RESUMO
A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)
Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Imunofenotipagem/instrumentação , Neoplasia Residual/diagnóstico , Citometria de Fluxo/instrumentaçãoRESUMO
BACKGROUND: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy. METHODS: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile. RESULTS: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related. CONCLUSIONS: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Paclitaxel/uso terapêutico , Panitumumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Causas de Morte , Término Precoce de Ensaios Clínicos , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Paclitaxel/efeitos adversos , Panitumumabe/efeitos adversos , Intervalo Livre de Progressão , Espanha , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
An analog computer makes use of continuously changeable quantities of a system, such as its electrical, mechanical, or hydraulic properties, to solve a given problem. While these devices are usually computationally more powerful than their digital counterparts, they suffer from analog noise which does not allow for error control. We will focus on analog computers based on active electrical networks comprised of resistors, capacitors, and operational amplifiers which are capable of simulating any linear ordinary differential equation. However, the class of nonlinear dynamics they can solve is limited. In this work, by adding memristors to the electrical network, we show that the analog computer can simulate a large variety of linear and nonlinear integro-differential equations by carefully choosing the conductance and the dynamics of the memristor state variable. We study the performance of these analog computers by simulating integro-differential models related to fluid dynamics, nonlinear Volterra equations for population growth, and quantum models describing non-Markovian memory effects, among others. Finally, we perform stability tests by considering imperfect analog components, obtaining robust solutions with up to 13% relative error for relevant timescales.
RESUMO
A series of tetrahydroisoquinolines functionalized with carbamates is reported here as highly selective ligands on the dopamine D2 receptor. These compounds were selected by means of a molecular modeling study. The studies were carried out in three stages: first an exploratory study was carried out using combined docking techniques and molecular dynamics simulations. According to these results, the bioassays were performed; these experimental studies corroborated the results obtained by molecular modeling. In the last stage of our study, a QTAIM analysis was performed in order to determine the main molecular interactions that stabilize the different ligand-receptor complexes. Our results show that the adequate use of combined simple techniques is a very useful tool to predict the potential affinity of new ligands at dopamine D1 and D2 receptors. In turn the QTAIM studies show that they are very useful to evaluate in detail the molecular interactions that stabilize the different ligand-receptor complexes; such information is crucial for the design of new ligands.
Assuntos
Carbamatos/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D2/agonistas , Tetra-Hidroisoquinolinas/farmacologia , Humanos , Ligantes , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
We propose a decoherence protected protocol for sending single photon quantum states through depolarizing channels. This protocol is implemented via an approximate quantum adder engineered through spontaneous parametric down converters, and shows higher success probability than distilled quantum teleportation protocols for distances below a threshold depending on the properties of the channel.
RESUMO
Objetivo: Determinar los cambios que se desarrollan en el pH sanguíneo de pacientes críticos en Cuidados Intensivos, según el tipo de trastorno. Diseño: Estudio cuantitativo, de observación, analítico, de tipo cohorte retrospectivo. Ámbito: Unidad de Cuidados Intensivos polivalente. Participantes, intervenciones y variables: 753 pacientes con pH normal, después de excluir a aquellos con registros insuficientes o antecedente de acidosis tubular renal. Se analizó la información de la base de datos clínica durante 21 meses. Mediante un análisis de supervivencia, se observó el cambio del pH, estratificando grupos de acuerdo con la alteración primaria y, luego, por morbilidad de ingreso. Se estimó la diferencia entre los grupos mediante la prueba del rango logarítmico. Los factores determinantes de acidemia metabólica se evaluaron mediante regresión de Cox. Resultados: Se evaluó a 753 pacientes (mediana de la edad 60 años [RIQ: 40- 71]). La mediana de estancia fue de 8 días (RIQ: 6-13). El 42% tenía alteración del pH. Predominó la acidemia, con más frecuencia en pacientes sépticos. La causa principal de acidemia parece ser la hipoperfusión. El desenlace es similar en pacientes alcalémicos. Conclusiones: Durante la estancia en la UCI, es frecuente el cambio del pH con igual proporción de acidemia y alcalemia. La mortalidad fue similar en pacientes con ambos trastornos. En pacientes acidémicos, la hipoperfusión parece ser el factor desencadenante más importante.(AU)
