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1.
Rev Med Liege ; 77(5-6): 345-353, 2022 May.
Artigo em Francês | MEDLINE | ID: mdl-35657193

RESUMO

Acute and/or chronic graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). It is a multisystemic inflammatory and/or fibrotic disease that occurs when the immune cells derived from the graft (and therefore originating from the donor) recognize recipient's healthy tissues as foreign and react against them. Acute GVHD is one of the main causes of non-relapse mortality after alloHSCT. Chronic GVHD can be very disabling in its severe form and can also be responsible for late mortality, mainly due to long-term immune deficiency and opportunistic infections. In contrast, GVHD can be associated with certain beneficial effects in patients transplanted for hematological malignancies, through simultaneous «graft versus tumour¼ positive effects. Therefore, one of the challenges of alloHSCT is the prevention and treatment of severe forms of GVHD without losing the beneficial anti-tumour effects of the graft.


: La maladie du greffon contre l'hôte («greffe-versus-hôte¼, GVH) aiguë et/ou chronique est une complication sérieuse de l'allogreffe de cellules souches hématopoïétiques (CSH). Elle correspond à des manifestations inflammatoires et/ou fibrotiques multisystémiques qui se produisent lorsque les cellules immunitaires dérivées de la greffe (et donc originaires du donneur) reconnaissent les tissus sains du receveur comme étrangers et réagissent contre eux. La GVH aiguë est l'une des principales causes de mortalité hors rechute post-greffe. La GVH chronique peut être très invalidante dans sa forme sévère et peut également être responsable d'une mortalité tardive, principalement due à un déficit immunitaire à long terme et à des infections opportunistes. À l'opposé, la GVH est associée à certains effets bénéfiques chez les patients transplantés pour des hémopathies malignes, par les effets simultanés favorables du «greffon contre la tumeur¼. Par conséquent, l'un des défis de l'allogreffe de CSH est la prévention et le traitement des formes sévères de GVH, sans perdre les effets bénéfiques anti-tumoraux du greffon.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Doença Crônica , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante Homólogo/efeitos adversos
2.
Med. infant ; 29(2): 123-131, Junio 2022. Tab, ilus
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1381849

RESUMO

Introducción: El uso de herramientas estandarizadas como estrategia de comunicación para brindar información relevante, precisa y actualizada, forma parte de las iniciativas de calidad en las instituciones que cumplen altos estándares en la atención de pacientes. Objetivo: Describir la implementación de un programa de traspaso (IPASS) en unidades de cuidados intensivos pediátricos específicos. Material y métodos: Estudio cuasi-experimental antes y después de una intervención, no controlado, utilizando como sujetos a los profesionales de la salud involucrados en traspasos de pacientes de la unidad de terapia intensiva cardiovascular (UCI 35) e inmunosuprimidos (UCI 72). La intervención consistió en la introducción de un paquete de medidas de estandarización del traspaso de pacientes que consta de: una herramienta escrita, una mnemotecnia oral, una capacitación de trabajo en equipo, observación y devolución estandarizada de los traspasos, basados en la metodología IPASS. Se realizó además una encuesta de percepción de seguridad, tanto en la etapa pre y post intervención. Se comparó el cumplimiento de cada componente del traspaso antes y después de la intervención mediante la prueba de chi2 . Resultados: Se realizaron 101 observaciones de traspaso y 56 encuestas. La mediana de pacientes por cada observación fue 6 (r: 4 a 12) y el tiempo promedio de 26± 11 min. Conclusiones: El uso de un paquete de medidas de estandarización del traspaso de pacientes posquirúrgicos cardiovasculares e inmunosuprimidos aumentó significativamente la presencia de información clave sobre criticidad de la enfermedad, acciones y situaciones de contingencia, junto con la inclusión de la síntesis por el receptor del traspaso (AU)


