A mutação do gene SLC11A2 está associada à anemia por deficiência de ferro refratária após cirurgia bariátrica? / Does slc11a2 gene mutation associate with iron-refractory iron-deficiency anemia after bariatric surgery?

ABSTRACT - BACKGROUND: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.

RESUMO - RACIONAL: Após cirurgia bariátrica, se houver anemia por deficiência de ferro e não responder à terapia de ferro suplementar, excluindo-se outras possíveis etiologias, alterações genéticas envolvidas no metabolismo férrico devem ser consideradas. OBJETIVO: Investigar a associação das mutações 1285G-C e 1246C-T, no gene SLC11A2, e a etiopatogênese da anemia refratária à suplementação de ferro em pacientes submetidos à cirurgia bariátrica pela técnica de derivação gástrica em Y-de-Roux. MÉTODOS: Estudo de caso-controle, no qual forma avaliados 100 pacientes em Grupos de Casos (subdividido em Grupo I - com Anemia e Grupo II - sem Anemia) e 100 indivíduos como Controles, de ambos os sexos. Causas hereditárias e adquiridas de anemia ferropriva refratária ao ferro, foram excluídas. O DNA foi extraído de leucócitos de sangue periférico e as regiões que abrangem ambas as mutações foram amplificadas pelas técnicas moleculares de Reação em Cadeia da Polimerase/Polimorfismo do Comprimento do Fragmento de Restrição. RESULTADOS: A mutação 1285G-C não foi determinada em quaisquer dos 400 alelos analisados. Em relação à mutação 1246C-T, o genótipo homozigoto selvagem CC foi encontrado com maior prevalência nos Controles (34%) (OR: 0,5475; 95%IC: 0,2920-1,027; p=0,0827). O genótipo homozigoto mutante TT foi encontrado apenas no Grupo I - com Anemia (13%). CONCLUSÃO: Os resultados demonstram a associação da mutação 1246C-T, no gene SLC11A2, e a etiopatogênese da anemia ferropriva refratária e persistente à suplementação de ferro, nesta amostra de pacientes. Há diferenças, em nível molecular, em pacientes com e sem anemia ferropriva refratária ao ferro após cirurgia bariátrica por derivação gástrica em Y-de-Roux.

Analysis on clinical efficacy and influencing factors of decitabine-based regimens in patients with myelodysplastic syndrome-refractory anemia with excess blasts / 中国医师杂志

Objective To analyze the clinical efficacy,safety and influencing factors of decitabine (DAC)-based regimens in patients with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB).Methods We performed a retrospective analysis of 63 patients with MDS-RAEB treated with DAC,evaluated the clinical efficacy and adverse reactions,and analyzed the influencing factors affecting survival.Results Among 63 patients,23 were RAEB-1 and 40 were RAEB-2.The median treatment was 4 (2-13) courses.The total effective rate of DAC for MDS-RAEB was 58.7％ (37/63),and the complete response rate was 20.6％ (13/63).Among 37 patients who were effective,20 (54.1％) patients performed efficacy after 2 courses.The median course of treatment to achieve the best effect was 3.5 (3-4) courses.With a median follow-up of 14 (2-68) months,63 patients had a overall survival rate (OS) of 84.2％ and a 1-year progression-free survival rate (PFS) of 73％.In univariate analysis,the factors that prolonged OS were that the best effect after medication was stable disease (SD) (to achieve complete remission,partial remission,complete bone marrow remission,hematological improvement) (P =0.009) and no thrombocytopenia at first diagnosis (P =0.019),the factor that prolongs PFS is the best effect above SD (P =0.003).Multivariate analysis suggested that the factors affecting OS and PFS were the best curative effects above SD (P =0.015 vs P =0.008).The adverse effects of decitabine in the treatment of MDSRAEB were mainly bone marrow suppression and pulmonary infection.Conclusions Decitabine is an effective and well-tolerated drug in the treatment of MDS-RAEB.Response to decitabine treatment is one of the independent factors affecting the prognosis.

Clinical research of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura / 中国医师进修杂志

