Assuntos
Azacitidina , Humanos , Azacitidina/administração & dosagem , Azacitidina/uso terapêutico , Masculino , Feminino , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , América do Sul , Esquema de Medicação , Pessoa de Meia-Idade , IdosoRESUMO
Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p = 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p = 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p = 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p < 0.001, OR=9.05 × 10-10), and intermediate (p < 0.001, OR=3.08 × 10-10), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p < 0.001, OR=4.03 × 10-13) and intermediate (p < 0.001, OR=2.54 × 10-13). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS.
RESUMO
Abstract Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p= 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p= 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p= 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p< 0.001, OR=9.05 × 10−10), and intermediate (p< 0.001, OR=3.08 × 10−10), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p< 0.001, OR=4.03 × 10−13) and intermediate (p< 0.001, OR=2.54 × 10−13). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS.
Assuntos
Humanos , Síndromes Mielodisplásicas , Polimorfismo Genético , Dano ao DNA , Reparo do DNARESUMO
SummarySystemic lupus erythematosus (SLE) is an autoimmune condition developing thrombocytopenia in about 10-15% of cases, however, mechanisms leading to low platelet count were not deeply investigated in this illness. Here we studied possible causes of thrombocytopenia, including different mechanisms of platelet clearance and impairment in platelet production. Twenty-five SLE patients with and without thrombocytopenia were included. Platelet apoptosis, assessed by measurement of loss of mitochondrial membrane potential, active caspase 3 and phosphatidylserine exposure, was found to increase in thrombocytopenic patients. Plasma from 67% SLE patients (thrombocytopenic and non-thrombocytopenic) induced loss of sialic acid (Ricinus communis agglutinin I and/or Peanut agglutinin binding) from normal platelet glycoproteins. Concerning platelet production, SLE plasma increased megakaryopoiesis (evaluated using normal human cord blood CD34+ hematopoietic progenitors), but inhibited thrombopoiesis (proplatelet count). Anti-platelet autoantibody depletion from SLE plasma reverted this inhibition. Overall, abnormalities were more frequently observed in thrombocytopenic than non-thrombocytopenic SLE patients and in those with active disease (SLEDAI≥5). In conclusion, platelet clearance due to apoptosis and desialylation, and impaired platelet production mainly due to inhibition of thrombopoiesis, could be relevant mechanisms leading to thrombocytopenia in SLE. These findings could provide a rational basis for the choice of proper therapies to correct platelet counts in these patients.[Figure: see text].
Assuntos
Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Autoanticorpos , Plaquetas , Humanos , Lúpus Eritematoso Sistêmico/complicações , Contagem de Plaquetas , Trombocitopenia/complicações , TrombopoeseRESUMO
The effective search for the missing and identification of persons, alive or dead, are core components in the prevention and in resolving the issue of Missing Persons. Despite the growing literature on this topic, there is still a lack of publications describing the Search as a process that includes different phases inherently composed of forensic investigative and identification principles for both living and deceased missing persons. This paper is the result of discussions between the Forensic Unit of the International Committee of the Red Cross (ICRC) and members of its external Forensic Advisory Board. It aims to present the Search process as an overarching concept that includes the investigation and identification phases of the missing in any state (dead or alive), in any scenario (with or without bodies), with an integrated, multidisciplinary, and multiagency approach for implementation by all actors involved in the investigation and identification phases of missing persons.
RESUMO
Knowledge on chronic myelomonocytic leukemia (CMML) patients from Argentina and Brazil is limited. Our series of 280 patients depicted an older age at diagnosis (median 72 years old), 26% of aberrant karyotypes, and a prevalence of myelodysplastic (60%) and CMML-0 subtypes (56%). The median overall survival (OS) was 48.2 months for patients in CMML-0 (Ref.), 24.7 months for those in CMML-1 (HR = 2.0, p = 0.001), and 8.8 months for patients in CMML-2 (HR = 4.6, p < 0.001). In the CMML-0 category, median OS were different between myelodysplastic and myeloproliferative subtypes (63.7 vs 21.2 months, p < 0.001); however, no differences were observed within CMML-1 and CMML-2 subtypes (24.7 vs 23.7 months, p = 0.540, and 9.1 vs 8.2 months, p = 0.160). The prognostic impact of 24 variables and 7 prognostic systems was adjusted to the WHO 2016 after validating their usefulness. Multivariate analysis were performed, and the final model revealed Hb ≥ 8 -< 10g/dL (HR 1.7), Hb < 8g/dL (HR 2.8), poor karyotypes (HR 2.1), WHO 2016-CMML-1 (HR 2.1), and CMML-2 (HR 3.5) as independent adverse clinical parameters in our cohort with a borderline influence of platelets count < 50 × 109/L (HR 1.4). We could validate several scoring systems, the WHO 2016 proposal and its prognostic capability, along with accessible covariates, on predicting the outcome in our series of CMML patients from Latin America.
