Effects of an Early Intensive Blood Pressure-lowering Strategy Using Remifentanil and Dexmedetomidine in Patients with Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial.

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.

Intracranial Pressure Monitoring in the Intensive Care Unit for Patients with Severe Traumatic Brain Injury: Analysis of the CENTER-TBI China Registry.

BACKGROUND: Although the current guidelines recommend the use of intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (sTBI), the evidence indicating benefit is limited. The present study aims to evaluate the impact of ICP monitoring on patients with sTBI in the intensive care unit (ICU). METHODS: The patient data were obtained from the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury China Registry, a prospective, multicenter, longitudinal, observational, cohort study. Patients with sTBI who were admitted to 52 ICUs across China, managed with ICP monitoring or without, were analyzed in this study. Patients with missing information on discharge survival status, Glasgow Coma Scale score on admission to hospital, and record of ICP monitoring application were excluded from the analysis. Data on demographic characteristics, injury, clinical features, treatments, survival at discharge, discharge destination, and length of stay were collected and assessed. The primary end point was survival state at discharge, and death from any cause was considered the event of interest. RESULTS: A total of 2029 patients with sTBI were admitted to the ICU; 737 patients (36.32%) underwent ICP monitoring, and 1292 (63.68%) were managed without ICP monitoring. There was a difference between management with and without ICP monitoring on in-hospital mortality in the unmatched cohort (18.86% vs. 26.63%, p < 0.001) and the propensity-score-matched cohort (19.82% vs. 26.83%, p = 0.003). Multivariate logistic regressions also indicated that increasing age, higher injury severity score, lower Glasgow Coma Scale score, unilateral and bilateral pupillary abnormalities, systemic hypotension (SBP ≤ 90 mm Hg), hypoxia (SpO2 < 95%) on arrival at the hospital, and management without ICP monitoring were associated with higher in-hospital mortality. However, the patients without ICP monitoring had a lower length of stay in the ICU (11.79 vs. 7.95 days, p < 0.001) and hospital (25.96 vs. 21.71 days, p < 0.001), and a higher proportion of survivors were discharged to the home with better recovery in self-care. CONCLUSIONS: Although ICP monitoring was not widely used by all of the centers participating in this study, patients with sTBI managed with ICP monitoring show a better outcome in overall survival. Nevertheless, the use of ICP monitoring makes the management of sTBI more complex and increases the costs of medical care by prolonging the patient's stay in the ICU or hospital.

Steered migration and changed morphology of human astrocytes by an applied electric field.

Direct current electric field (DC EF) plays a role in influencing the biological behaviors and functions of cells. We hypothesize that human astrocytes (HAs) could also be influenced in EF. Astrocytes, an important type of nerve cells with a high proportion quantitatively, are generally activated and largely decide the brain repair results after brain injury. So far, no electrotaxis study on HAs has been performed. We here obtained HAs derived from brain trauma patients. After purification and identification, HAs were seeded in the EF chamber and recorded in a time-lapse image system. LY294002 and U0126 were then used to probe the role of PI3K or ERK signaling pathway on cellular behaviors. The results showed that HAs could be guided to migrate to the anode in DC EFs, in a voltage-dependent manner. The HAs displayed elongated cell bodies and reoriented perpendicularly to the EF in morphology. When treated with LY294002 or U0126, alternation of parameters such as cellular verticality, track speed, displacement speed, long axis, vertical length and circularity were inhibited partly as expected, while the EF-induced directedness was not terminated even at a high drug dosage which was not consistent with previous electrotaxis studies. In conclusion, applied EFs steered the patient-derived HAs directional migration and changed morphology, in which PI3K and ERK pathways at least partially participate. The characteristics of HAs to EF stimulation may be involved in wound healing and neural regeneration, which could be utilized as a novel treatment strategy in brain injury.

Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA.

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.

The depth of catheter in chronic subdural haematoma: does it matter?

