Heng-Li Tian

Predicting outcomes after traumatic brain injury: The development and validation of prognostic models based on admission characteristics

BACKGROUND Early estimation of prognosis for the patient with traumatic brain injury is an important factor in making treatment decisions, resource allocation, classify patients, or communicating with family. We aimed to develop and validate practical prognostic models for mortality at 30 days and for 6 months unfavorable outcome after moderate and severe traumatic brain injury. METHODS Retrospectively collected data from our department were used to develop prognostic models for outcome. We developed four prognostic models based on admission predictors with logistic regression analysis. The performance of models was assessed with respect to discrimination and calibration. Discriminative ability was evaluated with C statistic, equal to the area under the receiver operating characteristic curve. Calibrative ability was assessed with the Hosmer-Lemeshow test (H-L test). The internal validity of models was evaluated with the bootstrap re-sampling technique. We validated three of the models in an external series of 203 patients that collected from another research center. Discrimination and calibration were further assessed to indicate the performance of the models in external patients. RESULTS Logistic regression showed that age, pupillary reactivity, motor Glasgow Coma Score, computed tomography characters, glucose, hemoglobin, D-dimer, serum calcium, and intracranial pressure were independent prognostic factors of outcome. The models discriminated well in the development patients (C statistic 0.709–0.939). We extensively validate three of the models. Internal validation showed no overoptimism in any of the models’ predictive C statistics. External validity was much better (C statistic 0.844–0.902). Calibration was also good (H-L tests, p > 0.05). Computer-based calculator that based on prognostic models was developed for clinical use. CONCLUSION Our validated prognostic models have good performance and are generalizable to be used to predict outcome of new patients. We recommend the use of prognostic models to complement clinical decision making. (J Trauma Acute Care Surg. 2012;73: 137–145. Copyright

SIRT2 inhibition exacerbates neuroinflammation and blood-brain barrier disruption in experimental traumatic brain injury by enhancing NF-κB p65 acetylation and activation.

Sirtuin 2 (SIRT2) is a member of the sirtuin family of NAD+‐dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI). We investigated the effects of SIRT2 inhibition on experimental TBI using the controlled cortical impact (CCI) injury model. Adult male mice underwent CCI or sham surgery. A selective brain‐permeable SIRT2 inhibitor, AK‐7, was administrated 30 min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with AK‐7 (20 mg/kg), compared with the vehicle group, following TBI (p < 0.05 at 1 day and p < 0.05 at 3 days, respectively). Concomitantly, AK‐7 administration greatly worsened neurobehavioral deficits on days 3 and 7 after CCI. Furthermore, blood–brain barrier disruption and matrix metalloproteinases (MMP)‐9 activity increased following SIRT2 inhibition. AK‐7 treatment increased TBI‐induced microglial activation both in vivo and in vitro, accompanied by a large increase in the expression and release of inflammatory cytokines. Mechanistically, SIRT2 inhibition increased both K310 acetylation and nuclear translocation of NF‐κB p65, leading to enhanced NF‐κB activation and up‐regulation of its target genes, including aquaporin 4 (AQP4), MMP‐9, and pro‐inflammatory cytokines. Together, these data demonstrate that SIRT2 inhibition exacerbates TBI by increasing NF‐κB p65 acetylation and activation. Our findings provide additional evidence of an anti‐inflammatory effect of SIRT2.

Clinical characterization of comatose patients with cervical spine injury and traumatic brain injury.

BACKGROUND Reports on the risk factors for combined craniocervical spine injury in comatose patients are rare. The incidence of concomitant cervical injury in comatose patients with traumatic brain injury (TBI) was determined herein. METHODS One thousand twenty-six comatose patients with TBI were examined. The clinical characteristics of combined craniocervical trauma were documented, including type and location of cervical injury, occurrence of hypotension, and dyspnea. RESULTS Seventy-one patients (6.92%) sustained cervical spine injury. The most common injury region included the upper cervical segments, demonstrated in 37 (52.11%) of 71 patients. Of the 71 patients who sustained combined craniocervical spine injury, 42 (59.15%) had hypotension, including 26 (36.62%) with dyspnea. With regard to the association between the severity of TBI and the incidence of the cervical injury, a significant difference was apparent between patients with an initial Glasgow Coma Scale (GCS) score of 3-5 and those with an initial GCS score of 9-12 (11.62% compared with 4.03%, p < 0.01). Regarding the relationship between the mechanism of injury and the occurrence of cervical spine injury, cervical spine injury was associated at a significantly higher incidence with motorcycle accident-related head trauma as compared with non motorcycle accident-related trauma (10.32% vs. 4.68%, p < 0.01). CONCLUSION Patients who sustained TBI as a result of motorcycle accidents and those exhibiting a lower GCS score are at the highest risk for concomitant cervical spine injury.

Inhibition of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Decreases Rat Cortical Neuron Injury and Blood-Brain Barrier Permeability, and Improves Neurological Functional Recovery in Traumatic Brain Injury Model

Background and Purpose Recent evidence has supported the neuroprotective effect of bpV (pic), an inhibitor of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in models of ischemic stroke. However, whether PTEN inhibitors improve long-term functional recovery after traumatic brain injury (TBI) and whether PTEN affects blood brain barrier (BBB) permeability need further elucidation. The present study was performed to address these issues. Methods Adult Sprague-Dawley rats were subjected to fluid percussion injury (FPI) after treatment with a well-established PTEN inhibitor bpV (pic) or saline starting 24 h before FPI. Western blotting, real-time quantitative PCR, or immunostaining was used to measure PTEN, p-Akt, or MMP-9 expression. We determined the presence of neuron apoptosis by TUNEL assay. Evans Blue dye extravasation was measured to evaluate the extent of BBB disruption. Functional recovery was assessed by the neurological severity score (NSS), and Kaplan-Meier analysis was used for survival analysis. Results PTEN expression was up-regulated after TBI. After bpV (pic) treatment, p-Akt was also up-regulated. We found that bpV (pic) significantly decreased BBB permeability and reduced the number of TUNEL-positive cells. We further demonstrated that PTEN inhibition improved neurological function recovery in the early stage after TBI. Conclusion These data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats.

Predicting Progressive Hemorrhagic Injury after Traumatic Brain Injury: Derivation and Validation of a Risk Score Based on Admission Characteristics

Previous studies have demonstrated that patients with traumatic brain injury (TBI) who also have progressive hemorrhagic injury (PHI), have a higher risk of clinical deterioration and worse outcomes than do TBI patients without PHI. Therefore, the early prediction of PHI occurrence is useful to evaluate the status of patients with TBI and to improve outcomes. The objective of this study was to develop and validate a prognostic model that uses information available at admission to determine the likelihood of PHI after TBI. Retrospectively collected data were used to develop a PHI prognostic model with a logistic regression analysis. The prediction model was validated in 114 patients from a separate hospital. Eight independent prognostic factors were identified: age ≥ 57 years (5 points), intra-axial bleeding/brain contusion (4 points), midline shift ≥ 5 mm (6 points), platelet (PLT) count<100×10⁹/L (10 points), PLT count ≥ 100 but <150×10⁹/L (4 points), prothrombin time>14 sec (7 points), D-dimer ≥ 5 mg/L (12 points), and glucose ≥ 10 mmol/L (10 points). Each patient was assigned a number of points proportional to the regression coefficient. We calculated risk scores for each patient and defined three risk groups: low risk (0-13 points), intermediate risk (14-22 points), and high risk (23-54 points). In the development cohort, the PHI rates after TBI for these three groups were 10.3%, 47.3%, and 85.2%, respectively. In the validation cohort, the corresponding PHI rates were 10.9%, 47.3%, and 86.9%. The C-statistic for the point system was 0.864 (p=0.509 by the Hosmer-Lemeshow test) in the development cohort, and 0.862 (p=0.589 by the Hosmer-Lemeshow test) in the validation cohort. In conclusion, a relatively simple risk score using admission predictors accurately predicted the risk for PHI after TBI.

A prospective clinical study of routine repeat computed tomography (CT) after traumatic brain injury (TBI)

Purpose: To discuss the repeated CT scanning in patients with traumatic brain injury (TBI) and to identify the conditions under which this approach is necessary. Methods: One hundred and seventy-one patients who suffered TBI but were not surgically treated were divided into two groups: the routine-repeat CT group (n = 89) and the non-routine-repeat CT group (n = 82). The patients’ clinical characteristics were compared. T-tests and stepwise logistic regression were used for analysis. Patients in the routine-repeat CT group were divided into three groups according to GCS scores to determine the need for routinely repeated CT scans. Results: The results revealed statistically significant differences between the two groups in terms of neuro-ICU-LOS and LOS (p < 0.01). No significant differences emerged with respect to hospital charges and GCS scores at discharge (p > 0.05). AGE, international normalized ratio (INR), D-dimer concentration (DD), GCS scores and number of hours between the first CT scan and the injury (HCT1) were influential factors of developing progressive haemorrhage. Conclusion: The routine-repeat CT group fared better than did the non-routine-repeat CT group. Routinely repeated CTs were minimally effective among those with mild TBI, whereas this procedure demonstrated a significant effect on patients with moderate and severe TBI.

