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Aziz S. Alali, Nancy Temkin, Monica S. Vavilala, Abhijit V. Lele, Jason Barber, Sureyya Dikmen and Randall M. Chesnut

OBJECTIVE

The aim of this study was to examine the relationship between early arterial oxygenation thresholds and long-term outcome after severe traumatic brain injury (TBI).

METHODS

In a post hoc analysis of a randomized trial, adults with severe TBI were classified based on exposure to different levels of arterial oxygenation as measured using the average of arterial partial pressure of oxygen (PaO2) values obtained within 24 hours of admission. Potentially important PaO2 thresholds were defined a priori. The primary outcome was Glasgow Outcome Scale–Extended (GOSE) score at 6 months. Secondary outcomes were cognitive outcomes measured using a battery of 9 neuropsychological tests administered at 6 months, and 6-month mortality.

RESULTS

In adjusted analyses, oxygenation thresholds of 150 and 200 mm Hg were associated with better functional outcome at 6 months (adjusted OR for better functional outcome on GOSE 1.82 [95% CI 1.12–2.94] and 1.59 [95% CI 1.06–2.37], respectively) and improved cognitive outcome at 6 months (adjusted beta coefficients for better cognitive percentile across 9 neuropsychological tests: 6.9 [95% CI 1.3–12.5] and 6.8 [95% CI 2.4–11.3], respectively). There was no significant association between oxygenation level and 6-month mortality except at a PaO2 threshold of 200 mm Hg (OR for death 0.36, 95% CI 0.18–0.71). Higher or lower oxygenation thresholds were not associated with functional or cognitive outcome.

CONCLUSIONS

In this observational study, the relationship between early arterial oxygenation and long-term functional and cognitive TBI outcomes appears to be U-shaped. Mild levels of hyperoxemia within the first 24 hours after injury were associated with better long-term functional and cognitive outcomes. These findings highlight the importance of examining balanced oxygen supplementation as a potential strategy to improve TBI outcomes in future research.

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Aziz S. Alali, Nancy Temkin, Jason Barber, Jim Pridgeon, Kelley Chaddock, Sureyya Dikmen, Peter Hendrickson, Walter Videtta, Silvia Lujan, Gustavo Petroni, Nahuel Guadagnoli, Zulma Urbina and Randall M. Chesnut

OBJECTIVE

While existing guidelines support the treatment of intracranial hypertension in severe traumatic brain injury (TBI), it is unclear when to suspect and initiate treatment for high intracranial pressure (ICP). The objective of this study was to derive a clinical decision rule that accurately predicts intracranial hypertension.

METHODS

Using Delphi methods, the authors identified a set of potential predictors of intracranial hypertension and a clinical decision rule a priori by consensus among a group of 43 neurosurgeons and intensivists who have extensive experience managing severe TBI without ICP monitoring. To validate these predictors, the authors used data from a Latin American trial (n = 150; BEST TRIP). To report on the performance of the rule, they calculated sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals. In a secondary analysis, the rule was validated using data from a North American trial (n = 131; COBRIT).

RESULTS

The final predictors and the clinical decision rule were approved by 97% of participants in the consensus working group. The predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of 1 major or ≥ 2 minor criteria. Major criteria are: compressed cisterns (CT classification of Marshall diffuse injury [DI] III), midline shift > 5 mm (Marshall DI IV), or nonevacuated mass lesion. Minor criteria are: Glasgow Coma Scale (GCS) motor score ≤ 4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the curve for the logistic regression model that contains all the predictors was 0.86. When high ICP was defined as > 22 mm Hg, the decision rule performed with a sensitivity of 93.9% (95% CI 85.0%–98.3%), a specificity of 42.3% (95% CI 31.7%–53.6%), a positive predictive value of 55.5% (95% CI 50.7%–60.2%), and a negative predictive value of 90% (95% CI 77.1%–96.0%). The sensitivity of the clinical decision rule improved with higher ICP cutoffs up to a sensitivity of 100% when intracranial hypertension was defined as ICP > 30 mm Hg. Similar results were found in the North American cohort.

