Epigenetic-based therapy in allogenic hematopoietic stem cell transplantation: Novel opportunities for personalized treatment.

Current management of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) lacks immunosuppressant drugs able to block the host immune response toward the graft antigens. Novel treatments may include epigenetic compounds (epidrugs) some of which have been yet approved by the Food and Drugs Administration for the treatment of specific blood malignancies. The most investigated in clinical trials for allo-HSCT are DNA demethylating agents (DNMTi), such as azacitidine (Vidaza) and decitabine (Dacogen) as well as histone deacetylases inhibitors (HDACi), such as vorinostat (Zolinza) and panobinostat (Farydak). Indeed, azacitidine monotherapy before allo-HSCT may reduce the conventional chemotherapy-related complications, whereas it may reduce relapse risk and death after allo-HSCT. Besides, a decitabine-containing conditioning regimen could protect against graft versus host disease (GVHD) and respiratory infections after allo-HSCT. Regarding HDACi, the addition of vorinostat and panobinostat to the conditioning regimen after allo-HSCT seems to reduce the incidence of acute GVHD. Furthermore, panobinostat alone or in combination with low-dose decitabine may reduce the relapse rate in high-risk patients with acute myeloid leukemia patients after allo-HSCT. We discuss the phase 1 and 2 clinical trials evaluating the possible beneficial effects of repurposing specific epidrugs which may guide personalized therapy in the setting of allo-HSCT.

Epigenetic-sensitive challenges of cardiohepatic interactions: clinical and therapeutic implications in heart failure patients.

Heart failure and liver dysfunction can coexist owing to complex cardiohepatic interactions including the development of hypoxic hepatitis and congestive hepatopathy in patients with heart failure as well as 'cirrhotic cardiomyopathy' in advanced liver disease and following liver transplantation. The involvement of liver dysfunction in patients with heart failure reflects crucial systemic hemodynamic modifications occurring during the evolution of this syndrome. The arterial hypoperfusion and downstream hypoxia can lead to hypoxic hepatitis in acute heart failure patients whereas passive congestion is correlated with congestive hepatopathy occurring in patients with chronic heart failure. Nowadays, liquid biopsy strategies measuring liver function are well established in evaluating the prognosis of patients with heart failure. Large randomized clinical trials confirmed that gamma-glutamyltransferase, bilirubin, lactate deihydrogenase, and transaminases are useful prognostic biomarkers in patients with heart failure after transplantation. Deeper knowledge about the pathogenic mechanisms underlying cardiohepatic interactions would be useful to improve diagnosis, prognosis, and treatments of these comorbid patients. Epigenetic-sensitive modifications are heritable changes to gene expression without involving DNA sequence, comprising DNA methylation, histone modifications, and noncoding RNAs which seem to be relevant in the pathogenesis of heart failure and liver diseases when considered in a separate way. The goal of our review is to highlight the pertinence of detecting epigenetic modifications during the complex cardiohepatic interactions in clinical setting. Moreover, we propose a clinical research program which may be useful to identify epigenetic-sensitive biomarkers of cardiohepatic interactions and advance personalized therapy in these comorbid patients.

Blood transfusions and adverse acute events: a retrospective study from 214 transfusion-dependent pediatric patients comparing transfused blood components by apheresis or by whole blood.

INTRODUCTION: Blood transfusion is a lifesaving procedure for patients affected by hematological diseases or hemorrhage risk. AIM: This retrospective study was aimed to evaluate clinical safety of pediatric transfusions by comparing the frequency of adverse events caused by apheretic blood components vs whole blood. METHODS: From 2011 to 2015, 214 patients (blood malignancy patients, n = 144 and thalassemic patients, n = 70) received 12 531 units of blood components. The adverse acute reactions occurred during patient hospitalization were reported to the Hemovigilance system and assessed by fitting a logistic mixed-effect model. RESULTS: A total of 33 (0.3%) adverse acute events occurred. Odds ratio (OR) of adverse events from apheresis vs whole blood transfusion adjusted by patient classification was not statistically significant (OR [95% CI], 0.75 [0.23-2.47]). CONCLUSION: Our findings showed no significant differences in the prevalence of adverse acute events between blood component collected by apheresis vs whole blood in our study center.

Compromised nutritional status in patients with end-stage liver disease: Role of gut microbiota.

BACKGROUND: Patients with end-stage liver disease (ESLD) have a compromised nutritional status because of the liver crucial role in regulating metabolic homeostasis and energy balance. DATA SOURCES: A systematic review of literature based on extensive relevant articles published from 2001 to 2017 in English in PubMed database was performed by searching keywords such as liver disease, non-alcoholic liver disease, alcoholic liver disease, malnutrition, epigenetics, gut microbiota, and probiotics. RESULTS: Liver transplantation would be one eligible therapy for ESLD patients, even if, the clinical outcome is negatively influenced by malnutrition and/or infections. The malnutrition is a condition of nutrient imbalance with a high incidence in ESLD patients. An accurate evaluation of nutritional status could be fundamental for reducing complications and prolonging the survival of ESLD patients including those undergoing liver transplantation. In addition, the interaction among nutrients, diet and genes via epigenetics has emerged as a potential target to reduce the morbidity and mortality in ESLD patients. The malnutrition induces changes in gut microbiota causing dysbiosis with a probable translocation of bacteria and/or pathogen-derived factors from the intestine to the liver. Gut microbiota contribute to the progression of chronic liver diseases as well as hepatocellular carcinoma. The administration of probiotics modulating gut microbiota could improve all chronic liver diseases. CONCLUSIONS: This review provides an update on malnutrition status linked to epigenetics and the potential benefit of some probiotics on the management of ESLD patients. In support of this view and to reveal the constant and growing interest in this field, some clinical trials are reported.

Screening tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus in blood donors: evaluation of two chemiluminescent immunoassay systems.

Automated chemiluminescent immunoassays (CLIAs) are useful for the detection of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus 1/2 antigen/antibodies (HIV 1/2 Ag/Ab) in blood donor screening. Eight hundred and forty serum samples were tested for hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), and HIV1/2 Ag/Ab in parallel using 2 different CLIAs (Abbott Architect i2000SR and Roche Cobas e411). The concordance between the 2 systems was high (Cohen's kappa 0.97 for HBsAg, 0.77 for anti-HCV, 0.92 for HIV1/2 Ag/Ab) and the specificity and the positive predictive value were comparable. Among the 12 discrepant results, 11 were false-positive and 1 (reactive by Architect) was true-positive for anti-HCV. Positivity for HBV DNA, HCV RNA, and HIV RNA was recorded in 90.9%, 38.9%, and 100% of true-positive samples, respectively. This study represents the first stringent comparison between Architect i2000SR and Cobas e411 in blood donors. We observed a good correlation and high agreement among HBV, HCV, and HIV with the 2 automated systems.

Efectividad de la estrategia para la prevención del dengue en un barrio del municipio de Floridablanca 2011-2012 / Effectiveness of the strategy for the prevention of dengue in a neighborhood of the municipality of Floridablanca 2011-2012

Introducción: El dengue representa un problema prioritario en salud pública en el país y en Santander. Como respuesta a esta problemática en el año 2006 se diseñó, se validó y se implementó la estrategia “lava tu pila y hazle imposible la vida al zancudo” enfocada hacia la adopción de comportamientos para la prevención y control del dengue, lo que permitió que en esta investigación se planteara como objetivo determinar la efectividad de las acciones desarrolladas a través de la estrategia para disminuir los casos de dengue en el barrio Lagos II del Municipio de Floridablanca durante los años 2011- 2012. Materiales y Métodos: Se realizó un estudio de intervención cuasi experimental. El tamaño de la muestra fue de 143 amas de casa y jefes de hogar en cada uno de los barrios. Resultados: En la población del barrio de intervención se encontró un comportamiento final orientado hacia las etapas de decisión, acción y mantenimiento. La población resalta la pila como el mayor criadero con un 62.8%. Existió una reducción del 78,1% en las pilas positivas. Al inicio del proceso se encontró un índice de 22,8 pasando a ser al final de 5.88. Se evitaran 25 casos de dengue, lo que determina un beneficio de $ 80.967.250 frente a un costo de $ 39.849.400. Desde lo cualitativo, los cambios de conducta alcanzados reconocen los cambios individuales y colectivos en la población intervenida. Discusión y Conclusiones: El 72.27% de la población intervenida adoptó el comportamiento promovido, ubicándose en la etapa de mantenimiento según el modelo Transteórico. La intervención realizada permitió la reducción del índice aédico y se reconoce que el beneficio económico al manejar estrategias de prevención de la enfermedad y promoción de la salud en lugar de brindar atención médica es del 50% menos de los gastos generados por atención clínica.

Introduction: The dengue represents a major public health problem in the country and in Santander. As a response to this problem in the year 2006 was designed, validated and implemented the strategy "wash your stack and make long-leg’s life hard” focus on the adoption of behaviors for the prevention and control of dengue, which allowed in this research to set as objective to determine the effectiveness of the actions developed through the strategy to reduce the cases of dengue in the Lakes district II of the Municipality of Floridablanca during the years 2011-2012. Materials and Methods: A quasi-experimental intervention study was carried out. The target population was 143 head of the family house wives in each neighborhood. Results: It was found in the target population a final behavior-oriented to the decision-making, action and maintenance stages. The population highlights the stack as the largest kennel with a 62.8 %. There was a positive reduction of 78.1 % positive in the stacks. At the beginning of the process, it was found an average of 22.8 compared to the 5.88 at the end. It was avoided 25 cases of dengue, which determines a profit of $80,967,250 compared to a cost of $39,849,400. From the qualitative point of view, the behavioral changes achieved are recognized not only individually but also and collectively in the population underwent. Discussion and Conclusions: The 72.27 % of the target population adopted the promoted behavior, ranking in the maintenance stage according to the trans-theoreticalc model. The carried out intervention led to the reduction of the aédico average and recognizes the economic benefit when managing strategies for the prevention of the disease and health promotion , instead of providing medical care. It is to say, 50% less than the costs generated by clinical care.