Assuntos
Leucemia Mielomonocítica Crônica/diagnóstico , Idoso , Argentina/epidemiologia , Brasil/epidemiologia , Feminino , Humanos , Leucemia Mielomonocítica Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Organização Mundial da SaúdeAssuntos
Azacitidina , Bases de Dados Factuais , Síndromes Mielodisplásicas , Idoso , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/mortalidadeRESUMO
Fabry disease is a rare inherited lysosomal storage disorder caused by the deficiency of the enzyme alpha-galactosidase A. There is uncertainty regarding the safety of enzyme replacement therapy during pregnancy. We describe the course and outcome of seven pregnancies in six patients with Fabry disease who continued or reinitiated enzyme replacement therapy during pregnancy. No adverse events, in both mothers and children, were observed.
RESUMO
INTRODUCTION: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood. OBJECTIVES: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU. METHODS: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI. RESULTS: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups. CONCLUSION: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.
Assuntos
Infecções Relacionadas a Cateter/complicações , Infecção Hospitalar/etiologia , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Estudos Transversais , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/microbiologiaRESUMO
BACKGROUND: The use of stress ulcer prophylaxis (SUP) has risen in recent years, even in patients without a clear indication for therapy. AIM: To evaluate the efficacy of an electronic medical record (EMR)-based alarm to improve appropriate SUP use in hospitalized patients. METHODS: We conducted an uncontrolled before-after study comparing SUP prescription in intensive care unit (ICU) patients and non-ICU patients, before and after the implementation of an EMR-based alarm that provided the correct indications for SUP. RESULTS: 1627 patients in the pre-intervention and 1513 patients in the post-intervention cohorts were included. The EMR-based alarm improved appropriate (49.6% vs. 66.6%, p<0.001) and reduced inappropriate SUP use (50.4% vs. 33.3%, p<0.001) in ICU patients only. These differences were related to the optimization of SUP in low risk patients. There was no difference in overt gastrointestinal bleeding between the two cohorts. Unjustified costs related to SUP were reduced by a third after EMR-based alarm use. CONCLUSIONS: The use of an EMR-based alarm improved appropriate and reduced inappropriate use of SUP in ICU patients. This benefit was limited to optimization in low risk patients and associated with a decrease in SUP costs.
Assuntos
Alarmes Clínicos , Registros Eletrônicos de Saúde , Prescrição Inadequada/prevenção & controle , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica/prevenção & controle , Antiulcerosos/uso terapêutico , Comorbidade , Custos e Análise de Custo , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Pacientes Internados , Unidades de Terapia Intensiva , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica Hemorrágica/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , Respiração Artificial , Risco , Centros de Atenção TerciáriaRESUMO
Resumen Introducción: Las infecciones urinarias asociadas a la atención de la salud (ITU-AAS) representan un importante problema sanitario, siendo poco conocidas sus características cuando no están asociadas a cateterización urinaria u ocurren fuera de unidades de cuidados intensivos (UCI). Objetivos: Determinar las características de los pacientes con ITU-AAS, etiología y susceptibilidad antimicrobiana de las mismas, tanto asociadas a catéter (ITU-C) como no asociadas a catéter (ITU-noC), en UCI y en sala general. Materiales y Métodos: Se realizó un estudio analítico retrospectivo de corte transversal entre 2009 y 2013 en un hospital universitario de tercer nivel. Se identificaron todos los episodios de ITU-AAS, diferenciándolas en ITU-C e ITU-noC. Resultados: Se incluyeron 253 episodios de ITU-AAS, siendo más frecuentes las ITU-C (60,9%) respecto a ITU-noC. Un 37,4% de ITU-noC y 59,7% de ITU-C ocurrieron en UCI. Los microorganismos aislados más frecuentemente fueron Escherichia coli, Klebsiella pneumoniae y Enterococcus sp. El 19% de los bacilos gramnegativos fueron productores de β-lactamasa de espectro extendido, siendo su frecuencia similar en ambos grupos. Conclusión: Las co-morbilidades de los pacientes con ITU-AAS, los agentes etiológicos responsables y sus correspondientes espectros de sensibilidad, fueron similares en los grupos de ITU-C e ITU-noC, tanto en sala general como en UCI.
