Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

Assessing the impact of blood alcohol concentration on the rate of in-hospital mortality following traumatic motor vehicle crash injury: A matched analysis of the National Trauma Data Bank

Background

The purpose of this study was to compare the outcomes of trauma patients who were injured in a motor vehicle crash and tested positive for alcohol upon hospital arrival versus those who tested negative.

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

Impact of stereotactic body radiation therapy on geriatric assessment and management for older patients with head and neck cancer using G8

PurposeManagement of head and neck cancers (HNC) in older adults is a common but challenging clinical scenario. We assess the impact of Stereotactic Body Radiation Therapy (SBRT) on survival utilizing the Geriatric-8 (G8) questionnaire.Materials and methods171 HNC patients, deemed medically unfit for definitive treatment, were treated with SBRT ± systemic therapy. G8 questionnaires were collected at baseline, at 4–6 weeks, and at 2–3 months post-treatment. Patients were stratified according to their baseline G8 score: <11 as ‘vulnerable’, 11–14 as ‘intermediate’, and >14 as ‘fit’. Overall survival (OS) was assessed through univariate Kaplan Meier analysis. Repeated measures ANOVA was used to determine if baseline characteristics affected G8 score changes.ResultsMedian follow-up was seventeen months. 60% of patients presented with recurrent HNC, 30% with untreated HNC primaries, and 10% with metastatic non-HNC primaries. Median age was 75 years. Median Charlson Comorbidity Index score was 2. 51% of patients were ‘vulnerable’, 37% were ‘intermediate’, and 12% were ‘fit' at baseline, with median survival of 13.2, 24.3, and 41.0 months, respectively (p = .004). Patients who saw a decrease in their follow-up G8 score (n = 69) had significantly lower survival than patients who had stable or increased follow-up G8 scores (n = 102), with median survival of 8.6 vs 36.0 months (p < .001).ConclusionThe G8 questionnaire may be a useful tool in upfront treatment decision-making to predict prognosis and prevent older patients from receiving inappropriate anti-cancer treatment. Decline in follow-up G8 scores may also predict worse survival and aid in goals of care following treatment.