Introduction: The use of standardized tools as a communication strategy to provide relevant, accurate, and up-to-date information is part of quality initiatives in institutions that adhere to high standards in patient care. Objective: To describe the implementation of a handoff program (IPASS) in specific pediatric intensive care units. Methods: An uncontrolled, quasi-experimental, beforeand-after study. Subjects were healthcare providers involved in patient handoffs in the cardiovascular (ICU 35) and immunocompromised-patient (ICU 72) intensive care units. The intervention consisted of the introduction of a bundle to standardize patient handoff consisting of: a written tool, an oral mnemonic, teamwork training, observation, and standardized feedback for handoffs based on the IPASS methodology. A safety perception survey was also carried out, both in the pre- and post-intervention stage. Compliance with each handoff component before and after the intervention was compared using the Chi-squared test. Results: 101 handoff observations and 56 surveys were conducted. The median number of patients per observation was 6 (r: 4 to 12) and the mean handoff time was 26±11 min. Conclusions: The use of a standardized handoff bundle for post-surgical cardiovascular and immunocompromised patients significantly increased the availability of key information on disease severity, actions, and contingency situations, as well as a synthesis by the handoff receiver (AU)


Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Unidades de Terapia Intensiva Pediátrica , Erros Médicos/prevenção & controle , Melhoria de Qualidade , Segurança do Paciente , Transferência da Responsabilidade pelo Paciente/normas , Transferência da Responsabilidade pelo Paciente/estatística & dados numéricos , Inquéritos e Questionários
3.
Rev Med Liege ; 77(4): 206-211, 2022 Apr.
Artigo em Francês | MEDLINE | ID: mdl-35389003

RESUMO

Cellular immunotherapy consists in using the cells of the immune system as a therapeutic weapon. In this constantly evolving field, the therapeutic strategies developed at the University Hospital of Liege are hematopoietic stem cell transplantation, mesenchymal stromal cells and targeted therapy with CAR-T cells (Chimeric Antigen Receptor T cells). The first two modalities represent a form of non-targeted cell therapy that has been developed over the past decades. While hematopoietic stem cell transplantation is established as the reference treatment for many hematological diseases, mesenchymal stromal cells are still under investigation in various pathologies (notably Crohn's disease, organ transplantation, COVID-19 and pulmonary fibrosis). By contrast, CAR-T cells represent a recently developed and extremely promising targeted immunotherapy. This therapeutic approach has already revolutionized the treatment of B-cell lymphopathies, and has the potential to do the same for many other diseases in the near future.


L'immunothérapie cellulaire consiste en l'utilisation de cellules du système immunitaire comme arme thérapeutique. Dans ce domaine en évolution constante, les stratégies thérapeutiques développées au CHU de Liège sont la greffe de cellules souches hématopoïétiques, les cellules stromales mésenchymateuses et la thérapie ciblée par cellules CAR-T («Chimeric Antigen Receptor T cells¼). Les deux premières approches représentent une forme de thérapie cellulaire non ciblée, développées depuis de nombreuses années. Si la greffe de cellules souches hématopoïétiques est établie comme le traitement de référence de nombreuses hémopathies, les cellules stromales mésenchymateuses sont, quant à elles, toujours à l'étude dans diverses pathologies (notamment maladie de Crohn, transplantation d'organes, COVID-19 et fibrose pulmonaire). À l'opposé, les cellules CAR-T représentent une immunothérapie ciblée, développée récemment et extrêmement prometteuse. Cette modalité thérapeutique a déjà révolutionné le traitement des lymphopathies B, et elle possède le potentiel d'en faire de même pour de nombreuses autres pathologies dans un avenir proche.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , COVID-19/terapia , Hospitais , Humanos , Imunoterapia
4.
Rev Med Liege ; 76(5-6): 464-469, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080381

RESUMO

Hematopoietic stem cell transplantation is a potentially curative therapeutic option for many oncologic and non-oncologic hematological diseases. There is a constant evolution regarding donor choice, conditioning regimen intensity and immunosuppressive treatments, which leads to a reduction in morbidity and mortality during and after transplantation. In this article, we describe the general principles of hematopoietic stem cell transplantation and discuss the progress of global patient management after transplantation.


