Evaluating mortality and 6-month functional outcomes of patients with dural venous sinus thrombosis in traumatic brain injury.

OBJECTIVE: Patients with dural venous sinus thrombosis (DVST) in select populations following traumatic brain injury (TBI), including those with blunt mechanism or depressed skull fractures, have been shown to have an increased risk of mortality. The purpose of this study was to assess these findings in a mixed population of head trauma patients. METHODS: The authors performed a case-control study using propensity score matching by reviewing 17 years (2004-2021) of data from their institutional trauma registry. Patients with imaging-confirmed DVST were matched to a control group of TBI patients without identified DVST based on age, sex, postresuscitation Glasgow Coma Scale (GCS) score, and Injury Severity Score. All age groups and injury mechanisms were included with a head Abbreviated Injury Scale score ≥ 3. Data on demographics, injury and radiographic characteristics, and patient outcomes were collected. Multivariable logistic regression was performed to identify predictors of inpatient mortality. An additional subgroup analysis of patients with concurrent DVST and blunt cerebrovascular injury (BCVI) was planned a priori. RESULTS: The authors identified 9875 patients who presented to their institution over the study period with TBIs, with a 1.64% incidence of DVST. Concurrent BCVI was diagnosed in 23.5% of patients with a DVST. Following matching, the presence of DVST itself was not significantly associated with inpatient mortality (OR 0.68, 95% CI 0.24-1.88). On regression analysis, penetrating injuries (8.19, 95% CI 1.21-80.0) and lower postresuscitation GCS scores (0.69, 95% CI 0.53-0.84) were independently associated with inpatient mortality for patients with traumatic DVST. Significantly worse functional outcomes were observed in those with DVST at 3 months, with no significant difference at 6 months. CONCLUSIONS: The authors observed a prevalence of traumatic DVST of 1.64% in a mixed population of head-injured patients, with 23.5% of patients with DVST having concurrent BCVI. Traumatic DVST alone was not associated with a significantly increased risk of inpatient mortality.

Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.

Cu (Cu) is essential for several biochemical pathways due to its role as a catalytic cofactor or allosteric regulator of enzymes. Its import and distribution are tightly controlled by transporters and metallochaperones and Cu homeostasis is maintained by balancing Cu uptake and export. Genetic diseases are caused by impaired Cu transporters CTR1, ATP7A, or ATP7B but little is known about the regulatory mechanisms by which these proteins meet the fluctuating demands of Cu in specific tissues. Cu is required for differentiation of skeletal myoblasts to myotubes. Here, we demonstrate that ATP7A is needed for myotube formation and that its increased abundance during differentiation is mediated by stabilization of Atp7a mRNA via the 3' untranslated region. Increased ATP7A levels during differentiation resulted in increased Cu delivery to lysyl oxidase, a secreted cuproenzyme that needed for myotube formation. These studies identify a previously unknown role for Cu in regulating muscle differentiation and have broad implications for understanding Cu-dependent differentiation in other tissues.