Case Report: Mycosis fungoides as an exclusive manifestation of common variable immunodeficiency in a family with a NFKB2 gene mutation.

Background: Common variable immunodeficiency disorders (CVIDs), which are primary immunodeficiencies characterized by the failure of primary antibody production, typically present with recurrent bacterial infections, decreased antibody levels, autoimmune features, and rare atypical manifestations that can complicate diagnosis and management. Although most cases are sporadic, approximately 10% of the patients may have a family history of immunodeficiency. Genetic causes involving genes related to B-cell development and survival have been identified in only a small percentage of cases. Case presentation: We present the case of a family with two brothers who presented with mycosis fungoides as an exclusive symptom of a common variable immunodeficiency disorder (CVID). Whole-exome sequencing of the index patient revealed a pathogenic variant of the NFKB2 gene. Based on this diagnosis and re-evaluation of other family members, the father and brother were diagnosed with this rare immune and preneoplastic syndrome. All CVID-affected family members presented with mycosis fungoides as their only symptom, which is, to the best of our knowledge, the first case to be reported. Conclusion: This case highlights the importance of high-throughput sequencing techniques for the proper diagnosis and treatment of hereditary hematological disorders.

Endothelium-biomarkers for postthrombotic syndrome: a case-control study.

BACKGROUND: The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase. METHODS: A case-control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry. RESULTS: Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/µl (0.34-1.5) vs. 0.20/µl (0.11-0.77); P  = 0.04) and EPC (0.75/µl (0.38-1.52) vs. 0.09/µl (0.05-0.82); P  = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30-597.90) vs. 98.00 pg/ml (82.30-193.02); P  = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r  = 0.86, P  < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups. CONCLUSIONS: The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.

Two mutations in the SBDS gene reveal a diagnosis of Shwachman-Diamond syndrome in a patient with atypical symptoms.

We present the case of a 53-yr-old woman with an inherited bone marrow failure coexisting with uncommon extrahematological symptoms, such as cirrhosis and skin abnormalities. Whole-exome sequencing revealed a diagnosis of Shwachman-Diamond syndrome (SDS) with an atypical presentation. Unexpected was the age of disease expression, normally around the pediatric age, with a predominantly median survival age of 36 yr. To our knowledge, she was the first adult patient with a molecular diagnosis of Shwachman-Diamond in Uruguay. The patient was referred to our service when she was 43-yr-old with a history of bone marrow failure with anemia and thrombocytopenia. All secondary causes of pancytopenia were excluded. Bone marrow aspirate and biopsy specimens were hypocellular for the patient's age. Numerous dysplastic features were observed in the three lineages. She had a normal karyotype and normal chromosomal fragility. A diagnosis of low-risk hypoplastic MDS was made. Dermatological examination revealed reticulate skin pigmentation with hypopigmented macules involving the face, neck, and extremities; nail dystrophy; premature graying; and thin hair. Extrahematological manifestations were present (e.g., learning difficulties, short stature). Last, she was diagnosed with cryptogenic liver cirrhosis CHILD C. This rules out all other possible causes of chronic liver disease. This clinical presentation initially oriented the diagnosis toward telomeropathy, so we did a telomeropathy NGS panel that came up negative. Finally, we did an exome sequencing that confirmed the diagnosis of SDS. Using whole-exome sequencing, we were able to find two compound heterozygous mutations in the SBDS gene that were responsible for the phenotype of a patient that was undiagnosed for 10 years. An earlier genetic diagnosis could have influenced our patient's outcome.

Esquemas desadaptativos tempranos en mujeres con cáncer de mama y su asociación con la calidad de vida relacionada con la salud

Resumen: El cáncer de mama es una enfermedad que genera alerta en las mujeres y se prevé que su incidencia aumente aún más. El diagnóstico y los tratamientos se presentan como un fenómeno disruptivo. Ante tales situaciones se estima que las mujeres activan patrones de pensamiento, emociones y pautas relacionales (esquemas desadaptativos tempranos, EDT). En este estudio se evaluaron los EDT prevalentes durante los diferentes tratamientos onco específicos y su relación con la Calidad de Vida Relacionada con la Salud (CVRS). Se utilizó un diseño descriptivo y correlacional. Se seleccionó una muestra de 228 pacientes ambulatorias, usuarias del sistema de salud público del Uruguay. Se aplicó un formulario sociodemográfico y biomédico, el Test de EDT y el FACT-B para valorar CVRS. Los EDT más utilizados fueron el de Autosacrificio y Metas inalcanzables. Los EDT resultaron ser sensibles a los diferentes tratamientos, en especial a la cirugía sin reconstrucción mamaria donde predominó la Sobrevaloración. La CVRS se asoció de forma directa con los EDT de Deprivación Emocional, Abandono, Apego, Vulnerabilidad y Vergüenza. Se concluye que las mujeres con cáncer de mama utilizan diferentes EDT con los que reaccionan ante la enfermedad y los tratamientos. El uso de los EDT impacta en la percepción de bienestar.

