Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Eur J Haematol ; 111(2): 293-299, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37232041

RESUMO

OBJECTIVE: To assess the impact of prophylaxis with rIX-FP, a fusion protein linking recombinant factor IX (FIX) with human albumin, on joint outcomes. METHODS: Joint outcomes were assessed in pediatric (<12 years) and adult/adolescent (≥12 years) patients receiving rIX-FP prophylaxis every 7, 10, or 14 days; patients (>18 years) well-controlled on a 14-day regimen could switch to a 21-day regimen. Target joints were defined as ≥3 spontaneous bleeds into a single joint within a 6-month period. RESULTS: For adult/adolescent (n = 63) and pediatric (n = 27) patients, median (Q1, Q3) annualized joint bleeding rate was 0.39 (0.00, 2.31), 0.80 (0.00, 2.85), 0.20 (0.00, 2.58), and 0.00 (0.00, 1.78) when treated with 7-, 10-, 14-, or 21-day prophylaxis. 50.0%, 38.9%, 45.5%, and 63.6% of adult/adolescent patients had no joint bleeds when treated with 7-, 10-, 14-, or 21-day prophylaxis, respectively, and 40.7%, 37.5%, and 37.5% of pediatric patients had no joint bleeds when treated with 7-, 10-, or 14-day prophylaxis. Ten adult and two pediatric patients developed target joints; all resolved by the end of the study. CONCLUSION: Prophylaxis with rIX-FP produced low joint bleeding rates and provided excellent hemostatic efficacy in the treatment of joint bleeds. All target joints reported resolved with rIX-FP prophylaxis.


Assuntos
Hemofilia A , Hemofilia B , Adulto , Adolescente , Humanos , Criança , Fator IX/uso terapêutico , Hemofilia B/complicações , Hemofilia B/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Hemostasia , Hemartrose/etiologia , Hemartrose/prevenção & controle , Hemofilia A/tratamento farmacológico
2.
J Clin Immunol ; 41(8): 1878-1892, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34477998

RESUMO

Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).


Assuntos
Ataxia Telangiectasia/imunologia , Ataxia Telangiectasia/mortalidade , Linfócitos B/imunologia , Deficiência de IgA/imunologia , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Deficiência de IgA/mortalidade , Deficiência de IgG/imunologia , Deficiência de IgG/mortalidade , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Rheumatol Int ; 38(9): 1705-1712, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29992441

RESUMO

Juvenile osteochondritis dissecans (JOCD) and juvenile idiopathic arthritis (JIA) are both common diseases which may affect joints and bony structures in pediatric patients. In some cases, JOCD and JIA occur at the same time. In this study, the course of JOCD in patients with JIA was therefore evaluated to provide possible recommendations for further treatment opportunities and control examinations. From 06/2012 to 03/2018 55 children with JOCD with or without JIA were examined. Inclusion criteria were: (1) age ≤ 16 years, (2) diagnosis of a JOCD with or without JIA and (3) two routine MRI controls. The JOCD evaluation based on the classification according to Bruns and the measurement of the largest extent via MRI. 18 of these 55 children met our criteria: 11 JOCD findings of 7 patients with JIA (group A) were matched according to age and localization of JOCD to 11 patients without JIA (group B). Mean age of disease onset of JIA was 8.2 years (oligo JIA) and of JOCD 11.6 years. The mean time follow-up was 17.7 months. At all observation time points more JOCD findings (with stage III° and IV°, respectively) along with a significant deterioration was seen in group A compared to group B. The comparison of the last MRI control between group A and group B shows a significant smaller defect size (decrease of 54.5%, p = 0.028) in group B (97.9 ± 48.9 mm2) as in group A (185.1 ± 102.9 mm2). In comparison of first (169.7 ± 84.2 mm2) and last MRI (97.9 ± 48.9 mm2) a significant decrease in lesion size of JOCD in group B was seen (decrease of 58.4%, p = 0.048). Patients with JIA show a more progressive and severe course of JOCD. Therefore, we recommend (1) the early use of MRI in patients with JIA and persistent joint pain to detect potential JOCD and (2) in presence of JIA and JOCD regular MRI follow-up controls to identify deteriorating JOCD findings and prevent early joint destruction in pediatric patients.


