ASSOCIATION BETWEEN LEUKEMIC EVOLUTION AND UNCOMMON CHROMOSOMAL ALTERATIONS IN PEDIATRIC MYELODYSPLASTIC SYNDROME

Background and objective: Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choosing the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases.  Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. Methods: The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Results: Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions, which represented 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT.  Conclusion: The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT.  Keywords: Pediatric MDS; Leukemic evolution; rare chromosomal altwerations; HSCT, Childre

Immunophenotypic Analysis of Acute Megakaryoblastic Leukemia: A EuroFlow Study

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL. AMKL patients were subdivided into transient abnormal myelopoiesis (TAM), myeloid leukemia associated with Down syndrome (ML-DS), AML—not otherwise specified with megakaryocytic differentiation (NOS-AMKL), and AMKL—other patients (AML patients with other WHO classification but with flowcytometric features of megakaryocytic differentiation). Flowcytometric analysis showed good discrimination between AMKL and non-AMKL patients based on differential expression of, in particular, CD42a.CD61, CD41, CD42b, HLADR, CD15 and CD13. Combining CD42a.CD61 (positive) and CD13 (negative) resulted in a sensitivity of 71% and a specificity of 99%. Within AMKL patients, TAM and ML-DS patients showed higher frequencies of immature CD34+/CD117+ leukemic cells as compared to NOS-AMKL and AMKL-Other patients. In addition, ML-DS patients showed a significantly higher expression of CD33, CD11b, CD38 and CD7 as compared to the other three subgroups, allowing for good distinction of these patients. Overall, our data show that the EuroFlow AML panel allows for straightforward diagnosis of AMKL and that ML-DS is associated with a unique immunophenotypic profile.The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for HematoOncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA). The work of C.E.P. and E.S.C. was partially supported by FAPERJ (Grant E26/200.840/2021- CNE; E26/210.379/2018 and E26/110.105/2014); CAPES-PROEX; and CNPq (Grant 306258/2019-6 and 303765/2018-6). M.N. and E.M. were supported by the Ministry of Health of the Czech Republic, grant number NU20J-07-00028. S.M. was supported by Acción Estratégica en Salud (AES) (Grant PI21_01115) and the grant of CIBERONC of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain and FONDOS FEDER (no. CB16/12/00400)

Assistência de enfermagem no atendimento de mulheres em situação de violência doméstica: revisão integrativa

Os diversos tipos de violência contra as mulheres têm sido historicamente incessantes em ambientes intra e extrafamiliar, tornando-se cada vez mais expostas e implausível no decorrer dos anos, evidenciados por danos causados na saúde mental e física das vítimas, resultando não só em um preconceito de gênero, mas também um problema de saúde pública. O presente estudo visa identificar a relevância da qualificação e do impacto da assistência de enfermagem, frente às vítimas de agressões domésticas, baseando-se no conhecimento do enfermeiro referente aos aspectos éticos e legais do cuidado. Trata-se de uma revisão integrativa da literatura com abordagem quantitativa com artigos extraídos das plataformas científicas virtuais SCIELO (Scientific Electronic Library On-line), MEDLINE (Medical Literature Analysis and Retrievel System Online), BVS (Biblioteca Virtual de Saúde), LILACS (Literatura Latina Americana do Caribe em Ciências da Saúde e WHOLIS (Sistema de informação da biblioteca da OMS) utilizando os seguintes Descritores em Ciências da Saúde (DeSC): violência contra mulher, cuidados de enfermagem e assistência de enfermagem. Os artigos foram pesquisados e revisados no período de março a novembro de 2021. Foram encontrados 126 artigos através dos descritores escolhidos, dos quais 19 foram selecionados, pois respondiam diretamente o objetivo da pesquisa. Os demais artigos excluídos não obedeceram aos critérios de inclusão apresentados neste artigo. O cuidado e o planejamento de enfermagem às mulheres vítimas de violência doméstica devem ser pautados em oferecer conforto, respeito, acolhimento e segurança. Essas medidas cautelosas devem ser sistêmicas na prevenção de problemas e agravos à vítima, onde nesse sentido, cada profissional busca uma melhor metodologia para conduzir essas mulheres, utilizando uma comunicação ativa como importante ferramenta. Com tudo, é notória a persistência no défice da assistência dos profissionais de enfermagem no acolhimento às vítimas, sendo imprescindível a implantação de protocolos e o investimento em capacitação dos profissionais, para que os mesmos possam prestar a assistência mais abrangente e especializada a estas vítimas

Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia

A fully-standardized EuroFlow 8–color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of £1025, comparable to real-time quantitative polymerase chain reaction (RQ-PCR)–based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses. After 5 multicenter design-test-evaluate-redesign phases with a total of 319 BCP-ALL patients at diagnosis, two 8-color antibody tubes were selected, which allowed separation between normal and malignant BCP cells in 99% of studied patients. These 2 tubes were tested with a new erythrocyte bulk-lysis protocol allowing acquisition of high cell numbers in 377 bone marrow follow-up samples of 178 BCP-ALL patients. Comparison with RQ-PCR–based MRD data showed a clear positive relation between the percentage concordant cases and the number of cells acquired. For those samples with >4 million cells acquired, concordant results were obtained in 93% of samples. Most discordances were clarified upon high-throughput sequencing of antigen-receptor rearrangements and blind multicenter reanalysis of flow cytometric data, resulting in an unprecedented concordance of 98% (97% for samples with MRD 98% of patients with sensitivities at least similar to RQ-PCR (£1025), if sufficient cells (>4 3 106, preferably more) are evaluated

B-cell regeneration profile and minimal residual disease status in bone marrow of treated multiple myeloma patients

Simple Summary B-cell regeneration during therapy has been associated with the outcome of multiple myeloma (MM) patients. However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated. Here, we show that hemodilution is present in a significant fraction of MM BM samples, leading to lower total B-cell, B-cell precursor (BCP), and normal plasma cell (nPC) counts. Among MM BM samples, decreased percentages (vs. healthy donors) of BCP, transitional/naive B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP, but not TBC/NBC, increased after induction therapy. At day+100 post-autolo-gous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19(-) nPC counts vs. non-CR specimens with no clear association between BM B-cell regeneration profiles and patient outcomes. B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (>= 50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naive B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19(-) nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome

Racemic etodolac is cytotoxic and cytostatic for B-cell precursor acute lymphoblastic leukemia cells

4 p. : il.Several epidemiological studies have provided evidence that administration of nonsteroidal anti-inflammatory drugs (NSAIDs) could have a prophylactic effect against some cancers such as sporadic colorectal cancer and leukemia. Indeed, various NSAIDs have been shown to induce apoptosis in malignant cells. We evaluated the effect of racemic Etodolac on proliferation and cell survival in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Etodolac decreased survival of Nalm-16 and Nalm-6 BCP-ALL cell lines and also decreased cell proliferation in Nalm-16 cell line. Ours findings indicate, for the first time to our knowledge, that Etodolac is cytotoxic and cytostatic for BCPALL cells

Risk factors for the development of hospital-acquired pediatric venous thromboembolism-Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis.

IntroductionHospital-acquired venous thromboembolism (HA-VTE) in children comprises multiple risk factors that should not be evaluated separately due to collinearity and multiple cause and effect relationships. This is one of the first case-control study of pediatric HA-VTE risk factors using a Directed Acyclic Graph (DAG) analysis.Material and methodsRetrospective, case-control study with 22 cases of objectively confirmed HA-VTE and 76 controls matched by age, sex, unit of admission, and period of hospitalization. Descriptive statistics were used to define distributions of continuous variables, frequencies, and proportions of categorical variables, comparing cases and controls. Due to many potential risk factors of HA-VTE, a directed acyclic graph (DAG) model was created to identify confounding, reduce bias, and increase precision on the analysis. The final model consisted of a DAG-informed conditional logistic regression.ResultsIn the initial conventional univariable model, the following variables were selected as potential risk factors for HA-VTE: length of stay (LOS, days), immobility, ICU admission in the last 30 days, LOS in ICU, infection, central venous catheter (CVC), number of CVCs placed, L-asparaginase, heart failure, liver failure, and nephrotic syndrome. The final model using the set of variables selected by DAG analysis revealed LOS (OR = 1.106, 95%CI = 1.021-1.198, p = 0.013), L-asparaginase (OR = 26.463, 95%CI = 1.609-435.342, p = 0.022), and nephrotic syndrome (OR = 29.127, 95%CI = 1.044-812.508, p = 0.004) as independent risk factors for HA-VTE.ConclusionThe DAG-based approach was useful to clarify the influence of confounders and multiple causalities of HA-VTE. Interestingly, CVC placement-a known thrombotic risk factor highlighted in several studies-was considered a confounder, while LOS, L-asparaginase use and nephrotic syndrome were confirmed as risk factors to HA-VTE. Large confidence intervals are related to the sample size; however, the results were significant

Cytogenetic as an Important Tool for Diagnosis and Prognosis for Patients with Hypocellular Primary Myelodysplastic Syndrome

We analyzed cytogenetically 105 patients with hypocellular primary MDS and their clinical implications. The main chromosomal abnormalities found were del(5q)/−5, del(6q)/+6, del(7q)/−7, del(11q), and del(17p). Pediatric patients had a higher frequency of abnormal karyotypes compared with adult patients (P < 0,05). From our patients, 18% showed evolution of the disease. The chromosomal abnormalities presented in the diagnosis of patients who evolved to AML included numerical (−7, +8) and structural del(6q), del(7q), i(7q), t(7;9), i(9q), and del(11q) abnormalities and complex karyotypes. Although the frequency of evolution from hypocellular MDS to AML is low, our results suggest that some chromosomal alterations may play a critical role during this process. We applied the IPSS in our patients because this score system has been proved to be useful for predicting evolution of disease. When we considered the patients according to group 1 (intermediate-1) and group 2 (intermediate-2 and high risk), we showed that group 2 had a high association with respect to the frequency of abnormal karyotypes (P < 0,0001), evolution of disease (P < 0,0001), and mortality (P < 0,001). In fact, the cytogenetic analysis for patients with hypocellular primary MDS is an important tool for diagnosis, prognosis, in clinical decision-making and in follow-up

Sepsis-Related Mortality of Very Low Birth Weight Brazilian Infants: The Role of Pseudomonas aeruginosa

The aim of this study is to identify risk factors for sepsis-related mortality in low birth weight (<1500 g) infants. We performed retrospective cohort study to investigate risk factors for sepsis-related mortality in all neonates birth weight <1500 g admitted to Level III neonatal intensive care unit, Brazil, April 2001/September 2004. Of the 203 cases, 71 (35%) had sepsis. Of those, gram-positive was identified in 52/87 blood cultures (59.8%), the most common Coagulase-negative Staphylococcus (31/87; 35.5%). Gram-negative was present in 29 of the 87 positive blood cultures (33.3%), with Pseudomonas aeruginosa (8/87; 9.1%), the most frequent agent. Overall 21 of 71 infants with sepsis (29.6%) died. Risk factors for sepsis-related mortality were gestational age ≤28 weeks, birth weight ≤1000 g (9.6 times more often than birth weight >1000 g), five-minute Apgar ≤7, gram-negative sepsis, mechanical ventilation (6.7 times higher than no use), and intravascular catheter. Sepsis-related mortality was due, mainly, to Pseudomonas aeruginosa; birth weight ≤1000 g and mechanical ventilation were strong sepsis-related mortality predictors