Abstract: Breast cancer is a disease that generates alert in women and its incidence is expected to increase even more. Cancer diagnosis and treatments are disruptive phenomenon. It is estimated that cancer women activates thought patterns, emotions and relational patterns (early maladaptive schemas, EDT). In this study, we evaluated the EDTs prevalence during different onco-specific treatments and their relationship with quality of life related to health (HRQoL). We use a descriptive and correlational design. We included 228 outpatients, users of the Uruguayan public health system. To assess HRQoL, we applied a sociodemographic and biomedical form, the EDT Test and the FACT-B. The most used EDTs were Self-Sacrifice and Unattainable Goals. The EDTs turned out to be sensitive to the different treatments, especially to surgery without breast reconstruction, where Overvaluation predominated. HRQoL was directly associated with the EDTs of Emotional Deprivation, Abandonment, Attachment, Vulnerability and Shame. We conclude that women with breast cancer use different EDTs with which they react to the disease and the treatments. The use of EDTs impacts the perception of well-being.

Resumo: O câncer de mama é uma doença que gera alerta nas mulheres e espera-se que sua incidência aumente ainda mais. O diagnóstico e os tratamentos apresentam-se como um fenômeno disruptivo. Em tais situações, estima-se que as mulheres ativem padrões de pensamento, emoções e padrões relacionais (esquemas desadaptativos precoces, EDT). Neste estudo, foram avaliados os EDTs prevalentes durante os diferentes tratamentos oncoespecíficos e sua relação com a qualidade de vida relacionada à saúde (QVRS). Foi utilizado um desenho descritivo e correlacional. Uma amostra de 228 pacientes ambulatoriais, usuários do sistema público de saúde uruguaio, foi selecionada. Um formulário sociodemográfico e biomédico, o EDT Test, e o FACT-B foram aplicados para avaliar a QVRS. Os EDTs mais utilizados foram Autossacrifício e Metas Inatingíveis. Os EDTs mostraram-se sensíveis aos diferentes tratamentos, principalmente à cirurgia sem reconstrução mamária, onde predominou a Supervalorização. A QVRS esteve diretamente associada às EDTs de Privação Emocional, Abandono, Apego, Vulnerabilidade e Vergonha. Conclui-se que as mulheres com câncer de mama utilizam diferentes TDEs com as quais reagem à doença e aos tratamentos. O uso de TDEs impacta a percepção de bem-estar.

Mobilized and apheresis-collected endothelial progenitor cells with plerixafor.

BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

Germline CEBPA mutation in familial acute myeloid leukemia.

Myeloid Neoplasms with germline predisposition become part of 2016 World Health Organization (WHO) classification of hematological malignancies since 2016. CCAAT/enhancer binding protein-alpha (CEBPA) is a myeloid transcription factor located in chromosome 19q. Acute myeloid leukemia (AML) with biallelic mutations of CEBPA AML with recurrent genetic abnormalities according to WHO classification. The inheritance of a germline CEBPA mutation predisposes to the development of AML with autosomal dominant inheritance. Familial CEBPA AML share characteristics with somatic CEBPA AML. However, a higher relapse incidence is reported. We present the case of a 46-years-old male with family history of acute leukemia who was diagnosed with single mutated CEBPA acute myeloid leukemia. The same mutation was found in two of his siblings. The clinical suspicion and proper diagnosis of familial cases is necessary, especially when a related allogenic transplant is indicated in order to select an adequate donor.

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

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.