Progressive Epidural Hematoma in Patients with Head Trauma: Incidence, Outcome, and Risk Factors

Progressive epidural hematoma (PEDH) after head injury is often observed on serial computerized tomography (CT) scans. Recent advances in imaging modalities and treatment might affect its incidence and outcome. In this study, PEDH was observed in 9.2% of 412 head trauma patients in whom two CT scans were obtained within 24 hours of injury, and in a majority of cases, it developed within 3 days after injury. In multivariate logistic regression, patient gender, age, Glasgow Coma Scale (GCS) score at admission, and skull fracture were not associated with PEDH, whereas hypotension (odds ratio (OR) 0.38, 95% confidence interval (CI) 0.17–0.84), time interval of the first CT scanning (OR 0.42, 95% CI 0.19–0.83), coagulopathy (OR 0.36, 95% CI 0.15–0.85), or decompressive craniectomy (DC) (OR 0.46, 95% CI 0.21–0.97) was independently associated with an increased risk of PEDH. The 3-month postinjury outcome was similar in patients with PEDH and patients without PEDH (χ 2 = 0.07, P = 0.86). In conclusion, epidural hematoma has a greater tendency to progress early after injury, often in dramatic and rapid fashion. Recognition of this important treatable cause of secondary brain injury and the associated risk factors may help identify the group at risk and tailor management of patients with TBI.

A Comparison between Endoscopic Transsphenoidal Surgery and Traditional Trans-Sphenoidal Microsurgery for Functioning Pituitary Adenomas

This retrospective study reviewed and compared the efficacy and safety outcomes following trans-sphenoidal endoscopy or microsurgery approaches in patients with functioning pituitary adenomas: 68 patients underwent endoscopic transsphenoidal resections and 59 patients had microsurgical resections. Tumours were classified according to diameter and clinical outcomes were evaluated. Overall disease control rates were 70.6% following endoscopy and 49.2% following microsurgery. The most obvious between-group difference was observed in macroadenomas: disease control rates were 63.9% following endoscopy and 27.3% following microsurgery. Cerebrospinal fluid leaks, diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion were observed postoperatively in both groups. The complication rate was lower following endoscopy compared with microsurgery (this difference was not statistically significant). Trans-sphenoidal endoscopy resection achieved good results in pituitary tumours, particularly for the complete removal of macroadenomas, and was an effective alternative to microsurgery.

Outcomes of Early Decompressive Craniectomy Versus Conventional Medical Management After Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

AbstractThis meta-analysis examined whether early decompressive craniectomy (DC) can improve control of intracranial pressure (ICP) and mortality in patients with traumatic brain injury (TBI).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until May 14, 2015, using the following terms: traumatic brain injury, refractory intracranial hypertension, high intracranial pressure, craniectomy, standard care, and medical management. Randomized controlled trials in which patients with TBI received DC and non-DC medical treatments were included.Of the 84 articles identified, 8 studies were selected for review, with 3 randomized controlled trials s having a total of 256 patients (123 DCs, 133 non-DCs) included in the meta-analysis. Patients receiving DC had a significantly greater reduction of ICP and shorter hospital stay. They also seemed to have lower odds of death than patients receiving only medical management, but the P value did not reach significance (pooled odds ratio 0.531, 95% confidence interval 0.209–1.350, Z = 1.95, P = 0.183) with respect to the effect on overall mortality; a separate analysis of 3 retrospective studies yielded a similar result.Whereas DC might effectively reduce ICP and shorten hospital stay in patients with TBI, its effect in decreasing mortality has not reached statistical significance.

Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose of this study was to identify the optimal neuroprotective dose of bpV when administrated after focal ischemia/reperfusion (I/R) injury in rats. Focal I/R injury was induced using the middle cerebral artery occlusion method. bpV at doses of 0.25, 0.50 and 1.0 mg/kg were injected intraperitoneally just after reperfusion, with saline serving as a vehicle control. A maximal reduction in brain injury was observed with 1.0 mg/kg bpV. This dose of bpV also significantly blocked apoptosis in the penumbral cortex of rats. This beneficial effect was associated with the increasing levels of Akt phosphorylation in the penumbral cortex. These results demonstrate that the pharmacological inhibition of PTEN protects against I/R injury in a dose-dependent manner and the protective effect might be induced through upregulation of the phosphoinositide-3 kinase/Akt pro-survival pathway, suggesting a new therapeutic strategy to combat ischemic brain injury.