Objective: To investigate the appropriate depth of drainage catheter in the patients with chronic subdural haematoma (CSDH). Methods: We retrospectively analysed the data of 190 patients with CSDH undergoing single parietal burr-hole evacuation and drainage. Results: According to the depth of catheter (DC), 190 patients were divided into three groups: shallow group (DC <4.3 cm), middle group (DC 4.3 ~ 5.4 cm) and deep group (DC > 5.4 cm). During postdischarge 6 months, two, six and nine patients had recurrences in shallow, middle and deep groups, respectively. The recurrence rate in shallow or middle group was significantly lower than that in deep group. No significant difference in preoperative haematoma volume (PHV) was observed in three groups. While the residual subdural space (RSS) in shallow group was significantly smaller than those in the other two groups. The duration of drainage in shallow, middle and deep groups increased successively, and the differences were statistically significant. The total drainage volume (TDV) in shallow group showed no significant difference when compared with the other two groups. Conclusion: The depth of catheter may affect the outcome of CSDH. Inserting drainage catheter shallowly might be a preferred choice in patients with CSDH undergoing burr-hole evacuation and drainage.

Intraventricular intracranial pressure monitoring improves the outcome of older adults with severe traumatic brain injury: an observational, prospective study.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely used in the management of patients with severe traumatic brain injury (TBI). However, there is limited evidence about the efficacy of ICP monitoring in older subjects (aged ≥65 years). This study evaluated the effect of intraventricular ICP monitoring on the outcome of older adults suffering from a severe TBI. METHODS: This prospective, observational study included 166 older TBI patients (aged ≥65 years) with Glasgow Coma scale (GCS) scores lower than 9 at admission. The study cohort was divided into two groups, intraventricular ICP monitoring and non-ICP monitoring. The primary outcome was in-hospital mortality. The secondary outcomes included the Glasgow Outcome Scale (GOS) score 6 months after injury, the ICU and total hospital lengths of stay, and mechanical ventilation days. RESULTS: There were 80 patients in the intraventricular ICP monitoring group and 86 patients in non-ICP monitoring group. There was no statistical difference between groups in demographics and severity of head injury. Patients treated with intraventricular ICP monitoring had lower in-hospital mortality (33.8 % vs 51.2 %, P < 0.05), a higher 6-month GOS score (3.0 ± 1.4 vs 2.5 ± 1.2 P < 0.05), and a lower dosage (514 ± 246 g vs 840 ± 323 g, P < 0.0001) and shorter duration (7.2 ± 3.6 days vs 8.4 ± 4.3 days, P < 0.01) of mannitol use. However, the ICU length of stay (14.3 ± 6.4 days vs 11.6 ± 5.8 days, P < 0.01) and mechanical ventilation days (6.7 ± 3.5 days vs 5.6 ± 2.4 days, P < 0.05) were longer in the ICP monitoring group. The total length of hospital stay did not differ between the two groups (28.5 ± 12.1 days vs 26.1 ± 13.5 days, P = 0.23). CONCLUSIONS: Intraventricular ICP monitoring may have beneficial effects on the decreased in-hospital mortality and improved 6-month outcome of older patients with severe TBI. However, given that this was an observational study conducted in a single institution, further well-designed randomized control trials are needed to evaluate the effect of intraventricular ICP monitoring on the outcome of older severe TBI patients.

Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms.

PURPOSE: It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs). METHODS: We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs. RESULTS: Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region. CONCLUSION: The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.

Improved neurite outgrowth on central nervous system myelin substrate by siRNA-mediated knockdown of Nogo receptor.

PURPOSE: To investigate the in vitro effect of short interfering RNAs (siRNAs) against Nogo receptor (NgR) on neurite outgrowth under an inhibitory substrate of central nervous system (CNS) myelin. METHODS: Three siRNA sequences against NgR were designed and transfected into cerebellar granule cells (CGCs) to screen for the most effcient sequence of NgR siRNA by using reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. NgR siRNA sequence 1 was found the most efficient which was then transfected into the CGCs grown on CNS myelin substrate to observe its disinhibition for neurite outgrowth. RESULTS: Compared with the scrambled control sequence of siRNA, the NgR siRNA sequence 1 significantly decreased NgR mRNA level at 24 h and 48 h (p <0.05), which was recovered by 96 h after transfection. NgR immunoreactivity was also markedly reduced at 24 and 48 h after the transfection of siRNA sequence 1 compared with that before transfection (p<0.05). The NgR immunoreactivity was recovered after 72 h post-transfection. Moreover, the neurite outgrowth on the myelin substrate was greatly improved within 72 h after the transfection with siRNA sequence 1 compared with the scrambled sequence-transfected group or non-transfected group (p<0.05). CONCLUSION: siRNA-mediated knockdown of NgR expression contributes to neurite outgrowth in vitro.