Variables predictivas de calidad de vida en mujeres con cáncer de mama / Predictive variables of quality of life in women with breast cancer

Objetivos: Estudiamos el valor predictivo que tiene sobre la calidad de vida relacionada con la salud (CVRS) de las mujeres con cáncer de mama en tratamiento, las variables sociodemográficas, clínicas (tipo de tratamiento) y psicológicas tales como los esquemas desadaptativos tempranos (EDT), las creencias y percepciones sobre la enfermedad y las estrategias de afrontamiento utilizadas. Métodos: Realizamos un estudio descriptivo, correlacional, de subtipo predictivo. Incorporamos una muestra de 228 pacientes adultas con cáncer de mama en tratamiento ambulatorio del sistema público asistencial. Se realizaron entrevistas en las que se aplicó un formulario de datos socio demográficos y clínicos, el Cuestionario FACT-B, el Test de Esquemas Tempranos (YSQ-CEY-VR), el Cuestionario de percepción de enfermedad (IPQ-R) y la escala Brief COPE. Se realizaron análisis descriptivos, de estadística inferencial, regresión lineal múltiple y regresión jerárquica. Resultados: Los diferentes tipos de tratamientos onco-específicos no registraron diferencias significativas en la CVRS, sin embargo las mujeres con mastectomía sin reconstrucción valoraron sensiblemente descendida la CVRS con respecto a los otros tipos de cirugía. Las variables que mostraron relación estadística en explicar el FACT-B global fueron los esquemas de Deprivación emocional, Abandono, Imperfección/vergüenza, Vulnerabilidad, Apego, Dominio 3 y Dominio 4. Así también todos los valores del IPQ-R guardaron relación significativa con la CVRS global. Las creencias y percepción global de la enfermedad (IPQ-R) y los dominios de los EDT, tienen valor predictivo sobre CVRS (AU)

Objective: We studied the predictive value of sociodemographic, clinical (type of treatment) and psychological variables such as early maladaptive schemas, beliefs and perceptions about the disease and the coping strategies used by patients on health-related quality of life (HRQOL) of women with breast cancer under treatment. Method: We conducted a descriptive and correlational predictive study. Two hundred twenty-eight adult breast cancer patients under outpatient treatment from the public healthcare system were included. Interviews were conducted and sociodemographic and clinical data were collected. Several questionnaires were applied: FACT-B questionnaire, early maladaptive schemas form, Brief Illness Perception Questionnaire (IPQ-R) and COPE dispositional questionnaires. Results: Descriptive and inferential analysis, multiple linear regression, and hierarchical regression were performed. Oncology treatments subtypes did not influence HRQoL. However, women who had undergone a mastectomy without reconstruction showed significantly decreased HRQoL values. Variables that showed a statistical relationship in explaining the global FACT-B were: schemes of emotional deprivation, abandonment, defectiveness/ shame, vulnerability, attachment, domain 3 and domain 4. Also, all the IPQ-R values were significantly related to the Global HRQoL. The beliefs and global perception of the disease (IPQ-R) and EDT domains, have shown predictive value on HRQL (AU)

Enfermedad Tromboembólica Venosa en el período grávido puerperal. Diagnóstico, tratamiento y profilaxis / Venous Thromboembolic Disease in the puerperal gravid period. Diagnosis, treatment and prophylaxis / Doença tromboembólica venosa no período gravídico puerperal. Diagnóstico, tratamento e profilaxia

Resumen: El embarazo y puerperio son situaciones asociadas fisiológicamente con un marcado aumento del riesgo de enfermedad tromboembólica venosa. El riesgo se estima entre 7 a 10 veces superior que en mujeres de igual edad y 15-35 veces superior que la población control, durante el puerperio y hasta la sexta semana post-parto. Los factores de riesgo son distintos durante el período prenatal y post-parto. Los métodos diagnósticos incluyen radiografía, angio-tomografía de tórax y centellograma pulmonar ventilación-perfusión, ecodoppler venoso y venografía por resonancia nuclear magnética. El tratamiento supone un desafío que va desde la elección de la droga anticoagulante, los cambios en la farmacocinética durante el embarazo, entre otros. Se presentan algoritmos diagnósticos y terapéuticos.

Abstract: Pregnancy and the puerperium are physiologically associated with a markedly increased risk of venous thromboembolic disease. The risk is estimated between 7 to 10 times higher than in women of the same age and 15-35 times higher than the control population, during the puerperium and up to the sixth week postpartum. Risk factors are different during the prenatal and postpartum period. Diagnostic methods include radiography, chest angio-tomography and ventilation-perfusion lung scintigraphy, venous Doppler ultrasound, and magnetic resonance venography. Treatment involves a challenge that ranges from the choice of anticoagulant drug, changes in pharmacokinetics during pregnancy, among others. Diagnostic and therapeutic algorithms are presented.

