Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

External validation of the Glasgow coma scale-pupils in low- to middle-income country patients with traumatic brain injury: Could "motor score-pupil" have higher prognostic value?

Background: The objective of this study is to validate the admission Glasgow coma scale (GCS) associated with pupil response (GCS-P) to predict traumatic brain injury (TBI) patient's outcomes in a low- to middle-income country and to compare its performance with that of a simplified model combining the better motor response of the GCS and the pupilar response (MS-P). Methods: This is a prospective cohort of patients with TBI in a tertiary trauma reference center in Brazil. Predictive values of the GCS, GCS-P, and MS-P were evaluated and compared for 14 day and in-hospital mortality outcomes and length of hospital stay (LHS). Results: The study enrolled 447 patients. MS-P demonstrated better discriminative ability than GCS to predict mortality (AUC 0.736 × 0.658; P < 0.001) and higher AUC than GCS-P (0.736 × 0.704, respectively; P = 0.073). For hospital mortality, MS-P demonstrated better discrimination than GCS (AUC, 0.750 × 0.682; P < 0.001) and higher AUC than GCS-P (0.750 × 0.714; P = 0.027). Both scores were good predictors of LHS (r2 = 0.084 [GCS-P] × 0.079 [GCS] × 0.072 [MS-P]). Conclusion: The predictive value of the GCS, GCS-P, and MS-P scales was demonstrated, thus contributing to its external validation in low- to middle-income country.

Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study.

PURPOSE: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. METHODS: We used the 18-kDa translocator protein (TSPO) tracer (R)-[11C]PK11195 and [11C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)-[11C]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [11C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). RESULTS: In the VOI-based analysis, [11C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[11C]PK11195 VT were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[11C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [11C]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[11C]PK11195 VT and lower [11C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [11C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[11C]PK11195 VT (P = 0.013). CONCLUSIONS: Widespread innate immune cells profile and marked loss of myelin in T2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.

Remote Follow-Up Technologies in Traumatic Brain Injury: A Scoping Review.

Traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Motivations for outcome data collection in TBI are threefold: to improve patient outcomes, to facilitate research, and to provide the means and methods for wider injury surveillance. Such data play a pivotal role in population health, and ways to increase the reliability of data collection following TBI should be pursued. As a result, technology-aided follow-up of patients with neurotrauma is on the rise; there is, therefore, a need to describe how such technologies have been used. A scoping review was conducted and reported using the PRISMA extension (PRISMA-ScR). Five electronic databases (Embase, MEDLINE, Global Health, PsycInfo, and Scopus) were searched systematically using keywords derived from the concepts of "telemedicine," "TBI," "outcome assessment," and "patient-generated health data." Forty studies described follow-up technologies (FUTs) utilizing telephones (52.5%, n = 21), short message service (SMS; 10%, n = 4), smartphones (22.5%, n = 9), videoconferencing (10%, n = 4), digital assistants (2.5%, n = 1), and custom devices (2.5%, n = 1) among cohorts of patients with TBI of varying injury severity. Where reported, clinical facilitators, remote follow-up timing and intervals between sessions, synchronicity of follow-up instances, proxy involvement, outcome measures utilized, and technology evaluation efforts are described. FUTs can aid more temporally sensitive assessments and capture fluctuating sequelae, a benefit of particular relevance to TBI cohorts. However, the evidence base surrounding FUTs remains in its infancy, particularly with respect to large samples, low- and middle-income patient cohorts, and the validation of outcome measures for deployment via such remote technology.

Preoperative level of neutrophil-lymphocyte ratio: Comparison between cyanotic and acyanotic congenital heart disease.

INTRODUCTION: Elevated neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcomes in children undergoing congenital heart surgery under cardiopulmonary bypass (CPB). OBJECTIVE: To compare preoperative NLR levels between cyanotic and acyanotic children undergoing surgical repair with CPB. METHODS: We performed a retrospective cohort study in 60-paired children (30 with tetralogy of Fallot [TOF] and 30 with ventricular septal defect [VSD]) between January 2018 and December 2019 matched by age, weight, and gender. Preoperative NLR was measured from the last complete blood count test before the surgery. All of them had negative viral screening. RESULTS: The median age in VSD children was 9.5 months (interquartile range [IQR]: 5-12), weight 7 kg (IQR: 5.5-8.7), 19 (63%) was female, and NLR was 0.45 (IQR: 0.3-0.65). The median age in TOF children was 8.5 months (IQR: 5-12), weight 7.6 kg (IQR: 5.8-8.7), 16 (53%) were female, and NLR was 0.67 (IQR: 0.41-1.1). Demographic parameters did not show any statistically significant difference between groups (p > .05). Children with TOF had higher preoperative NLR compared with VSD patients (p = .004). As lower O2 saturation as higher the NLR (p = .005). CONCLUSION: The preoperative level of NLR was higher in cyanotic congenital heart disease patients.

