Impacto del tipo de hospital en la supervivencia de pacientes con mieloma múltiple: estudio MICORE / The impact of the type of hospital on survival of multiple myeloma patients: the MICORE study

Objetivo. Analizar el impacto del tipo de hospital en la supervivencia global de los pacientes con mieloma múltiple. Pacientes y método. Análisis de supervivencia de todos los pacientes (n=431) diagnosticados en 5 hospitales públicos (4 comarcales y uno universitario), durante el periodo 1993-2006. Resultados. Los pacientes atendidos en los hospitales comarcales difieren significativamente de los atendidos en el hospital de referencia en las siguientes variables: edad media (70 años [rango 31-92] versus 67,9 [rango 35-91]; p=0,038), porcentaje de pacientes en estadio iii (62,6 versus 69,1%; p=0,033), y porcentaje de pacientes sometidos a trasplante autólogo de médula ósea (8,2 versus 18,2%; p=0,026). En el análisis multivariante, las variables asociadas de forma significativa con la mortalidad fueron la edad (p<0,001), el estadio (iii respecto a i; p=0,03) y la insuficiencia renal (p=0,04). El tipo de hospital no alcanzó significación estadística (hazard ratio de 0,72 [intervalo de confianza al 95% 0,48-1,07], p=0,1). Conclusiones. El tipo de hospital no se asocia de forma significativa con la mortalidad en pacientes con mieloma múltiple. Estos datos apoyan el actual modelo de atención a estos pacientes, en el que los hospitales comarcales son responsables de su manejo primario, de forma coordinada con el hospital universitario (AU)

Objective. To analyze the impact of the type of hospital in overall survival of multiple myeloma patients. Patients and method. A survival analysis was performed of all patients (n=431) diagnosed in 5 public hospitals (4 community hospitals and one university hospital) during the period 1993-2006. Results. Patients attended to in community hospitals differ significantly from those seen in the university hospital in the following variables: mean age (70 years [31-92] versus 67.9 (35-91), P=.038); percentage of stage iii patients (62.6% versus 69.1%, P=.033), and percentage of patients who had autologous stem cell transplant (8.2% versus 18.2%, P=.026). The variables associated with mortality in the multivariate analysis were age (P<.001), stage (iii versus i; P=.03) and renal failure (P=.04). The type of hospital did not reach statistical significance (hazard ratio of 0.72 (95% confidence interval 0.48-1.07), P=.1]. Conclusions. The type of hospital is not significantly associated with mortality in multiple myeloma patients. These data support our current model of health care, in which the community hospitals are responsible for the primary care of these patients, in a coordinated work with the university hospital (AU)

The impact of the type of hospital on survival of multiple myeloma patients: the MICORE study.

OBJECTIVE: To analyze the impact of the type of hospital in overall survival of multiple myeloma patients. PATIENTS AND METHOD: A survival analysis was performed of all patients (n=431) diagnosed in 5 public hospitals (4 community hospitals and one university hospital) during the period 1993-2006. RESULTS: Patients attended to in community hospitals differ significantly from those seen in the university hospital in the following variables: mean age (70 years [31-92] versus 67.9 (35-91), P=.038); percentage of stage iii patients (62.6% versus 69.1%, P=.033), and percentage of patients who had autologous stem cell transplant (8.2% versus 18.2%, P=.026). The variables associated with mortality in the multivariate analysis were age (P<.001), stage (iii versus i; P=.03) and renal failure (P=.04). The type of hospital did not reach statistical significance (hazard ratio of 0.72 (95% confidence interval 0.48-1.07), P=.1]. CONCLUSIONS: The type of hospital is not significantly associated with mortality in multiple myeloma patients. These data support our current model of health care, in which the community hospitals are responsible for the primary care of these patients, in a coordinated work with the university hospital.

Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells.

BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin (LT)α(1)ß(2), cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP, factors involved in the differentiation (decidualization) of DSC. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, α-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LTα(1)ß(2). DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and cAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy.

[Long-term treatment with low molecular weight heparin, of chronic disseminated intravascular coagulation]. / Tratamiento a largo plazo de coagulación intravascular diseminada crónica con heparina de bajo peso molecular.

The term "disseminated intravascular coagulation" (DIC) defined a pathologic process which complicates the clinical course of many diseases; it is characterized by huge amounts of thrombin and plasmin within the circulation. There are a lot of causes of these intermediary mechanism of disease, among these, infections and neoplasia are the most frequent. Aortic aneurysm is a vascular disease than can be complicated with DIC. We report a case of a patient affected of chronic disseminated intravascular coagulation complicated with systemic hemorrhagic syndrome, of vascular origin (an aortic aneurysm). It was treated with a low molecular weight heparin (LMWH), but in the presence of an allergy disorder the drug was discontinued and substituted by another LMWH. The hemorrhagic complications were treated with antifibrinolytics associated to the LMWH. The drug was held up 30 months with an acceptable performance status and no significant secondary effects except osteoporosis.

Tratamiento a largo plazo de coagulación intravascular diseminada crónica con heparina de bajo peso molecular / Long-term treatment with low molecular weight heparin of chronic disseminated intravascular coagulation

El termino "Coagulación intravascular diseminada" (CID) define un proceso patológico que complica la evolución clínica de diversas enfermedades, se caracteriza por la presencia de grandes cantidades de trombina y plasmina en la circulación. La lista de posibles causas de este mecanismo fisiopatológico de la enfermedad es amplia, dentro de ellas la patologia infecciosa y tumoral son las más frecuentes; entre las menos frecuentes, la existencia de un aneurisma aórtico. Describimos el caso de un paciente afecto de CID crónica con clínica hemorrágica, que en el curso del estudio etiológico se diagnosticó de un aneurisma aórtico. Se inició tratamiento con una heparina de bajo peso molecular (HBPM), pero ante la aparición de un cuadro alérgico atribuido a la misma, se modificó el tratamiento sustituyéndola por otra HBPM. Las complicaciones hemorrágicas fueron tratadas asociando fármacos antifibrinolíticos a la HBPM. El tratamiento se mantuvo durante 30 meses con una aceptable calidad de vida asociada a la aparición de efectos secundarios generalmente menores salvo el desarrollo de osteporosis clínicamente significativa. (AU)

[Familial study of factor XI deficiency. Presurgical prophylactic treatment with desmopressin plus antifibrinolytics]. / Estudio familiar de déficit de factor XI. Tratamiento profiláctico prequirúrgico con desmopresina y antifibrinolíticos.

Factor XI deficiency is a rare inherited coagulation disorder. It rarely produces spontaneous bleeding although patients with this disorder are at risk for hemorrhagic complications after trauma or surgery. Because there is no clear correlation between the tendency to bleed and the severity of the disease itself, predicting hemorrhagic complications after surgery in patients with mild disease is difficult. This hereditary deficiency is characterized by prolongation of activated partial thromboplastin time with normal prothrombin time, and the demonstration of selective plasma factor XI deficit. Currently available products in the therapeutic arsenal are transfusion of fresh-frozen plasma, virus-inactivated factor XI concentrates, desmopressin (DDAVP) and antifibrinolytic drugs, whether alone or in combination. We describe a family with two affected children, in which the deficiency was identified as an autosomal recessive trait. Of the two patients, one required prophylactic treatment with desmopressin and tranexamic acid before surgery; the treatment was successful and no related complications were observed. The long-term outcome of individuals with this disease seems to be good with continuous follow up and early control of hemorrhagic episodes. Prophylactic therapy is not required, except when surgery is anticipated.

Estudio familiar de déficit de factor XI. Tratamiento profiláctico prequirúrgico con desmopresina y antifibrinolíticos / Familial study of factor xi deficiency. presurgical prophylactic treatment with desmopressin plus antifibrinolytics

La deficiencia de factor XI es una coagulopatía hereditaria poco frecuente, caracterizada por presentar raramente sintomatología hemorrágica espontánea, aunque sí existe el riesgo de complicaciones hemorrágicas graves inducidas por un traumatismo o cirugía. No se puede establecer una correlación clara entre los niveles de factor XI y la tendencia hemorrágica, por lo que es difícil predecir las posibles complicaciones hemorrágicas posquirúrgicas en pacientes con déficit leve. Este déficit se caracteriza por presentar un tiempo de tromboplastina parcial activado (TTPA) alargado, con un tiempo de protrombina (TP) normal, y la demostración mediante estudio con plasma deficiente de un déficit selectivo de factor XI. Las posibilidades terapéuticas y profilácticas en esta enfermedad incluyen: transfusión de plasma fresco congelado, concentrado de factor XI sometido a procesos de inactivación viral, fármacos antifibrinolíticos y desmopresina, ya sea como terapia única o combinada. Se describe una familia con los 2 hijos afectados en el que se demuestra una herencia autosómica recesiva del déficit. De los 2 casos, uno ha requerido tratamiento profiláctico prequirúrgico con desmopresina (DDAVP) y ácido tranexámico, con buena respuesta a éste, sin que presentara complicaciones asociadas al mismo. La evolución a largo plazo de este proceso parece ser buena, con un adecuado seguimiento y un control precoz de los episodios hemorrágicos. No es necesario realizar ningún tratamiento profiláctico, salvo en caso de cirugía (AU)

[Continuous treatment with colony stimulating factors (G-CSF) for neutropenia associated with type Ib glycogenosis]. / Tratamiento continuo con factores estimulantes de colonias (G-CSF) de la neutropenia asociada a la glucogenosis tipo Ib.

In the last few years, granulocyte colony stimulating factors (G-CSF), or hematopoietic growth factors, have created new possibilities for treating severe neutropenias, with high clinical efficacy and minimal adverse effects. Moreover, due to genetic recombinant techniques, the therapeutic use of these glycoproteins is increasing. We report the case of a 4-year-old girl who was diagnosed with glycogenosis IB at the age of 7 months. From the age of 2 years, she presented severe established neutropenia secondary to the main disease. Subcutaneus G-CSF therapy was started. The patient has shown no serious infections, has maintained normal growth and development, and has not required hospitalization. Adverse effects have been minimal. The therapeutic efficacy demonstrated by this case justifies the continuous use of G-CSF, although the lack of long-term perspectives should not be forgotten.

Tratamiento continuo con factores estimulantes de colonias (G-CSF) de la neutropenia asociada a la glucogenosis tipo Ib / Treatment with granulocyte colony stimulating factors for neutropenia in glycogenosis ib

En los últimos años, los factores estimulantes de colonias (CSF) o de crecimiento hemopoyético han abierto una vía para el tratamiento de las neutropenias graves, con alta eficacia clínica y efectos secundarios irrelevantes. Además, su uso se ha generalizado gracias a la síntesis mediante técnicas de recombinación genética. Se expone el caso clínico de una niña de 4 años, diagnosticada de glucogenosis Ib desde los 7 meses de vida. Desde hace 2 años presenta neutropenia grave establecida, derivada de la enfermedad principal. Se inició tratamiento con CSF de granulocitos (G-CSF) subcutáneo: la paciente no ha presentado infecciones de importancia, ha mantenido un crecimiento y desarrollo adecuados y no ha precisado hospitalización. Los efectos adversos han sido mínimos, hasta el momento. La eficacia terapéutica en este caso justifica el uso de G-CSF de manera continua, pero no debe olvidarse la falta de perspectiva temporal de dicho tratamiento (AU)

El uso de factores de crecimiento hematopoyéticos, ¿es seguro a largo plazo? / Is the long-term use of hematopoietic growth factors safe?

Los factores de crecimiento hematopoyéticos (G-CSF) son fármacos de reciente adquisición en nuestro arsenal terapéutico; su descubrimiento y posterior síntesis mediante técnicas de recombinación genética ha abierto una posibilidad de tratamiento en diversas situaciones clínicas en las que las opciones terapéuticas eran como mínimo limitadas. El tratamiento con G-CSF es generalmente bien tolerado, y sus escasos efectos secundarios, así como su facilidad de administración, son los responsables de su amplia utilización. Describimos el caso de una paciente de 16 años diagnosticada de neutropenia cíclica a los 9, tratada desde entonces con G-CSF por vía subcutánea mediante autoadministración. Después de un seguimiento de 66 meses, la paciente no ha padecido efectos secundarios relevantes, su calidad de vida es buena y únicamente ha necesitado antibioticoterapia en 2 ocasiones durante estos 7 años. Por tanto, la utilidad clínica del tratamiento con G-CSF, medida en términos de calidad de vida, es evidente, ya que permite el desarrollo de la actividad habitual para su edad, sin complicaciones infecciosas ni consultas médicas continuas (AU)

[Basophilic blast crisis in chronic myeloid leukemia]. / Crisis blástica basófila de leucemia mieloide crónica.

Acute basophilic leukaemia is usually characterized by a very rapid clinical course, hyperhistaminemia, resistance to antineoplastic therapy and early death due to complications related to disease. This entity is a rare condition, accounting for less than two percent of all haematopoietic malignancies. Most of the case reports are basophilic blast crisis in patients with a previous lympho or myeloproliferative disorder. A 62-year-old woman who was diagnosed as Philadelphia positive chronic myelogenous leukaemia after four years of evolution developed a basophilic blast crisis, whose characteristics are reported. Accompanying this transformation there was also a cytogenetic change. Despite chemotherapy the patient died of disease progression.