Gan Wang

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

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.

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.

Proteomic Analysis of the Cerebrospinal Fluid of Parkinson's Disease Patients Pre- and Post-Deep Brain Stimulation

Aims: To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action. Methods: Cerebrospinal fluid (CSF), obtained from six Parkinsons disease (PD) patients (pre- and post-DBS) and from six normal healthy controls, was studied for differentially expressed proteins. 2-D DIGE, in combination with MALDI-TOF and TOF-TOF Mass Spectrometry (MS) or ESI-MS, was used to identify the changed proteins (3 PD patients and 3 controls). Selected proteins were further studied using western blotting (6 PD patients and 6 controls). Results: Twenty-one proteins were identified after MS and protein database interrogation. Apart from apolipoprotein A-I (apoA-I), the expression levels of complement C4 (C4), IgA, tetranectin, and extracellular superoxide dismutase (EC-SOD), detected by western blotting, correlated well with the 2-D DIGE results. In the follow-up period, the expression levels of C4, apoA-I and IgA were stable whereas EC-SOD and tetranectin were significantly elevated. In addition, when DBS was ceased in one patient due to a suicide attempt, the levels of EC-SOD and tetranectin significantly decreased. Conclusion: Our preliminary results suggest that variations in the expression levels of EC-SOD and tetranectin in CSF is related to DBS.

The Influence of Hemocoagulation Disorders on the Development of Posttraumatic Cerebral Infarction and Outcome in Patients with Moderate or Severe Head Trauma

Posttraumatic cerebral infarction (PTCI) is a severe secondary insult of head injury and often leads to a poor prognosis. Hemocoagulation disorder is recognized to have important effects on hemorrhagic or ischemic damages. We sought to assess if posttraumatic hemocoagulation disorders were associated with cerebral infarction, and evaluate their influence on outcome among patients with moderate or severe head trauma. In this study, PTCI was observed in 28 (10.57%) of the 265 patients within the first week after injury. In multivariate analysis, the thrombocytopenia (odds ratio (OR) 2.210, 95% confidence interval (CI) 1.065–4.674), abnormal prothrombin time (PT) (OR 3.241, 95% CI 1.090–7.648), D-dimer (>2 mg/L) (OR 7.260, 95% CI 1.822–28.076), or disseminated intravascular coagulation (DIC) scores (≥5) (OR 4.717, 95% CI 1.778–12.517) were each independently associated with an increased risk of PTCI. Admission Glasgow Coma Scale (GCS) score, abnormal activated partial thromboplastin time (APTT) and fibrinogen, and D-dimer (>2 mg/L) and DIC scores (≥5) showed an independent predictive effect on poor outcome. In conclusion, recognition of this important treatable cause of PTCI and the associated risk factors may help identify the group at risk and tailor management of patients with TBI.

Tetranectin knockout mice develop features of Parkinson disease.

Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs) may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD). Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN) gene (TN-/-) and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old) TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia) and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc) and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT) mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

Induction of apoptosis in glioma cells and upregulation of Fas expression using the human interferon-β gene.

We investigated whether IFN-β inhibits the growth of human malignant glioma and induces glioma cell apoptosis using the human IFN-β gene transfected into glioma cells. A eukaryonic expression vector (pSV2IFNβ) for IFN-β was transfected into the glioma cell line SHG44 using liposome transfection. Stable transfection and IFN-β expression were confirmed using an enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was also assessed by Hoechst staining and electron microscopy. In vivo experiments were used to establish a SHG44 glioma model in nude mice. Liposomes containing the human IFN-β gene were injected into the SHG44 glioma of nude mice to observe glioma growth and calculate tumor size. Fas expression was evaluated using immunohistochemistry. The IFN-β gene was successfully transfected and expressed in the SHG44 glioma cells in vitro. A significant difference in the number of apoptotic cells was observed between transfected and non- transfected cells. Glioma growth in nude mice was inhibited in vivo, with significant induction of apoptosis. Fas expression was also elevated. The IFN-β gene induces apoptosis in glioma cells, possibly through upregulation of Fas. The IFN-β gene modulation in the Fas pathway and apoptosis in glioma cells may be important for the treatment of gliomas.

Use of multisequence 3.0-T MRI to detect severe traumatic brain injury and predict the outcome

OBJECTIVE The aim of this study was to evaluate multisequence 3.0-T MRI in the detection of severe traumatic brain injury (sTBI) and in predicting the outcome. METHODS 32 patients with sTBI were prospectively enrolled, and multisequence 3.0-T MRI was performed 4-8 weeks post injury. Quantitative data were recorded on each sequence. The ability to display the parenchymal lesions was compared with that of 64-slice spiral CT. The clinical and radiological results were correlated with the Glasgow Outcome Scale Extended scores 6 months after injury. RESULTS 3.0-T MRI could display more lesions than CT, especially when the lesion was deeply located. The lesion volumes and diffuse axonal injury (DAI) scores were different between good and poor outcome groups on fluid attenuated inversion recovery (p < 0.05). The apparent diffusion coefficient (ADC) values of the splenium of the corpus callosum and brain stem were also different (p < 0.05). Patients with unfavourable outcome showed a significantly higher volume of haemorrhage on susceptibility-weighted imaging than those with favourable outcomes and had haemorrhages generally located more deeply. Logistic regression analysis revealed that the location of haemorrhage and the ADC values of the splenium of the corpus callosum were independent risk factors for poor outcome, with an overall predictive accuracy of 91.4%. CONCLUSION The joint use of conventional and advanced sequences of 3.0-T MRI can comprehensively detect the pathological changes occurring after sTBI. Haemorrhagic and non-haemorrhagic DAIs in deep structures strongly suggest poor outcome. ADVANCES IN KNOWLEDGE This article improves the understanding of advanced MRI sequences in the detection of patients with sTBI and prediction of prognosis.