Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury.

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6-12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8-8.8, p < 0.01; T-Tau 7.2-11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2-17.5, p < 0.01; T-Tau 8.7-12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8-9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.

Age-dependent thrombin generation predicts 30-day mortality and symptomatic thromboembolism after multiple trauma.

Trauma-induced coagulopathy (TIC) is a risk factor for death and is associated with deviations in thrombin generation. TIC prevalence and thrombin levels increase with age. We assayed in vivo and ex vivo thrombin generation in injured patients (n = 418) to specifically investigate how age impacts thrombin generation in trauma and to address the prognostic ability of thrombin generation. Biomarkers of thrombin generation were elevated in young (< 40 years) and older (≥ 40 years) trauma patients. In vivo thrombin generation was associated with Injury Severity Score (ISS) and this association was stronger in young than older patients. In vivo thrombin generation decreased faster after trauma in the young than the older patients. Across age groups, in vivo thrombin generation separated patients dying/surviving within 30 days at a level comparable to the ISS score (AUC 0.80 vs. 0.82, p > 0.76). In vivo and ex vivo thrombin generation also predicted development of thromboembolic events within the first 30 days after the trauma (AUC 0.70-0.84). In conclusion, younger trauma patients mount a stronger and more dynamic in vivo thrombin response than older patients. Across age groups, in vivo thrombin generation has a strong ability to predict death and/or thromboembolic events 30 days after injury.

Improved cardiopulmonary exercise function after modified Nuss operation for pectus excavatum.

OBJECTIVES: Patients with pectus excavatum have compromised cardiac function during exercise. We hypothesized that the Nuss technique would improve cardiopulmonary function during exercise. METHODS: We investigated 75 teenagers (49 patients and 26 controls) at rest and during bicycle exercise prior to surgery and 1 year postoperative. RESULTS: Prior to surgery, patients had a lower cardiac index 6.6 ± 1.1 l/min/m(2) when compared with controls 8.1 ± 1.0 l/min/m(2) during submaximal exercise, P = 0.0001. There was no difference in heart rate or increase in heart rate between the two groups. One year after surgery, cardiac index had significantly increased in the pectus group, P = 0.0054 although cardiac index was still significantly lower 7.2 ± 1.0 l/min/m(2) when compared with the control subjects (8.5 ± 1.6 l/min/m(2), P = 0.0008). Both the patients and the controls increased their VO(2) max during the one-year study period although the controls increased most. Right ventricular diastolic dimension increased in both groups over the one-year study period and left ventricular dimensions increased in the patients. Before operation, the patients had lower forced expiratory capacity FEV(1) 86 ± 13% when compared with controls 94 ± 10%, P = 0.009. Patients increased FEV(1)/forced vital capacity over the one-year long study course although there were no differences between groups. CONCLUSION: Patients with pectus excavatum have lower cardiac index at submaximal exercise when compared with healthy age-matched controls. Their cardiac index and FEV(1) are increased one year after the modified Nuss operation.

Compromised cardiac function in exercising teenagers with pectus excavatum.

Patients with pectus excavatum complain about fatigue, tachypnea, discomfort and dyspnea, but the existence of an equivalent underlying pathophysiology has been questioned. We investigated 75 teenagers (49 pectus excavatum patients and 26 age matched controls) at rest and during bicycle exercise at submaximal exercise levels. At rest cardiac function was determined using echocardiography. During rest and exercise, cardiac output, heart rate and aerobic exercise capacity were measured using photo-acoustic gas-rebreathing technique for non-invasive determination of the cardiopulmonary function. At rest, no cardiac differences were found between control subjects and patients with pectus excavatum. During submaximal exercise, cardiac index was lower 6.6(6.3-7.0) l/min/m(2) among the pectus patients as compared to the control subjects 8.0(7.3-8.8) l/min/m(2), P=0.0001. The lower cardiac output among the pectus patients was due to a lower stroke index 42(39-45) ml/beat/m(2) as compared to controls 54(44-64) ml/beat/m(2), P=0.0022, whereas heart rate was unchanged. Cardiac function is significantly impaired at submaximal exercise level compared to healthy age matched controls.