Herramientas diagnostico-terapéuticas en síndromes mielodisplásicos en Uruguay / Diagnostic and therapeutic tools in myelodysplastic syndromes in Uruguay / Instrumentos diagnóstico-terapêuticos nas síndromes mielodisplásicas no Uruguai

Los Síndromes Mielodisplásicos (SMD) son un grupo heterogéneo de enfermedades mieloides. Esta heterogeneidad en la presentación clínica complejiza el diagnóstico requiriendo diversos estudios complementarios. El tratamiento debe ser individualizado y adaptado al riesgo, desde terapias de soporte hasta intervenciones de alto costo. Para conocer la accesibilidad a las herramientas diagnóstico y terapéuticas se realizó una encuesta online dirigida a los hematólogos que asisten pacientes con SMD en Uruguay en 2016 y 2019. Las encuestas fueron respondidas por 32.5% y 26.6% de los miembros de la Sociedad de Hematología del Uruguay. Más del 90% tienen acceso a estudios histológicos, citogenéticos, FISH y citometría de flujo. La posibilidad de realizar paneles de secuenciación masiva se encuentra restringida a menos de 10% derivando la muestra al exterior, siendo mayor en 2019 en comparación a 2016. Los sistemas de estratificación de riesgo más utilizados son el sistema internacional de puntuación de riesgo (IPSS) y su versión revisada (IPSS-R). La disponibilidad de tratamientos de soporte (transfusiones, eritropoyetina y G-CSF), de azacitidina y del trasplante alogénico de precursores hematopoyéticos es amplia. Existió un aumento en indicación de azacitidina en 2019 con respecto a 2016. Sin embargo, el acceso a decitabina, lenalidomida y fármacos quelantes de hierro es escaso y no se cuenta con ensayos clínicos donde incluir pacientes que fallan o no responden a los tratamientos convencionales. La presente encuesta, realizada en dos períodos, describe la realidad y su evolución en nuestro país en cuanto a accesibilidad a herramientas diagnósticas y terapéuticas extrapolables a otras patologías oncohematológicas. Los datos recabados permitirán plantear estrategias tendientes a mejorar el abordaje diagnóstico-terapéutico de los pacientes con SMD en Uruguay.

Myelodysplastic Syndromes (MDS) constitutes an heterogenous group of hematological malignancies. Reaching an accurate diagnosis, represents in an important number of cases, a major challenge that requires different diagnostic tools. In order to acknowledge the scope of access to those tools in our country, we performed a survey addressed to Uruguayan hematologists who care for MDS patients in their clinical practice. The survey was carried out in 2016 and 2019 among Uruguayan Hematology Society members. Response rate was 32.5% and 26.6% respectively. Access to bone marrow biopsy, cytogenetics, FISH and flow cytometry was accessible to more than 90% of physicians. Less than 10% of respondents were able to request next generation sequencing (NGS) studies and in that case, they have to send them abroad. IPSS and R-IPSS were the most frequently used risk scores. Support treatment such as growth factors and transfusions are widely accessible. Azacytidine and allogenic transplant are available as well. However, access to decitabine, lenalidomide and iron chelating drugs is scarce and there are no clinical trials to include patients who fail or do not respond to conventional treatments. This survey, carried out in two periods, describes the reality and its evolution in our country in terms of accessibility to diagnostic and therapeutic tools that can be extrapolated to other oncohematological pathologies. We were able to get to know our country reality regarding diagnostic and therapeutic tools for MDS patients. This, would represent an important input in order to design health strategies aiming to improve clinical care for our patients.