Assuntos
Artrite Juvenil/patologia , Progressão da Doença , Osteocondrite Dissecante/patologia , Adolescente , Artrite Juvenil/classificação , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Osteocondrite Dissecante/classificação , Osteocondrite Dissecante/complicações , Osteocondrite Dissecante/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
Immunol Cell Biol ; 95(7): 630-639, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28377612

RESUMO

Aberrantly activated CD4+ T memory cells play a central role in the development of type-1-diabetes. Interleukin-7 promotes generation of autoimmune memory T cells and increased Interleukin-7 availability is associated with type-1-diabetes susceptibility. T-cell-mediated immune pathology at onset of type-1-diabetes is well defined, but characteristics of long-term symptomatic disease stages remain largely elusive. In the present study, memory CD4+ T-cell activation and cytokine expression as well as sensitivity to Interleukin-7 in vitro were compared between patients with type-1-diabetes at clinical onset (n=25), long-term symptomatic disease (median duration 4.5 years, n=19) and matched healthy controls (n=21). T-cell responses of type-1-diabetes patients were characterized by higher frequencies of cytokine and activation marker expressing CD4+ memory T cells as compared to healthy controls. Notably, correction for individual cytokine expression levels revealed qualitative differences of cytokine profiles characterized by significantly increased TNFα and decreased IL-2-expressing T-cell proportions in long-term type-1-diabetes patients. IL-7-mediated T-cell co-stimulation induced quantitative and qualitative cytokine expression differences highly similar to type-1-diabetes-specific profiles. In addition, CD4+ memory T cells from children with long-term type-1-diabetes were more sensitive to in vitro IL-7 co-stimulation. Global transcriptome analysis revealed IL-7 induced expression differences of CD4+ T cells, including increased IL-2R expression and effects on subsequent T-cell receptor activation. We conclude that long-term symptomatic type-1-diabetes patients differed in memory T-cell cytokine profiles and Interleukin-7 co-stimulation. Regulation of IL-2 expression and sensitivity are affected with possible consequences for disease course and severity at long-term type-1-diabetes stages.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Interleucina-2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Linfócitos T CD4-Positivos/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Memória Imunológica/efeitos dos fármacos , Interferon gama/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-7/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores CCR7/metabolismo
5.
Haematologica ; 101(11): 1295-1305, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27742768

RESUMO

The morbidity and toxicity associated with current intensive treatment protocols for acute lymphoblastic leukemia in childhood become even more important as the vast majority of children can be cured and become long-term survivors. Osteonecrosis is one of the most common therapy-related and debilitating side effects of anti-leukemic treatment and can adversely affect long-term quality of life. Incidence and risk factors vary substantially between study groups and therapeutic regimens. We therefore analyzed 22 clinical trials of childhood acute lymphoblastic leukemia in terms of osteonecrosis incidence and risk factors. Adolescent age is the most significant risk factor, with patients >10 years old at the highest risk. Uncritical modification or even significant reduction of glucocorticoid dosage cannot be recommended at this stage. A novel and innovative approach to reduce osteonecrosis-associated morbidity might be systematic early screening for osteonecrosis by serial magnetic resonance images. However, discriminating patients at risk of functional impairment and debilitating progressive joint disease from asymptomatic patients still remains challenging.


