Serum Caffeine Concentration at the Time of Traumatic Brain Injury and Its Long-Term Clinical Outcomes.

Caffeine is one of the most widely consumed psychoactive drugs in the general population. It has a neuroprotective effect in degenerative neurological disorders; however, the association between caffeine and traumatic brain injury (TBI) outcomes is contradictory. The objective of this study was to evaluate the association between serum caffeine concentration at the time of injury and long-term functional outcomes of patients with TBI visiting the emergency department (ED). This was a prospective multi-center cohort study including adult patients with intracranial injury confirmed by radiological examination, who visited five participating EDs within 72 h after TBI. The main exposure was the serum caffeine level within 4 h after injury, and the study outcome was a favorable functional recovery at 6 months after injury. Multi-variable logistic regression analysis adjusted for potential confounders was performed to calculate adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Among the 334 study participants, caffeine was not detected in 102 patients (30.5 %). In patients with identifiable caffeine level, serum caffeine level was categorized into tercile groups; low (0.01-0.58 µg/mL), intermediate (0.59-1.66 µg/mL), and high (1.67-10.00 µg/mL). The proportions of patients with a 6-month favorable functional recovery were 56.9% in the no-caffeine group, 79.2% in the low-caffeine group, 75.3% in the intermediate-caffeine group, and 66.7% in the high-caffeine group (p = 0.006). In multi-variable logistic regression analysis, the low- and intermediate-caffeine groups were significantly associated with a higher probability of 6-month favorable functional recovery compared with the no-caffeine group [AORs (95% CI): 2.82 (1.32-6.02) and 2.18 (1.06-4.47], respectively. This study showed a significant association between a serum caffeine concentration of 0.01 to 1.66 µg/mL and good functional recovery at 6 months after injury compared with the no-caffeine group of patients with TBI with intracranial injury. These results suggest the possibility of using serum caffeine level as a potential biomarker for TBI outcome prediction and of using caffeine as a therapeutic agent in the clinical care of patients with TBI.

Serum Acylcarnitine and Long-Term Functional Prognosis after Traumatic Brain Injury with Intracranial Injury: A Multi-Center Prospective Study.

Serum biomarkers have potential to help predict prognosis of traumatic brain injury (TBI). The objective of this study was to evaluate the association between serum acylcarnitine levels and functional outcomes at 1 month/6 months after injury for TBI patients with intracranial hemorrhage or diffuse axonal injury. This study is a multi-center prospective cohort study in which adult TBI patients with intracranial injury visiting the emergency departments (EDs) from December 2018 to June 2020 were enrolled. Serum acylcarnitine levels at the time of ED arrival were categorized into four groups: low (1.2-5.5 µmol/L), low-normal (5.6-10.0 µmol/L), high-normal (10.1-14.5 µmol/L), and high (1.4.6-56.6 µmol/L). The study outcome was set as poor functional recovery at 1 month/6 months after injury (Glasgow Outcome Scale score, 1-3). Multi-level logistic regression analyses were conducted to estimate association between serum acylcarnitine and functional outcomes. Among total of 549 patients, poor functional recovery at 1 month and 6 months after injury were observed in 29.1% (160/549) and 29.1% (158/543, follow-up loss n = 6). The odds for 1-month poor functional outcome increased in the high-normal and the high groups [adjusted odds ratios, AORs (95% confidence intervals, CIs): 1.56 (1.09-2.23) and 2.47 (1.63-3.75)], compared with the low-normal group) and also as a continuous variable [1.05 (1.03-1.07) for each 1 µmol/L]. Regarding 6-month mortality, the high group had significantly higher odds when compared with the low-normal group [AOR (95% CI): 2.16 (1.37-3.40)]. Higher serum acylcarnitine levels are associated with poor functional outcomes at 1 month/6 months after injury for TBI patients with intracranial injury.

Serum vitamin E level and functional prognosis after traumatic brain injury with intracranial injury: A multicenter prospective study.

