A Review of Key Regulators of Steady-State and Ineffective Erythropoiesis.

Erythropoiesis is initiated with the transformation of multipotent hematopoietic stem cells into committed erythroid progenitor cells in the erythroblastic islands of the bone marrow in adults. These cells undergo several stages of differentiation, including erythroblast formation, normoblast formation, and finally, the expulsion of the nucleus to form mature red blood cells. The erythropoietin (EPO) pathway, which is activated by hypoxia, induces stimulation of the erythroid progenitor cells and the promotion of their proliferation and survival as well as maturation and hemoglobin synthesis. The regulation of erythropoiesis is a complex and dynamic interaction of a myriad of factors, such as transcription factors (GATA-1, STAT5), cytokines (IL-3, IL-6, IL-11), iron metabolism and cell cycle regulators. Multiple microRNAs are involved in erythropoiesis, mediating cell growth and development, regulating oxidative stress, erythrocyte maturation and differentiation, hemoglobin synthesis, transferrin function and iron homeostasis. This review aims to explore the physiology of steady-state erythropoiesis and to outline key mechanisms involved in ineffective erythropoiesis linked to anemia, chronic inflammation, stress, and hematological malignancies. Studying aberrations in erythropoiesis in various diseases allows a more in-depth understanding of the heterogeneity within erythroid populations and the development of gene therapies to treat hematological disorders.

Predictors for anaemia, blood transfusion and outcome in plastic surgery patients.

OBJECTIVE: In patients undergoing plastic surgery, to identify specific risk factors for anaemia and use of blood products, and assess their impact on patient outcome. METHOD: For this retrospective study, data were analysed from patients who attended the Plastic Surgery Department at our hospital over a three-year period (2018 to 2020). Adult patients who presented with traumatic injuries, oncologic patients who underwent reconstructive procedures, and patients with soft tissue infections (STIs) who required plastic surgery for tissue coverage were included. Demographic and injury data, hospital admission characteristics, surgical procedures, laboratory test results, transfusion events, and in-hospital complications were extracted from patient records. RESULTS: Of the 350 patients included in the study, 228 (65%) presented with trauma, 76 (22%) underwent reconstructive surgery for cancers and 46 (13%) had STIs. In total, 175 (50%) patients developed anaemia, and 37 (11%) received blood transfusions; these were 20 (54%), 5 (14%), and 12 (32%) patients in the trauma, cancer and STI groups, respectively. Associated comorbidities and upper and lower limb surgery were the most significant risk factors for anaemia, while the number of surgeries and NSTIs were identified as risk factors for blood transfusions. Direct wound closure was consistently a protective factor for both anaemia and blood transfusions. Blood transfusions were independently associated with a high risk of sepsis, wound complications, and prolonged hospital stay. CONCLUSION: While transfusions are necessary and even lifesaving in surgical patients, blood is a finite resource and its use may negatively impact patient outcome. Therefore, ongoing research must focus on providing safe and restrictive clinical practices while developing sustainable and accessible alternatives.

PARP inhibitors in acute myeloid leukaemia therapy: How a synthetic lethality approach can be a valid therapeutic alternative.

Acute myeloid leukaemia (AML) is a malignancy in need of new therapeutic options. The current standard of care chemotherapy, leads to complete remission (CR) in the vast majority of adult patients under the age of 60. In contrast, CR rates in patients over the age of 60 reaches only 40-60%. While achievement of a CR is an important stepping stone in the treatment of AML, the majority of these patients experience relapse and die of their disease without adequate consolidation chemotherapy. Blood and marrow transplantation (BMT) can improve outcome in a select patient with AML but unfortunately, it is not a valid treatment option for the majority of older patients. Thus, the development of novel chemotherapy regimens that capitalizes on AML biology to eliminate the malignant clone with little to no side effects on the normal haematopoiesis is paramount in the treatment of elderly patients. In the current paper, we propose to take advantage of the dysfunctional DNA repair mechanisms present in AML cells and induce synthetic lethality using a combination of PARP inhibitors with low dose anthracycline and DNMT inhibitors. Such a combination, while effectively eliminating leukaemia should be well tolerated and thus, suitable for the treatment of frail patients.