ABSTRACT
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19pos, CD27neg, CD38lo, CD45pos, CD81pos, CD117neg and CD138lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38lowCD81posCD117neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.
Subject(s)
Antigens, CD/metabolism , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm, Residual/metabolism , Neoplasm, Residual/pathology , PrognosisABSTRACT
Objetivo: evaluar la diferencia de los valores de Presión arterial (PA) entre ambos brazos, medida simultáneamente, durante una prueba de esfuerzo. Diseño del estudio: estudio transversal. Series de casos. Nivel de evidencia: 3. Material y Métodos: La población se compone de 225 deportistas sanos que realizaron una prueba de esfuerzo en nuestro centro. 128 hombres y 97 mujeres. Edad: 17± 5,5 años. Resultados: La PA tanto sistólica como diastólica no difiere significativamente entre ambos miembros superiores. No obstante, hemos encontrado casos de variabilidad individual donde la PA predomina en un brazo durante el reposo y en el otro brazo durante el máximo esfuerzo. Los valores de TA son independientes del brazo dominante. Conclusiones: La posibilidad que el brazo donde predomina la PA de Reposo no coincida durante el máximo esfuerzo, hace necesario, en nuestra opinión, que se mida la PA en ambos miembros superiores durante la prueba de esfuerzo (AU)
Objective: To evaluate different blood pressure readings between both arms. Study design: cross-sectional study. Case series. Level of evidence: 3. Methods: a population of 225 healthy athletes underwent stress tests in our center: 128 males and 97 females. Age range: 17 +/- 5.5 years. Results: no significant differences in systolic or diastolic blood pressure readings were found between the right or left arm. We did, however, find cases where blood pressure is higher in one arm while resting and in the other arm during maximal exercise. Blood pressure readings were not associated with the dominant arm. Conclusions: The possibility that the arm in which there is a predominant rest blood pressure does not coincide during maximum stress, makes it necessary, according to our judgment, to measure blood pressure in both upper limbs during stress tests (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Arterial Pressure/physiology , Monitoring, Physiologic/methods , Exercise Test/instrumentation , Physical Exertion/physiology , Arm/physiology , Exercise Test/standards , Sports/physiology , Cross-Sectional Studies , Helsinki Declaration , Informed Consent/standardsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , High-Throughput Nucleotide Sequencing/methods , Multiple Myeloma/drug therapy , Neoplasm, Residual/physiopathology , Aged , Female , Humans , Male , Monitoring, Physiologic , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Survival AnalysisABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Chylothorax/diagnosis , Chylothorax/epidemiology , Chylothorax/therapy , Thoracic Duct/surgery , Thoracic Duct/injuries , LigationABSTRACT
Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.
Subject(s)
Multiple Myeloma/genetics , Cell Separation , Coculture Techniques , Disease Progression , Drug Resistance, Neoplasm , Flow Cytometry , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Multiple Myeloma/classification , Phenotype , Plasma Cells/cytology , Principal Component Analysis , Prognosis , Stromal Cells/cytologyABSTRACT
Introducción. Los síndromes de Distonía-Parkinsonismo son distonías plus, en las que además de manifestaciones distónicas, hay otros trastornos del movimiento asociados, en este caso parkinsonismo. Objetivo. Realizar una actualización y revisión bibliográfica de los síndromes de Distonía-Parkinsonismo. Desarrollo. Se revisan las manifestaciones clínicas, diagnóstico, tratamiento y pronóstico de: Parkinsonismo-distonía ligado al cromosoma X, Distonía con respuesta a levodopa, Distonía-parkinsonismo de inicio rápido, y Distonía-parkinsonismo precoz. Y se realiza un diagnóstico diferencial con otras causas que cursan con una combinación de síntomas de parkinsonismo y distonía. Conclusiones. Se encuentran identificadas múltiples causas, entre las distonías monogénicas se han identificado aproximadamente 20, de acuerdo al trastorno genético causal. La mayoría de los tratamientos son de tipo sintomático, esperando que en el futuro el mejor conocimiento de las alteraciones genéticas, brinde posibilidades terapéuticas efectivas (AU)
Introduction. Dystonia-parkinsonism syndromes are dystonias-plus, in which, in addition to dystonic manifestations, there are also other associated movement disorders - in this case parkinsonism. Aims. The aim of this study is to carry out an updated review of the literature on Dystonia-parkinsonism syndromes. Development. The study reviews the clinical manifestations, diagnosis, treatment and prognosis of X-linked dystoniaparkinsonism, dopa-responsive dystonia, rapid-onset dystonia-parkinsonism and early-onset dystonia-parkinsonism. Differential diagnosis is also performed with other causes that are accompanied by a combination of symptoms of parkinsonism and dystonia. Conclusions. A number of different causes have been identified - approximately 20 among the monogenic dystonias, according to the causal genetic disorder. Most of the treatments are of the symptomatic type, although in the future a deeper understanding of genetic disorders is expected to yield effective therapeutic possibilities (AU)