L'allogreffe de cellules souches hématopoïétiques constitue un traitement potentiellement curatif pour de nombreuses pathologies hématologiques cancéreuses ou non cancéreuses. Une évolution constante dans le choix du donneur, de l'intensité du conditionnement et des stratégies de traitements immunosuppresseurs, permet une réduction de la morbidité et de la mortalité durant et après la greffe. Cet article a pour but de réexpliquer les principes généraux d'une allogreffe et de discuter des nouvelles avancées et adaptations dans la prise en charge globale des patients greffés.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores , Condicionamento Pré-Transplante , Transplante Homólogo
5.
Rev Med Liege ; 76(5-6): 470-475, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080382

RESUMO

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted¼ treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.


Les leucémies aiguës sont un ensemble hétérogène d'hémopathies malignes qui se subdivisent, en fonction de l'orientation cytologique de la cellule blastique pathologique, en formes lymphoblastique (LLA) et myéloblastique (LMA). Les récents progrès dans la compréhension biologique et génétique de ces maladies ont permis d'améliorer les traitements. Le traitement spécifique de chimiothérapie ou traitements dits «ciblés¼, les progrès de la greffe de moelle et de meilleurs soins de support ont permis d'améliorer graduellement le pronostic. Cette revue, centrée sur le patient adulte, a pour objectif de décrire les progrès récents en termes de diagnostic, de marqueurs pronostiques ainsi que thérapeutiques.


Assuntos
Leucemia Mieloide Aguda , Doença Aguda , Adulto , Transplante de Medula Óssea , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Prognóstico
6.
J Appl Microbiol ; 127(5): 1501-1510, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31357234

RESUMO

AIMS: To assess the bacterial diversity in the French egg processing industry and to explore the adhesion and spoilage potential of selected bacteria. METHODS AND RESULTS: Sterile stainless steel chips were suspended for 2 months inside the pipelines of seven egg processing companies, before and after the pasteurizer, at warm and cold seasons. After exposure, the bacterial diversity was assessed by 16S rDNA sequencing. The 231 collected isolates were mainly facultative anaerobic Gram positive bacteria, such as Streptococcus, Staphylococcus, Bacillus and Kocuria. Sixty-five representative isolates were further characterized in vitro regarding the potential for adhesion and egg product spoilage. A high diversity was observed from one genus to another. Kocuria and Rothia isolates showed significantly higher adhesion than the isolates of the other genera. Only the isolates belonging to the genera Bacillus and Lysinibacillus, associated with high enzymatic activities on a solid egg-based medium, were able to induce spoilage of liquid whole egg. CONCLUSIONS: Bacteria collected on stainless steel surfaces placed in egg processing industries could be associated to liquid egg product spoilage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new insights on the bacterial contamination in egg processing companies and represents a first step for the effective control of undesirable bacteria in liquid egg products.


Assuntos
Bactérias/isolamento & purificação , Biodiversidade , Ovos/microbiologia , Contaminação de Alimentos/análise , Manipulação de Alimentos/instrumentação , Aço Inoxidável/análise , Bactérias/classificação , Bactérias/genética , Ovos/análise , Microbiologia de Alimentos , Pasteurização
7.
J Intern Med ; 285(4): 446-454, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30561052

RESUMO

BACKGROUND: We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML). METHODS: Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS: One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS: We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
8.
Matrix Biol ; 70: 140-157, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29649548