Objective To investigate the efficacy and safety of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura. Methods Thirty-three patients with refractory idiopathic thrombocytopenic purpura received intravenous rituximab at the dose of 100 mg once a week for 4 consecutive weeks. Complete blood cell count and serum concentrations of immunoglobulin (IgG,IgM and IgA) were monitored regularly. The numbers of CD3+ and CD19+ CD20+ lymphocyte cells were assayed by flow cytometry before and after therapy. Twenty-five patients with responses(complete response and response) were divided into maintained group (12 patients) and control group (13 patients) by random digits table method. The patients in maintained group were treated with rituximab 100 mg every 6 months. The efficacy of maintenance therapy was evaluated through long-term follow-up. Results The complete response(CR) rate, response (R) rate and no response(NR) rate were 48.48%(16/33), 27.27%(9/33) and 24.24% (8/33), respectively. As a result, total effective rate was 75.76% (25/33). There were no significant changes of peripheral blood white blood cell count,hemoglobin,serum immunoglobulin and CD3+lymphocyte counts before and after treatment (P>0.05). However, CD19+ CD20+ cells were almost depleted in patients treated with rituximab: (3.71±2.64)×106/L vs. (279.33±92.78)×106/L, P<0.01. Five patients suffered from allergic response, and 1 patient developed pneumonia and respiratory failure. The relapse rates of maintained group and control group were 1/12 and 4/13, respectively. Conclusions Treatment with low-dose rituximab may be an effective and safe approach in patients with idiopathic thrombocytopenic purpura. Relapse rates can be decreased through maintenance therapy with refractory low-dose rituximab. However, the optimal therapeutic schedule need further investigation.

Perfil sociodemográfico e clínico de portadores de síndromes mielodisplásicas / Sociodemographic and clinical profile of patients with myelodysplastic syndromes

Estudos epidemiológicos sobre Síndromes Mielodisplásicas (SMD) não são encontrados na literatura brasileira, o que requer investigação dessa doença prevalente em idosos e com incidência maior com o aumento da idade. Esse trabalho objetivou investigar o perfil sociodemográfico e clínico dos pacientes portadores de SMD. Tratase de um corte transversal, desenvolvido no Rio Grande do Norte, realizado de janeiro de 2000 a dezembro de 2010. Para análise descritiva foi utilizado o programa Epi Info 2002, versão 3.5.2. Os cálculos da probabilidade de associação entre as características analisadas e o gênero foram realizados pelos Testes do qui-quadrado, de Fisher e Exato de Fisher. O nível de significância considerado foi de 0,05. O trabalho foi aprovado em seus aspectos éticos e metodológico pelo Comitê de Ética em Pesquisa CEP/HUOL protocolo 432/10. Dos 29 pacientes selecionados, houve predomínio de idosos, do sexo masculino, com baixa escolaridade, que apresentaram anemia como sintoma inicial. A maior parte foi de pessoas de pele branca, residentes em casa própria, moradores em zona urbana e com renda inferior a dois salários mínimos. Todos utilizaram terapia com hemoderivados, principalmente o concentrado de hemácias, numa frequência de quatro ou mais unidades por mês de consumo, sendo que 20% realizou dosagem de ferritina sérica, todos com valores acima do normal referenciado. Conclui-se que se faz necessário a realização de pesquisas com maiores populações, de caráter multicêntrico a fim de melhor evidenciamento dos dados sociodemográficos e clínicos com possibilidade de avaliação por regiões do país.

Epidemiological studies on Myelodysplastic Syndromes (MDS) are not found in Brazilian literature, which requires investigation of this prevalent disease in the elderly and higher incidence with increasing age. This study aimed to investigate the sociodemographic and clinical characteristics of patients with MDS to characterize this population at a referral center for high complexity. It is a cross-performed from January 2000 to December 2010. For descriptive analysis was conducted using Epi Info 2002, version 3.5.2. The calculations of the likelihood of association between the characteristics analyzed and gender were performed using the chi-square, Fisher and Fisher's Exact. The level of significance was 0.05. The study was approved in its ethical aspects and the methodological Ethics Committee in Research ECR/HUOL Protocol 432/10. We selected 29 patients. The sample was characterized mainly by elderly male with lower education, who had anemia as initial symptom. Most were white-skinned people living in their own homes, residents in urban areas and with income less than two minimum wages. All blood products used therapy, especially red blood cells, a frequency of four or more units per month of consumption. Only 20% performed dosage of serum ferritin, all with values referenced above normal. We conclude that it is necessary to conduct research with larger populations, multicenter character in order to best evidence on the demographic data and clinical evaluation with the possibility of the country.

Anemia de las enfermedades crónicas asociada a obesidad: papel de la hepcidina como mediador central / Hepcidin as a central mediator of anemia of chronic diseases associated with obesity

Recent evidence suggests that obesity-related inflammation may play a central role in hepcidin regulation. Hepcidin is a key regulator ofiron homeostasis and has now been suggested as a central mediator ofiron metabolism disorders involved in the pathogenesis of anemia of chronic disease. In this review, we focus on subclinical inflammation in obesity and its effect on hepcidin levels, as the most plausible explanation for the relationship between anemia of chronic disease and obesity.

