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1.
Nat Rev Immunol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740804

RESUMO

Genetic defects that accumulate in haematopoietic stem cells (HSCs) are thought to be responsible for age-related changes in haematopoiesis that include a decline in lymphopoiesis and skewing towards the myeloid lineage. This HSC-centric view is based largely on studies showing that HSCs from aged mice exhibit these lineage biases following transplantation into irradiated young recipient mice. In this Opinion article, we make the case that the reliance on this approach has led to inaccurate conclusions regarding the effects of ageing on blood-forming stem cells; we suggest instead that changes in the environment contribute to haematopoietic system ageing. We propose that a complete understanding of how ageing affects haematopoiesis depends on the analysis of blood cell production in unperturbed mice. We describe how this can be achieved using in situ fate mapping. This approach indicates that changes in downstream progenitors, in addition to any HSC defects, may explain the reduced lymphopoiesis and sustained myelopoiesis that occur during ageing.

2.
Immunity ; 51(2): 351-366.e6, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31303400

RESUMO

Aging results in increased myelopoiesis, which is linked to the increased incidence of myeloid leukemias and production of myeloid-derived suppressor cells. Here, we examined the contribution of plasma cells (PCs) to age-related increases in myelopoiesis, as PCs exhibit immune regulatory function and sequester in bone marrow (BM). PC number was increased in old BM, and they exhibited high expression of genes encoding inflammatory cytokines and pathogen sensors. Antibody-mediated depletion of PCs from old mice reduced the number of myeloid-biased hematopoietic stem cells and mature myeloid cells to levels in young animals, but lymphopoiesis was not rejuvenated, indicating that redundant mechanisms inhibit that process. PCs also regulated the production of inflammatory factors from BM stromal cells, and disruption of the PC-stromal cell circuitry with inhibitors of the cytokines IL-1 and TNF-α attenuated myelopoiesis in old mice. Thus, the age-related increase in myelopoiesis is driven by an inflammatory network orchestrated by PCs.


Assuntos
Envelhecimento/fisiologia , Medula Óssea/fisiologia , Células-Tronco Hematopoéticas/patologia , Inflamação/metabolismo , Mielopoese/fisiologia , Plasmócitos/fisiologia , Animais , Células Cultivadas , Humanos , Interleucina-1/metabolismo , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator de Necrose Tumoral alfa/metabolismo
3.
J Palliat Med ; 22(12): 1515-1521, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31184989

RESUMO

Background: The most important decision after diagnosing terminal cancer is whether to provide active therapy or withhold treatment. Objective: To analyze the aggressiveness of care by evaluating systemic anticancer therapy (SACT) given near to death, describing this care and identifying factors that determine its use. Design: This involves retrospective observational cohorts study. Setting/Subjects: This involves patients with metastatic tumors who died at a University Hospital in Spain between 2015 and 2016. Measurements: Data obtained from prescribing oncologists and patients' clinical records, type of cancer, and information on treatment. The dependent variable used was the interval between the date of the last dose and date of death. Results: Ninety-four (32.60%) of 288 patients received SACT in the last month of life. This cohort had a higher frequency of lung cancer (OR: 1.58; CI 95%: 1.14-2.18), received more care from oncologist 2 (OR: 1.50; CI 95%: 1.08-2.08), had fewer last-line treatment cycles (OR: 1.28; CI 95%: 1.13-1.45), a lower subjective response (OR: 3.13; CI 95%: 1.34-7.29), less clinical benefit (OR: 2.38; CI 95%: 1.04-5.55), more visits to the Emergency Department (OR: 1.59; CI 95%: 1.06-2.38), and less care from the Palliative Care Unit (OR: 4.55; CI 95%: 2.69-7.70). In multivariate analysis, the predictors of having received SACT close to death remained: receiving fewer cycles of treatment (OR: 1.28; CI 95%: 1.12-1.47) and less palliative care (OR: 4.54; CI 95%: 2.56-7.69). Conclusions: A third of cancer patients received SACT in the last month of life with less efficacy and poorer quality of care than patients not receiving it.