Background: Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury. Methods: A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0-5.4), low-normal (5.5-10.9), high-normal (11.0-16.9), and high (17.0-). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1-4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes. Results: Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0-12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1-4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62-8.27) and 2.60 (1.15-5.85) for the low group and 1.63 (1.08-2.48) and 1.60 (1.04-2.43) for the low-normal group, respectively). Conclusion: Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury.

Serum Zinc and Long-Term Prognosis after Acute Traumatic Brain Injury with Intracranial Injury: A Multicenter Prospective Study.

Serum zinc levels in the acute stages after traumatic brain injury (TBI) may be capable of predicting cinical and functional prognoses. This study aimed to evaluate the association between serum zinc levels and long-term survival and neurological outcomes in TBI patients with intracranial injury. This multicenter prospective cohort study enrolled adult TBI patients with intracranial injury who visited emergency departments between December 2018 and June 2020. Serum zinc levels drawn within 24 h after injury were categorized into four groups: low (<80.0 mcg/dL), low−normal (80.0−100.0 mcg/dL), high−normal (100.1−120.0 mcg/dL), and high (>120.0 mcg/dL). The study outcomes were 6-month mortality and disability (Glasgow Outcome Scale, 1−3). A multilevel multivariable logistic regression analysis was conducted to estimate associations between serum zinc and study outcomes. From the eligible TBI patients (N = 487), the median (interquartile range) serum zinc level was 112.0 mcg/dL (95.0−142.0). Six-month mortality and disability were 21.1% (103/487) and 29.6% (144/487), respectively. Compared to the high−normal zinc group, there were significant associations with 6-month mortality and disability observed in the low zinc group (aORs (95% CIs): 1.91 (1.60−2.28) and 1.95 (1.62−2.36) for the low group; 1.14 (0.67−1.94) and 1.15 (0.91−1.46) for the low−normal group; and 0.72 (0.44−1.16) and 0.88 (0.61−1.27) for the high group, respectively). Among the 122 TBI patients with diabetes mellitus, the low zinc group showed a higher incidence of 6-month mortality (aOR (95% CI): 9.13 (4.01−20.81)) compared to the high−normal zinc group. Moreover, the low and low−normal groups had higher odds for 6-month disability (aORs (95% CIs): 6.63 (3.61−12.15) for the low group and 2.37 (1.38−4.07) for the low−normal group). Serum zinc deficiency is associated with a higher incidence of 6-month mortality and disability after injury for TBI patients with intracranial injury.

Vitamin D Deficiency and Prognosis after Traumatic Brain Injury with Intracranial Injury: A Multi-Center Observational Study.

Vitamin D may be important for neuroprotection after traumatic brain injury (TBI) by modifying the inflammatory response. The objective of this study was to evaluate the association between vitamin D deficiency and functional and survival outcomes in patients with TBI and intracranial injury. This study was a prospective multi-center cohort study conducted on adult TBI patients, with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination, admitted to five participating emergency departments (EDs) from December 2018 to June 2020. The study outcomes were good functional recovery at hospital discharge and survival at 6-months after injury. The primary exposure was serum vitamin D deficiency (0-10 ng/mL). Multi-level logistic regression analysis was performed to estimate the association between vitamin D deficiency and the study outcomes. Among 606 patients, 101 (16.7%) patients had vitamin D deficiency at the time of ED arrival. Good functional recovery was observed in 65.2% (395/606) of total population, and this proportion was significantly lower in the vitamin D deficiency group than the non-deficiency group (56.4 vs. 66.9%, p = 0.04, adjusted odds ratio (OR; 95% confidence interval [CI]): 0.56 (0.36-0.88)). Overall survival rate at 6 months after injury was 79.5% (434/546), and patients with vitamin D deficiency had significantly lower likelihood of survival at 6 months than patients without deficiency [75.0 vs. 80.3%, adjusted OR (95% CI): 0.59 (0.39-0.89)]. Vitamin D deficiency is associated with poor functional outcomes at hospital discharge and mortality at 6-months after injury in TBI patients with intracranial hemorrhage or diffuse axonal injury.