BACKGROUND: The recovery of severe traumatic brain injury (TBI) survivors with long-term favorable outlook is understudied. Time to follow commands varies widely in this patient population but has important clinical implications. OBJECTIVE: To (1) evaluate time to follow commands in severe patients with TBI with favorable outcomes, (2) characterize their trajectory of recovery, and (3) identify predictors associated with delayed cognitive improvement. METHODS: Participants were recruited prospectively at a Level I trauma center through the Brain Trauma Research Center from 2003 to 2018. Inclusion criteria were age 16 to 80 years, Glasgow Coma Scale score ≤8 and motor score <6, and Glasgow Outcome Scale-Extended measure ≥4 at 2 years postinjury. RESULTS: In 580 patients, there were 229 (39.5%) deaths and 140 (24.1%) patients had favorable outcomes at 2 years. The mean age was 33.7 ± 14.5 years, median Glasgow Coma Scale was 7 (IQR 6-7), and median Injury Severity Score was 30 (IQR 26-38). The mean time to follow commands was 12.7 ± 11.8 days. On multivariable linear regression, the presence of diffuse axonal injury (B = 9.2 days [4.8, 13.7], P < .0001) or intraventricular hemorrhage (B = 6.4 days [0.5, 12.3], P < .035) was associated with longer time before following commands and patients who developed nosocomial infections (B = 6.5 days [1.6-11.4], P < .01). CONCLUSION: In severe TBI survivors with favorable outcomes, time to follow commands varied widely. Most patients began to follow commands within 2 weeks. Evidence of diffuse axonal injury, intraventricular hemorrhage, and infections can delay cognitive improvement in the acute period. Patients make considerable recovery up to 2 years after their injury.

Severe traumatic brain injury (TBI) activates the apoptotic cascade in neurons and glia as part of secondary cellular injury. B-cell lymphoma 2 (Bcl-2) gene encodes a pro-survival protein to suppress programmed cell death, and variation in this gene has potential to affect intracranial pressure (ICP). Participants were recruited from a single clinical center using a prospective observational study design. Inclusion criteria were: age 16-80 years; Glasgow Coma Scale (GCS) score 4-8; and at least 24 h of ICP monitoring treated between 2000-2014. Outcomes were mean ICP, spikes >20 and >25 mm Hg, edema, and surgical intervention. Odds ratios (OR), mean increases/decreases (B), and 95% confidence intervals (CIs) were reported. In 264 patients, average age was 39.2 years old and 78% of patients were male. Mean ICPs were 11.4 ± 0.4 mm Hg for patients with homozygous wild-type (AA), 12.8 ± 0.6 mm Hg for heterozygous (AG), and 14.3 ± 1.2 mm Hg for homozygous variant (GG; p = 0.023). Rs17759659 GG genotype was associated with more ICP spikes >20 mm Hg (p = 0.017) and >25 mm Hg (p = 0.048). Multi-variate analysis showed that GG relative to AA genotype had higher ICP (B = 2.7 mm Hg, 95% CI [0.5,4.9], p = 0.015), edema (OR = 2.5 [1.0, 6.0], p = 0.049) and need for decompression (OR = 3.7 [1.5-9.3], p = 0.004). In this prospective severe TBI cohort, Bcl-2 rs17759659 was associated with increased risk of intracranial hypertension, cerebral edema, and need for surgical intervention. The variant allele may impact programmed cell death of injured neurons, resulting in elevated ICP and post-traumatic secondary insults. Further risk stratification and targeted genotype-based therapies could improve outcomes after severe TBI.

Objective

To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk.

Methods

Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF).

Results

Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for.

Conclusions

Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity.