio todos los pacientes registrados de forma prospectiva en la base de datos del grupo de trabajo GE-VATS reclutados entre el 20 de diciembre de 2106 y el 20 de marzo de 2018, sometidos a resección pulmonar anatómica por CPNM tras tratamiento de inducción. La población se dividió en dos grupos: pacientes que obtuvieron respuesta completa patológica tras inducción (RCp) y pacientes que no obtuvieron una respuesta patológica completa tras inducción (no-RCp). Se realizó un análisis multivariante mediante una regresión logística binaria para determinar los factores predictores de RCp y se analizaron los resultados postoperatorios de los pacientes. Resultados De los 241 pacientes analizados, 36 pacientes (14,9%) alcanzaron RCp. Los factores predictores de RCp fueron el sexo masculino (OR 2,814, IC 95% 1,015-7,806), la histología de carcinoma escamoso (OR 3,065, IC 95% 1,233-7,619) u otra distinta de adenocarcinoma (ADC) (OR 5788, IC 95% 1,878-17,733), la terapia de inducción que incluye radioterapia (OR 4,096, IC 95% 1,785-9,401) y terapias dirigidas (OR 7,625, IC 95% 2,147-27,077). La ocurrencia de complicaciones respiratorias postoperatorias fue superior en los pacientes que recibieron quimio-radioterapia de inducción (p = 0,032). Conclusiones El sexo masculino, la histología de carcinoma escamoso o diferente de ADC y la terapia de inducción que incluye radioterapia o terapia dirigida son factores predictores positivos para la obtención de RCp. La quimio-radioterapia de inducción se asocia con un mayor riesgo de complicaciones respiratorias postoperatorias (AU)


Introduction To analyze the predictors of pathological complete response (pCR) in not small cells lung carcinoma (NSCLC) patients who underwent anatomical lung resection after induction therapy and to evaluate the postoperative results of these patients. Methods All patients prospectively registered in the database of the GE-VATS working group undergone anatomic lung resection by NSCLC after induction treatment and recruited between December 20th 2016, and March 20th 2018, were included in the study. The population was divided into two groups: patients who obtained a complete pathological response after induction (pCR) and patients who did not obtain a complete pathological response after induction (non-pCR). A multivariate analysis was performed using a binary logistic regression to determine the predictors of pCR and the postoperative results of patients were analyzed. Results Of the 241 patients analyzed, 36 patients (14.9%) achieved pCR. Predictive factors for pCR are male sex (OR 2.814, 95% CI 1.015-7.806), histology of squamous carcinoma (OR 3.065, 95% CI 1.233-7.619) or other than adenocarcinoma (ADC) (OR 5.788, 95% CI 1.878-17.733) and induction therapy that includes radiation therapy (OR 4.096, 95% CI 1.785-9.401) and targeted therapies (OR 7.625, 95% CI 2.147-27.077). Prevalence of postoperative pulmonary complications was higher in patients treated with neoadjuvant chemo-radiotherapy (p = 0.032). Conclusions Male sex, histology of squamous carcinoma or other than ADC, and induction therapy that includes radiotherapy or targeted therapy are positive predictors for obtaining pCR. Induction chemo-radiotherapy is associated with a higher risk of postoperative pulmonary complications (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Complicações Pós-Operatórias , Cirurgia Torácica Vídeoassistida , Estadiamento de Neoplasias , Resultado do Tratamento , Estudos Prospectivos , Indução de Remissão , Pneumonectomia
5.
Microbiome ; 9(1): 112, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039416

RESUMO

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.


Assuntos
Microbiota , Bactérias/genética , Geografia , Hong Kong , Humanos , Metagenoma/genética , Microbiota/genética
7.
Phys Med ; 66: 88-96, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31574423

RESUMO

PURPOSE: To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses. METHODS AND MATERIALS: Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking. RESULTS: Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques. CONCLUSIONS: According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed.