5.
Stem Cell Reports ; 12(3): 584-596, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30799276

RESUMO

Current models propose that reductions in the number of lymphoid-biased hematopoietic stem cells (Ly-HSCs) underlie age-related declines in lymphopoiesis. We show that Ly-HSCs do not decline in number with age. Old Ly-HSCs exhibit changes in gene expression and a myeloid-biased genetic profile, but we demonstrate that they retain normal lymphoid potential when removed from the old in vivo environment. Additional studies showing that interleukin-1 inhibits Ly-HSC lymphoid potential provide support for the hypothesis that increased production of inflammatory cytokines during aging underlies declines in lymphocyte production. These results indicate that current models proposing that lymphopoiesis declines with age due to loss of Ly-HSCs require revision and provide an additional perspective on why lymphocyte development in the elderly is attenuated.

6.
J Air Waste Manag Assoc ; 69(3): 362-372, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30373487

RESUMO

One of the most significant environmental problems arising from landfills is the emission of methane into the atmosphere. In this study, methane emissions from a currently in-use Spanish landfill were modeled as well as being experimentally measured using a two-step method. The first step involved a qualitative walkover survey to detect where gases were being emitted on the surface of the landfill. The second stage comprised a quantitative analysis of these surface methane emissions at a selected number of points on the landfill surface using a specially designed flux chamber. The statistical analysis of the data obtained was based on the Sichel function and resulted in an average emission rate of 74.9 g·m-2·day-1, with 27.8 and 202.1 g·m-2·day-1 as the lower and upper limits of the 95% confidence interval, respectively. The total emission for the landfill, with an emitting surface of 335,000 m2, is 9.16 × 103 ton/yr. These values have been compared with those from three different models, with the model results being above the calculated mean emissions measured at the landfill, but below the upper confidence limit at 95%. Implications: One of the main environmental problems arising from the presence of landfills is the emission of biogas (which mainly contains methane and carbon dioxide) into the atmosphere. Several experimental methods as well as models have been developed to quantify these emissions. In this work, the authors have compared the results obtained using experimental measurements with those provided by some local and international models using the default parameters proposed. The results obtained from the experimental method are in accordance with those provided by the models, although the models could be slightly overestimating these emissions.

7.
Resuscitation ; 134: 127-132, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30428308

RESUMO

BACKGROUND: The use of online teaching methodology for basic life support (BLS) courses is progressively increasing. OBJECTIVE: The objective of this study was to verify whether the blended-learning methodology (virtual course with a short face-to-face complement) was more efficient than a course that followed the classical or face-to-face methodology in our university. MATERIALS AND METHODS: A cost minimization analysis was performed for two BLS and automatic external defibrillation (AED) courses, one of which was conducted face-to-face (Control Group) and the second of which was conducted via blended-learning (Experimental Group). The courses had the same duration and content according to the European Resuscitation Council (ERC) recommendations. In the face-to-face course, direct costs were considered those generated by the faculty and derived from the academic activity. Other costs were those generated by the use of classrooms and the amortization of manikins and AED training. The perspective of the analysis was that of the provider, the academic, and a time horizon of six months. The costs are expressed in € 2017. RESULTS: The savings of a course in BLS-AED based on the blended-learning methodology calculated for a total of 160 university nursing and medical students were € 2328.8 for the first year of its implementation and € 9048.8 for its second edition compared with the same course using a face-to-face methodology. CONCLUSIONS: The blended-learning methodology supposes a cost savings for BLS-AED courses, mainly due to the reduction of expenses of the teaching staff. The blended-learning methodology seems to be more efficient than the face-to-face methodology.

8.
Med. clín (Ed. impr.) ; 151(12): 469-475, dic. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182276

RESUMO

Antecedentes y objetivos: En el cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, la presencia de un riesgo genómico bajo permite tratar solo con hormonoterapia adyuvante, obteniendo unas excelentes tasas de supervivencia. La justificación de este estudio es demostrar que también se obtienen unas excelentes tasas de supervivencia tratando solo con hormonoterapia adyuvante mediante la evaluación del riesgo clínico. Pacientes y métodos: Estudio descriptivo, observacional y retrospectivo entre 2006 y 2016 de la cohorte de cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, tamaño del tumor mayor de 1cm o entre 0,6 y 1cm con características desfavorables. Revisión retrospectiva de los registros de salud. Datos de mortalidad del Registro Nacional de Defunciones. Resultados: Un total de 203 pacientes fueron evaluables para la supervivencia. Ciento veintitrés (60,50%) fueron tratadas solo con hormonoterapia adyuvante, 77 (37,90%) con quimioterapia-hormonoterapia, una (0.50%) solo con quimioterapia y 2 (1%) no recibieron ningún tratamiento. La tasa de supervivencia global a los 5 años fue del 97% (intervalo de confianza [IC] del 95% 94-100). La tasa de intervalo libre de metástasis a distancia fue del 94% (IC 95% 90-98). En el subgrupo de pacientes tratadas solo con hormonoterapia la tasa de supervivencia global y del intervalo libre de metástasis a distancia a los 5 años fue del 98% (IC 95% 95-100) y 97% (IC 95% 93-100), respectivamente. Conclusiones: Las pacientes con cáncer de mama hormonosensible, HER-2-negativo, con ganglios negativos, tratadas solo con hormonoterapia según su riesgo clínico, obtienen resultados de supervivencia similares a los descritos cuando son tratadas solo con hormonoterapia según su riesgo genómico


Background and objectives: In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. Patients and methods: A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. Results: A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Conclusions: Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Genes erbB-2 , Quimioterapia Adjuvante/métodos , Análise de Sobrevida , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Receptor ErbB-2/genética
9.
J Air Waste Manag Assoc ; : 1-11, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30325261

RESUMO

A model was developed to simulate the sewage sludge gasification in an atmospheric fluidised bed gasifier using Aspen Plus. The model here presented was based on the Gibbs free energy minimisation and the restricted equilibrium method was used to calibrate it against previously published experimental data obtained in a lab-scale gasification plant. A sensitivity analysis of the model was carried out by modifying parameters such as the temperature, equivalence ratio (ER) and the steam-to-biomass ratio. The modeled results were in good agreement with the experimental data (especially when air was used as gasifying agent) and reproduced satisfactorily the experimental trends found for the gas composition, the carbon conversion (Xc) and the cold gas efficiency (CGE) under different gasification conditions. Operating at higher temperatures increased the production of H2 and CO, as well as the Xc and the CGE. The increase in ER produced higher Xc, yet the CGE experienced slight changes due to a decrease in the lower heating value of the resulting syngas, as well as the oxidation of combustible gases. The use of air+steam as gasifying agent increased the H2 content of the produced gases but decreased the accuracy of the model.

10.
BMJ Open ; 8(5): e019852, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29730621

RESUMO

OBJECTIVES: To verify whether a citizens' jury study is feasible to the Andalusian population and to know if women, when better informed, are able to answer the research question of whether the Andalusian Public Health System must continue offering screening mammography to women aged 50-69. The reasons for the pertinent decision and recommendations to the political authorities will be stated. DESIGN: Qualitative research study with the methodology of citizens' jury. SETTING: Breast cancer screening programme in Andalusia (Spain). PARTICIPANTS: Thirteen women aged 50-69 with secondary school or higher education accepted to participate as a jury. Two epidemiologists were the expert witnesses. The main researcher was the neutral moderator. INTERVENTIONS: Jury met on Monday, 15 February 2016. The moderator indicated to the jury that it had to assess the screening programme's key benefits and main harm. On Tuesday, 16 February, the expert witnesses positioned for and against the programme. On Thursday, 18 February, the jury deliberated, reached final conclusions, submitted its vote and stated its recommendations to politicians. The deliberation session was transcribed and analysed with the support of ATLAS.ti.5.2 software. PRIMARY AND SECONDARY OUTCOME MEASURES: Feasibility in the Andalusian population, women's vote and opinion, reasons for votes and recommendations to political authorities. RESULTS: Eleven participants voted yes and two voted no. There are three reasons to vote 'yes': health, the test nature, and individual freedom. Some women invoke the lack of efficacy and the cost to justify their negative vote, at least in universal terms. On completion, they made suggestions to be submitted to the pertinent authorities for the improvement of information, psychology services and research. CONCLUSIONS: The deliberative strategy is feasible and causes a favourable positioning regarding screening mammography, although information changes the opinion of some women, who desire informed decision making and to keep or increase medicalisation in their lives.


Assuntos
Neoplasias da Mama/diagnóstico , Tomada de Decisões , Mamografia , Programas de Rastreamento , Aceitação pelo Paciente de Cuidados de Saúde , Participação do Paciente/métodos , Opinião Pública , Idoso , Análise Custo-Benefício , Detecção Precoce de Câncer , Estudos de Viabilidade , Feminino , Processos Grupais , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde , Humanos , Consentimento Livre e Esclarecido , Julgamento , Pessoa de Meia-Idade , Saúde Pública , Pesquisa Qualitativa , Espanha
11.
Nurse Educ Today ; 65: 232-238, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29605787

RESUMO

AIM OF THE STUDY: The objective of this study was to compare the immediate and 6-month efficacy of basic life support (BLS) and automatic external defibrillation (AED) training using standard or blended methods. METHODS: First-year students of medicine and nursing (n = 129) were randomly assigned to a control group (face-to-face training based on the European Resuscitation Council [ERC] Guidelines) or to an experimental group that trained with a self-training video, a new website, a Moodle platform, an intelligent manikin, and 45 min of instructor presence. Both groups were homogeneous and were evaluated identically. Theoretical knowledge was evaluated using a multi-choice questionnaire (MCQ). Skill performance was evaluated by the instructor's rubric and on a high-fidelity Resusci Anne QCPR manikin. RESULTS: Immediately after the course, there were no statistically significant differences in knowledge between the two groups. The median score of practical evaluation assessed by the instructor was significantly better in the experimental group (8.15, SD 0.93 vs 7.7, SD 1.18; P = 0.02). No differences between groups were found when using a high-fidelity manikin to evaluate chest compressions and lung inflations. At six months, the scores in knowledge and skill performance were significantly lower compared to the evaluations at the end of the instruction, but they remained still higher compared to baseline. The experimental group had higher scores in practical skills evaluated by the instructor than the control group (7.44, SD 1.85 vs 6.10, SD 2.6; P = 0.01). CONCLUSIONS: The blended method provides the same or even higher levels of knowledge and skills than standard instruction both immediately after the course and six months later.


Assuntos
Reanimação Cardiopulmonar/educação , Competência Clínica/normas , Desfibriladores/psicologia , Estudantes/psicologia , Ensino/normas , Reanimação Cardiopulmonar/métodos , Avaliação Educacional/métodos , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Estatísticas não Paramétricas , Adulto Jovem
12.
Med Clin (Barc) ; 151(12): 469-475, 2018 12 21.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29501438

RESUMO

BACKGROUND AND OBJECTIVES: In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. PATIENTS AND METHODS: A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. RESULTS: A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. CONCLUSIONS: Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/química , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Intervalos de Confiança , Feminino , Humanos , Linfonodos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Tamoxifeno/uso terapêutico , Fatores de Tempo
13.
Rev. senol. patol. mamar. (Ed. impr.) ; 31(1): 4-11, ene.-mar. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-174313

RESUMO

Objetivos. En España las mujeres no toman una decisión informada sobre su participación en el programa de cribado mamográfico. Se analizó si proporcionar información individualizada y precisa sobre los beneficios y riesgos del programa de cribado mamográfico incrementaba su grado de conocimiento. Pacientes y método. Se realizó un ensayo clínico aleatorizado y controlado en el que participaron 434 mujeres de entre 45 y 69 años, convocadas a la mamografía de cribado. Doscientas dieciocho fueron aleatorizadas al grupo control y 216 al de intervención. Se evaluó el grado de conocimiento sobre beneficios y riesgos del cribado mamográfico mediante un cuestionario específico, en la segunda entrevista, al mes. Secundariamente se analizaron la actitud, la ansiedad y la depresión, así como la preocupación por el cáncer de las participantes. Resultados. Adquirieron un buen conocimiento 15 de 178 mujeres (8,4%) en el grupo control y 32 de 177 (18,1%) en el de intervención (p=0,008). Las mujeres del grupo de intervención tienen un riesgo relativo 2,39 veces mayor de adquirir un buen conocimiento que las del grupo control (IC 95% 1,24-4,60). No se hallaron diferencias en ninguno de los objetivos secundarios evaluados. Conclusiones. Las mujeres poseen un nivel de conocimientos muy pobre sobre el programa de cribado con mamografía, siendo la televisión su principal fuente de información. La información individualizada incrementó significativamente el grado de buen conocimiento, aunque persistió en porcentajes muy bajos. Tienen una actitud muy positiva sobre el mismo y no se aprecia un impacto negativo en la esfera psicosocial por su participación en este tipo de procedimientos


Objectives. Spanish women do not make an informed choice about their participation in breast cancer screening. Our study hypothesised that providing individualised and accurate information about the benefits and risks of the mammography screening programme in Spain would increase their knowledge. Patients and method. A randomised controlled clinical trial was conducted in 434 women aged between 45 and 69 years: 216 were assigned to the intervention group and 218 to the control group. The degree of knowledge about the benefits and risks of mammography screening was determined from questionnaires administered at baseline and after one month. Secondarily, the participants’ attitudes, anxiety and depression and cancer worry were analysed. Results. Good knowledge was acquired by 15 of 178 women (8.4%) in the control group and 32 of 177 (18.1%) in the intervention group (P=.008). The relative risk of acquiring a good level of knowledge about the programme was 2.39 times higher in women in the intervention group than in those in the control group (95% CI 1.24-4.60). No differences were found in the secondary endpoints. Conclusions. Women have a very poor level of knowledge about mammography screening, with their main information source being television. Individualized information significantly increased the proportion of women with good knowledge but the percentages remained very low. Women had a very positive attitude to screening and a negative impact in the psychosocial sphere due to their participation was not observed


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Mamografia/métodos , Diagnóstico Precoce , Conhecimentos, Atitudes e Prática em Saúde , Mamografia/tendências , Estresse Psicológico , Inquéritos e Questionários , Serviços de Informação , Afeto
14.
J Immunol ; 200(6): 2046-2056, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29436414

RESUMO

The PU.1 transcription factor plays a critical role in the regulation of T cell development, so a report that it is dispensable for fetal thymopoiesis is puzzling. To understand this paradox, we examined the requirement for PU.1, encoded by Spi1, during fetal, neonatal, and adult thymopoiesis in a PU.1 hypomorphic mouse generated by deletion of the Spi1 14-kb upstream regulatory element and by analysis of patterns of gene expression in fetal and adult T cell progenitors. Our data demonstrate that the initiation of thymopoiesis during early gestation is less dependent on PU.1 compared with T cell differentiation in adults and that fetal T cell progenitors express lower levels of Spi1 compared with their adult counterparts. We also show that expression of the core network of T lineage transcription factors regulated by PU.1 differs in fetal and adult T cell progenitors. In particular, PU.1-regulated genes that promote T cell differentiation are differentially expressed in fetal versus adult early T lineage progenitors. These results indicate that the transcriptional differences between the fetal and adult T cell developmental programs are driven in part by differential levels of PU.1 expression and that this likely underlies the differences in the properties of fetal and adult T cell progenitors.


Assuntos
Linhagem da Célula/fisiologia , Feto/metabolismo , Feto/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Linfócitos T/fisiologia , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular/fisiologia , Expressão Gênica/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Células Precursoras de Linfócitos T/fisiologia
15.
Rev. esp. quimioter ; 30(5): 368-371, oct. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-167154

RESUMO

El shock séptico en ocasiones se inicia con síntomas inespecíficos que dificultan el diagnóstico clínico y por tanto el tratamiento adecuado. Cuando la evolución es fulminante y el resultado es fatal, el único diagnóstico etiológico posible es el post mortem. Las muertes súbitas e inesperadas en los niños y adultos jóvenes son objeto con frecuencia de las autopsias forenses. Algunas muertes súbitas tienen origen infeccioso, lo que obliga a realizar análisis complementarios, incluidos los microbiológicos, para establecer la causa de la muerte. Se presenta el caso de un varón de 19 meses de edad que, tras sufrir un cuadro banal de una herida en el pie, evolucionó hasta shock séptico y fallecimiento como consecuencia de una sepsis por Streptococcus pyogenes, como se demostró en los estudios post mortem (AU)


Septic shock sometimes starts with unspecific symptoms that hamper the clinical diagnosis and, therefore an appropriate treatment. When the septic shock follows a fulminating course with a fatal outcome, the etiological diagnosis has to be conducted post-mortem. Sudden unexpected deaths in children and young adults are frequently the object of medico-legal autopsies. Some sudden unexpected deaths have an infectious origin, which requires further analyses, including microbiology, to establish the cause of death. Here, the case of a fatal septic shock in a 19-month old male infant is presented. After a mild foot injury, an infection by Streptococcus pyogenes progressed to septic shock with a fatal outcome as post-mortem studies demonstrated (AU)


Assuntos
Humanos , Masculino , Lactente , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Autopsia/métodos , Streptococcus pyogenes/isolamento & purificação , Exantema/complicações , Eritema/complicações , Antipiréticos/administração & dosagem , Medicina Legal/métodos , Mudanças Depois da Morte , Hiperemia/complicações , Streptococcus pyogenes
16.
Farm. hosp ; 41(3): 382-390, mayo-jun. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-162876

RESUMO

Objective: The use of antineoplastic medicines in special situations is common in clinical practice; it is strongly regulated and there is little information on its outcomes. We have analysed such use and health outcomes. Methods: All off-label cases between 2005 and 2015, with any type of cancer and in any stage were included. Health histories of a single health centre were reviewed to gather information on treatment features, response, survival, and toxicity. Results: 85 men and 83 women, aged 56, had largely metastatic tumours treated with a median of 4 cycles (0-118) of chemotherapy, hormone therapy, or biotherapy, for palliative purposes between 1st and 4th lines (80% of cases). The subjective response rate was 32.5%, complete objective 1.9%, partial 8.8%, stabilisation 15.6%, progression 38.8%, and not assessable 35.1%. The median duration of response was 2.5 months (1-17), progression-free survival (PFS) 5 months (4 - 21.3), and overall survival (OS) 11 months (9.2-20.6). In the univariate analysis, performance status, treatment line, number of cycles, and type of response influenced on OS. In the multivariate model, the functional status (HR 0.36; CI 95% 0.17-0.77. P= 0.009) and number of cycles (HR 3.66; CI 95% 2.08-6.44. P= 0.0001) influenced independently on overall survival. The most frequent grade 3 and 4 toxicity were asthenia (19%), neutropenia (10.7%), and nausea and vomiting (8.9%). Conclusions: Off-label antineoplastic drugs were mostly used in metastatic tumours, with little effectiveness. The functional status must be considered to select the patients to be treated (AU)


Objetivos: El uso de medicamentos antineoplásicos en situaciones especiales es común en la práctica clínica, está fuertemente regulado y hay poca información sobre sus resultados. Hemos analizado su empleo y los resultados en salud. Método: Se analiza una cohorte de todos los casos off label entre 2005 y 2015, en cualquier cáncer y estadio. Se revisaron historias de salud de un centro para extraer información sobre tratamiento, respuesta, supervivencia y toxicidad. Resultados: 85 hombres y 83 mujeres, de 56 años de mediana de edad, tenían mayoritariamente tumores metastásicos tratados con una mediana de 4 ciclos (0-118) de quimioterapia, hormonoterapia o bioterapia, con finalidad paliativa entre 1.ª y 4.ª línea (80% de casos). La tasa de respuesta subjetiva fue 32,5%, objetiva completa 1,9%, parcial 8,8%, estabilización 15,6%, progresión 38,8% y no valorable 35,1%. La mediana de duración de la respuesta fue 2,5 meses (1-17), de supervivencia libre de progresión (SLE) 5 meses (4 - 21,3) y global (SG) 11 meses (9,2-20,6). En el análisis univariante, el estado funcional, la línea de tratamiento, el número de ciclos y el tipo de respuesta influyeron en la SG. En el modelo multivariante, el estado funcional (HR 0,36; IC 95% 0,17-0,77. P= 0,009) y el número de ciclos (HR 3,66; IC 95% 2,08-6,44. P= 0,0001) influían de forma independiente en la SG. La toxicidad grado 3 y 4 más frecuente fue la astenia (19%), la neutropenia (10,7%) y la emesis (8,9%). Conclusiones: Los medicamentes antineoplásicos en situaciones especiales de uso se emplearon mayoritariamente en tumores metastásicos, con poca efectividad. El estado funcional debe ser tenido en cuenta para seleccionar los pacientes a tratar (AU)


Assuntos
Humanos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Uso Off-Label/estatística & dados numéricos , Aprovação de Drogas , Uso de Medicamentos/estatística & dados numéricos , Segurança do Paciente , Ensaios de Uso Compassivo
17.
Farm Hosp ; 41(3): 382-390, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28478752

RESUMO

OBJECTIVE: The use of antineoplastic medicines in special situations is common in clinical practice; it is strongly regulated and there is little information on its outcomes. We have analysed such use and health outcomes. METHODS: All off-label cases between 2005 and 2015, with any type of cancer and in any stage were included. Health histories of a single health centre were reviewed to gather information on treatment features, response, survival, andtoxicity. RESULTS: 85 men and 83 women, aged 56, had largely metastatic tumours treated with a median of 4 cycles (0-118) of chemotherapy, hormone therapy, or biotherapy, for palliative purposes between 1st and 4th lines (80% of cases). The subjective response rate was 32.5%, complete objective 1.9%, partial 8.8%, stabilisation 15.6%, progression 38.8%, and not assessable 35.1%. The median duration of response was 2.5 months (1-17), progression-free survival (PFS) 5 months (4 - 21.3), and overall survival (OS) 11 months (9.2-20.6). In the univariate analysis, performance status, treatment line, number of cycles, and type of response influenced on OS. In the multivariate model, the functional status (HR 0.36; CI 95% 0.17-0.77. P= 0.009) and number of cycles (HR 3.66; CI 95% 2.08-6.44. P= 0.0001) influenced independently on overall survival. The most frequent grade 3 and 4 toxicity were asthenia (19%), neutropenia (10.7%), and nausea and vomiting (8.9%). CONCLUSIONS: Off-label antineoplastic drugs were mostly used in metastatic tumours, with little effectiveness. The functional status must be considered to select the patients to be treated.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Uso Off-Label , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Adulto Jovem
18.
Immunity ; 45(3): 527-539, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27566938