Resumo: A gravidez e o puerpério estão fisiologicamente associados a um risco acentuadamente aumentado de doença tromboembólica venosa. O risco é estimado entre 7 a 10 vezes maior do que em mulheres da mesma idade e 15 a 35 vezes maior do que na população controle, durante o puerpério e até a sexta semana pós-parto. Os fatores de risco são diferentes durante o período pré-natal e pós-parto. Os métodos de diagnóstico incluem radiografia, angiotomografia de tórax e cintilografia pulmonar de ventilação-perfusão, ultrassom Doppler venoso e venografia por ressonância magnética nuclear. O tratamento envolve um desafio que vai desde a escolha do anticoagulante, mudanças na farmacocinética durante a gravidez, entre outros. Algoritmos diagnósticos e terapêuticos são apresentados.

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia.

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that "real-world" assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.

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.

[Iron deficiency in reproductive age university women at the School of Medicine, Uruguay]. / Deficiencia de hierro en mujeres universitarias en edad reproductiva en la Facultad de Medicina, Uruguay.

Introduction: Disorders of iron metabolism are very common pathological conditions. Iron deficiency, with or without anemia, is estimated to affect more than 2 billion people.The aim of this study was to determine the prevalence of iron deficiency and anemia and their predisposing factors in a group of premenopausal women, university students of the School of Medicine of the University of the Republic in Uruguay. Methods: An observational cross-sectional study was carried out, including women of reproductive age, university students of the Faculty of Medicine. They were interviewed in order to collect clinical data and monthly menstrual volume was recorded through a pictogram. A hemogram was performed and ferritin levels were determined. Results: 196 women aged from 18 to 37 years were included. The prevalence of iron deficiency was 8.7% (n = 17) and the prevalence of anemia was 2.1% (n = 4). The presence of iron deficiency was associated with a lower consumption of red meat (p = 0.024), a higher menstrual volume (p = 0.018) and a higher frequency of abnormal uterine bleeding (p = 0.019). Conclusions: This study shows the high frequency of iron deficiency in healthy women in relation to abnormal uterine bleeding and low consumption of red meat, which raises the need to implement programs that promote educational measures in order to promote early consultation and avoid anemia and iron deficiency in these women of reproductive age.

Introducción: Los trastornos del metabolismo del hierro son condiciones patológicas muy frecuentes. La deficiencia de hierro, con o sin anemia, se estima que afecta a más de 2 billones de personas. El objetivo de este estudio fue determinar la prevalencia de deficiencia de hierro y anemia y los factores predisponentes en un grupo de mujeres premenopáusicas, estudiantes universitarias de la Facultad de Medicina de la Universidad de la República en Uruguay. Métodos: Se realizó un estudio observacional de corte transversal donde se incluyeron mujeres en edad reproductiva estudiantes universitarias de la Facultad de Medicina. Se les realizó una entrevista con el objetivo de recabar los datos clínicos y se registró el volumen menstrual mensual a través de un pictograma. Se realizó un hemograma y se determinaron los niveles de ferritina. Resultados: Se incluyeron 196 mujeres de 18 a 37 años. La prevalencia de ferropenia fue 8.7% (n=17) y la prevalencia de anemia fue de 2.1% (n=4). La presencia de ferropenia se asoció a un menor consumo de carne roja (p=0.024), a un mayor volumen menstrual (p=0.018) y a una mayor frecuencia de sangrado uterino anormal (p=0,019). Conclusión: Este estudio pone de manifiesto la frecuencia elevada de deficiencia de hierro en mujeres sanas en relación con sangrado uterino anormal y bajo consumo de carne roja, lo que plantea la necesidad de implementar programas que promuevan medidas educativas a fin de promover la consulta precoz y evitar la anemia y ferropenia en estas mujeres en edad reproductiva.

TH17/Treg imbalance and IL-17A increase after severe aneurysmal subarachnoid hemorrhage.