As Síndromes Mielodisplásicas (SMD) são um grupo heterogêneo de doenças mielóides. Essa heterogeneidade na apresentação clínica torna o diagnóstico mais complexo, exigindo vários estudos complementares. O tratamento deve ser individualizado e adaptado ao risco, desde terapias de suporte até intervenções de alto custo. Para conhecer a acessibilidade de ferramentas diagnósticas e terapêuticas, foi realizada uma pesquisa online dirigida aos hematologistas que atendem pacientes com SMD no Uruguai em 2016 e 2019. As pesquisas foram respondidas por 32,5% e 26,6% dos membros da Sociedad de Hematologia do Uruguai. Mais de 90% têm acesso a estudos histológicos, citogenéticos, FISH e citometria de fluxo. A possibilidade de realização de painéis de sequenciamento massivo está restrita a menos de 10% provenientes da amostra no exterior, sendo maior em 2019 em relação a 2016. Os sistemas de estratificação de risco mais utilizados são o sistema internacional de pontuação de risco (IPSS) e sua versão revisada (IPSS -R). Tratamentos de suporte (transfusões, eritropoietina e G-CSF), azacitidina e transplante alogênico de células-tronco hematopoiéticas estão amplamente disponíveis. Houve aumento da indicação de azacitidina em 2019 em relação a 2016. No entanto, o acesso a decitabina, lenalidomida e quelantes de ferro é escasso e não há ensaios clínicos para incluir pacientes que falham ou não respondem aos tratamentos convencionais. Este inquérito, realizado em dois períodos, descreve a realidade e a sua evolução no nosso país em termos de acessibilidade a instrumentos diagnósticos e terapêuticos que podem ser extrapolados para outras patologias onco-hematológicas. Os dados coletados permitirão propor estratégias destinadas a melhorar a abordagem diagnóstico-terapêutica de pacientes com SMD no Uruguai.

Adherencia a las recomendaciones de tromboprofilaxis post-cesárea: estudio de corte transversal / Compliance with post-cesarean section thromboprophylaxis recommendations. A cross sectional study in 233 women

Background: Cesarean section increases four times the risk of venous thromboembolism compared to vaginal delivery. The Royal College of Obstetricians and Gynecologists guidelines are used at our service. A written alert was designed to stratify patients at high, intermediate or low risk making a suggestion for thromboprophylaxis. Aim: To assess the compliance with the guidelines and to evaluate the impact of a written alert in the thromboprophylaxis compliance in women subjected to caesarean section. Patients and Methods: Review of medical records of 233 women aged 19 to 32 years, subjected to a caesarean section in a Gynecology Service, between 2016-2017. Results: Compliance with recommendations was observed in 29% of patients (68/233), 86% in the low-risk group, 26% in the intermediate risk group and 100% in the high risk group. In 41/233 (18%) of patients, a written alert was included in the medical record. Compliance with recommendations in the presence of the written alert was 61% (25/41 women) compared to 22% (43/192) in those lacking the alert (p < 0.01). In women whose emergency caesarean section was the only risk factor, the compliance with the recommendation was 8%, compared with 30% among those who had at least one thrombotic risk factor associated with caesarean section (p < 0.01). Conclusions: In this cross-sectional study, we observed a low compliance with thromboprophylaxis guidelines in cesarean women. We observed that the use of a written alert improved the compliance with thromboprophylaxis.

5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients

Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological diseases. In addition to defects in hematologic progenitor and stem cells, dysfunctions in the bone marrow microenvironment (BMM) participate in the MDS pathogenesis. Furthermore, the immune response is deregulated by the pro-inflammatory response prevailing in low-risk MDS, while immunosuppression predominates in high-risk MDS. Mesenchymal stromal cells (MSC), part of the BMM, are characterized by plastic adherent growth and multipotentiality. They exhibit immunomodulatory properties and sustain hematopoiesis. There is conflicting evidence regarding their status in MDS. The aim of this study was to characterize MDS-MSC and evaluate the effect of 5-Azacytidine. Methods: The MSC from MDS patients and controls were cultured and characterized according to the International Society of Cell Therapy recommendations. Immunomodulatory properties were assessed by studying the MSD cytokine production, using the cytometric bead array. We evaluated the effect of 5-Azacytidine on the MSC cytokine production. Results: We included 35 MDS patients and 22 controls. The MSC from patients and controls were cultured and characterized. The MSC from patients showed morphological differences, but there were no differences in immunophenotype or multipotentiality. The interleukin 6 (IL-6) was the main MSC secreted cytokine. The MDS-MSC produced higher levels of IL-6, IL-17, interferon gamma, or interferon γ (INF-γ), and tumor necrosis factor alpha (TNF-α). The in vitro 5-Azacytidine treatment induced a significant decrease in the IL-6 production by MDS-MSC. Conclusions: The MDS-MSC show an increased production of pro-inflammatory cytokines. The in vitro treatment with 5-Azacytidine lead to a significant reduction in the IL-6 production by the MDS-MSC, restoring the IL-6 levels to those found in controls. The MSC produced inflammatory cytokines involved in the MDS pathogenesis, representing a potential future therapeutic target. Moreover, 5-Azacytidine may have a stromal effect, modulating the immune response in MDS.