CONCLUSIONS

A simple clinical decision rule based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing patients with severe TBI who would suffer intracranial hypertension. It could be used to identify patients who require ICP monitoring in high-resource settings or start ICP-lowering treatment in environments where resource limitations preclude invasive monitoring.

Clinical trial registration no.: NCT02059941 (clinicaltrials.gov).

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Salvatore Di Maio, Nancy Temkin, Dinesh Ramanathan and Laligam N. Sekhar

Object

The role of surgery and adjuvant radiation therapy for cranial base chordomas is not well established. This meta-analysis measures the relationship of complete resection and type of adjuvant radiation therapy to 5-year progression-free survival (PFS) and overall survival (OS) of cranial base chordomas.

Methods

A systematic MEDLINE search (1999–present) yielded 23 observational studies and 807 patients who fit inclusion criteria. The following analyses were performed: 1) Kaplan-Meier 5-year PFS and OS compared based on the extent of resection and type of adjuvant radiation therapy using the log-rank method; 2) a random-effects model comparing 5-year PFS with complete or incomplete resection; and 3) paired z-test comparisons of weighted average 5-year OS and PFS grouped by type of adjuvant radiation therapy.

Results

The weighted average follow-up was 53.6 months. The weighted average 5-year PFS and OS were 50.8% and 78.4%, respectively. Complete resection conferred a higher 5-year PFS than incomplete resection from the random effects model (mean difference in PFS 20.7%; 95% CI 6.57%–34.91%). Patients with incomplete resection were 3.83 times more likely to experience a recurrence (95% CI 1.63–9.00) and 5.85 times more likely to die (95% CI 1.40–24.5) at 5 years versus patients with complete resection. There was no difference in 5-year OS by type of adjuvant radiation, although 5-year PFS was lower in patients receiving Gamma Knife surgery relative to carbon ion radiotherapy (p = 0.042) on paired z-test. No survival difference occurred between radiation therapy techniques on Kaplan-Meier analysis of compiled patient data.

Conclusions

Patients with complete resection of cranial base chordomas have a prolonged 5-year PFS and OS. Adjuvant proton-beam, carbon ion, and modern fractionated photon radiation therapy techniques offered a similar rate of PFS and OS at 5 years.

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J. Paul Elliott, G. Evren Keles, Michael Waite, Nancy Temkin and Mitchel S. Berger

✓ The ventricular system is not infrequently entered during the course of maximum cytoreductive surgery for high-grade supratentorial gliomas. It is unclear if ventricular entry during surgery and/or proximity of the tumor to the ventricular system affects cerebrospinal fluid (CSF) tumor dissemination or the patients' overall survival rate. The authors retrospectively reviewed hospital records and neuroradiological studies of 51 patients operated on at the University of Washington between 1987 and 1991. Inclusion in this study necessitated a pathological diagnosis of malignant glioma and the availability of preoperative and postoperative computerized tomography scans or magnetic resonance images. Patients were excluded from the study if they had radiographic evidence of ventricular entry or CSF tumor dissemination prior to referral to the authors' institution. The index operation was defined as the first operation at the University of Washington or (in those patients with ventricular entry) the operation in which the ventricle was entered. Patients were followed until time of death or, in the case of survivors, until February, 1992. The effect of both ventricular entry and the proximity of the tumor to the ventricular system on CSF tumor dissemination and survival rate was assessed using statistical survival methodology.

There was no significant difference in time from diagnosis to the index operation between groups compared (Mann-Whitney U-test, p > 0.40). Cerebrospinal fluid dissemination was radiographically documented in 18 patients (35%) following the index operation. This occurrence was not significantly influenced by either ventricular entry during surgery (Mantel-Cox test, p = 0.13), the proximity of the tumor to the ventricular system (p = 0.63), or these two variables combined (p = 0.28). Survival rate following the index operation was not significantly affected by ventricular entry (p = 0.66), proximity of the tumor to the ventricular system (p = 0.61), or these two variable considered in combination (p = 0.44). However, survival rate was significantly decreased once CSF tumor dissemination had occurred (Cox model, p = 0.03).