RESUMO

B cell development is often depicted as a linear process initiating in the fetus and continuing postnatally. Using a PU.1 hypomorphic mouse model, we found that B-1 and B-2 lymphopoiesis occurred in distinct fetal and adult waves differentially dependent on the Sfpi1 14 kB upstream regulatory element. The initial wave of fetal B-1 development was absent in PU.1 hypomorphic mice, while subsequent fetal and adult waves emerged. In contrast, B-2 lymphopoiesis occurred in distinct fetal and adult waves. Whole-transcriptome profiling of fetal and adult B cell progenitors supported the existence of three waves of B-1 and two waves of B-2 development and revealed that the network of transcription factors governing B lineage specification and commitment was highly divergent between B-1 and B-2 progenitors. These findings support the view that the B-1 and B-2 lineages are distinct and provide a genetic basis for layering of immune system development.


Assuntos
Subpopulações de Linfócitos B/imunologia , Redes Reguladoras de Genes/imunologia , Linfopoese/imunologia , Animais , Linhagem da Célula/imunologia , Feto/imunologia , Perfilação da Expressão Gênica/métodos , Camundongos , Células Precursoras de Linfócitos B/imunologia , Fatores de Transcrição/imunologia
19.
Cancer Med ; 4(12): 1923-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26377150

RESUMO

Spanish women do not make an informed choice regarding breast cancer screening (BCS). Our aim was to evaluate the impact of receiving information regarding real BCS benefits and risks on knowledge, attitude, decision, feelings, and worries about cancer. Randomized controlled clinical trial of 355 women aged between 45 and 67 years, 177 and 178 assigned to the intervention group (IG) and control group (CG), respectively. After breast screening, women received either Nordic Cochrane Centre information on BCS or standard information. The primary outcome (knowledge) was determined from questionnaire administered at baseline and after a month. Answers were scored from 0 to 10 and scores of 5 or more indicated that women were well informed (had "good knowledge"). Questionnaires regarding attitudes, future screening intentions, and psychosocial impact were also administered. The Chi-squared and Student's t-tests were used to compare qualitative and quantitative variables, respectively. Good knowledge was acquired by 32 (18.10%) IG women and 15 (8.40%) CG women (P = 0.008). Mean scores from first to second interview increased from 2.97 (SD 1.16) to 3.43 (SD 1.39) in the CG and from and from 2.96 (SD 1.23) to 3.95 (SD 1.78) (P = 0.002) in the IG. No differences were found in the secondary endpoints. Women receiving information based on the Nordic Cochrane Centre document were better informed. This means of providing information is not very efficacious, nor does it modify attitude, decision, feelings, or worries about cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer , Consentimento Livre e Esclarecido , Mamografia , Idoso , Ansiedade , Neoplasias da Mama/psicologia , Estudos de Casos e Controles , Comportamento de Escolha , Tomada de Decisões , Depressão , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Biópsia de Linfonodo Sentinela , Espanha/epidemiologia , Inquéritos e Questionários
20.
PLoS One ; 10(5): e0125414, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25933067

RESUMO

Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy.


Assuntos
Envelhecimento/metabolismo , Células-Tronco Embrionárias/metabolismo , Células-Tronco Fetais/metabolismo , Proteína HMGA2/genética , Linfócitos T/metabolismo , Timócitos/metabolismo , Timo/metabolismo , Envelhecimento/imunologia , Animais , Animais Recém-Nascidos , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD/metabolismo , Diferenciação Celular , Proliferação de Células , Embrião de Mamíferos , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/imunologia , Células-Tronco Fetais/citologia , Células-Tronco Fetais/imunologia , Feto , Regulação da Expressão Gênica no Desenvolvimento , Proteína HMGA2/imunologia , Proteína HMGA2/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Organogênese/genética , Organogênese/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Timócitos/citologia , Timócitos/imunologia , Timo/citologia , Timo/embriologia
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