Abstract Objective: To determine which changes are seen in serum pH in critical care patients, during their stay in the Intensive Care Unit, stratifying findings according to the main disorder. Design: Quantitative, observational, analytical study of a retrospective cohort. Setting: Polyvalent Intensive Care Unit. Patients, interventions, variables: 753 patients with normal pH after excluding those with insufficient records and history of tubular acidosis. Data was gathered from the clinical database during a 21-month interval. Using a survival analysis, serum pH changes were stratified in their relation to the basic alteration and morbidity. Difference between groups was estimated using the log-rank test. In patients with metabolic acidosis Cox regression was used to search for determining factors. Results: A total of 753 patients were evaluated (median age: 60 years [IQR: 40-71]). The median length of stay was 8 days (IQR: 6-13). pH was abnormal in 42% of the population. Metabolic acidosis was the predominant finding being more frequent in septic patients. The main cause of acidosis seems to be hypoperfusion; outcomes were similar in alkalotic patients. Conclusions: Changes in pH are frequent in patients admitted to intensive care unit, with an equal proportion of acidosis and alkalosis. Mortality was similar in both disorders. pH can be related with a negative outcome in both alkalosis and acidosis. In the latter group hypoperfusion seems to be the major trigger.(AU)
Assuntos
Acidose , Alcalose , Concentração de Íons de Hidrogênio , SepseRESUMO
Atypical enteropathogenic Escherichia coli (EPEC) strains from chicken and chicken-derived products were isolated and characterised. The strains presented a wide variety of serotypes, some have been reported in other animal species (O2:H40, O5:H40) and in children with diarrhoea (O8:H-). Most of the strains carried intimin ß. The results indicate that chicken and chicken products are important sources of atypical EPEC strains that could be associated with human disease, and highlight the need to improve hygiene practices in chicken slaughtering and meat handling.
Assuntos
Galinhas , Escherichia coli Enteropatogênica/isolamento & purificação , Infecções por Escherichia coli/veterinária , Carne/microbiologia , Doenças das Aves Domésticas/epidemiologia , Animais , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Doenças das Aves Domésticas/microbiologia , PrevalênciaRESUMO
During periodontitis, alveolar bone resorption is associated with activation of T helper type 17 (Th17) lymphocytes and receptor activator of nuclear factor-κB ligand (RANKL) -induced osteoclasts. We previously reported that serotype b of Aggregatibacter actinomycetemcomitans has a higher capacity to trigger Th17-type differentiation and function in activated T lymphocytes and its lipopolysaccharide is a more potent immunogen compared with the other serotypes. This study aimed to investigate whether serotype b of A. actinomycetemcomitans induces higher Th17-associated RANKL production, RANKL-induced osteoclast activation, and antigen-specific memory T lymphocyte proliferation. On naive CD4(+) T lymphocytes stimulated with autologous dendritic cells primed with different A. actinomycetemcomitans serotypes, RANKL production, T-bet, GATA-3, RORC2 and Foxp3 expression, RORC2/RANKL intracellular double-expression, TRAP(+) osteoclast activation, and bone resorption were quantified. The frequency of proliferating memory T lymphocytes in response to A. actinomycetemcomitans serotypes was determined in periodontitis and healthy subjects. Naive CD4(+) T lymphocytes stimulated by serotype b-primed dendritic cells elicited higher levels of RANKL, RORC2, TRAP(+) osteoclasts, and bone resorption than the same cells stimulated with the other serotypes. RANKL positively correlated and co-expressed with RORC2. Memory T lymphocytes responding to serotype b were more frequently detected in periodontitis patients than healthy subjects. These results indicate that serotype b of A. actinomycetemcomitans is associated with higher production of RANKL and these increased levels are associated with Th17 lymphocyte induction, osteoclast activation, and bone resorption.