RESUMO

Since its first description, ADAMTS14 has been considered as an aminoprocollagen peptidase based on its high similarity with ADAMTS3 and ADAMTS2. As its importance for procollagen processing was never experimentally demonstrated in vivo, we generated Adamts14-deficient mice. They are healthy, fertile and display normal aminoprocollagen processing. They were further crossed with Adamts2-deficient mice to evaluate potential functional redundancies between these two highly related enzymes. Initial characterizations made on young Adamts2-Adamts14-deficient animals showed the same phenotype as that of Adamts2-deficient mice, with no further reduction of procollagen processing and no significant aggravation of the structural alterations of collagen fibrils. However, when evaluated at older age, Adamts2-Adamts14-deficient mice surprisingly displayed epidermal lesions, appearing in 2 month-old males and later in some females, and then worsening rapidly. Immunohistological evaluations of skin sections around the lesions revealed thickening of the epidermis, hypercellularity in the dermis and extensive infiltration by immune cells. Additional investigations, performed on young mice before the formation of the initial lesions, revealed that the primary cause of the phenotype was not related to alterations of the epidermal barrier but was rather the result of an abnormal activation and differentiation of T lymphocytes towards a Th1 profile. However, the primary molecular defect probably does not reside in the immune system itself since irradiated Adamts2-Adamts14-deficient mice grafted with WT immune cells still developed lesions. While originally created to better characterize the common and specific functions of ADAMTS2 and ADAMTS14 in extracellular matrix and connective tissues homeostasis, the Adamts2-Adamts14-deficient mice revealed an unexpected but significant role of ADAMTS in the regulation of immune system, possibly through a cross-talk involving mesenchymal cells and the TGFß pathways.


Assuntos
Proteínas ADAMTS/imunologia , Dermatite Atópica/imunologia , Derme/imunologia , Epiderme/imunologia , Pró-Colágeno/imunologia , Linfócitos T/imunologia , Proteínas ADAMTS/deficiência , Proteínas ADAMTS/genética , Animais , Diferenciação Celular , Movimento Celular , Dermatite Atópica/genética , Dermatite Atópica/patologia , Derme/patologia , Epiderme/patologia , Matriz Extracelular/imunologia , Matriz Extracelular/patologia , Feminino , Regulação da Expressão Gênica , Imunidade Inata , Isoenzimas/deficiência , Isoenzimas/genética , Isoenzimas/imunologia , Masculino , Camundongos , Camundongos Knockout , Pró-Colágeno/genética , Transdução de Sinais , Linfócitos T/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia
9.
J Intern Med ; 283(2): 178-189, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28977716

RESUMO

BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Adulto Jovem
10.
Nature ; 553(7688): 310-312, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29258298

RESUMO

Convection plays a major part in many astrophysical processes, including energy transport, pulsation, dynamos and winds on evolved stars, in dust clouds and on brown dwarfs. Most of our knowledge about stellar convection has come from studying the Sun: about two million convective cells with typical sizes of around 2,000 kilometres across are present on the surface of the Sun-a phenomenon known as granulation. But on the surfaces of giant and supergiant stars there should be only a few large (several tens of thousands of times larger than those on the Sun) convective cells, owing to low surface gravity. Deriving the characteristic properties of convection (such as granule size and contrast) for the most evolved giant and supergiant stars is challenging because their photospheres are obscured by dust, which partially masks the convective patterns. These properties can be inferred from geometric model fitting, but this indirect method does not provide information about the physical origin of the convective cells. Here we report interferometric images of the surface of the evolved giant star π1 Gruis, of spectral type S5,7. Our images show a nearly circular, dust-free atmosphere, which is very compact and only weakly affected by molecular opacity. We find that the stellar surface has a complex convective pattern with an average intensity contrast of 12 per cent, which increases towards shorter wavelengths. We derive a characteristic horizontal granule size of about 1.2 × 1011 metres, which corresponds to 27 per cent of the diameter of the star. Our measurements fall along the scaling relations between granule size, effective temperature and surface gravity that are predicted by simulations of stellar surface convection.

12.
Leukemia ; 31(6): 1408-1414, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28119528

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FMS-like tyrosine kinase 3+ (FLT3+) acute myeloid leukemia (AML), which has poor prognosis because of high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126) (hazard ratio (HR) 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2.32, P=0.02), but not vs URD (HR 1.72, P=0.07). All three cohorts had statistically nonsignificant 3-year LFS: 39% (95% confidence interval (CI): 30-47) after UCB, 43% (95% CI: 30-54) after sibling and 50% (95% CI: 40-60) after URD. Chronic graft-versus-host disease rates were significantly lower after UCB compared with either sibling (HR 0.59, P=0.03) or URD (HR 0.49, P=0.001). Adverse factors for LFS included high leukocyte count at diagnosis and HCT during CR2 (second CR). UCB is a suitable option for adults with FLT3+ AML in the absence of an human leukocyte antigen-matched sibling and its immediate availability may be particularly important for FLT3+ AML where early relapse is common, thus allowing HCT in CR1 (first CR) when outcomes are best.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Doadores não Relacionados , Adulto Jovem
13.
Leukemia ; 31(1): 26-33, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27416910

RESUMO

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Medicina de Precisão/métodos , Indução de Remissão , Medição de Risco , Taxa de Sobrevida , Sequências de Repetição em Tandem , Condicionamento Pré-Transplante/métodos , Adulto Jovem
14.
Aliment Pharmacol Ther ; 45(2): 205-221, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27878827

RESUMO

BACKGROUND: Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. AIM: To review the current data on mesenchymal stromal cell therapy in IBD. METHOD: We searched PubMed and 'ClinicalTrials.gov' databases using the terms 'mesenchymal stromal cells', 'mesenchymal stem cell transplantation', 'inflammatory bowel diseases', 'Crohn disease' and 'colitis, ulcerative'. Additional publications were identified from individual article reference lists. RESULTS: MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen-presenting cells into a regulatory-like profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn's disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission. CONCLUSIONS: Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn's disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials.


Assuntos
Doenças Inflamatórias Intestinais/terapia , Transplante de Células-Tronco Mesenquimais , Animais , Colo/fisiologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Células-Tronco Mesenquimais/imunologia , Regeneração
15.
Med. intensiva ; 34(1): [1-10], 2017. fig
Artigo em Espanhol | LILACS | ID: biblio-883767

RESUMO

Recientemente un grupo de expertos estableció la definición del síndrome de dificultad respiratoria aguda en niños y las recomendaciones relativas a su tratamiento. La ventilación de alta frecuencia oscilatoria es considerada por este consenso como una alternativa válida a la ventilación mecánica convencional en pacientes con este síndrome e hipoxemia resistente. La incorporación de la ventilación de alta frecuencia oscilatoria en el ámbito clínico data de la década de 1970, su utilización se sustenta en que este modo ventilatorio respeta los objetivos fisiológicos de reclutamiento y protección pulmonar. La literatura alberga numerosas publicaciones referidas a la ventilación de alta frecuencia oscilatoria en niños con síndrome de dificultad respiratoria aguda y su comparación con la ventilación mecánica convencional, la mayoría de los trabajos con diseños limitados, a excepción de dos estudios controlados y aleatorizados que objetivan menor daño inducido y menor enfermedad pulmonar crónica en los pacientes tratados con ventilación de alta frecuencia oscilatoria. A la luz de la evidencia analizada, esta ventilación en pacientes con síndrome de dificultad respiratoria aguda pediátrico sería una terapia aceptable ante el fracaso de las medidas convencionales(AU)


Recently, a group of experts established the definition of pediatric acute respiratory distress syndrome and the recommendations regarding its treatment. High-frequency oscillatory ventilation is considered by this consensus as a valid alternative to conventional mechanical ventilation in children with acute respiratory distress syndrome and refractory hypoxemia. There are numerous publications about high-frequency oscillatory ventilation in pediatric patients with this syndrome and its comparison with the conventional mechanical ventilation, most of the studies with limited designs, except for two randomized controlled studies that reported less induced injury and less chronic lung disease in patients treated with high-frequency oscillatory ventilation. Incorporation of this type of ventilation in the clinical setting dates back to the 70s, its use is supported by the fact that this ventilation mode respects the physiological aims of recruitment and lung protection. In light of the analyzed evidence, high-frequency oscillatory ventilation in children with acute respiratory distress syndrome would be an acceptable therapy when conventional measures fail.(AU)


Assuntos
Humanos , Pediatria , Síndrome do Desconforto Respiratório do Recém-Nascido , Ventilação de Alta Frequência , Unidades de Terapia Intensiva
16.
Bone Marrow Transplant ; 51(11): 1431-1438, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27295272

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.


