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In Europe, most HTLV-1-infected individuals originate from highly endemic regions such as West Indies, sub-Saharan Africa, and South America. The only genuine endemic region for HTLV-1 in Europe is Romania where ATL series have been reported among Romanian patients. Our objective is to better understand the origin of this endemic focus based on a study of the genetic diversity of HTLV-1 in Romanians. DNA was obtained from PBMCs/buffy coats of 11 unrelated HTLV-1-infected individuals of Romanian origin. They include 9 ATL cases and 2 asymptomatic carriers. LTR sequences were obtained for all specimens. Complete genomic HTLV-1 sequences were obtained using four PCR series on 10 specimens. Phylogenetic trees were generated from multiple alignments using HTLV-1 prototypic sequences and the new generated sequences. Most of the complete LTR sequences (756-bp) showed low nucleotide diversity, ranging from 0% to 0.8% difference, and were closely related (less than 0.8% divergence) to the only previously characterized Romanian strain, RKI2. One strain, ROU7, diverged slightly (1.5% on average) from the others. Phylogenetic analyses both on partial LTR and the complete genome demonstrate that the 11 sequences belong to the HTLV-1a cosmopolitan genotype and 10 of them belong to the previously denominated a-TC Mozambique-Southern Africa A subgroup. In this study, we demonstrated that the HTLV-1 present in Romania most probably originated in Southern Africa. As most Romanian HTLV-1 strains are very closely related, we can assume that HTLV-1 has been introduced into the Romanian population recently. Further studies are ongoing to decipher the routes of arrival and dissemination of these HTLV-1 strains, and to date the emergence of this endemic focus in Central Europe.
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Variação Genética , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Filogenia , Sequências Repetidas Terminais , Romênia/epidemiologia , Humanos , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Infecções por HTLV-I/virologia , Infecções por HTLV-I/epidemiologia , Sequências Repetidas Terminais/genética , Masculino , Feminino , Análise de Sequência de DNA , DNA Viral/genética , Pessoa de Meia-Idade , Adulto , África Austral/epidemiologia , IdosoRESUMO
Introduction: Minimally invasive surgical techniques for hallux valgus have gained popularity, showing good results characterized by smaller postoperative scars, less pain, lower infection risk, and fewer wound complications. Given the lack of evidence available in our country regarding this subject, especially about this type of surgical technique, our paper aims to compare open and MIS approaches for chevron osteotomy. We evaluated the outcome and complications after 12 months. Materials and Methods: We undertook a prospective, randomized, controlled, single-center study between October 2017 and December 2020. The patients were randomized into two groups: one group that received percutaneous chevron osteotomy (MIS), and the other, open chevron osteotomy (OC). For clinical assessment, we determined the function and the level of pain using the Visual Analogue Scale (VAS) and The American Orthopaedic Foot and Ankle Surgery score (AOFAS). The VAS scale was measured before the surgical procedure, at discharge, and at 3 weeks, 6 weeks, 6 months, and 12 months after surgery. The AOFAS score was calculated preoperatively and after 6 months. The hallux angle (HVA) and intramedullary angle (IMA) were measured preoperatively, and at 6 weeks, 6 months and 12 months. Results: We included 26 cases in the open chevron osteotomy group (24 female, 2 male) and 24 in the MIS group (24 female, 0 male). Both groups demonstrated improvements regarding the IMA and HVA at the last follow-up without any significant differences between the groups at the final assessment. The VAS showed significantly better post-operative results for the MIS group at discharge (p < 0.001) and 3 weeks (p < 0.001), 6 weeks (p < 0.001), and 6 months (p = 0.004) post-surgery. The AOFAS showed no significant differences either before or after surgery. Four cases with screw prominence were reported, three of which belonged to the MIS group. Only one case with metatarsalgia was found in the OC group. Conclusions: This paper demonstrates that minimally invasive chevron osteotomy has comparable results with open chevron osteotomy, even though surgical time and radiological exposure are significantly longer. More studies are required to evaluate the complications and the risk of recurrences.