Assuntos
Osteonecrose/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Osso e Ossos/irrigação sanguínea , Criança , Humanos , Osteonecrose/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Qualidade de Vida , Fatores de Risco
6.
BMC Pregnancy Childbirth ; 13: 22, 2013 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-23347580

RESUMO

BACKGROUND: Antiretroviral drugs including zidovudine (ZDV) are effective in reducing HIV mother to child transmission (MTCT), however safety concern remains. The optimal duration of postnatal ZDV has not been established in clinical studies and there is a lack of consensus regarding optimal management. The objective of this study was to investigate the effectiveness and safety of a risk adapted two week course of oral postnatal ZDV as part of a combined intervention to reduce MTCT. METHODS: 118 mother infant pairs were treated according to the German-Austrian recommendations for HIV therapy in pregnancy and in HIV exposed newborns between 2000-2010. In the absence of factors associated with an increased HIV-1 transmission risk, children were assigned to the low risk group and treated with an abbreviated postnatal regimen with oral ZDV for 2 weeks. In the presence of risk factors, postnatal ZDV was escalated accordingly. RESULTS: Of 118 mother-infant pairs 79 were stratified to the low risk group, 27 to the high risk group and 11 to the very high risk group for HIV-1 MTCT. 4 children were lost to follow up. Overall Transmission risk in the group regardless of risk factors and completion of prophylaxis was 1.8% (95% confidence interval (CI) 0.09-6.6). If transmission prophylaxis was complete, transmission risk was 0.9% (95% CI 0.01-5.7). In the low risk group receiving two week oral ZDV transmission risk was 1.4% (95% CI 0.01-8.4) CONCLUSION: These data demonstrate the effectiveness of a short neonatal ZDV regimen in infants of women on stable ART and effective HIV-1 suppression. Further evaluation is needed in larger studies.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/administração & dosagem , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Quimioterapia Combinada , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Humanos , Recém-Nascido , Lamivudina/administração & dosagem , Masculino , Nevirapina/administração & dosagem , Gravidez , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Zidovudina/efeitos adversos
7.
J Pediatr Hematol Oncol ; 34(4): 283-92, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22531495

RESUMO

Because of the diversity of clinical symptoms, the diagnosis of mitochondrial DNA (mtDNA) deletion disorders can be difficult. Here, we describe an 8-month-old boy presenting clinically exclusively with refractory anemia. Mutation analysis in our patient revealed a large, novel deletion in his mtDNA encompassing ATPase 6, cytochrome oxidase subunit III, NADH dehydrogenase genes ND3 to ND6, and cytochrome b. Comparison with other cases from the literature showed that there is no genotype-phenotype correlation regarding hematologic features. It is not possible to predict whether our patient will develop additional features from Pearson syndrome or Kearns-Sayre syndrome, both syndromic mitochondrial disorders with hematological manifestations.


Assuntos
Anemia Refratária/genética , Anemia Sideroblástica/genética , DNA Mitocondrial/genética , Síndrome de Kearns-Sayre/genética , Doenças Mitocondriais/genética , Deleção de Sequência , Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Síndrome Congênita de Insuficiência da Medula Óssea , Análise Mutacional de DNA , Humanos , Lactente , Erros Inatos do Metabolismo Lipídico , Masculino , Proteínas Mitocondriais/genética , Doenças Musculares
8.
Blood ; 112(4): 1028-34, 2008 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-18552209

RESUMO

CD40 and CD27, members of the tumor necrosis factor receptor (TNFR) family, are critical regulators of lymphocyte growth and differentiation. In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), we prospectively assessed the impact of CD40 and CD27 on outcome in 121 children treated according to the CoALL06-97 protocol. Expression of both CD40 and CD27 was found to be significantly higher in low- than in high-risk patients as defined by standard clinical risk parameters such as age and white blood cell count. In addition, in multivariable analysis, a very high percentage of CD40(+) blasts at diagnosis was identified as an independent favorable prognostic factor for relapse-free survival. Of note, high CD40 expression particularly protected against late relapse. In B cells, CD40 is known to enhance both antigen-presenting capacity and sensitivity to proapoptotic signals. Yet, although CD40 ligation does result in significant up-regulation of CD80/CD86 in our cohort, it is up-regulation of the death receptor CD95 that significantly correlates with the percentage of CD40(+) blasts. Thus very high expression of CD40 on BCP-ALL blasts is an independent prognostic marker indicative of superior relapse-free survival that may in part be due to CD40-dependent death receptor up-regulation.