Subject(s)
Humans , Male , Female , X Chromosome/genetics , Levodopa/administration & dosage , Dystonia/physiopathology , Tomography Scanners, X-Ray Computed/standards , Therapeutics/methods , Dystonia/diagnosis , X Chromosome/classification , Levodopa , Dystonia/complications , Tomography Scanners, X-Ray Computed , Therapeutics/instrumentationABSTRACT
No disponible
No disponible
Subject(s)
Female , Adult , Humans , Flunarizine/adverse effects , Hallucinations/chemically induced , Calcium Channel BlockersABSTRACT
FUNDAMENTO: La elevada prevalencia de la Enfermedad pulmonar obstructiva crónica (EPOC) en nuestro medio provoca un considerable gasto sanitario. PACIENTES Y METODO: Se realizó un estudio prospectivo desde los años 1996-1999 en el que se analizan los gastos derivados de costes directos (medicación, exploraciones complementarias y asistencia, que incluye atención médica e ingresos hospitalarios) en 336 pacientes con EPOC seguidos durante un año en una consulta extrahospitalaria de neumología, y su relación con el grado de afectación funcional respiratoria de los mismos. RESULTADOS: El gasto medio global fue de 893 por paciente/año, distribuyéndose el mismo en un 46% (409), debidos a los gastos en asistencia, 43% (384) por medicación y el 11% (100) por técnicas complementarias. El gasto total y sus apartados de medicación y técnicas complementarias se correlacionó con peor situación funcional. Este hecho no ocurrió con el apartado de gasto por asistencia. CONCLUSIÓN: El coste directo en pacientes EPOC es elevado, siendo el mayor porcentaje debido a la asistencia. Los pacientes más deteriorados funcionalmente presentan mayores gastos, pero no necesariamente mayor coste por ingreso (AU)
INTRODUCTION: Chronic obstructive disease is a high prevalece disease which is increased with age and elevated cost. OBJETIVE: To estimate the direct medical cost of patients with chronic obstructive pulmonary disease(COPD) followed one year in a neumology consult, and the relationship with their respiratory function status. We perform a prospective study in 1996 which include 336 patients, and was analized the cost due to medications, diagnosis procedures and physician services. RESULTS: mean cost were 893 , including 46% (409), derived for physician services, 43% (384) for medications and 11% for diagnosis procedures. The global cost and each part of medication cost and diagnosis procedures cost were related with a deteriorated funcional status but we dont found this correlation with physician services costs. We didnt found correlation of mayor cost with age. CONCLUSION: The cost due of patients with COPD is high, especially the percentage of physician services. The more deteriorated functional status the more cost, but it not included hospital care cost (AU)
Subject(s)
Humans , Direct Service Costs/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/economics , Bronchitis, Chronic/economics , Pulmonary Disease, Chronic Obstructive/epidemiology , Ambulatory Care Facilities/economics , Economics, Hospital/statistics & numerical data , Bronchitis, Chronic/epidemiologyABSTRACT
Introducción: En los últimos años se han publicado varios estudios en los que se ha propuesto que el alelo e4 del gen de la apolipoproteína E (APOE) es un marcador de progresión de la esclerosis múltiple. Pretendemos evaluar la validez de dicha determinación en nuestro medio. Pacientes y métodos: Se estudian 42 pacientes con esclerosis múltiple en su forma remitente recidivante o secundaria progresiva y de más de 2 años de evolución. Se correlaciona la presencia o ausencia del alelo e4 de la APOE con diferentes marcadores clínicos de progresión de la enfermedad, como son las edades de inicio y diagnóstico, años de evolución, número total de brotes, puntuaciones EDSS a los 1, 2, 5 y 10 años, índice de progresión y tasa de brotes. Resultados: Ninguno de los parámetros evaluados se correlaciona significativamente con la presencia o ausencia del alelo e4 de la APOE. Conclusiones: A pesar de la limitación impuesta por el pequeño número de casos estudiados, nuestro estudio no demuestra que el alelo e4 del gen de la APOE tenga valor como marcador pronóstico de la esclerosis múltiple (AU)
Subject(s)
Middle Aged , Adult , Male , Female , Humans , Polymorphism, Genetic , Polymorphism, Genetic , Spain , Disease Progression , Multiple Sclerosis , Apolipoproteins E , Alleles , Genotype , Predictive Value of TestsABSTRACT
No disponible
Subject(s)
Aged , Male , Humans , Spondylitis, Ankylosing , Glomerulonephritis, MembranousABSTRACT
La amiloidosis secundaria es una complicación frecuente de distintos trastornos inflamatorios e infecciosos crónicos. Aunque inicialmente la patología asociada con mayor frecuencia eran las infecciones crónicas, como la tuberculosis o la sífilis, en la actualidad se presenta más frecuentemente en relación con procesos reumatológicos, fundamentalmente la artritis reumatoide. Presentamos el caso de una mujer de 16 años, diagnosticada de tuberculosis pulmonar con un síndrome nefrótico, y cuya biopsia renal demuestra la presencia de una amiloidosis. El tratamiento de la enfermedad causal llevó a la remisión clínica del cuadro renal dos años más tarde (AU)
