Isabel Cristina Céspedes

Alcohol Use Disorder (AUD) is a multifactorial condition shaped by genetic predispositions and neurophysiological, behavioural, and environmental factors. Chronic stress and trauma are key drivers of harmful alcohol use. This study aimed to investigate, in a Brazilian admixed population, the associations and interactions between genetic variants related to the CRFergic, noradrenergic, and glucocorticoid receptor systems and exposure to childhood and adulthood stressors, as well as perceived stress, in individuals with and without AUD. We evaluated 227 inpatients with AUD and 174 controls. Alcohol involvement was assessed using the AUDIT and IDS‐42. Childhood trauma, adult‐life stressors, and perceived stress were measured using the CTQ, LES, and PSS, respectively. Genetic variants were characterised using next‐generation sequencing. Individuals with AUD showed more severe childhood trauma, more adverse adult‐life experiences, and higher perceived stress. Two CRHR2 variants were significantly associated with AUD after correction for multiple testing (rs8175360 increasing risk; rs41417745 decreasing risk). Stress‐related genetic variation, particularly in CRHR2 , was associated with AUD diagnosis in interaction with environmental stressors across the lifespan. These findings highlight the importance of integrating genetic and environmental factors to better understand the heterogeneity of AUD and may inform future approaches to personalised prevention and intervention strategies.

Alcohol use disorder (AUD) is a chronic and progressive disease that affects individuals worldwide. AUD individuals exhibit epigenetic alterations across tissues, mainly in the brain. Despite advances in the field, there is a gap in epigenome‐wide association studies (EWAS) conducted in a Brazilian cohort that is genetically and culturally diverse. This study aimed to describe an exploratory EWAS conducted in Brazilian males with AUD and to identify DNA methylation signatures associated with brain‐related biological pathways. Peripheral blood samples were collected from 54 patients with AUD in the early stages of withdrawal (AUD group) and 70 control individuals (CON group) (Brazil, São Paulo). Genome‐wide DNA methylation was assessed using the Infinium MethylationEPIC BeadChip v2.0. We identified four differentially methylated loci in genes involved in intracellular signalling and cellular stress responses. Focusing on the nervous system, enrichment analyses revealed pathways related to neuronal/axon development and synaptic organization hypomethylated in the AUD group ( p . adjust < 0.05). Differentially methylated regions (DMRs) showed hypomethylation in regulatory and exonic regions of ABAT, DLX5, PHGDH, TRPM2 and GABBR1 genes, which are within the enriched pathways. In conclusion, to the best of our knowledge, this is the first EWAS in a Brazilian cohort with AUD to identify alterations in DNA methylation, highlighting genes and pathways involved in neurogenesis, synaptic and GABAergic signalling. These epigenetic modifications suggest an impact of chronic alcohol consumption on critical biological processes of the CNS, potentially contributing to the cognitive and behavioural impairments observed in AUD. The results reinforce the importance of epigenetic studies in mixed‐race populations.

Blood transfusion is associated with adverse clinical and surgical outcomes. Strategies like the Patient Blood Management program, which includes blood cell salvage, contribute to reducing the use of blood components. Blood cell salvage is very useful in heart surgeries where the patient's blood loss can be massive. The present study aimed to evaluate the impact of using the blood cell salvage in the intraoperative and postoperative periods (up to 24 hours) on the hemoglobin and hematocrit values, transfusion of red blood cells, infection rates, and postoperative length of stay in patients undergoing cardiac surgery with cardiopulmonary bypass. Forty-one patients who underwent cardiac surgery with cardiopulmonary bypass according to the inclusion criteria were selected in an observational study and separated into two groups: with the use of the blood cell salvage group (BCS, n = 21) and without the use of the blood cell salvage (WBCS, n = 20). Patients in the group using blood cell salvage had higher postoperative hemoglobin (P = 0.018) and postoperative hematocrit levels (P = 0.009), lower consumption of red blood cells in the postoperative period and hospital discharge (P < 0.001), shorter postoperative length of stay (P = 0.020), and lower infection rates (P = 0.009). Patient Blood Management strategies, particularly the use of blood cell salvage in the intraoperative and immediate postoperative periods of patients undergoing cardiac surgery with cardiopulmonary bypass, are associated with less use of blood components and consequently better clinical outcomes.

Successful Case of Double Valve Replacement Surgery Using Autologous Blood Transfusion: A Patient's Autonomy Preserved with Excellent Clinical Outcome - Article abstract #943675