Assessing the Relevance of Non-molecular Prognostic Systems for Myelodysplastic Syndrome in the Era of Next-Generation Sequencing.

Background: The Molecular International Prognostic Scoring System (IPSS-M) has improved the prediction of clinical outcomes for myelodysplastic syndromes (MDS). The Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS), based on classical clinical parameters, has outperformed the IPSS, revised version (IPSS-R). For the first time, we validated the IPSS-M and other molecular prognostic models and compared them with the established IPSS-R and AIPSS-MDS models using data from South American patients. Methods: Molecular and clinical data from 145 patients with MDS and 37 patients with MDS/myeloproliferative neoplasms were retrospectively analyzed. Results: Prognostic power evaluation revealed that the IPSS-M (Harrell's concordance [C]-index: 0.75, area under the receiver operating characteristic curve [AUC]: 0.68) predicted overall survival better than the European MDS (EuroMDS; C-index: 0.72, AUC: 0.68) and Munich Leukemia Laboratory (MLL) (C-index: 0.70, AUC: 0.64) models. The IPSS-M prognostic discrimination was similar to that of the AIPSS-MDS model (C-index: 0.74, AUC: 0.66) and outperformed the IPSS-R model (C-index: 0.70, AUC: 0.61). Considering simplified low- and high-risk groups for clinical management, after restratifying from IPSS-R (57% and 32%, respectively, hazard ratio [HR]: 2.8; P=0.002) to IPSS-M, 12.6% of patients were upstaged, and 5% were downstaged (HR: 2.9; P=0.001). The AIPSS-MDS recategorized 51% of the low-risk cohort as high-risk, with no patients being downstaged (HR: 5.6; P<0.001), consistent with most patients requiring disease-modifying therapy. Conclusions: The IPSS-M and AIPSS-MDS models provide more accurate survival prognoses than the IPSS-R, EuroMDS, and MLL models. The AIPSS-MDS model is a valid option for assessing risks for all patients with MDS, especially in resource-limited centers where molecular testing is not currently a standard clinical practice.

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.

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)

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.