To evaluate cerebrospinal fluid (CSF) and peripheral blood (PB) Treg, TH17 cells, TH1, TH2 and related cytokines in the acute phase of aSAH we assessed TH17, TH1, TH2, T regulatory cells and neutrophils in 39 aneurysmal subarachnoid hemorrhage (aSAH) patients and 56 controls. PB TH17 cells and TH17/Treg ratio were higher in CSF and PB of aSAH patients. Serum and CSF IL-17A levels were increased in aSAH. Serum IL-17A levels were associated with vasospasm and ICU mortality. Study results support the role of TH17/IL17 axis in aSAH pathogenesis, turning it into a potential clinical biomarker and a novel target for research.

Emergence of BCR-ABL1 Chronic Myeloid Leukemia in a JAK2-V617F Polycythemia Vera.

Emergence of a new chronic myeloid neoplasm in the setting of a previous one, or their concomitant appearance seems to be a rare event, but plenty of cases have been reported. We describe the case of a patient with JAK2-V617F polycythemia vera, which looses JAK2 clone and develops overt BCR-ABL1 chronic myeloid leukemia after 6 years. Once treatment with tyrosine kinase inhibitors controls BCR-ABL1 clone, JAK2 clone arises again. In this report, we review the literature and discuss the clonal relationship of this event in light of the new molecular data.

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice.

We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients' conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP-Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting.

Evaluación de las competencias clínicas de estudiantes de Posgrado de Pediatría utilizando el Mini-Clinical Evaluation Excercise (Mini-CEX) / Evaluation of Pediatric postgraduate students' clinical competences with the Mini-Clinical Evaluation Exercise (Mini-CEX)

Resumen: La evaluación formativa es uno de los ejes principales del proceso de enseñanza-aprendizaje del posgrado de Pediatría. El Mini Clinical Evaluation Exercise (Mini CEX) es un método de observación directa de la práctica profesional dirigido a evaluar competencias semiológicas y de razonamiento clínico. Los objetivos fueron describir la utilización y valorar la confiabilidad de esta herramienta en la evaluación de posgrados de Pediatría. Se realizaron 76 encuentros a 38 estudiantes de posgrado en una rotación de 6 meses por una unidad de internación de cuidados moderados. Las evaluaciones fueron realizadas por 2 docentes en forma simultánea e independiente. Se evalúo el puntaje obtenido en cada una de las competencias, siendo las de mejor puntajes el profesionalismo, el criterio clínico, el asesoramiento y la competencia clínica global. El instrumento fue bien aceptado por parte de los docentes y estudiantes. El promedio del tiempo de duración de las observaciones fue de 21 minutos y el de devolución (feed back) de 12 minutos. La confiabilidad del instrumento y la concordancia entre los observadores para los diferentes ítems evaluados fueron muy satisfactorias. Nuestra experiencia en el uso de MiniCEX para la evaluación de estudiantes de posgrado de Pediatría en el Uruguay, sugiere que se trata de un instrumento confiable y bien aceptado por docentes y estudiantes.

Summary: Formative assessment is one of the cornerstones of the teaching-learning process in Pediatric training. The Mini Clinical Evaluation Exercise (MiniCEX) is one of the tools available for direct observation to assess performance-based clinical skills.The study aims to describe the use of MiniCEX for the evaluation of Pediatrics fellows and to evaluate its reliability. 76 observations were performed to 38 students of Pediatrics during a 6 months rotation in a secondary care setting. Observations were carried out simultaneously and independently by 2 clinical teachers. Scores were obtained for each competency evaluated, the higher ones being professionalism, clinical judgement, patient and family education and counseling and overall clinical care. The tool was positively accepted by both teachers and students. Average observation time was 21 minutes, and feedback accounted for 12 minutes. Reliability and inter-observer agreement for the different skills evaluated were very satisfactory. Finally, our experience with the MiniCEX performed to Pediatric students proved it is not only a feasible and reliable tool to assess clinical skills, attitudes and behaviors, but also it is well accepted by teachers and students.

Compliance with the 2009 Royal College of Obstetricians and Gynaecologists guidelines for venous thromboembolic disease prophylaxis in pregnancy and postpartum period in Uruguay.