Glial fibrillary acidic protein as a biomarker in severe traumatic brain injury patients: a prospective cohort study.

INTRODUCTION: Glial fibrillary acidic protein (GFAP) may serve as a serum marker of traumatic brain injury (TBI) that can be used to monitor biochemical changes in patients and gauge the response to treatment. However, the temporal profile of serum GFAP in the acute period of brain injury and the associated utility for outcome prediction has not been elucidated. METHODS: We conducted a prospective longitudinal cohort study of consecutive severe TBI patients in a local tertiary neurotrauma center in Shanghai, China, between March 2011 and September 2014. All patients were monitored and managed with a standardized protocol with inclusion of hypothermia and other intensive care treatments. Serum specimens were collected on admission and then daily for the first 5 days. GFAP levels were measured using enzyme-linked immunosorbent assay techniques. Patient outcome was assessed at 6 months post injury with the Glasgow Outcome Scale and further grouped into death versus survival and unfavorable versus favorable. RESULTS: A total of 67 patients were enrolled in the study. The mean time from injury to admission was 2.6 hours, and the median admission Glasgow Coma Scale score was 6. Compared with healthy subjects, patients with severe TBI had increased GFAP levels on admission and over the subsequent 5 days post injury. Serum GFAP levels showed a gradual reduction from admission to day 3, and then rebounded on day 4 when hypothermia was discontinued with slow rewarming. GFAP levels were significantly higher in patients who died or had an unfavorable outcome across all time points than in those who were alive or had a favorable outcome. Results of receiver operating characteristic curve analysis indicated that serum GFAP at each time point could predict neurological outcome at 6 months. The areas under the curve for GFAP on admission were 0.761 for death and 0.823 for unfavorable outcome, which were higher than those for clinical variables such as age, Glasgow Coma Scale score, and pupil reactions. CONCLUSIONS: Serum GFAP levels on admission and during the first 5 days of injury were increased in patients with severe TBI and were predictive of neurological outcome at 6 months.

Predicting the Severity and Discharge Prognosis of Traumatic Brain Injury Based on Intracranial Pressure Data Using Machine Learning Algorithms.

OBJECTIVE: This study aimed to explore the potential of employing machine learning algorithms based on intracranial pressure (ICP), ICP-derived parameters, and their complexity to predict the severity and short-term prognosis of traumatic brain injury (TBI). METHODS: A single-center prospectively collected cohort of neurosurgical intensive care unit admissions was analyzed. We extracted ICP-related data within the first 6 hours and processed them using complex algorithms. To indicate TBI severity and short-term prognosis, Glasgow Coma Scale score on the first postoperative day and Glasgow Outcome Scale-Extended score at discharge were used as binary outcome variables. A univariate logistic regression model was developed to predict TBI severity using only mean ICP values. Subsequently, 3 multivariate Random Forest (RF) models were constructed using different combinations of mean and complexity metrics of ICP-related data. To avoid overfitting, five-fold cross-validations were performed. Finally, the best-performing multivariate RF model was used to predict patients' discharge Glasgow Outcome Scale-Extended score. RESULTS: The logistic regression model exhibited limited predictive ability with an area under the curve (AUC) of 0.558. Among multivariate models, the RF model, combining the mean and complexity metrics of ICP-related data, achieved the most robust ability with an AUC of 0.815. Finally, in terms of predicting discharge Glasgow Outcome Scale-Extended score, this model had a consistent performance with an AUC of 0.822. Cross-validation analysis confirmed the performance. CONCLUSIONS: This study demonstrates the clinical utility of the RF model, which integrates the mean and complexity metrics of ICP data, in accurately predicting the TBI severity and short-term prognosis.

Random forest-based prediction of intracranial hypertension in patients with traumatic brain injury.

BACKGROUND: Treatment and prevention of intracranial hypertension (IH) to minimize secondary brain injury are central to the neurocritical care management of traumatic brain injury (TBI). Predicting the onset of IH in advance allows for a more aggressive prophylactic treatment. This study aimed to develop random forest (RF) models for predicting IH events in TBI patients. METHODS: We analyzed prospectively collected data from patients admitted to the intensive care unit with invasive intracranial pressure (ICP) monitoring. Patients with persistent ICP > 22 mmHg in the early postoperative period (first 6 h) were excluded to focus on IH events that had not yet occurred. ICP-related data from the initial 6 h were used to extract linear (ICP, cerebral perfusion pressure, pressure reactivity index, and cerebrospinal fluid compensatory reserve index) and nonlinear features (complexity of ICP and cerebral perfusion pressure). IH was defined as ICP > 22 mmHg for > 5 min, and severe IH (SIH) as ICP > 22 mmHg for > 1 h during the subsequent ICP monitoring period. RF models were then developed using baseline characteristics (age, sex, and initial Glasgow Coma Scale score) along with linear and nonlinear features. Fivefold cross-validation was performed to avoid overfitting. RESULTS: The study included 69 patients. Forty-three patients (62.3%) experienced an IH event, of whom 30 (43%) progressed to SIH. The median time to IH events was 9.83 h, and to SIH events, it was 11.22 h. The RF model showed acceptable performance in predicting IH with an area under the curve (AUC) of 0.76 and excellent performance in predicting SIH (AUC = 0.84). Cross-validation analysis confirmed the stability of the results. CONCLUSIONS: The presented RF model can forecast subsequent IH events, particularly severe ones, in TBI patients using ICP data from the early postoperative period. It provides researchers and clinicians with a potentially predictive pathway and framework that could help triage patients requiring more intensive neurological treatment at an early stage.

Non-Invasive Assessment of Intracranial Hypertension in Patients with Traumatic Brain Injury Using Computed Tomography Radiomic Features: A Pilot Study.

This study aimed to assess intracranial hypertension in patients with traumatic brain injury non-invasively using computed tomography (CT) radiomic features. Fifty patients from the primary cohort were enrolled in this study. The clinical data, pre-operative cranial CT images, and initial intracranial pressure readings were collected and used to develop a prediction model. Data of 20 patients from another hospital were used to validate the model. Clinical features including age, sex, midline shift, basilar cistern status, and ventriculocranial ratio were measured. Radiomic features-i.e., 18 first-order and 40 second-order features- were extracted from the CT images. LASSO method was used for features filtration. Multi-variate logistic regression was used to develop three prediction models with clinical (CF model), first-order (FO model), and second-order features (SO model). The SO model achieved the most robust ability to predict intracranial hypertension. Internal validation showed that the C-statistic of the model was 0.811 (95% confidence interval [CI]: 0.691-0.931) with the bootstrapping method. The Hosmer Lemeshow test and calibration curve also showed that the SO model had excellent performance. The external validation results showed a good discrimination with an area under the curve of 0.725 (95% CI: 0.500-0.951). Although the FO model was inferior to the SO model, it had better prediction ability than the CF model. The study shows that the radiomic features analysis, especially second-order features, can be used to evaluate intracranial hypertension non-invasively compared with conventional clinical features, given its potential for clinical practice and further research.

An independently validated nomogram for individualised estimation of short-term mortality risk among patients with severe traumatic brain injury: a modelling analysis of the CENTER-TBI China Registry Study.