Introduction: Nosocomially acquired urinary tract infections (NAUTI) represent an important public health issue, but its characteristics when they are not catheter associated (CA-UTI) or when they take place outside intensive care units (ICU) are poorly understood. Objectives: To determine the patients' characteristics, etiology and antimicrobial susceptibility of NAUTI, both CA-UTI and no CA-UTI, in general ward and ICU. Methods: We conducted a retrospective analytic cross-sectional study, between 2009 and 2013, in a third level universitary hospital. All NAUTI episodes were identified, classifying them as CA-UTI and no CA-UTI. Results: We included 253 episodes of NAUTI, being CA-UTI (60,9%) more frequent than no CA-UTI. A 37,4% of no CA-UTI and 59,7% of CA-UTI were identified in ICU. The most frequently isolated microorganisms were Escherichia coli, Klebsiella pneumoniae and Enterococcus sp. A 19% of extended spectrum betalactamase producing gram negative bacilli were found, without differences between groups. Conclusion: Patients's comorbidities, microorganisms associated to NAUTI and its antimicrobial susceptibility were similar in CA-UTI and no CA-UTI, as in general ward and ICU.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Infecções Urinárias/etiologia , Cateterismo Urinário/efeitos adversos , Infecção Hospitalar/etiologia , Infecções Relacionadas a Cateter/complicações , Infecções Urinárias/microbiologia , Testes de Sensibilidade Microbiana , Infecção Hospitalar/microbiologia , Estudos Transversais , Estudos Retrospectivos , Bactérias Aeróbias Gram-Negativas/isolamento & purificação , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Hospitais Universitários , Unidades de Terapia Intensiva , Antibacterianos/farmacologiaRESUMO
Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematologic disorders characterized by cytopenia(s) and predisposition to leukemic progression. An immune dysregulation and an aberrant bone marrow microenvironment seem to be key elements in the physiopathological process of MDS. In order to evaluate a possible association between susceptibility and clinic-pathologic features, we genotyped 153 MDS patients for functional cytokine polymorphisms: TNF (-308 G/A), IFNG (+874 A/T and +875 CAn), IL6 (-174 G/C), and TGFB1 (+869 C/T and +915 G/C). The frequency of TNF and IL6 polymorphisms was different between patients and healthy controls (n = 131), suggesting a relatedness to MDS susceptibility in our population. Furthermore, the presence of each or both high-producing genotypes [TNF: p = 0.048, odds ratio (OR): 3.979; IL6: p = 0.001, OR: 6.835; both: p = 0.010, OR: 6.068] and thrombocytopenia at platelet counts of <50,000/µL (p = 0.004, OR: 4.857) were independently associated with an increased risk of manifesting a hemoglobin level of <8 g/dL at diagnosis. In particular, a severe bicytopenia was more frequently observed in patients with the TNF (high)_IL6 (high) combined genotype (p = 0.004, OR: 8.357), who consistently became transfusion dependent earlier (2.9 vs. 34.6 months; p = 0.001); and this likelihood was more evident in patients with lower bone marrow blast counts. The contribution of the remaining functional polymorphisms to the disease phenotype was less relevant. Our results demonstrate that TNF and IL6 gene polymorphisms, as underlying host features, are likely to play a key role in influencing the severity of the cytopenias in MDS and they may be instrumental for tailoring cytokine-target therapies.
Assuntos
Predisposição Genética para Doença/genética , Interleucina-6/genética , Síndromes Mielodisplásicas/genética , Pancitopenia/complicações , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina , Feminino , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/complicações , Pancitopenia/patologia , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombocitopenia/complicações , Adulto JovemRESUMO
There are previously reported data describing differences between Asian and European patients with Myelodysplastic Syndromes (MDS), few direct comparisons based on cancer registration characteristics or using cohorts to validate scoring systems. This is the first study from South-America, which attempts to describe demographic, clinical features, and outcome of MDS patients. We retrospectively analyzed 1,080 patients with de novo MDS from Argentina (635), Brazil (345), and Chile (100). Chilean patients were younger (P = 0.001) with female preponderance (P = 0.071). Brazilian series showed a higher predominance of RARS subtype regarding FAB and WHO classifications (P < 0.001). Hemoglobin levels were significantly lower in Brazilian and Chilean series (P < 0.001), and Chilean series also showed a lower platelet count (P = 0.028), with no differences concerning the neutrophil count, % BM blast, and the distribution of cytogenetic risk groups (P > 0.05). Chilean series depicted a lower overall survival (OS; 35 months vs. 56 months-Argentine; 55 months-Brazil, P = 0.030), which was consistent with a higher predominance of the high-risk group according both to the IPSS and IPSS-R (P = 0.046 and P < 0.001). The IPSS-R system and its variables showed a good reproducibility to predict clinical outcome for the whole South-American population. Epidemiological and clinical characteristics, distribution among prognostic subgroups, the OS, and the access to disease modifying therapies were more similar between Argentinean and Brazilian compared with Chilean MDS series. This will need further analysis in a larger group of patients. Descriptive and comparative studies are necessary to establish epidemiological features useful for public health attitudes to generate suitable therapeutic schemes.
Assuntos
Síndromes Mielodisplásicas/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , América do Sul/epidemiologiaRESUMO
Este artículo expone la carta dental como medio de identificación, su importancia y el procedimiento científico donde se aplica, como también la ley 38 de 1993, donde se obliga a los odontólogos a levantar una carta dental en los consultorios públicos y privados, pero no a su actualización.