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Hallux Valgus , Feminino , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Masculino , Osteotomia/efeitos adversos , Osteotomia/métodos , Estudos Prospectivos , Radiografia , Resultado do TratamentoRESUMO
Concomitant diagnosis of non-Hodgkin lymphoma (NHL) and acute myeloid leukemia secondary to chronic myeloproliferative neoplasms (MPNs) is rarely reported. Patients with MPNs may have a second neoplasm, and the risk of lymphoid line neoplasms is 2.5-3.5 times for lymphoid line neoplasms. The explanation for this association is the genetic instability of hematopoietic progenitors in MPNs. An 80-year-old Caucasian man, with many comorbidities, presents for physical asthenia, sweating. The right inguinal adenopathy was known one month before the examination. The patient was diagnosed concomitantly with diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) secondary to primary myelofibrosis (PMF) and presented trisomy 8, trisomy 13, and triple-negative PMF status. The patient initially received two well-tolerated R mini CHOP series. This type of treatment was selected to treat DLBCL for one unfit patient for intensive chemotherapy due to his age and comorbidities. R mini CHOP administration was followed by severe aplasia that lasted approximately two weeks followed by severe thrombocytosis that reached 4000 x109/L, and Thromboreductin recommendation was mandatory. The result of the treatment was a partial response but with severe adverse events like neutropenia G4, due to the delay of the treatment the patient lost the response. It was mandatory to select another treatment line and the chosen was venetoclax; it was selected for the simultaneous treatment of DLBCL and the underlying AML. It was obtained a significant reduction in the size of the inguinal lymph node block in two weeks of treatment. Severe neutropenia was diagnosed and complicated with sepsis. The evolution is unfavorable with the installation of multiple organ dysfunction. The presence of a complex karyotype (trisomy 8, trisomy 13) in a patient with myeloid metaplasia with triple-negative PMF was associated with blast transformation and severe thrombocytosis. The patient was diagnosed concomitantly with DLBCL, making the therapeutic decision difficult. Venetoclax has been shown to be useful in the treatment of DLBCL but has been associated with severe neutropenia, which has led to infectious complications.
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Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were investigated with an integrated approach, including classical and molecular cytogenetics, array-based comparative genomic hybridization and targeted next generation sequencing (NGS). Various genetic defects were identified in all the patients using our strategy. Targeted NGS revealed known pathogenic mutations as well as rare or unreported variants with deleterious predictions. The mutational screening of the normal karyotype (NK) group identified clinically relevant variants in 86.2% of the patients; in the abnormal cytogenetics group, the mutation detection rate was 87.5%. Overall, the highest mutation prevalence was observed for the NPM1 gene, followed by DNMT3A, FLT3 and NRAS. An unexpected co-occurrence of KMT2A translocation and DNMT3A-R882 was identified; alterations of these genes, which are involved in epigenetic regulation, are considered to be mutually exclusive. A microarray analysis detected CNVs in 25% of the NK AML patients. In patients with complex karyotypes, the microarray analysis made a significant contribution toward the accurate characterization of chromosomal defects. In summary, our results show that the integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance.
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Leucemia Mieloide Aguda/genética , Taxa de Mutação , Variações do Número de Cópias de DNA , DNA Metiltransferase 3A/genética , GTP Fosfo-Hidrolases/genética , Testes Genéticos/estatística & dados numéricos , Sequenciamento de Nucleotídeos em Larga Escala , Histona-Lisina N-Metiltransferase/genética , Humanos , Leucemia Mieloide Aguda/patologia , Proteínas de Membrana/genética , Proteína de Leucina Linfoide-Mieloide/genética , Nucleofosmina/genética , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
BACKGROUND AND OBJECTIVES: In acute myeloid leukemia (AML), extensive bleeding is one of the most frequent causes of death. Impaired activation and aggregation processes were identified in previous studies on platelet behaviour associated with this disease. This study's aim was to examine platelet function in correlation with other haemorrhage risk factors (fever, sepsis, recent bleeding, uraemia, leucocytosis, haematocrit value, treatment). DESIGN AND METHODS: The analysis of platelet surface proteins (Glycoprotein Ib-IX (CD42b, CD42a), Glycoprotein IIb-IIIa (CD41, CD61), p-selectin (CD62P), granulophysin (CD63)) was conducted by flowcytometry from samples of whole blood in patients with acute myeloid leukaemia in different stages of diagnosis and therapy (n = 22) in comparison with healthy human controls (n = 10). RESULTS AND INTERPRETATIONS: Our results show a significant decrease in fluorescence level associated with platelet activation markers (CD63 (14.11% vs. 40.78 % p < 0.05); CD62P (15.26% vs. 28.23% p < 0.05)); adhesion markers (CD42b (69.08% vs. 84.41% p < 0.05)) and aggregation markers (CD61 (83.79% vs. 98.62% p < 0.001)) in patients compared to controls. The levels of CD41 (80.62% vs. 86.31%, p = 0.290) and CD42a (77.98% vs. 94.15%, p = 0.99) demonstrate no significant differences in the two groups. CONCLUSION: The AML patients present changes in adhesion receptors and activation markers, suggesting a functional defect or denatured intracellular signalling in platelets. The exposed data indicate that flow cytometry can effectively identify multiple functional platelet impairments in AML pathogenesis.
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INTRODUCTION: FLT3 internal tandem duplication (ITD) mutations are found in around 25% of all acute myeloid leukaemia (AML) cases and is associated with shorter disease-free and overall survival. Previous reports have shown that FLT3-ITD induces a specific phenotype in leukemic blasts, which is characterized by high levels of CD33 and CD123, and that expression of CD33 and CD123 is directly influenced by the DNA FLT3-ITD/wild-type FLT3 allelic ratio (AR). METHODS: A total of 42 FLT3-ITD and 104 FLT3-ITD-negative AML patients were analysed. Immunophenotyping data were used to calculate antigen expression levels as the ratio between the geometric mean fluorescence intensities (MFIs) of leukemic blasts and MFIs of negative lymphocyte populations. FLT3-ITD-DNA and RNA analysis was performed, under the same conditions, by capillary electrophoresis. RESULTS: Compared with the control group, the FLT3-ITD cohort presented significantly higher CD7, CD33 and CD123 levels. In order to assess the impact of FLT3-ITD abundance on antigen expression, the patients were grouped for each parameter into two cohorts using the following threshold values: (a) 0.5 for the AR, according to current AML guidelines; (b) 0.7 for the FLT3-ITD/FLT3-WT mRNA ratio (RR); and (c) 1.3 for the FLT3-ITD RR/AR ratio. We found higher values of CD33 for RR/AR ≥1.3, and no other statistical differences between CD7, CD33 and CD123 levels of the other FLT3-ITD groups. In terms of correlations between MFI values and FLT3-ITD parameters, we only observed a moderate interdependence between CD33 MFI and the RR/AR ratio, and a weak negative correlation between CD123 MFI and AR. CONCLUSION: FLT3-ITD mutations induce a specific antigen profile in AML blasts, and our data do not onfirm previous reports of FLT3-ITD AR influencing both CD33 and CD123 expression.
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Antígenos CD7/metabolismo , DNA/genética , Duplicação Gênica , Regulação Leucêmica da Expressão Gênica , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Leucemia Mieloide Aguda/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Tirosina Quinase 3 Semelhante a fms/genética , Antígenos de Neoplasias/metabolismo , Fluorescência , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
Patients with chronic lymphocytic leukemia (CLL) treated with Ibrutinib often present hemorrhagic complications. Platelets dysfunction is well documented by aggregometry and flow cytometry, but the mechanisms by which Ibrutinib treatment influences the platelets status is yet to be evaluated. The aim of this study is to identify platelet membrane parameters in chronic lymphocytic leukemia (CLL) that could be altered by Ibrutinib administration. In this paper we propose a set of fluorescence measurements of the following parameters: membrane fluidity, resting membrane potential, and reactive oxygen species production of platelets suspensions obtained from CLL patients treated or not with Ibrutinib as markers for platelets status in this pathological situation. Platelets from CLL patients treated with Ibrutinib have higher membrane fluidity, lower resting membrane potential and higher level of reactive oxygen species production compared to the untreated CLL patients. These patients are also presenting higher membrane fluidity and lower resting membrane potential compared to healthy volunteers.
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UNLABELLED: Diffuse large B-cell lymphoma (DLBCL) represent the most frequently non-Hodgkin's lymphoma (NHL) (over 30%), especially in developing countries. Many associations of NHL with another neoplasia were described following chemotherapy or radiotherapy regimens. The coexistence of DLBCL with myeloproliferative neoplasms (MPNs) JAK2V617F positive at the onset was very rare reported in the literature. We describe a clinical case of a 52-year-old man who presented both diagnoses at the onset - DLBCL and MPN - polycythemia vera (PV) type. The patient was treated with two CHOP cycles (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone) followed by six R-CHOP (Rituximab-CHOP) cycles, together with a platelet-reducing agent, achieving remission for 20 months, followed by a relapse which is under treatment. The clonally expansion of an abnormal pluripotent hematopoetic stem cell could be responsible for both, PV and DLBCL. However, recent reports suggested the possible involvement of two different clones. The clinical significance and the role of JAK2 mutation in the evolution of patients with NHLs, including DLBCL are still unknown. Further genetic and clinical studies have to point out common gene mutations for the two diseases and their connection with the diseases behavior under the treatment. CONCLUSIONS: The coexistence of NHLs and especially DLBCLs and MPNs JAK2 positive is very rare. Although DLBCL alone has good prognosis, other prognostic factors should be checked when it is associated with PV. The presence of JAK2V617F seems to be a candidate but whose role in DLBCL evolution, natural or under treatment has to be cleared up.