Assuntos
Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Quimerismo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Transfusão de Linfócitos , Monitorização Fisiológica/métodos , Neoplasia Residual/diagnóstico , Recidiva , Prevenção Secundária
17.
Bone Marrow Transplant ; 51(7): 906-12, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27183098

RESUMO

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Adulto , Biomarcadores , Diagnóstico Precoce , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
18.
Nature ; 533(7602): 217-20, 2016 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-27144357

RESUMO

Sunspots are cool areas caused by strong surface magnetic fields that inhibit convection. Moreover, strong magnetic fields can alter the average atmospheric structure, degrading our ability to measure stellar masses and ages. Stars that are more active than the Sun have more and stronger dark spots than does the Sun, including on the rotational pole. Doppler imaging, which has so far produced the most detailed images of surface structures on other stars, cannot always distinguish the hemisphere in which the starspots are located, especially in the equatorial region and if the data quality is not optimal. This leads to problems in investigating the north-south distribution of starspot active latitudes (those latitudes with more starspot activity); this distribution is a crucial constraint of dynamo theory. Polar spots, whose existence is inferred from Doppler tomography, could plausibly be observational artefacts. Here we report imaging of the old, magnetically active star ζ Andromedae using long-baseline infrared interferometry. In our data, a dark polar spot is seen in each of two observation epochs, whereas lower-latitude spot structures in both hemispheres do not persist between observations, revealing global starspot asymmetries. The north-south symmetry of active latitudes observed on the Sun is absent on ζ And, which hosts global spot patterns that cannot be produced by solar-type dynamos.

20.
Med. intensiva ; 33(4): [1-5], 2016. tab, fig
Artigo em Espanhol | LILACS | ID: biblio-884092

RESUMO

La lesión pulmonar aguda producida por transfusión (TRALI) es un grave síndrome clínico que se presenta con hipoxemia aguda y edema pulmonar no cardiogénico dentro de las 6 h de una transfusión con productos sanguíneos. La incidencia reportada oscila entre 1 caso cada 5000-100.000 transfusiones. Se han propuesto dos teorías sobre su fisiopatología: inmunomediada y no inmune. El diagnóstico es clínico y el tratamiento, de sostén. La tasa de mortalidad puede llegar al 10%, y la morbilidad es alta. Presentamos un paciente que, durante el posoperatorio inmediato de una artrodesis posterior instrumentada por escoliosis, evoluciona con hipoxemia resistente. En la cirugía, requirió múltiples transfusiones con hemoderivados por sangrado activo, por lo que se arriba al diagnóstico de TRALI. Requirió asistencia respiratoria mecánica con altos parámetros por 72 h y sostén hemodinámico por bajo gasto cardíaco. La evolución fue favorable y recibió el alta hospitalaria a los 11 días, sin complicaciones(AU)


Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome that occurs with acute hypoxemia and non-cardiogenic pulmonary edema within 6 hours of a transfusion with blood products. The reported incidence ranges from 1 case per 5,000-100,000 transfusions. Two theories have been proposed about its pathophysiology, an immune-mediated one and a non-immune one. The diagnosis is clinical, and the treatment is supportive. Mortality may reach 10%, with high morbidity. We report a patient who in the immediate postoperative period of posterior instrumented arthrodesis for scoliosis developed refractory hypoxemia. During surgery, he required multiple blood products transfusions due to active bleeding, so we diagnosed TRALI. The patient required mechanical ventilation with high parameters during 72 hours and hemodynamic support for low cardiac output. The outcome was favorable and he was discharged at day 11 without complications. (AU)


Assuntos
Humanos , Síndrome do Desconforto Respiratório do Recém-Nascido , Transfusão de Sangue , Lesão Pulmonar Aguda Relacionada à Transfusão , Edema Pulmonar , Hipóxia
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