The objective is to describe the epidemiology and outcomes of DNR orders in trauma patients. Methods: We included all adults with trauma to a community Level I Trauma Center over 6 years (2008-2013). We used chi-square, Wilcoxon rank-sum, and multivariate stepwise logistic regression tests to characterize DNR (established in-house vs. pre-existing), describe predictors of establishing an in-house DNR, timing of an in-house DNR (early [within 1 day] vs late), and outcomes (death, ICU stay, major

complications). Vorinostat mw Results: Included were 10,053 patients with trauma, of which 1523 had a DNR order in place (15%); 715 (7%) had a pre-existing DNR and 808 (8%) had a DNR established in-house. Increases were observed over time in both the proportions of patients with DNRs established in-house (p = 0.008) and age bigger than = 65 (p smaller than 0.001). Over 90% of patients with an in-house DNR were bigger than = 65 years. The following covariates were independently associated with establishing a DNR in-house: age bigger than = 65, severe neurologic deficit (GCS 3-8), fall mechanism of injury, ED tachycardia, female gender, and comorbidities (p smaller than 0.05 for all). Age

bigger than = 65, female gender, non-surgical service admission and transfers-in were associated with a DNR established early (p smaller than 0.05 for all). As expected, mortality was greater in patients with DNR than those without (22% vs. 1%), as was the development Torin 1 PI3K/Akt/mTOR inhibitor Fer-1 of a major complication (8% vs. 5%), while ICU admission was similar (19% vs. 17%). Poor outcomes were greatest in patients with DNR orders executed later in the hospital stay. Conclusions: Our analysis of a broad cohort of patients with traumatic injury establishes the relationship between DNR and patient characteristics and outcomes. At 15%, DNR orders are prevalent in our general trauma population, particularly in patients bigger than = 65 years, and are placed early after arrival. Established prognostic factors, including age and physiologic severity, were determinants for in-house DNR orders.

These data may improve physician predictions of outcomes with DNR and help inform patient preferences, particularly in an environment with increasing use of DNR and increasing age of patients with trauma.”
“The mammalian nucleotide excision repair (Ner) pathway removes dangerous bulky adducts from genomic DNA. Failure to eliminate these lesions can lead to oncogenesis, developmental abnormalities and accelerated ageing. TFIIH is a central Ner factor that opens the damaged DNA through the action of its two helicases (XPB and XPD) prior to incision. Here we review our recently published data that suggest specific and distinct roles for these two helicases in Ner. we also discuss the regulation of XPB and XPD enzymatic activities within TFIIH and repair complexes, and show that mutations impeding enzyme-regulator interaction contribute to genetic disorders.