Sobrevida e evolução leucêmica de portadores de síndromes mielodisplásicas / Survival and leukemic evolution of patients with myelodysplastic syndromes

As síndromes mielodisplásicas constituem um grupo de doenças de ordem clonal hematopoética evidenciadas por estudos em todo o mundo. A estimativa de sobrevida dos pacientes e de casos que apresentam evolução leucêmica requer investigação na população brasileira, pois não se conta com nenhum dado dessa natureza. Assim, este estudo objetivou caracterizar e estimar a sobrevida e evolução leucêmica de portadores de síndromes mielodisplásicas acompanhados em um serviço de referência. Trata-se de um estudo de coorte retrospectiva realizada de janeiro de 2000 a dezembro de 2010. Para análise descritiva foi utilizado o programa Epi Info 2002, versão 3.5.2, e para os cálculos das probabilidades de sobrevida foi empregado o método de Kaplan-Meier pelo uso do programa Statistic Package for Social Sciences (SPSS), versão 10.0. Os cálculos da probabilidade de associação entre as características analisadas e o gênero foram realizados pelos testes do qui-quadrado de tendência, de Fisher, Mann Whitney, e de Log Rank. O nível de significância considerado foi de 0,05. O trabalho foi aprovado em seus aspectos ético e metodológico pelo Comitê de Ética em Pesquisa do Hospital Universitário Onofre Lopes (HUOL), sob o Protocolo n. 432/10. Dos 29 pacientes selecionados, houve predomínio de idosos, do sexo masculino, com baixa escolaridade. Apresentaram baixa probabilidade acumulada de sobrevida e índices de evolução leucêmica em torno de 27%, sem nenhum resultado satisfatório para o tratamento quimioterápico, bem como nenhuma indicação de transplante de medula óssea como possibilidade de cura. Fazem-se necessárias pesquisas com populações maiores para caracterização em todo território nacional.

Myelodysplastic syndromes constitute a group of clonal hematopoietic diseases shown by studies all around the world. The survival estimation of the patients and the cases presenting leukemic evolution demand investigation in the Brazilian population, as there's no data with regard to this theme. Thus, this study aimed to characterize and estimate the survival and leukemic evolution of patients with myelodysplastic syndromes followed up in a reference service. This is a retrospective cohort study carried out from January 2000 to December 2010. The software Epi Info 2002, version 3.5.2, was used for descriptive analysis, and for the calculations of survival probabilities the Kaplan-Meier method was employed through the software Statistic Package for Social Sciences (SPSS), version 10.0. The calculations of the association probability between the characteristics analyzed and gender were performed using the chi-square for trend, Fisher, Mann Whitney, and Log Rank tests. The significance level was 0.05. The ethical and methodological aspects of the study were approved by the Research Ethics Committee of HUOL, under the Protocol 432/10. Out of the 29 selected patients, there was a predominance of elderly people, males, with low education. They showed low cumulative probability of survival and leukemic evolution rates around 27%, with no satisfactory outcome from chemotherapy, as well as no indication of bone marrow transplantation as a possible cure. There is a need for researches with larger populations for the characterization all over the national territory.

A case report of myelodysplastic syndrome treated with allogeneic transplantation of HLA-identical sibling using culture-expanded mesenchymal stem cells and hematopoietic stem cells originated from HBV infected donor / 白血病·淋巴瘤

Objective To evaluate the safety, efficiency and feasibility of HLA-identical sibling using culture-expanded mesenchymal stem cells and hematopoietic stem cells in treatment for myelodysplastic syndrome (MDS). Also to investigate for valid preventive measures to avoid the infection of HBV originated from donor. Methods A 46-years-old male patient with myelodysplastic syndrome-refractory anemia (MDSRA) got a cotransplantation of culture-expanded mensenchymal stem cells (MSC) and hematopoietic stem cells (HSCs) from HLA-identical sibling donor (his sister) who was infected by hepatitis B virus (HBV). Some measures were applicated in order to avoid the recipient from getting a HBV infection. The antiviral therapy to the donor was began early at the time 1 month before transplant, and HBV vaccine inoculation was used 2 month before transplant. High titer of anti-hepatis B immunoglobulin was used 1 week before transplant and 1 month after transplant the use of prophylactic anti-hepatis B drug treatment was begun. A non-myeloablative preparative regimen included fludarabine monophosphate (Flu, 120 mg/m2), cyclophosphamide (Cy, 1200 mg/m2)and antithymocyte globulin (ATG, 15 mg/kg) was given to him before culture-expanded mesenchymal stem cell and allogeneic peripheral blood stem cell from his HLA-matched sister. Results The regimen was well tolerated, and hemopoiesis was reconstituted on day 10 after transplant, idiochromosome detected by fluorescent in situ hybridization on day 30 showed XY 47/300 and on day 90 it was 7/300. No evidence of HBV infection was detected on day 60 after transplant. Conclusion The clinical course of this patient indicate that HLA-identical sibling culture-expanded mesenchymal stem cell transplantation combined with non-myeloablative stem cell transplantation can be an effective and safe approach in treatment of MDS.