Assuntos
Fótons/uso terapêutico , Neoplasias da Próstata/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional , Humanos , Masculino , Probabilidade , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Tomografia Computadorizada por Raios X
8.
Radiat Prot Dosimetry ; 185(2): 183-195, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-30649534

RESUMO

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.


Assuntos
Filtração/instrumentação , Segunda Neoplasia Primária/epidemiologia , Neoplasias/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Filtração/métodos , Humanos , Incidência , Neoplasias/classificação , Neoplasias/patologia , Segunda Neoplasia Primária/diagnóstico , Órgãos em Risco/efeitos da radiação , Prognóstico , Dosagem Radioterapêutica , Espanha/epidemiologia
9.
Leukemia ; 32(4): 971-978, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29099494

RESUMO

Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19pos, CD27neg, CD38lo, CD45pos, CD81pos, CD117neg and CD138lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38lowCD81posCD117neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.


Assuntos
Antígenos CD/metabolismo , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/metabolismo , Neoplasia Residual/patologia , Prognóstico
11.
Leukemia ; 31(9): 1922-1927, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28111466

RESUMO

The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2-3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).


Assuntos
Bortezomib/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Talidomida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Interferon-alfa/uso terapêutico , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxa de Sobrevida
12.
Leukemia ; 31(2): 382-392, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27479184

RESUMO

The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19-CD81-) clones, 38% intermediate-differentiated (CD19-CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P=0.005) and overall survival (HR: 2.1; P=0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n=40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/metabolismo , Plasmócitos/metabolismo , Plasmócitos/patologia , Adulto , Antígenos CD/metabolismo , Biomarcadores , Medula Óssea/metabolismo , Medula Óssea/patologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Estudos de Casos e Controles , Ciclo Celular , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Heterogeneidade Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mutação , Gradação de Tumores , Fenótipo , Prognóstico , Análise de Célula Única , Adulto Jovem
13.
J Geriatr Oncol ; 6(5): 353-61, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26139300

RESUMO

OBJECTIVES: The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. MATERIALS AND METHODS: The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. RESULTS: Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). CONCLUSION: Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.


Assuntos
Avaliação Geriátrica/métodos , Nível de Saúde , Neoplasias Hematológicas/psicologia , Psicometria/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Seguimentos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Espanha/epidemiologia , Inquéritos e Questionários
14.
Leukemia ; 29(5): 1186-94, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25388955

RESUMO

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.


Assuntos
Mieloma Múltiplo/genética , Separação Celular , Técnicas de Cocultura , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Citometria de Fluxo , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Mieloma Múltiplo/classificação , Fenótipo , Plasmócitos/citologia , Análise de Componente Principal , Prognóstico , Células Estromais/citologia
15.
J Environ Manage ; 133: 275-83, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24412590

RESUMO

This paper assess the mechanical an environmental behaviour of cement mortars manufactured with addition of fly ash (FA) and bottom ash (BA), as partial cement replacement (10%, 25% and 35%). The environmental behaviour was studied by leaching tests, which were performed under several temperature (23 °C and 60 °C) and pH (5 and 10) conditions, and ages (1, 2, 4 and 7 days). Then, the accumulated amount of the different constituents leached was analysed. In order to obtain an environmental burden (EB) value of each cement mixture, a new methodology was developed. The EB value obtained is related to the amount leached and the hazardous level of each constituent. Finally, the integral study of compressive strength and EB values of cement mixtures allowed their classification. The results showed that mortars manufactured with ordinary Portland cement (OPC) and with coal BA had similar or even better environmental and mechanical behaviour than mortars with FA. Therefore, the partial replacement of cement by BA might be as suitable or even better as the replacement by FA.


Assuntos
Cinza de Carvão , Materiais de Construção , Teste de Materiais
16.
Diabetes Metab ; 39(5): 445-53, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23886784

RESUMO

INTRODUCTION: Our objective was to assess the frequency of lipohypertrophy (LH) and its relationship to site rotation, needle reuse, glucose variability, hypoglycaemia and use of insulin. METHODS: The study included 430 outpatients injecting insulin who filled out a wide-ranging questionnaire regarding their injection technique. Then, a diabetes nurse examined their injection sites for the presence of LH. RESULTS: Nearly two-thirds (64.4%) of patients had LH. There was a strong relationship between the presence of LH and non-rotation of sites, with correct rotation technique having the strongest protective value against LH. Of the patients who correctly rotated sites, only 5% had LH while, of the patients with LH, 98% either did not rotate sites or rotated incorrectly. Also, 39.1% of patients with LH had unexplained hypoglycaemia and 49.1% had glycaemic variability compared with only 5.9% and 6.5%, respectively, in those without LH. LH was also related to needle reuse, with risk increasing significantly when needles were used > 5 times. Total daily insulin doses for patients with and without LH averaged 56 and 41 IU/day, respectively. This 15 IU difference equates to a total annual cost to the Spanish healthcare system of > €122 million. This was also the first study in which the use of ultrasound allowed the description of an "echo signature" for LH. CONCLUSION: Correct injection site rotation appears to be the critical factor in preventing LH, which is associated with reduced glucose variability, hypoglycaemia, insulin consumption and costs.


Assuntos
Tecido Adiposo/patologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas/efeitos adversos , Insulina/administração & dosagem , Tecido Adiposo/lesões , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Guias como Assunto , Humanos , Hipertrofia/epidemiologia , Hipertrofia/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Atenção Primária à Saúde , Fatores de Risco , Espanha/epidemiologia , Adulto Jovem
17.
Microb Ecol ; 64(1): 242-55, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22202889

RESUMO

Wildfires subject soil microbes to extreme temperatures and modify their physical and chemical habitat. This might immediately alter their community structure and ecosystem functions. We burned a fire-prone shrubland under controlled conditions to investigate (1) the fire-induced changes in the community structure of soil archaea, bacteria and fungi by analysing 16S or 18S rRNA gene amplicons separated through denaturing gradient gel electrophoresis; (2) the physical and chemical variables determining the immediate shifts in the microbial community structure; and (3) the microbial drivers of the change in ecosystem functions related to biogeochemical cycling. Prokaryotes and eukaryotes were structured by the local environment in pre-fire soils. Fire caused a significant shift in the microbial community structure, biomass C, respiration and soil hydrolases. One-day changes in bacterial and fungal community structure correlated to the rise in total organic C and NO(3)(-)-N caused by the combustion of plant residues. In the following week, bacterial communities shifted further forced by desiccation and increasing concentrations of macronutrients. Shifts in archaeal community structure were unrelated to any of the 18 environmental variables measured. Fire-induced changes in the community structure of bacteria, rather than archaea or fungi, were correlated to the enhanced microbial biomass, CO(2) production and hydrolysis of C and P organics. This is the first report on the combined effects of fire on the three biological domains in soils. We concluded that immediately after fire the biogeochemical cycling in Mediterranean shrublands becomes less conservative through the increased microbial biomass, activity and changes in the bacterial community structure.


Assuntos
Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Ecossistema , Fungos/isolamento & purificação , Microbiologia do Solo , Archaea/genética , Archaea/crescimento & desenvolvimento , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Incêndios , Fungos/genética , Fungos/crescimento & desenvolvimento , Região do Mediterrâneo , Solo/química
18.
Artigo em Espanhol | IBECS | ID: ibc-91083

RESUMO

Introducción. El acontecimiento vital estresante que supone el fenómeno migratorio puede suponer un factor de mayor riesgo de enfermedad mental. Objetivo. Comparar la prevalencia de ansiedad-depresión en población latinoamericana residente en Canarias con la población autóctona. Material y métodos. Estudio descriptivo-transversal cualitativo y cuantitativo en marzo-agosto de 2009 de los adultos latinoamericanos residentes en Canarias seleccionados en consultas de atención primaria. Encuesta mediante entrevista clínica estructurada y escalas de ansiedad-depresión. Análisis estadístico. Análisis exploratorio de datos y de relación entre variables incluyendo estudio cualitativo de las variables susceptibles. Resultados. Se incluyeron 125 pacientes. Edad media 38,9 años (DE 12,07). El 73,6% eran mujeres, 42,4%casados y el 77,6% tiene empleo. Presentan ansiedad el 44% (IC 95%: 0,527-0,353) y depresión el 63,2% (IC 95%: 0,714-0,546). Un 13,6% refieren haber sufrido malos tratos. Un 19,2% síntomas psicopatológicos infantiles. Un 64,6% tiene antecedentes personales de enfermedad mental. La depresión se asocia al «estado civil» (p=0,012), la «situación familiar» (p<0,0001), el «tiempo en España» (5,75 años ± 3,88 vs 7,50 años ± 7,39; p=0,002) y el «motivo de inmigración» (p=0,050). La ansiedad, con la «edad» (41,1 años ± 12,51 vs 37,2 años ± 11,5; p=0,070) y con el «desempleo» (p=0,014). La ansiedad-depresión con «malos tratos» (76,5 vs 23,5%; p=0,004) (100 vs 0% p=0,001), «síntomas psicopatológicos en infancia» (62,5 vs 37,5%; p=0,042), (83,3 vs 16,7%; p=0,023) y «antecedentes de enfermedad mental» (68,4 vs 31,6%; p<0,001) (84,2 vs 15,8%; p=0,001). Es un factor de riesgo para la ansiedad presentar «antecedentes de salud mental», «sufrir malos tratos» y «no tener trabajo». La depresión se asocia a la «situación familiar» como factor protector y como factor de riesgo «antecedentes de salud mental» y «síntomas psicopatológicos infantiles». El análisis cualitativo ofrece como buenas «relaciones sociales», «visión de la sociedad» y presencia de la «ilusión/esperanza por volver al país». Conclusiones. La prevalencia de ansiedad no es diferente a la de la población general y los factores del hecho migratorio parecen no influir en nuestro estudio (AU)


Introduction. Immigration is a vital stressful event that could be a higher risk of suffering a mental illness. Objective. To compare the prevalence of anxiety-depression in the Latin-American immigrant population living in the Canary Islands and compare them with the non-immigrant population. Material and Method. Exploratory analysis of dates and the relationship between variables, including the qualitative analysis. Results. The study included 125 patients, with a mean age of 38.9 years (SD: 12.07), of whom 73.6% were women, 42.4% married and 77.6% employed. A total of 44% suffered anxiety (95% CI: 0.527-0.353) and 63.2% had depression (95% CI: 0.714-0.546). Abuse was reported by 13.6% and the 19.2% had psychopathological symptoms in childhood. A history of mental illness was reported in 64.6%. Depression was associated with “marital status” (P=.012), “family situation” (P=.0001), “time in Spain” (5.75 years± 3.88 vs. 7.50 years± 7.39 P=.002) and “reason for immigration” (P=.050). Anxiety was associated with “age” (41.1 years± 12.51 vs. 37.2 years± 11.5 P=.070) and “unemployment” (P=.014). Anxiety-depression with “abuses” (76.5 vs. 23.5% P=.004), (100 vs. 0% P=.001), “psychopathological symptoms in childhood” (62.5 vs. 37.5% P=.042), (83.3 vs. 16.7% P=.023) and “clinical history of mental illness” (68.4 vs. 31.6% P=.001), (84.2 vs. 15.8% P=.001). “Clinical history of mental illness”, “abuses” and “unemployment” are risk factors for anxiety. Depression is associated with “family situation” as a protective factor and “clinical history of mental illness” and “psychopathological symptoms in childhood” as a risk factor. The qualitative analysis showed “relationships”, “vision of society” and “hope of going back home” as positive factors. Conclusions. The prevalence of anxiety is no different to the general population, and the migration factors do not appear to modify our study (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Ansiedade/complicações , Ansiedade/diagnóstico , Depressão/complicações , Emigrantes e Imigrantes/classificação , Emigração e Imigração , Fatores de Risco , Transtornos Mentais/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Estudos Transversais/métodos , Análise Multivariada , Modelos Logísticos , 25783/métodos
19.
Leukemia ; 25(4): 697-706, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21252988