Background: Severe traumatic brain injury (sTBI) is extremely disabling and associated with high mortality. Early detection of patients at risk of short-term (≤14 days after injury) death and provision of timely treatment is critical. This study aimed to establish and independently validate a nomogram to estimate individualised short-term mortality for sTBI based on large-scale data from China. Methods: The data were from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry (between Dec 22, 2014, and Aug 1, 2017; registered at ClinicalTrials.gov, NCT02210221). This analysis included information of eligible patients with diagnosed sTBI from 52 centres (2631 cases). 1808 cases from 36 centres were enrolled in the training group (used to construct the nomogram) and 823 cases from 16 centres were enrolled in the validation group. Multivariate logistic regression was used to identify independent predictors of short-term mortality and establish the nomogram. The discrimination of the nomogram was evaluated using area under the receiver operating characteristic curves (AUC) and concordance indexes (C-index), the calibration was evaluated using calibration curves and Hosmer-Lemeshow tests (H-L tests). Decision curve analysis (DCA) was used to evaluate the net benefit of the model for patients. Findings: In the training group, multivariate logistic regression demonstrated that age (odds ratio [OR] 1.013, 95% confidence interval [CI] 1.003-1.022), Glasgow Coma Scale score (OR 33.997, 95% CI 14.657-78.856), Injury Severity Score (OR 1.020, 95% CI 1.009-1.032), abnormal pupil status (OR 1.738, 95% CI 1.178-2.565), midline shift (OR 2.266, 95% CI 1.378-3.727), and pre-hospital intubation (OR 2.059, 95% CI 1.472-2.879) were independent predictors for short-term death in patients with sTBI. A nomogram was built using the logistic regression prediction model. The AUC and C-index were 0.859 (95% CI 0.837-0.880). The calibration curve of the nomogram was close to the ideal reference line, and the H-L test p value was 0.504. DCA curve demonstrated significantly better net benefit with the model. Application of the nomogram in external validation group still showed good discrimination (AUC and C-index were 0.856, 95% CI 0.827-0.886), calibration, and clinical usefulness. Interpretation: A nomogram was developed for predicting the occurrence of short-term (≤14 days after injury) death in patients with sTBI. This can provide clinicians with an effective and accurate tool for the early prediction and timely management of sTBI, as well as support clinical decision-making around the withdrawal of life-sustaining therapy. This nomogram is based on Chinese large-scale data and is especially relevant to low- and middle-income countries. Funding: Shanghai Academic Research Leader (21XD1422400), Shanghai Medical and Health Development Foundation (20224Z0012).

Mortality Prediction in Severe Traumatic Brain Injury Using Traditional and Machine Learning Algorithms.

Abstract Prognostic prediction of traumatic brain injury (TBI) in patients is crucial in clinical decision and health care policy making. This study aimed to develop and validate prediction models for in-hospital mortality after severe traumatic brain injury (sTBI). We developed and validated logistic regression (LR), LASSO regression, and machine learning (ML) algorithms including support vector machines (SVM) and XGBoost models. Fifty-four candidate predictors were included. Model performance was expressed in terms of discrimination (C-statistic) and calibration (intercept and slope). For model development, 2804 patients with sTBI in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China Registry study were included. External validation was performed in 1113 patients with sTBI in the CENTER-TBI European Registry study. XGBoost achieved high discrimination in mortality prediction, and it outperformed logistic and LASSO regression. The XGBoost model established in this study also outperformed prediction models currently available, including the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) core and International Mission for Prognosis and Analysis of Clinical Trials (CRASH) basic models. When including 54 variables, XGBoost and SVM reached C-statistics of 0.87 (95% confidence interval [CI]: 0.81-0.92) and 0.85 (95% CI: 0.79-0.90) at internal validation, and 0.88 (95% CI: 0.87-0.88) and 0.86 (95% CI: 0.85-0.87) at external validation, respectively. A simplified version of XGBoost and SVM using 26 variables selected by recursive feature elimination (RFE) reached C-statistics of 0.87 (95% CI: 0.82-0.92) and 0.86 (95% CI: 0.80-0.91) at internal validation, and 0.87 (95% CI: 0.87-0.88) and 0.87 (95% CI: 0.86-0.87) at external validation, respectively. However, when the number of variables included decreased, the difference between ML and LR diminished. All the prediction models can be accessed via a web-based calculator. Glasgow Coma Scale (GCS) score, age, pupillary light reflex, Injury Severity Score (ISS) for brain region, and the presence of acute subdural hematoma were the five strongest predictors for mortality prediction. The study showed that ML techniques such as XGBoost may capture information hidden in demographic and clinical predictors of patients with sTBI and yield more precise predictions compared with LR approaches.

Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial.

PURPOSE: Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI. METHODS: This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 µs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set. RESULTS: Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device. CONCLUSION: Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury: A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group.

Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.

Is management of acute traumatic brain injury effective? A literature review of published Cochrane Systematic Reviews.