: Venous thromboembolism remains as one of the leading causes of maternal death. Prevention of venous thromboembolism in the obstetric population is challenging as recommendations for prophylaxis have low grade of evidence. Risk factors and prophylaxis guidelines have been highlighted by Royal College of Obstetricians and Gynaecologists. In 2014, we developed a written alert following this guidelines to guide thromboprophylaxis. The aim of this study is to assess recommendations compliance. This study was conducted at University-Hospital in Uruguay from January 2014 to December 2016. A total of 1035 women were enrolled and stratified in high, intermediate or low risk based on Royal College of Obstetricians and Gynaecologists guidelines. Thromboprophylaxis was recommended for women at intermediate and high risk. Women were followed up to assess symptomatic thromboembolism or haemorrhagic complications. A total of 309 were pregnant and 731 puerperal. Median age was 24 (19-29) years old. Of them, 3.0% (n = 31) were at high risk and 35.4% (n = 366) at intermediate risk. All high-risk women received prophylaxis with low-molecular-weight heparin. Of the 366 intermediate-risk women, 52.7% received prophylaxis. Venous thromboembolism was developed in only one woman of the intermediate group, who had received prophylaxis. Bleeding complications were not observed. Awareness of the thrombotic risk, as conferred by an easy and suitable risk assessment, has the potential to improve venous thromboembolism prophylaxis in pregnant and puerperal women. We have a good guidelines compliance with the written alert in the high-risk women group. However, we have to improve low-molecular-weight heparin indication in intermediate-risk group, especially in postcaesarean women.

Estudio de una cohorte de pacientes con enfermedad tromboembólica venosa en seguimiento ambulatorio / Cohort study of pacients with venous thromboembolic disease assisted in ambulatory care / Estudo de umacoorte de pacientes comdoença tromboembólica venosa em acompanhamentoambulatorial

Resumen: La enfermedad tromboembólica venosa (ETEV) es una patología con morbilidad y mortalidad elevadas. Su manejo diagnóstico y terapéutico está en permanente revisión. La ausencia de estudios epidemiológicos en nuestro medio implica un desconocimiento de la forma de presentación, etiología y recurrencia de la misma. Se propone un estudio descriptivo sobre la población de pacientes con ETEV en seguimiento en la policlínica de Trombosis y Hemostasis del Hospital Pasteur de Montevideo, durante el período 2015-2016. Se registraron 35 pacientes con ETEV. La ETEV provocada se asoció predominantemente a factores de riesgo mayor y en los cuales falló la adecuada prescripción de tromboprofilaxis. En los pacientes con ETEV no provocada, las trombofilias diagnosticadas fueron el síndrome de anticuerpos anti fosfolípidos, déficit de Antitrombina y mutación del gen de la protrombina heterocigoto. Los pacientes con ETEV no provocada tuvieron un elevado porcentaje de recurrencias, la mitad de ellas asociadas a trombofilia y la otra mitad sin factor de riesgo predisponente (ETEV idopática).

Abstract: Venous thromboembolic disease (VTD) is a condition with high rates of morbidity and mortality. The etiologic diagnosis and therapeutics are in a continuous review process. In our country there are still no epidemiologic studies about the clinic presentation, etiology and recurrence of VTD. This is a cohort study of patients assisted in ambulatory care at the Thrombosis and Haemostasis Clinic of the Hospital Pasteur in Montevideo, for the 2015-2016 period. 35 patients were registered with VTD. Provoked VTD was associated with major risk factors in which optimal prescription of thromboprofilaxis failed. In patients with unprovoked VTD, testing for trombophiliashowed Antitrombin deficiency, hetrocigotic mutation of the Protrombin and antiphospholipid antibodies. Patients with unprovoked VTD showed a high percentage of recurrences, half of them with associated trombophilia and the otherhalf with no risk factor (idiopatic VTD).

Resumo: O tromboembolismo venoso (VTE) é umadoençacom elevada morbilidade e mortalidade. Diagnóstico e manejo terapêutico está em constante revisão. A ausência de estudos epidemiológicos em nosso ambiente implica uma falta de apresentação, etiologia e recorrência do mesmo. Umestudodescritivonapopulação de pacientes com TEV monitorizaçãoproposto no polyclinic de Thrombosis and Haemostasis Hospital Pasteur em Montevidéu, durante o período de 2015-2016. 35 doentescom tromboembolismo venoso foramregistados. TEV causado predominantemente associada a fatores de risco aumentado e que falhou a prescriçãoadequada de tromboprofilaxia. Em pacientes com TEV não provocado os trombofilia foram diagnosticados síndrome anti fosfolipídiosdeficiência de antitrombina e mutação do heterozigoto protrombina. TEV pacientes nãocausaramuma elevada taxa de recorrência, metade delas associadacom trombofilia e meiasempredispondo factor de risco (idiopática VTD).