Aim: To determine the clinical and genetic markers associated with erythropoietin deficiency anemia in predialysis individuals. Materials & methods: Patients were categorized into cases and control group. Demographic characteristics and clinical parameters were obtained from medical record review and serum EPO and ferritin were obtained with ELISA. HIF-1α (rs2057482), IL-1β (rs1143627) and EPO (rs1617640) gene polymorphism were genotyped. Results: Female gender, glomerular filtration rate, treatment with hematinics, anticoagulant and diuretic were strong predictors of EPO-deficient anemia in predialysis chronic kidney disease patients. Genetic polymorphism in the HIF-1α recessive model was associated with non-EPO-deficiency, followed by EPO recessive allele associated with low-serum erythropoietin and IL-1β recessive model with low hemoglobin level. Conclusion: EPO-deficiency anemia can be diagnosed more conveniently in the presence of biomarkers.
Context: Several interventions are available for the management of hypoxic ischemic encephalopathy (HIE), but no studies have compared their relative efficacy in a single analysis. This study aims to compare and determine the effectiveness of available interventions for HIE using direct and indirect data. Methods: Large randomized trials were identified from PubMed, EMBASE, CINAHL Plus, AMED, and Cochrane Library of Clinical Trials database from inception until June 30, 2018. Two independent reviewers extracted study data and performed quality assessment. Direct and network meta-analysis of randomized controlled trials was performed to obtained pooled results comparing the effectiveness of different therapies used in HIE on mortality, neurodevelopmental delay at 18 months, as well as adverse events. Their probability of having the highest efficacy and safety was estimated and ranked. The certainty of evidence for the primary outcomes of mortality and mortality or neurodevelopmental delay at 18 months was evaluated using GRADE criteria. Results: Fifteen studies comparing five interventions were included in the network meta-analysis. Whole body cooling [Odds ratio: 0.62 (95% credible interval: 0.46-0.83); 8 trials, high certainty of evidence] was the most effective treatment in reducing the risk of mortality, followed by selective head cooling (0.73; 0.48-1.11; 2 trials, moderate certainty of evidence) and use of magnesium sulfate (0.79; 0.20-3.06; 2 trials, low certainty of evidence). Whole body hypothermia (0.48; 0.33-0.71; 5 trials), selective head hypothermia (0.54; 0.32-0.89; 2 trials), and erythropoietin (0.36; 0.19-0.66; 2 trials) were more effective for reducing the risk of mortality and neurodevelopmental delay at 18 months (moderate to high certainty). Among neonates treated for HIE, the use of erythropoietin (0.36; 0.18-0.74, 2 trials) and whole body hypothermia (0.61; 0.45-0.83; 7 trials) were associated with lower rates of cerebral palsy. Similarly, there were lower rates of seizures among neonates treated with erythropoietin (0.35; 0.13-0.94; 1 trial) and whole body hypothermia (0.64; 0.46-0.87, 7 trials). Conclusion: The findings support current guidelines using therapeutic hypothermia in neonates with HIE. However, more trials are needed to determine the role of adjuvant therapy to hypothermia in reducing the risk of mortality and/or neurodevelopmental delay.
Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.