Assuntos
Antígenos CD40/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Receptor fas/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Humanos , Lactente , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/análise , Regulação para Cima/genética
9.
Haematologica ; 92(8): 1043-50, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17640858

RESUMO

BACKGROUND AND OBJECTIVES: Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood. DESIGN AND METHODS: In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL. RESULTS: Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis. INTERPRETATION AND CONCLUSIONS: Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.


Assuntos
Proteínas Inibidoras de Apoptose/análise , Proteínas Associadas aos Microtúbulos/análise , Proteínas de Neoplasias/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Adolescente , Apoptose , Medula Óssea/patologia , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Lactente , Proteínas Inibidoras de Apoptose/fisiologia , Estimativa de Kaplan-Meier , Masculino , Proteínas Associadas aos Microtúbulos/fisiologia , Proteínas de Neoplasias/fisiologia , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Survivina , Resultado do Tratamento
10.
Pediatrics ; 123(3): 877-84, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19255017

RESUMO

OBJECTIVE: We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis. METHODS: This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m(2) on day 1, followed by 50 mg/m(2) per day (maximum: 70 mg/day), as primary or salvage monotherapy. Favorable response was defined as complete resolution of clinical findings and microbiologic (or radiographic/endoscopic) eradication (complete response) or significant improvement in these parameters (partial response). Efficacy was assessed at the end of caspofungin therapy in patients with a confirmed diagnosis who received >/=1 dose of caspofungin. The primary safety evaluation was the proportion of patients with clinical or laboratory drug-related adverse events. RESULTS: Of the 49 patients enrolled, 3 were <2 years of age, 30 were 2 to 11 years of age, and 16 were 12 to 17 years of age. Forty-eight patients had confirmed disease: invasive aspergillosis (10), invasive candidiasis (37), and esophageal candidiasis (1). Eight of 10 patients with invasive aspergillosis had pulmonary involvement; 34 of 37 patients with invasive candidiasis had candidemia. Caspofungin was given for 2 to 87 days. Success at end of therapy was achieved in 5 of 10 patients with invasive aspergillosis, 30 of 37 with invasive candidiasis, and 1 of 1 with esophageal candidiasis. One patient (invasive candidiasis) relapsed during the 28-day follow-up period. Drug-related clinical or laboratory adverse events occurred in 27% and 35% of patients, respectively. There were no serious drug-related adverse events or discontinuations of caspofungin because of toxicity. CONCLUSIONS: Caspofungin was generally well tolerated in pediatric patients aged 6 months through 17 years. Efficacy outcomes in patients with invasive aspergillosis or invasive candidiasis were consistent with previous adult studies in these indications.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Candidíase/tratamento farmacológico , Equinocandinas/uso terapêutico , Doenças do Esôfago/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Aspergilose Pulmonar/tratamento farmacológico , Adolescente , Antifúngicos/efeitos adversos , Caspofungina , Criança , Pré-Escolar , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Equinocandinas/efeitos adversos , Feminino , Humanos , Lactente , Infusões Intravenosas , Lipopeptídeos , Testes de Função Hepática , Masculino , Estudos Prospectivos , Recidiva , Resultado do Tratamento
11.
Br J Haematol ; 139(3): 450-7, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17910636

RESUMO

Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11-100%). In patients classified as low-risk at diagnosis, p75NTR expression was significantly higher than in high-risk patients (P = 0.001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0.038). Accordingly, relapse-free survival was significantly better in patients expressing high surface p75NTR (P = 0.041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas do Tecido Nervoso/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangue , Receptores de Fator de Crescimento Neural/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Lactente , Contagem de Leucócitos , Masculino , Proteínas de Neoplasias/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA