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It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.
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Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Células-Tronco Hematopoéticas , Humanos , América Latina , Síndromes Mielodisplásicas/terapia , Sistema de Registros , Estudos Retrospectivos , Transplante HomólogoRESUMO
Sickle cell disease (SCD) is a hereditary condition characterized by homozygosis of the hemoglobin S (HbS) gene. Marked morbimortality is observed due to chronic hemolysis, endothelial injury, and episodes of vaso-occlusion, which leads to multi-organ damage. Renal impairment is common and may have different presentations, such as deficiency in urinary acidification or concentration, glomerulopathies, proteinuria, and hematuria, frequently resulting in end-stage renal disease (ESRD). Novel biomarkers of renal function, such as kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein 1 (MCP-1) are being studied in order to enable early diagnosis of kidney damage in SCD.
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Anemia Falciforme/urina , Quimiocina CCL2/urina , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Falência Renal Crônica/urina , Rim/metabolismo , Lipocalina-2/urina , Anemia Falciforme/complicações , Biomarcadores/urina , Humanos , Falência Renal Crônica/etiologiaRESUMO
OBJECTIVE: This study aims to evaluate the markers of tubular phosphate handling in adults with sickle cell anemia (SCA) and the influence of hydroxyurea (HU), the degree of anemia and Hb F concentration on these markers. METHODS: Eighty-eight steady state SCA patients in outpatient follow-up in Fortaleza, Ceara, Brazil and 31 healthy individuals were included in this study. Vitamin D (25OHD) was measured by enzyme-bound fluorescence assay, intact parathyroid hormone (iPTH) by electrochemiluminescence, and serum and urinary phosphate and creatinine by colorimetric methods. Details of Hb F and HU use were obtained from clinical records. Tubular reabsorption of phosphate (TRP) and maximum tubular reabsorption of phosphate (MTRP) were calculated. SCA patients were stratified according to the use of HU, degree of anemia and percentage of Hb F. The significance level was set for p-values <0.05. RESULTS: Compared to controls the 25OHD level (25 ± 11 vs. 30 ± 9 pg/mL) was lower in SCA, while serum phosphate and MTRP were higher (3.86 ± 0.94 vs. 3.46 ± 0.72 and 3.6 ± 1.21 vs. 3.21 ± 0.53, respectively). There was no significant difference in iPTH, TRP and phosphaturia. Serum phosphate showed correlation with TRP (r = 0.32; p-value = 0.008) and MTRP (r = 0.9; p-value <0.001) in SCA. Patients taking HU, especially those with Hb F >10 % presented reduced serum phosphate levels, and TRP and MTRP rates. Those with mild anemia presented reduced serum phosphate levels and MTRP rates. CONCLUSION: Serum phosphate levels and renal phosphate reabsorption rate were increased in SCA. HU use, high Hb F concentration and total Hb were associated with better control of tubular phosphate handling markers.
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Acute kidney injury (AKI) is a common finding in Neotatal Intensive Care Units (NICU). Sepsis is one the main causes of AKI in preterm newborns. AKI has been associated with significant death rates. Early detection of the condition is the first step to improving prevention, treatment, and outcomes, while decreasing length of hospitalization, care costs, and morbimortality. AKI may progress to chronic kidney disease (CKD), a condition linked with dialysis and greater risk of cardiovascular disease. This review article aims to discuss cases of AKI in preterm newborns with sepsis, the use of biomarkers in lab workup, and the use of non-conventional biomarkers for the early identification of AKI.
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Injúria Renal Aguda , Sepse , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Biomarcadores , Diagnóstico Precoce , Humanos , Recém-Nascido , Unidades de Terapia Intensiva , Diálise Renal/efeitos adversos , Fatores de Risco , Sepse/complicações , Sepse/diagnósticoRESUMO
Clinical Background: Renal involvement in sickle cell disease (SCD), called sickle cell nephropathy (SCN), includes several renal manifestations, such as renal acidification defect, distal nephron dysfunction, renal papillary necrosis, and proteinuria related to glomerular injury, leading to end-stage renal disease. Epidemiology: Many patients with SCD have a defect in urinary concentration, a problem caused by the destruction of the renal medulla that initiates in childhood. The presence of proteinuria in SCD is age-related and starts as microalbuminuria in adolescence and progresses to macroalbuminuria. Proteinuria is responsible for the progression to chronic kidney disease in some patients with SCD with glomerular filtration rate (GFR) decreased due to interactions between various processes involving the vascular, glomerular, tubular, and interstitial compartments of the kidney. Challenges: Renal complications are hardly identifiable in the early stages, as serum creatinine increases only in the final stages of SCN. Subnormal GFR and elevated serum creatinine levels develop only when there is significant proteinuria. Prevention and Treatment: The identification of biomarkers of early, non-invasive kidney injury, and their inclusion in clinical practice will contribute to the identification of the mechanisms involved in the development of renal syndromes, facilitating the development of more effective strategies in the prevention and treatment of SCD.
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Anemia Falciforme , Nefropatias , Insuficiência Renal Crônica , Adolescente , Anemia Falciforme/complicações , Biomarcadores , Taxa de Filtração Glomerular , Humanos , Rim , Nefropatias/etiologia , Insuficiência Renal Crônica/complicaçõesRESUMO
The COVID-19 (SARS-CoV-2) infection started in China, Wuhan City, Hubei Province, in December 2019, and it was declared a pandemic in mid-March 2020, caused by a new coronavirus strain called SARS-CoV-2. The pathogenesis of kidney injury attributed to SARS- CoV-2 is not well defined yet. Observations show that the kidney damage caused by the new virus mutation is mainly tubular, with impairment of glomerular filtration and high levels of urea and creatinine. A study with seriously ill patients with COVID-19 showed that acute kidney injury was present in 29%. In the face of this evidence, based on recent studies, we can see the great renal contribution as an impact factor in the evolution of COVID-19, not just as a complicator of severity, but maybe part of the initial cascade of the process, requiring a deeper analysis using conventional biomarkers of kidney injury and more aggressive clinical intervention in patients at risk, in an attempt to reduce mortality.
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Injúria Renal Aguda/virologia , Infecções por Coronavirus/patologia , Rim/virologia , Pneumonia Viral/patologia , Betacoronavirus , COVID-19 , Humanos , Rim/fisiopatologia , Pandemias , SARS-CoV-2RESUMO
OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.
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Epoetina alfa/uso terapêutico , Hematínicos/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Brasil , Progressão da Doença , Feminino , Hemoglobinas/análise , Humanos , Estimativa de Kaplan-Meier , Cariótipo , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Intervalo Livre de Progressão , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI) and chromosomal damage in leukocytes of adult patients with SCA with and without HU. The DI was assessed by the comet assay and chromosomal damage by the leukocyte micronucleus test of adult patients treated with HU (SCA-HU) and without the use of HU (SCA-NoHU). This is a cross-sectional study with 77 patients with SCA who attended a referral hospital in Fortaleza, Brazil. The control group (CG) consisted of 58 reportedly healthy individuals. The comparisons of means were performed by analysis of variance and Tukey's post-test. Values of P < 0.05 were considered statistically significant. SCA-NoHU patients had statistically higher DI values and a statistically significantly higher frequency of micronuclei compared to the CG. In addition, HU treatment accentuated DNA lesions by significantly increasing both parameters in treated patients (SCA-HU). HU potentiates DNA damage and the occurrence of chromosomal damage, which may promote genomic instability, mutation occurrence, and carcinogenesis. Studies are needed to evaluate the involved pathways, repair mechanisms, and the clinical impact that such damage can cause. Environ. Mol. Mutagen. 60:302-304, 2019. © 2018 Wiley Periodicals, Inc.
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Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/efeitos adversos , Antidrepanocíticos/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Adolescente , Adulto , Brasil , Estudos Transversais , Dano ao DNA/genética , Feminino , Humanos , Leucócitos/citologia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Mutagênicos/efeitos adversos , Mutagênicos/uso terapêutico , Adulto JovemRESUMO
INTRODUCTION AND OBJECTIVE: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. METHODS: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. RESULTS: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65×103/L, 396×103/L, and 327.05×103/L, respectively (p=0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p=0.395 and p=0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p>0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p=0.226) CONCLUSION: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.
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BACKGROUND/AIM: Although risk stratification using the Prognostic Scores Systems (IPSS, WPSS and IPSS-R) incorporate key information about prognosis of patients with Myelodysplastic syndromes (MDS), patients classified as low-risk may evolve rapidly and aggressively, despite a "favorable" prognostic stratification. The aim of this study was to identify biomarkers for predicting prognosis, and for better stratification and management of these patients. MATERIALS AND METHODS: Expression of CD34 and p53 in megakaryocytes was examined by immunohistochemistry in 71 MDS patients classified as low-risk. RESULTS: CD34 staining in megakaryocytes was associated with p53 expression (p=0.0166). CD34 and p53 expression were associated to worse overall survival in patients (p=0.0281). CONCLUSION: The presence of CD34 in megakaryocytes is associated with p53 expression and an adverse prognosis for MDS patients.
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Antígenos CD34/genética , Síndromes Mielodisplásicas/genética , Prognóstico , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Megacariócitos/metabolismo , Megacariócitos/patologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Medição de Risco , Fatores de RiscoRESUMO
Objetivo: realizar dosagens de biomarcadores de função renal não convencionais em pacientes com anemia falciforme e associar com os níveis séricos de vitamina D. Métodos: trata-se de um estudo observacional, analítico de corte transversal. Participaram do estudo 51 pacientes adultos com anemia falciforme, e o grupo controle foi composto por 17 adultos saudáveis doadores de sangue. Os níveis séricos de 25- hidroxi-vitamina D foram determinados por imunoensaio quimioluminecente de micropartículas (CMIA), e a função renal foi avaliada pelas dosagens de molécula-1 de lesão renal (KIM-1) e proteína-1 quimiotática de monócitos (MCP-1). Os resultados foram expressos como mediana (intervalo interquartil). Os testes t-Student de amostras independentes, análise de variância de Welch e teste não paramétrico de Kruskal-Wallis foram realizados para comparar as diferenças entre os grupos. Resultados: os pacientes apresentaram níveis séricos de vitamina D superiores ao grupo controle, além de uma maior prevalência de suficiência de vitamina D. Os níveis urinários de KIM-1 e MCP-1 estavam aumentados nos pacientes em relação ao grupo controle. Não houve relação entre baixos níveis séricos de vitamina D e a probabilidade de desenvolvimento de doença renal. Conclusões: este estudo fornece dados importantes sobre a prevalência da deficiência de vitamina D em pacientes com anemia falciforme e demonstra não haver relação entre baixos níveis de vitamina D e desenvolvimento de doença renal.
Objective: to measure non-conventional renal function biomarkers in patients with sickle cell anemia and associate them with serum levels of vitamin D. Method: this is an observational, analytical, cross-sectional study. Fifty-one adult patients with sickle cell anemia participated in the study, and the control group consisted of 17 healthy adult blood donors. Serum levels of 25-hydroxyvitamin D were determined by chemiluminescent microparticle immunoassay (CMIA), and renal function was assessed by measuring urinary Kidney Injury Molecule-1 (KIM-1) and Monocyte Chemoattractant Protein-1 (MCP-1). Results were expressed as median (interquartile range). Student's t-test, Welch analysis of variance, and non-parametric Kruskal-Wallis test were performed to compare differences between groups. Results: patients had higher serum levels of vitamin D than the control group, besides a higher prevalence of vitamin D sufficiency. Urinary levels of KIM-1 and MCP-1 were increased in patients compared to the control group. There was no relationship between low serum vitamin D levels and the likelihood of developing kidney disease. Conclusions: this study provides important data on the prevalence of vitamin D deficiency in patients with sickle cell anemia and demonstrates that there is no relationship between low levels of vitamin D and the development of kidney disease.
