Risk Analysis Index and Its Recalibrated Version Predict Postoperative Outcomes Better Than 5-Factor Modified Frailty Index in Traumatic Spinal Injury

Objective To assess the discriminative ability of the Risk Analysis Index-administrative (RAI-A) and its recalibrated version (RAI-Rev), compared to the 5-factor modified frailty index (mFI-5), in predicting postoperative outcomes in patients undergoing surgical intervention for traumatic spine injuries (TSIs). Methods The Current Procedural Terminology (CPT) and International Classification of Disease-9 (ICD-9) and ICD-10 codes were used to identify patients ≥ 18 years who underwent surgical intervention for TSI from National Surgical Quality Improvement Program (ACS-NSQIP) database 2015–2019 (n = 6,571). Multivariate analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the comparative discriminative ability of RAI-Rev, RAI-A, and mFI-5 for 30-day postoperative outcomes. Results Multivariate regression analysis showed that with all 3 frailty scores, increasing frailty tiers resulted in worse postoperative outcomes, and patients identified as frail and severely frail using RAI-Rev and RAI-A had the highest odds of poor outcomes. In the ROC curve/C-statistics analysis for prediction of 30-day mortality and morbidity, both RAI-Rev and RAI-A outperformed mFI-5, and for many outcomes, RAI-Rev showed better discriminative performance compared to RAI-A, including mortality (p = 0.0043, DeLong test), extended length of stay (p = 0.0042), readmission (p < 0.0001), reoperation (p = 0.0175), and nonhome discharge (p < 0.0001). Conclusion Both RAI-Rev and RAI-A performed better than mFI-5, and RAI-Rev was superior to RAI-A in predicting postoperative mortality and morbidity in TSI patients. RAI-based frailty indices can be used in preoperative risk assessment of spinal trauma patients

Abstract Number: LBA6 Mechanical Thrombectomy for Basilar Artery Occlusion: Systematic Review and Meta‐analysis of Randomized Controlled Trials

Introduction Acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) is known to be associated with high rates of mortality and lifelong disability. In the past few years, two clinical trials (the BEST and the BASICS trials) investigated the benefits and safety of mechanical thrombectomy (MT) for BAO and did not provide evidence to support the efficacy of MT in BAO patients. Given the recent positive results from the ATTENTION and the BAOCHE clinical trials, we conducted this meta‐analysis to provide updated collective evidence regarding the benefits of MT in patients with BAO. Methods We searched for eligible papers till June 1st, 2021, in five databases: PubMed, Web of Science, Scopus, and Embase databases using keywords and/or medical subject (MeSH) terms. We included all randomized controlled trials (RCTs) with no restrictions on publication date, data, or language of the included studies to avoid missing any relevant papers. All data were analyzed using R software. We computed the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI), using a random‐effect model or fixed‐effect model depending on heterogeneity among the included studies. Heterogeneity was assessed with Q statistics and the I2 test considering it significant with I2 value > 50% or P‐value < 0.05. Results Four trials were included in this meta‐analysis, namely the BEST, the BASICS, the BAOCHE, and the ATTENTION trials. The four trials recruited a total of 988 patients. The MT group achieved a significantly higher rate of modified Rankin scale (mRS) score of 0–3 was as compared to the best medical treatment (BMT) one (RR = 1.54; 95% CI = 1.16‐2.04; P‐value = 0.002). Similarly, the mRS 0–2 rate was significantly higher in the MT group as compared to the BMT group (RR = 1.79; 95% CI = 1.09‐2.95; P‐value = 0.022). Nevertheless, heterogeneity was noticed amongst the included studies. Moreover, there was a significant reduction in the 90‐day mortality in the MT group as compared to the BMT group (RR = 0.76; 95% CI = 0.65‐0.89; P‐value = 0.002). On the other hand, there was a significantly higher rate of symptomatic intracerebral hemorrhage (sICH) in the MT group compared to the BMT group (RR = 7.48; 95% CI = 2.27‐24.61; P‐value< 0.001). There with no heterogeneity observed in both outcomes of mortality and sICH. Noted that there were no significant differences in overall parenchymal hemorrhage (PH) and type I PH rates, yet type II PH was more prevalent in the MT group compared to the BMT one (RR = 5.53; 95% CI = 1.47‐20.84; P‐value = 0.011). Conclusions The current evidence favors MT for basilar artery occlusions over the conservative approach in terms of achieving higher rates of good functional outcomes and decreasing mortality rates. Further large‐scale trials of different populations are needed to corroborate these results and also to ensure generalizability

Increase in Ruptured Cerebral Arteriovenous Malformations and Mortality in the United States: Unintended Consequences of the ARUBA Trial?

Background The findings of the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformation) trial, which determined that medical management was superior to prophylactic interventional therapy for the treatment of unruptured cerebral arteriovenous malformations (cAVMs), remain polarizing and controversial. Methods Adult cAVM patient admissions were identified in the National Inpatient Sample from 2009 to 2019. The incidence of cAVM rupture and in‐hospital mortality were compared between the pre‐ (2009–2013) and post‐ARUBA trial eras (2014–2019) using complex samples‐weighted estimates and multivariable logistic regression analyses. A control cohort composed of an alternate pathology (ruptured and unruptured cerebral aneurysms) was also assessed during the study period to evaluate potential bias. Results Among 121 415 hospitalizations for cAVM during the study period, 31 389 (25.9%) were admissions for ruptured malformations. The incidence of ruptured cAVM increased in the post‐ARUBA trial era (13.3% versus 34.4%; P<0.001) as well as rates of in‐hospital mortality (2.0% versus 7.6%; P<0.001). Following multivariable regression analysis adjusting for age, illness severity, and acute neurological condition, the post‐ARUBA trial era was independently associated with both cAVM rupture (adjusted odds ratio [OR], 1.99; [95% CI, 1.72–2.29]; P<0.001) and in‐hospital mortality (adjusted OR, 1.94; [95% CI, 1.37–2.75]; P<0.001). Control cohort comparative analysis revealed that rates of hospitalizations for ruptured cerebral aneurysms relative to all aneurysm admissions did not differ before and after 2014 (84.5% versus 84.3%; P=0.185). Conclusion The incidence of ruptured cAVM increased following 2014, potentially a reflection of a paradigm shift to conservative and noninterventional management strategies in patients with unruptured cAVM. Further studies may be necessary to exclude other confounders contributing to this rise

Leptomeningeal Disease in Glioblastoma: Endgame or Opportunity?

INTRODUCTION: Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies. METHODS: The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed. RESULTS: LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6-3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge. CONCLUSION: Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care

Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions

Medulloblastoma (MB) is the most common malignant pediatric posterior fossa tumor. Recent genetic, epigenetic, and transcriptomic analyses have classified MB into three subgroups, Wingless Type (WNT), Sonic Hedgehog (SHH), and non-WNT/non-SHH (originally termed Group 3 and Group 4), with discrete patient profiles and prognoses. WNT is the least common subgroup with the best prognosis, characterized by nuclear β-catenin expression, mutations in Catenin beta-1 (CTNNB1), and chromosome 6 monosomy. SHH tumors contain mutations and alterations in GLI1, GLI2, SUFU, and PTCH1 genes, which constitutively activate the SHH pathway. Originally, the presence of TP53 gene alterations and/or MYC amplifications was considered the most reliable prognostic factor. However, recent molecular analyses have subdivided SHH MB into several subtypes with distinct characteristics such as age, TP53 mutation, MYC amplification, presence of metastases, TERT promoter alterations, PTEN loss, and other chromosomal alterations as well as SHH pathway-related gene mutations. The third non-WNT/non-SHH MB (Group3/4) subgroup is genetically highly heterogeneous and displays several molecular patterns, including MYC and OTX2 amplification, GFI1B activation, KBTBD4 mutation, GFI1 rearrangement, PRDM6 enhancer hijacking, KDM6A mutation, LCA histology, chromosome 10 loss, isochromosome 17q, SNCAIP duplication, and CDK6 amplification. However, based on molecular profiling and methylation patterns, additional non-WNT/non-SHH MB subtypes have been described. Recent WHO (2021) guidelines stratified MB into four molecular subgroups with four and eight further subgroups for SHH and non-WNT/non-SHH MB, respectively. In this review, we discuss advancements in genetics, epigenetics, and transcriptomics for better characterization, prognostication, and treatment of MB using precision medicine

Comparative Associations of Baseline Frailty Status and Age With Postoperative Mortality and Duration of Hospital Stay Following Metastatic Brain Tumor Resection

Metastatic brain tumors are the most common intracranial neoplasms diagnosed in the United States. Although baseline frailty status has been validated as a robust predictor of morbidity and mortality across various surgical disciplines, evidence within cranial neurosurgical oncology is limited. Adult metastatic brain tumor patients treated with resection were identified in the National Inpatient Sample during the period of 2015-2018. Frailty was quantified using the 11-point modified frailty index (mFI-11) and its association with clinical endpoints was evaluated through complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses. Among 13,650 metastatic brain tumor patients identified (mean age 62.8 years), 26.8% (n = 3665) were robust (mFI = 0), 31.4% (n = 4660) were pre-frail (mFI = 1), 23.2% (n = 3165) were frail (mFI = 2), and 15.8% (n = 2160) were severely frail (mFI ≥ 3). On univariable assessment, these cohorts stratified by increasing frailty were significantly associated with postoperative complications (13.6%, 15.9%, 23.9%, 26.4%; p \u3c 0.001), mortality (1.2%, 1.4%, 2.7%, 3.2%; p = 0.028), and extended length of stay (eLOS) (15.7%, 22.5%, 28.9%, 37.7%; p \u3c 0.001). Following multivariable logistic regression analysis, frailty (by mFI-11) was independently associated with postoperative mortality (aOR 1.34, 95% CI 1.08, 1.65) and eLOS (aOR 1.26, 95% CI 1.17, 1.37), while increasing age was not associated with these endpoints. ROC curve analysis demonstrated superior discrimination of frailty (by mFI-11) in comparison with age for both mortality (AUC 0.61 vs. 0.58) and eLOS (AUC 0.61 vs. 0.53). Further statistical assessment through propensity score adjustment and decision tree analysis confirmed and extended the findings of the primary analytical models. Frailty may be a more robust predictor of postoperative outcomes in comparison with age following metastatic brain tumor resection