Incremental Prognostic Value of Coagulopathy in Addition to the Crash Score in Traumatic Brain Injury Patients.

BACKGROUND/OBJECTIVE: Multivariable prognostic scores play an important role for clinical decision-making, information giving to patients/relatives, benchmarking and guiding clinical trial design. Coagulopathy has been implicated on trauma and critical care outcomes, but few studies have evaluated its role on traumatic brain injury (TBI) outcomes. Our objective was to verify the incremental prognostic value of routine coagulopathy parameters in addition to the CRASH-CT score to predict 14-day mortality in TBI patients. METHODS: This is a prospective cohort of consecutive TBI patients admitted to a tertiary university hospital Trauma intensive care unit (ICU) from March/2012 to January/2015. The prognostic performance of the coagulation parameters platelet count, prothrombin time (international normalized ratio, INR) and activated partial thromboplastin time (aPTT) ratio was assessed through logistic regression adjusted for the original CRASH-CT score. A new model, CRASH-CT-Coag, was created and its calibration (Brier scores and Hosmer-Lemeshow (H-L) test), discrimination [area under the receiver operating characteristic curve (AUC-ROC) and the integrated discrimination improvement (IDI)] and clinical utility (net reclassification index) were compared to the original CRASH-CT score. RESULTS: A total 517 patients were included (median age 39 years, 85.1% male, median admission glasgow coma scale 8, neurosurgery on 44.9%). The 14-day mortality observed and predicted by the original CRASH-CT was 22.8% and 26.2%, respectively. Platelet count < 100,000/mm3, INR > 1.2 and aPTT ratio > 1.2 were present on 11.3%, 65.0% and 27.2%, respectively, (at least one of these was altered on 70.6%). All three variables maintained statistical significance after adjustment for the CRASH-CT score. The CRASH-CT-Coag score outperformed the original score on calibration (brier scores 0.122 ± 0.216 vs 0.132 ± 0.202, mean difference 0.010, 95% CI 0.005-0.019, p = 0.036, respectively) and discrimination (AUC-ROC 0.854 ± 0.020 vs 0.813 ± 0.024, p = 0.014; IDI 5.0%, 95% CI 1.3-11.0%). Both scores showed the satisfactory H-L test results. The net reclassification index favored the new model. Considering the strata of low (< 10%), moderate (10-30%) and high (> 30%) risk of death, the CRASH-CT-Coag model yielded a global net correct reclassification of 22.9% (95% CI 3.8-43.4%). CONCLUSIONS: The addition of early markers of coagulopathy-platelet count, INR and aPTT ratio-to the CRASH-CT score increased its accuracy. Additional studies are required to externally validate this finding and further investigate the coagulopathy role on TBI outcomes.

The World Federation of Neurosurgical Societies Young Neurosurgeons Survey (Part I): Demographics, Resources, and Education.

BACKGROUND: Providing a comprehensive and effective neurosurgical service requires adequate numbers of well-trained, resourced, and motivated neurosurgeons. The survey aims to better understand 1) the demographics of young neurosurgeons worldwide; 2) the challenges in training and resources that they face; 3) perceived barriers; and 4) needs for development. METHODS: This was a cross-sectional study in which a widely disseminated online survey (April 2018-November 2019) was used to procure a nonprobabilistic sample from current neurosurgical trainees and those within 10 years of training. Data were grouped by World Bank income classifications and analyzed using χ2 tests because of its categorical nature. RESULTS: There were 1294 respondents, with 953 completed responses included in the analysis. Of respondents, 45.2% were from high-income countries (HICs), 23.2% from upper-middle-income countries, 26.8% lower-middle-income countries, and 4.1% from low-income countries. Most respondents (79.8%) were male, a figure more pronounced in lower-income groups. Neuro-oncology was the most popular in HICs and spinal surgery in all other groups. Although access to computed tomography scanning was near universal (98.64%), magnetic resonance imaging access decreased to 66.67% in low-income countries, compared with 98.61% in HICs. Similar patterns were noted with access to operating microscopes, image guidance systems, and high-speed drills. Of respondents, 71.4% had dedicated time for neurosurgical education. CONCLUSIONS: These data confirm and quantify disparities in the equipment and training opportunities among young neurosurgeons practicing in different income groups. We hope that this study will act as a guide to further understand these differences and target resources to remedy them.

