RESUMEN
Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis the regular administration of therapeutic products to maintain hemostasis and prevent bleeding is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs.
Asunto(s)
Humanos , Masculino , Femenino , Factor VIII/uso terapéutico , Hemofilia B/prevención & control , Hemofilia A/prevención & controlRESUMEN
The history of hemophilia is ancient, with descriptions dated to the 2nd century AD. The first modern narratives appeared in 1800s, when total blood transfusion was the only available treatment and life expectancy was remarkably low. Advances occurred with the use of plasma and cryoprecipitate, but only the discovered of factor concentrates revolutionized the treatment. The implantation of prophylaxis allowed hemophilic patients to prevent bleeding and the development of chronic arthropathy, although with a significant burdensome with the regular infusions. In the past 20 years, this field has witnessed major improvements, including the development of gene therapy and other pharmacological approaches.
Asunto(s)
Humanos , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Factor IX/historia , Factor VIII/historia , Hemofilia B/historia , Hemofilia A/historia , Hemofilia B/terapia , Hemofilia A/terapiaRESUMEN
Multiple myeloma (MM) is a malignant neoplasm of monoclonal plasma cells that accumulate in bone marrow (BM). Malignant pleural effusions (MPE), as part of multiple myeloma clinical presentation, are unusual. Is even more rare as the first sign of presentation, occurring in less than 1% of the cases. The most common associated immunoglobulin with malignant pleural effusions is IgA subtype (80%). This condition carry a poor prognosis. We aim to describe a refractory case of multiple myeloma with extensive disease that presented with extramedullary relapse with malignant pleural effusions , besides discussing the importance of differential diagnosis.
O mieloma múltiplo (MM) é uma neoplasia maligna de células plasmáticas monoclonais que se acumulam na medula óssea (MO). Os derrames pleurais malignos (EPM), como parte da apresentação clínica do mieloma múltiplo, são incomuns. É ainda mais raro como primeiro sinal de apresentação, ocorrendo em menos de 1% dos casos. A imunoglobulina associada mais comum a derrames pleurais malignos é o subtipo IgA (80%). Esta condição carrega um mau prognóstico. Nosso objetivo é descrever um caso refratário de mieloma múltiplo com doença extensa que apresentou recidiva extramedular com derrame pleural maligno, além de discutir a importância do diagnóstico diferencial
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Derrame Pleural Maligno/etiología , Mieloma Múltiple/complicaciones , Inmunohistoquímica , Radiografía , Leucemia de Células Plasmáticas/diagnóstico , Tomografía Computarizada por Rayos X , Derrame Pleural Maligno/patología , Derrame Pleural Maligno/diagnóstico por imagen , Resultado FatalAsunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 7/genética , Factor de Transcripción GATA2/genética , Trasplante de Células Madre Hematopoyéticas , Deficiencia de IgG , Adolescente , Niño , Femenino , Humanos , Deficiencia de IgG/genética , Deficiencia de IgG/patología , Deficiencia de IgG/terapiaRESUMEN
Predicting the individual response to chemotherapy is a crucial challenge in cancer treatment. DNA damage caused by antitumor therapies evokes different repair mechanisms responses, such as Nucleotide Excision Repair (NER), whose components are being studied as prognosis biomarkers and target therapies. However, few reports have addressed DNA damages in pediatric Acute Lymphoid Leukemia (ALL). Hence, we conducted an observational follow-up study with pediatric patients to assess DNA damage (by Comet Assay) and gene expression from NER pathway during chemotherapy induction. Bone marrow samples from diagnosis, 15th(D15) and 35th (D35) days of the treatment were collected from 28 patients with ALL. There was no increase in damage index. However, there was a reduction of cells with low damages on D35 compared with diagnosis. NER pathway expression remained the same, however, in a single patient, a significant decrease was observed, maybe due to silencing or downregulation of repair pathways. DNA damage levels and repair may influence the clinical outcome, being involved in drug resistance and risk of relapse. In pediatric ALL, we analyzed for the first time DNA damage and repair behavior in BM samples. Monitoring patient's outcomes will help to access the implication of our findings in survival and relapse rates.
Asunto(s)
Daño del ADN/efectos de los fármacos , Quimioterapia de Inducción/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Médula Ósea/patología , Niño , Ensayo Cometa , Reparación del ADN , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Factores de TiempoRESUMEN
BACKGROUND: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related receptor kinase B (TrkB) are involved in the maturation of B lymphocytes in the bone marrow (BM), promote cell differentiation in B-cell malignancies, and are associated with poor prognosis in adults with acute leukemia (AL). However, the role of BDNF in pediatric AL remains poorly understood. OBJECTIVE: We carried out a cohort observational study to evaluate BDNF levels in BM or peripheral blood (PB) samples from children with AL. METHODS: BM or PB samples were collected from 57 children and adolescents with acute lymphoid leukemia (ALL), 14 children and adolescents with acute myeloid leukemia (AML), and 44 healthy individuals (HI) of the same age range. RESULTS: BDNF levels at diagnosis in AL patients were significantly lower when compared to HI. Samples from patients in complete remission from disease had higher levels of BDNF compared to those obtained from patients with malignant cells. Moreover, BDNF levels at diagnosis in patients who died were significantly lower compared to those found in survivors. CONCLUSIONS: These findings provide the first evidence for a possible role of BDNF as a marker of active disease and poor prognosis in pediatric AL.