Assuntos
HumanosRESUMO
Objective: Although hypothyroidism has been linked to oxidative stress, data regarding the relationship between thyroid hormone levels and oxidative stress is still inconsistent. This study was designed to evaluate the effect of levothyroxine replacement on oxidative stress in women with primary hypothyroidism. Design: A total of 25 female patients with primary hypothyroidism were included. Oxidative stress markers were measured before and after levothyroxine replacement treatment in all patients. Methods: Oxidative stress was evaluated through the measurement of oxidants (thiobarbituric acid reactive substances [TBARS] and nitrite/nitrate levels), and antioxidants (superoxide dismutase and catalase activity). Results: Antioxidant catalase activity (63.77 ± 23.8 vs. 50.12 ±12.75 atv/min; p = 0.03) was significantly increased and the levels of TBARS (3.02 ± 0.86 vs. 3.55 ± 0.87 µM; p = 0.03) were significantly decreased in the state of euthyroidism after levothyroxine replacement compared to the hypothyroidism before levothyroxine treatment. No significant change in neither nitrite/nitrate concentration (p = 0.18) nor in superoxide dismutase activity (p = 0.93) after L-T4 adjustment was found. Conclusions: Our data demonstrate that levothyroxine replacement improved oxidative status in patients with primary hypothyroidism, indexed by the significantly decreased levels of malonaldehyde (MDA) and increased catalase (CAT) activity.
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Wernick's Encephalopathy (WE) is an acute neuropsychiatric syndrome caused by thiamine deficiency post hematopoietic stem cell transplant (HSCT). WE is associated with high mortality and morbidity rates, but due to its rare occurrence, it is rarely considered in patients submitted to this procedure. Considering that, the manuscript reports the clinical characteristics and the possible factors that predisposed the occurrence of WE in a patient with non-Hodgkin's lymphoma post-Autologous HSCT. We conclude that WE should be considered in patients submitted to autologous HSCT associated with prolonged use of TPN and malnutrition.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/terapia , Deficiência de Tiamina/complicações , Encefalopatia de Wernicke/etiologia , Adulto , Feminino , Humanos , Fatores de Risco , Transplante Autólogo , Encefalopatia de Wernicke/diagnóstico por imagemRESUMO
Abstract Acute kidney injury (AKI) is a common finding in Neotatal Intensive Care Units (NICU). Sepsis is one the main causes of AKI in preterm newborns. AKI has been associated with significant death rates. Early detection of the condition is the first step to improving prevention, treatment, and outcomes, while decreasing length of hospitalization, care costs, and morbimortality. AKI may progress to chronic kidney disease (CKD), a condition linked with dialysis and greater risk of cardiovascular disease. This review article aims to discuss cases of AKI in preterm newborns with sepsis, the use of biomarkers in lab workup, and the use of non-conventional biomarkers for the early identification of AKI.
Resumo A lesão renal aguda (LRA) é comum na Unidade de Terapia Intensiva Neonatal (nUTI) e a sepse é uma de suas principais causas, especialmente em prematuros. Apresenta altas taxas de mortalidade e sua detecção precoce é o primeiro passo para a prevenção dessa condição, pois permite o tratamento adequado e melhora o desfecho, diminui o tempo de internação, os custos não médicos e a morbimortalidade. Destaca-se ainda que a LRA pode evoluir para doença renal crônica (DRC), havendo a necessidade de diálise, com maior risco de desenvolver doenças cardiovasculares. Este artigo de revisão tem como objetivo discutir a LRA em recém-nascidos (RNs) prematuros com sepse, abordando biomarcadores utilizados na rotina laboratorial e principalmente a utilização de biomarcadores não tradicionais para identificação precoce de LRA.
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Objetivo: Avaliar o perfil clínico-terapêutico e a resposta à profilaxia em pacientes hemofílicos A e B em um centro de referência no Ceará. Métodos: Estudo de coorte retrospectivo, com dados de 133 hemofílicos A e B, em profilaxia entre 2016 e 2021, por meio de prontuários médicos e sistema Web Coagulopatias. Resultados: Os pacientes todos do sexo masculino em sua maioria foram hemofílicos A (93,2%), na forma grave, residentes em Fortaleza, com maior prevalência do município de Guaiúba. A maioria fazia uso de Fator VIII recombinante e em profilaxia secundária, em relação ao comprometimento articular a maioria não apresentou relato de hemartroses (66,9%), articulação-alvo (87,9%) ou artropatia (54,9%), porém os hemofílicos em profilaxia terciária apresentaram um maior comprometimento articular em relação a profilaxia primária e secundária. Verificou-se uma correlação negativa entre o tempo de profilaxia e a dose de fator utilizada, demonstrando que quanto maior o tempo de profilaxia menor a dose do fator utilizada. Um total de 13 hemofílicos A grave desenvolveram inibidor de fator VIII realizando imunotolerância (ITI) com sucesso total em 84,6%. Por meio da curva ROC, foi verificado uma associação entre a necessidade de ITI e a dose de fator de coagulação, com acurácia de 67,7% de que o uso de doses maiores de fator predispõe ao desenvolvimento de inibidores. Conclusão: Os dados do estudo permitem inferir que quanto mais precoce o tratamento de profilaxia menor é comprometimento articular, dose do fator utilizada e menor predisposição de desenvolver inibidores dos fatores da coagulação.
Objective: to evaluate the clinical-therapeutic profile and response to prophylaxis in hemophiliac A and B patients at a referral center in Ceará. Methods: Retrospective cohort study, with data from 133 hemophiliacs A and B, undergoing prophylaxis between 2016 and 2021, using medical records and the Web Coagulopathies system. Results: Most of the patients were male patients with severe hemophilia A (93.2%), residing in Fortaleza, with a higher prevalence in the city of Guaiúba. Most made use of recombinant Factor VIII and in secondary prophylaxis, in relation to joint involvement, the majority did not report hemarthroses (66.9%), target joint (87.9%) or arthropathy (54.9%). however, hemophiliacs on tertiary prophylaxis showed greater joint impairment in relation to primary and secondary prophylaxis. There was a negative correlation between the prophylaxis time and the factor dose used, demonstrating that the longer the prophylaxis time, the lower the factor dose used. A total of 13 severe A hemophiliacs developed factor VIII inhibitor performing immunotolerance (ITI) with total success in 84.6%. Using the ROC curve, an association was verified between the need for ITI and the dose of coagulation factor, with an accuracy of 67.7% that the use of higher doses of factor predisposes to the development of inhibitors. Conclusion: The study data allow us to infer that the earlier the prophylaxis treatment, the less joint impairment, the dose of the factor used and the less predisposition to develop coagulation factor inhibitors.
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Humanos , Animais , Masculino , Adulto Jovem , Hemofilia B/prevenção & controle , Hemofilia A/prevenção & controle , Coagulação Sanguínea , Brasil/epidemiologia , Fatores de Coagulação Sanguínea/administração & dosagem , Prevalência , Estudos Retrospectivos , Hemofilia B/epidemiologia , Prevenção de Doenças , Avaliação de Eficácia-Efetividade de Intervenções , Hemartrose/prevenção & controle , Hemofilia A/epidemiologia , Artropatias/prevenção & controleRESUMO
BACKGROUND: Myelodysplastic syndromes are heterogeneous disorders. Patients with myelodysplastic syndrome disease often have ineffective hematopoiesis, cytopenias, blood cell dysplasia in one or more cell types, and are at high risk for developing acute myeloid leukemia. In myelodysplastic syndrome, mutations of TP53 gene are usually associated with complex karyotype and confer a worse prognosis. In the present study, two mutations in this gene are presented and discussed with the clinical evolution of the patients. CASE PRESENTATION: The first case is a 77-year-old Brazilian woman diagnosed as having multiple lineage dysplasia myelodysplastic syndrome according to World Health Organization 2016 and classified as very low-risk by Revised International Prognostic Scoring. The second case is an 80-year-old Brazilian man also diagnosed as having multiple lineage dysplasia myelodysplastic syndrome and classified as low risk. The mutation described in the first case was already identified in some neoplasias and it is associated with a poor prognosis, but it had never been reported before in myelodysplastic syndrome. The second mutation has never been described. CONCLUSIONS: This is a novel report for the scientific community and may be very helpful as we can better understand the disease and the impact of mutations through the follow-up of these patients and others in the future. Both patients are in a good clinical condition, suggesting that these mutations may not alter the clinical course of the disease or may be associated with a good prognosis, but their role in the disease must be investigated more deeply in a larger population.
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Genes p53/genética , Leucemia Mieloide Aguda/genética , Mutação/genética , Síndromes Mielodisplásicas/genética , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Síndromes Mielodisplásicas/patologia , PrognósticoRESUMO
BACKGROUND: Visceral leishmaniasis is a zoonosis characterized by chronic evolution of symptoms; it usually appears 2 to 4 months after the initial infection, with multiple cutaneous lesions and systemic involvement, which if left untreated results in death in 90 % of cases. CASE PRESENTATION: We present a case of 29-year-old white male farmer, with chronic myeloid leukemia treated with imatinib who developed significant pancytopenia, leading to discontinuation of treatment. His neutrophil count fell to 0.5 × 10(9)/L, his platelets dropped to 85 × 10(9)/µL, and his hemoglobin was 6.4 g/dL. A bone marrow study was performed, showing complete remission of chronic myeloid leukemia and numerous Leishmania amastigotes within the macrophages. He used pentavalent antimonials replaced by amphotericin B due to acute cardiac toxicity. After 3 months, imatinib was restarted, and he again showed adequate control of the disease. The last polymerase chain reaction assessment showed a deep molecular response. CONCLUSION: The hypothesis of an adverse event or secondary resistance to tyrosine kinase inhibitors, with subsequent progression to advanced disease, was initially raised, although a detailed evaluation has shown that it was an associated infectious disease.
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Mesilato de Imatinib/uso terapêutico , Leishmaniose Visceral/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pancitopenia/complicações , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pancitopenia/diagnósticoRESUMO
Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the ßS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The ßS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was p < 0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p < 0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.
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Anemia Falciforme/metabolismo , Arginase/metabolismo , Biomarcadores/análise , Haplótipos/genética , Hidroxiureia/farmacologia , Globinas beta/genética , Adulto , Anemia Falciforme/genética , Anemia Falciforme/patologia , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , PrognósticoRESUMO
OBJECTIVE/BACKGROUND: Sickle-cell anemia (SCA) is a genetic blood disease characterized by chronic inflammation and a heterogeneous clinical picture. Serum tumor necrosis factor (TNF-alpha) and interleukin 10 (IL-10) levels are associated with the clinical course of SCA. This study aimed to evaluate the association between the frequency of the polymorphisms TNF-alpha-308 GâA, IL-10-1082 GâA, IL-10-819 CâT, and IL-10-592 AâC; serum TNF-alpha; and IL-10 levels, and the incidence of clinical events in SCA patients. METHODS: Polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay were performed on 25 adults with SCA at the steady state; their data were compared with those for 26 healthy individuals. RESULTS: The most frequent genotype of the TNF-alpha polymorphism was GG (low producer), and the most frequent genotype of the IL-10 polymorphisms was "low producer" (ACC ACC, ACC ATA, ATA ATA). The TNF-alpha levels were significantly higher in SCA in patients with acute chest syndrome (ACS). The IL-10 levels were reduced in polytransfusion and in patients with ACS. CONCLUSION: The patients presented prevalence of TNF-alpha and IL-10 low-profile producer. The cytokine serum levels presented an association with the presence of polytransfusion and ACS in SCA patients.
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Anemia Falciforme/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Estudos Transversais , Feminino , Genótipo , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
The hematopoietic stem cell transplantation (HSCT) is the only curative alternative for Myelodysplastic Syndrome (MDS), but many patients are not eligible for this treatment, as there are several limiting factors, especially in the case of patients with low-risk MDS. The aim of this study is to discuss the factors that can guide the decision-making on referring or not a patient to HSCT. Three cases of MDS, two of which were submitted to HSCT are presented. We intend to report the difficulties in referring patients with MDS to transplant and the prognostic factors that contribute to define eligibility.