RESUMO

Disappearance of normal bone marrow (BM) plasma cells (PC) predicts malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) into symptomatic multiple myeloma (MM). The homing, behavior and survival of normal PC, but also CD34(+) hematopoietic stem cells (HSC), B-cell precursors, and clonal PC largely depends on their interaction with stromal cell-derived factor-1 (SDF-1) expressing, potentially overlapping BM stromal cell niches. Here, we investigate the distribution, phenotypic characteristics and competitive migration capacity of these cell populations in patients with MGUS, SMM and MM vs healthy adults (HA) aged >60 years. Our results show that BM and peripheral blood (PB) clonal PC progressively increase from MGUS to MM, the latter showing a slightly more immature immunophenotype. Of note, such increased number of clonal PC is associated with progressive depletion of normal PC, B-cell precursors and CD34(+) HSC in the BM, also with a parallel increase in PB. In an ex vivo model, normal PC, B-cell precursors and CD34(+) HSC from MGUS and SMM, but not MM patients, were able to abrogate the migration of clonal PC into serial concentrations of SDF-1. Overall, our results show that progressive competition and replacement of normal BM cells by clonal PC is associated with more advanced disease in patients with MGUS, SMM and MM.


Assuntos
Células da Medula Óssea/citologia , Células-Tronco Hematopoéticas/citologia , Mieloma Múltiplo/patologia , Paraproteinemias/patologia , Plasmócitos/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/citologia , Linfócitos B/metabolismo , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Células Clonais , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Paraproteinemias/metabolismo , Plasmócitos/metabolismo , Estudos Prospectivos
20.
J Acquir Immune Defic Syndr ; 51 Suppl 1: S21-5, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19384097

RESUMO

BACKGROUND: Mexican migrants are at higher risk for HIV than Mexicans who do not migrate to the United States. Migration to the United States was the driving factor of the early Mexican HIV epidemic, and it is likely that it continues to strongly influence incidence. An overview of migration of Mexicans to the United States identifies many pervasive environmental and structural factors as well as risk behaviors that render migrants vulnerable to HIV infection. However, published studies sampling Mexicans while in the United States suggest a relatively low prevalence of HIV among the general migrant population. To better understand this apparent paradox, we sought to identify any demographic variables among Mexicans while in Mexico that may indicate that migrants have or acquire resources that have a protective effect from their vulnerability due to migration. METHODS: A California-Mexico binational collaboration project, with a respondent-driven sample with population-based quotas, was conducted in five Mexican states from December 2004 to January 2005, in areas with a high index of migration to the United States. We compared demographic and behavior variables of Mexicans with a history of migration to the United States in the past 12 months to nonmigrant Mexicans living in the same community. RESULTS: A total of 1539 migrants and 1236 nonmigrants were recruited from five Mexican states. Migrants (men and women) reported more HIV risk behavior than nonmigrants in the past 12 months. Migrants reported more sexual partners and noninjected drug use. Migrants reported higher condom use during vaginal sex and were more likely to have taken an HIV test. CONCLUSION: Though migrants reported higher HIV-related risk behaviors, they also reported higher condom use. Migrants were more likely to have accessed an HIV test indicating an opportunity for a prevention intervention. More binational collaborations are needed to research the different levels of vulnerability among Mexican migrants and actual acquisition of HIV infection. In addition, more research is needed to identify protective factors for HIV prevention interventions among Mexican migrant communities in Mexico and in the United States.


Assuntos
Infecções por HIV/epidemiologia , Adolescente , Adulto , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Incidência , Masculino , Americanos Mexicanos , México , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias , Migrantes , Estados Unidos , Adulto Jovem
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