Association of Baseline Frailty Status and Age with Postoperative Morbidity and Mortality Following Intracranial Meningioma Resection

PURPOSE: Although numerous studies have established advanced patient age as a risk factor for poor outcomes following intracranial meningioma resection, large-scale evaluation of frailty for preoperative risk assessment has yet to be examined. METHODS: Weighted discharge data from the National Inpatient Sample were queried for adult patients undergoing benign intracranial meningioma resection from 2015 to 2018. Complex samples multivariable logistic regression models and receiver operating characteristic curve analysis were performed to evaluate adjusted associations and discrimination of frailty, quantified using the 11-factor modified frailty index (mFI), for clinical endpoints. RESULTS: Among 20,250 patients identified (mean age 60.6 years), 35.4% (n = 7170) were robust (mFI = 0), 34.5% (n = 6985) pre-frail (mFI = 1), 20.1% (n = 4075) frail (mFI = 2), and 10.0% (n = 2020) severely frail (mFI ≥ 3). On univariable analysis, these sub-cohorts stratified by increasing frailty were significantly associated with the development of Clavien-Dindo grade IV (life-threatening) complications (inclusive of those resulting in mortality) (1.3% vs. 3.1% vs. 6.5% vs. 9.4%, p \u3c 0.001) and extended length of stay (eLOS) (15.4% vs. 22.5% vs. 29.3% vs. 37.4%, p \u3c 0.001). Following multivariable analysis, increasing frailty (aOR 1.40, 95% CI 1.17, 1.68, p \u3c 0.001) and age (aOR 1.20, 95% CI 1.05, 1.38, p = 0.009) were both independently associated with development of life-threatening complications or mortality, whereas increasing frailty (aOR 1.20, 95% CI 1.10, 1.32, p \u3c 0.001), but not age, was associated with eLOS. Frailty (by mFI-11) achieved superior discrimination in comparison to age for both endpoints (AUC 0.69 and 0.61, respectively). CONCLUSION: Frailty may be more accurate than advanced patient age alone for prognostication of adverse events and outcomes following intracranial meningioma resection

Associations of Baseline Frailty Status and Age With Outcomes in Patients Undergoing Vestibular Schwannoma Resection

IMPORTANCE: Although numerous studies have evaluated the influence of advanced age on surgical outcomes following vestibular schwannoma (VS) resection, few if any large-scale investigations have assessed the comparative prognostic effects of age and frailty. As the population continues to age, it is imperative to further evaluate treatment and management strategies for older patients. OBJECTIVE: To conduct a population-based evaluation of the independent associations of chronological age and frailty (physiological age) with outcomes following VS resection. DESIGN, SETTING, AND PARTICIPANTS: In this large-scale, multicenter, cross-sectional analysis, weighted discharge data from the National Inpatient Sample were searched to identify adult patients (≥18 years old) who underwent VS resection from 2002 through 2017 using International Classification of Diseases, Ninth Revision, Clinical Modification and Tenth Revision, Clinical Modification codes. Data collection and analysis took place September to December 2020. MAIN OUTCOMES AND MEASURES: Complex samples regression models and receiver operating characteristic curve analysis were used to evaluate the independent associations of frailty and age (along with demographic confounders) with complications and discharge disposition. Frailty was evaluated using the previously validated 11-point modified frailty index (mFI). RESULTS: Among the 27 313 patients identified for VS resection, the mean (SEM) age was 50.4 (0.2) years, 15 031 (55.0%) were women, and 4720 (21.0%) were of non-White race/ethnicity, as determined by the National Inpatient Sample data source. Of the included patients, 15 090 (55.2%) were considered robust (mFI score = 0), 8204 (30.0%) were prefrail (mFI score = 1), 3022 (11.1%) were frail (mFI score = 2), and 996 (3.6%) were severely frail (mFI score ≥3). On univariable analysis, increasing frailty was associated with development of postoperative hemorrhagic or ischemic stroke (odds ratio [OR], 2.44 [95% CI, 2.07-2.87]; area under the curve, 0.73), while increasing age was not. Following multivariable analysis, increasing frailty and non-White race/ethnicity were independently associated with both mortality (adjusted OR [aOR], 2.32 [95% CI, 1.70-3.17], and aOR, 3.05 [95% CI, 1.02-9.12], respectively) and extended hospital stays (aOR, 1.54 [95% CI, 1.41-1.67], and aOR, 1.71 [95% CI, 1.42-2.05], respectively), while increasing age was not. Increasing frailty (aOR, 0.61 [95% CI, 0.56-0.67]), age (aOR, 0.98 [95% CI, 0.97-0.99]), and non-White race/ethnicity (aOR, 0.62 [95% CI 0.51-0.75]) were all independently associated with routine discharge. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, findings suggest that frailty may be more accurate for predicting outcomes and guiding treatment decisions than advanced patient age alone following VS resection