OBJECTIVE: To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI) mentioned in Cochrane Systematic Reviews published in the Cochrane Database of Systematic Reviews (CDSR). METHODS: An exhausted literature search for all published Cochrane Systematic Reviews discussing therapeutic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Cochrane Injury Group, excluded the duplications, and eventually obtained 20 results, which stand for critical appraisal for as many as 20 different measures for TBI patients. The important data of each systematic review, including total population, intervention, outcome, etc, were collected and presented in a designed table. Besides, we also tried to find out the possible weakness of these clinical trials included in each review. RESULTS: Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI. (2) A majority of the systematic reviews include a small number of clinical trials and the modest numbers of patients, largely due to the uncertainty of the effectiveness. (3) The quality of most trials reported in the systematic reviews is more or less questionable. (4) In addition, lots of other complex factors together may lead to the inconclusive results demonstrated in the Cochrane Systematic Reviews. CONCLUSIONS: For clinical physicians, to translate these conclusions into practice with caution is essential. Basic medication and nursing care deserve additional attention as well and can be beneficial. For researchers, high quality trials with perfect design and comprehensive consideration of various factors are urgently required.

The application value of CT radiomics features in predicting pressure amplitude correlation index in patients with severe traumatic brain injury.

Purpose: To explore the application value of a machine learning model based on CT radiomics features in predicting the pressure amplitude correlation index (RAP) in patients with severe traumatic brain injury (sTBI). Methods: Retrospectively analyzed the clinical and imaging data in 36 patients with sTBI. All patients underwent surgical treatment, continuous ICP monitoring, and invasive arterial pressure monitoring. The pressure amplitude correlation index (RAP) was collected within 1 h after surgery. Three volume of interest (VOI) was selected from the craniocerebral CT images of patients 1 h after surgery, and a total of 93 radiomics features were extracted from each VOI. Three models were established to be used to evaluate the patients' RAP levels. The accuracy, precision, recall rate, F1 score, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were used to evaluate the predictive performance of each model. Results: The optimal number of features for three predicting models of RAP was five, respectively. The accuracy of predicting the model of the hippocampus was 77.78%, precision was 88.24%, recall rate was 60%, the F1 score was 0.6, and AUC was 0.88. The accuracy of predicting the model of the brainstem was 63.64%, precision was 58.33%, the recall rate was 60%, the F1 score was 0.54, and AUC was 0.82. The accuracy of predicting the model of the thalamus was 81.82%, precision was 88.89%, recall rate was 75%, the F1 score was 0.77, and AUC was 0.96. Conclusions: CT radiomics can predict RAP levels in patients with sTBI, which has the potential to establish a method of non-invasive intracranial pressure (NI-ICP) monitoring.

Epidemiological Characteristics of Older Patients with Traumatic Brain Injury in China.

Increasing traumatic brain injury (TBI) among older adults constitutes a substantial socioeconomic burden, in step with the growing aging global population. Here, we aimed to investigate the profile of geriatric TBI in the CENTER-TBI China registry, a prospective observational study conducted in 56 centers of 22 provinces across China. Patients admitted to the hospital with a clinical diagnosis of TBI were enrolled in the study. Data on demographic characteristics, injury, clinical features, treatments, and survival at discharge were collected and assessed. The primary end point was survival state at discharge. We analyzed a total of 2415 patients aged ≥65 years, accounting for 18.34% of the overall population. The median age was 72 years (interquartile range [IQR]: 68-78), and 1588 (65.76%) were men. Incidental falls (n = 1044, 43.23%) were the leading cause of TBI, followed by road traffic injuries (n = 1034, 42.82%). Roads and homes were the main sites of injury. The median Glasgow Coma Scale (GCS) score was 13 (IQR: 9-15); 1397 (57.85%) patients had mild TBI (GCS 13-15), while 530 (21.95%) and 488 (20.21%) presented with moderate (GCS 9-12) and severe TBI (sTBI; GCS 3-8), respectively. A total of 546 (22.61%) patients underwent intracranial surgery. The overall in-hospital mortality rate was 8.24% (n = 199), and most survivors were transferred home. This study revealed that the demographic patterns and injury mechanisms are changing among elderly patients with TBI in China. More attention should be given to the high incidence of geriatric TBI to improve prevention and management strategies.