Mortality, Morbidity, and Prognostic Factors in the Surgical Resection of Brain Metastases: A Contemporary Cohort Study.

OBJECTIVE: Despite advances in systemic therapy and radiotherapy (RT), neurosurgical resection (NSR) remains a mainstay of the treatment of brain metastases (BMs). Although it is unequivocal in instances of diagnostic doubt, radioresistance, and risk of death due to neurologic causes, NSR may be controversial in other situations. Many aspects related to NSR have not yet been well established, and the primary prognostic indices were proposed only in the last decade. This study evaluates the survival and the morbidity, causes of death, prognostic factors, and the impact of RT in patients with BMs treated by NSR in the current era. METHODS: A total of 200 patients with BMs who were treated by NSR were evaluated sequentially and followed prospectively. We used logistic regression and Cox regression models to identify independent factors associated with mortality at 4 weeks and at 1 year, respectively. Clinical features, morbidity, recurrence, and causes of death were also studied. RESULTS: Lung cancer was the most prevalent cancer (36.5%); the median Karnofsky Performance Status (KPS) score was 60. Total resection was achieved in 89%, and adjuvant RT was applied in 63% of the cases. The rates of surgical mortality, morbidity, and mortality at 4 weeks were 1.5%, 17%, and 7.5%, respectively. Systemic infections were the leading cause of death in 62.5% of the cases. The median survival was 5 months, and 34.5% of patients lived > 1 year. The postoperative KPS (KPSpo) score remained unchanged or improved in 94.5% of the cases. In the multivariate analysis, a KPSpo score ≥ 80 and the application of adjuvant RT were associated with a lower risk of death at 12 weeks and at 1 year. Interestingly, the variables of primary tumor site, number of BMs, and presence of carcinomatous meningitis were not significant. CONCLUSION: Morbidity and mortality were high, a third of the patients lived > 1 year, and the KPS score improved or remained unchanged in most cases. Prognostic indices and health conditions were important predictive factors, but the KPSpo score and adjuvant RT were independent variables for survival at 12 weeks and at 1 year. Therefore, new studies are needed to assess the influence of new therapies and specific molecular profiles.

Adjuvant Radiotherapy Did Not Reduce Recurrence of World Health Organization Grade I Meningiomas with Venous Sinus Involvement: A Propensity Score Adjusted Analysis and Literature Review.

BACKGROUND: Most meningiomas are classified as World Health Organization (WHO) grade I. Adjuvant radiation therapy (RT) is commonly recommended for subtotal resections with documented progressive regrowth of lesions with venous sinus involvement. We investigated if recurrence of WHO grade I meningiomas was influenced by adjuvant RT. METHODS: From 2000 to 2014, patients with grade I meningiomas with at least one venous sinus involvement and at least 4 years of follow-up were included. Demographics, venous sinus involvement, histology, and extent of resection (EOR) were characterized. Because patients undergoing RT tend to differ from those for whom adjuvant therapy was not prescribed, we used propensity scores to adjust for confounding variables. RESULTS: Sixty-two patients were included; of these, 18 (29.0%) had recurrences. The mean age was 52.8 ± 12.3 years, and 79.0% were women. A total of 34 cases (54.8%) were submitted to adjuvant RT. Adjuvant RT was more frequent in those who had tumor recurrence (77.8% vs. 45.5%, P = 0.020). RT was more frequent in superior sagittal sinus (SSS) invasion (76.5% vs. 50.0%, P = 0.030) and less prevalent after gross total resection (GTR) (32.4% vs. 67.9%, P = 0.005). Propensity score adjusted analysis suggested no adjuvant RT benefit (odds ratio [OR], 2.51; 95% confidence interval [CI], 0.68-9.28; P = 0.167), independent of the EOR. SSS involvement increased recurrence risk (OR, 12.69; 95% CI, 1.46-110.27; P = 0.021), whereas GTR tended to decrease it (OR, 0.26; 95% CI, 0.06-1.09; P = 0.065). CONCLUSIONS: Adjuvant RT does not seem to be a pivotal criterion to reduce the recurrence rate in patients with grade I meningioma, even when venous sinuses are involved.