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Background: Intensive care unit (ICU) delirium is associated with a proinflammatory state and poor outcomes. An epigenetic mechanism may modify inflammation., Objective: To identify inflammatory gene methylation trajectory groups and explore their clinical and demographic variability., Methods: Patients were at least 18 years old; received mechanical ventilation for at least 24 hours; had no brain disorder/injury, preexisting dementia, or positive toxicology screen; and were admitted to a medical or surgical/trauma ICU. Delirium was assessed (Confusion Assessment Method for the ICU) and blood samples were collected daily for up to 10 days. Methylation of 3 genes in the inflammatory pathway was quantified. Latent class analysis identified gene methylation trajectories, and variables (including delirium) were compared between trajectory groups., Results: Of 68 patients (53% female, 88% White), 65% developed delirium. Of 3 methylation trajectories for IL6ST, the group with low initial methylation increasing over time included younger male patients who were less likely to have delirium, and the group with high initial methylation decreasing over time included older (P = .01) female (P = .05) patients who more often had delirium (P = .05). IL17C had 2 methylation trajectories without significant differences in delirium, age, or sex. IL13RA1 had 2 methylation trajectories without differences in delirium or age; the group with sustained high methylation had more female patients (P = .003)., Conclusions: Temporal variability in inflammatory gene methylation occurs after ICU admission. Delirium, female sex, and older age were more common with higher IL6ST methylation that decreased over time. Larger studies are needed to further elucidate these relationships., (©2022 American Association of Critical-Care Nurses.)

AbstractTraumatic brain injury (TBI) triggers a cascade of apoptotic-related events that include BCL2 expression, a pro-survival protein in the apoptosis pathway. The purpose of this study was to use tagging single nucleotide polymorphism (tSNP) genotypes to screen the BCL2gene to determine if genetic variability in the BCL2gene influences outcomes in 205 patients with severe TBI. Outcomes (Glasgow Outcome Scale [GOS], Disability Rating Scale [DRS], mortality, and Neurobehavioral Rating Scale–Revised [NRS-R]) were analyzed at 3, 6, 12, and 24 months. Multivariate analysis demonstrates that there were four tSNPs of significant interest: rs17759659, rs1801018, rs7236090, and rs949037. Presence of the variant allele for rs17759659 was associated with poorer outcomes (GOS p= 0.001; DRS p= 0.002), higher mortality (p= 0.02; OR = 4.23; CI 1.31,13.61), and worse NRS-R scores (p= 0.05). Presence of the variant allele for rs1801018 was associated with poorer outcomes (GOS p= 0.02; DRS p= 0.009), and mortality (p= 0.03; OR = 3.86; CI 1.18,12.59). Being homozygous for the wild-type allele for rs7236090 was associated with favorable outcomes on the NRS-R (p= 0.007), while homozygosity for the variant genotype was associated with favorable outcomes on the GOS (p= 0.007) and DRS (p= 0.006). The homozygous variant for rs949037 was associated with favorable outcomes (GOS p= 0.04; DRS p= 0.03), and the homozygous wild-type was associated with increased mortality at 3 months (p= 0.005; OR = 3.67; CI 1.08,12.49). The only finding that stood up to Bonferroni correction was rs17759659 for GOS. These data support the possibility that genetic variability for pro-survival proteins, particularly genetic variation in the BCL2gene, impacts outcomes after severe TBI. [ABSTRACT FROM AUTHOR]

AbstractNeuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). However, to date an association between genetic variation within the human neuroglobin (NGB) gene and recovery post-TBI has not been reported. The purpose of this study was to explore the relationship between NGBgenotypes and outcomes (as assessed by the Glasgow Outcome Scale [GOS], the Disability Rating Scale [DRS], and the Neurobehavioral Rating Scale-Revised [NRS-R]) after severe TBI. Genotyping using TaqMan allele discrimination for two tagging single nucleotide polymorphisms (tSNPs) that represent the two haplotype blocks for NGB(rs3783988 and rs10133981) was completed on DNA obtained from 196 Caucasian patients recovering from severe TBI. Patients were dichotomized based on the presence of the variant allele for each tSNP. Chi-square and Fisher's exact tests were used to compare characteristics between groups. Multivariate linear regression was used to examine NGBtSNPs and recovery from severe TBI. Subjects with the TT genotype (wild-type) for rs3783988 were more likely to have better GOS and DRS scores at 3, 6, 12, and 24 months, while rs10133981 genotype was not significantly related to functional outcome. After controlling for age, gender, and Glasgow Coma Scale (GCS) score, those subjects with the rs3783988 TT genotype had more than a 2.65-times greater likelihood of better functional outcomes than individuals with genotypes harboring a variant allele. Data suggest that the haplotype block represented by rs3783988 in NGBappears to influence recovery after severe TBI. Represented within this haplotype block of NGBis the region that codes for the oxygen-binding portion of NGB. [ABSTRACT FROM AUTHOR]