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Background: Evidence regarding the utilization and outcomes of endovascular thrombectomy (EVT) for pediatric ischemic stroke is limited, and justification for its use is largely based on extrapolation from clinical benefits observed in adults. Methods: Weighted discharge data from the National Inpatient Sample were queried to identify pediatric patients with ischemic stroke ( Results: Among 7365 pediatric patients with ischemic stroke identified, 190 (2.6%) were treated with EVT. Utilization significantly increased in the post-EVT clinical trial era (2016–2019; 1.7% versus 4.0%; P P P =0.830; adjusted hazard ratio, 1.01 [95% CI, 0.51–2.03]; P =0.972 for unfavorable outcome). Among patients with baseline National Institutes of Health Stroke Scale score >11 (75th percentile of scores in cohort), EVT-treated patients trended toward higher rates of favorable functional outcomes compared with those treated medically only (71.4% versus 55.6%; P =0.146). In a subcohort assessment of EVT-treated patients, those administered preceding thrombolytic therapy (n=79, 41.6%) trended toward higher rates of favorable functional outcomes (63.3% versus 49.5%; P =0.060). Conclusions: This cross-sectional evaluation of the clinical course and short-term outcomes of pediatric patients with ischemic stroke treated with EVT demonstrates that EVT is likely a safe modality which confers high rates of favorable functional outcomes.

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.

There is minimal information on COVID-19 pandemic’s national impact on pediatric neurosurgical operative volumes. In this study, using a national database, TriNetX, we compared the overall and seasonal trends of pediatric neurosurgical procedure volumes in the United States during the pandemic to pre-pandemic periods. In the United States, the incidence of COVID-19 began to rise in September 2020 and reached its maximum peak between December 2020 and January 2021. During this time, there was an inverse relationship between pediatric neurosurgical operative volumes and the incidence of COVID-19 cases. From March 2020 to May 2021, there was a significant decrease in the number of pediatric shunt (-11.7% mean change, p = 0.006), epilepsy (-16.6%, p < 0.001), and neurosurgical trauma (-13.8%, p < 0.001) surgeries compared to pre-pandemic years. The seasonal analysis also yielded a broad decrease in most subcategories in spring 2020 with significant decreases in pediatric spine, epilepsy, and trauma cases. To the best of our knowledge, this is the first study to report a national decline in pediatric shunt, epilepsy, and neurosurgical trauma operative volumes during the pandemic. This could be due to fear-related changes in health-seeking behavior as well as underdiagnosis during the COVID-19 pandemic.

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. 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. 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. 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.

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. 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. 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

Background and Aims: Although intravenous thrombolysis (IVT) represents standard-of-care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence-based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aimed to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry. Methods: Weighted hospitalizations for pediatric (Results: Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT-treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity-score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH (5.6% vs 5.4%, p = 0.931; adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI) = 0.48–2.14, p = 0.971), nor with favorable functional outcome (71.9% vs 74.5%, p = 0.489; aOR = 0.88, 95% CI = 0.60–1.29, p = 0.511) in comparison with other medical therapy. Conclusions: Twenty years of population-level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation.

Objective In this systematic review, preoperative educational interventions for patients undergoing neurosurgical treatment are identified and their impact on patient knowledge acquisition and satisfaction is assessed. Methods The review was conducted in accordance with the PRISMA guidelines and used PubMed, Google Scholar, and MEDLINE databases. Studies evaluating before and after cohort or control group comparison were identified between 2007 and 2019 and were independently scored and evaluated by 3 authors. Results Eighty-one articles were assessed for eligibility and 15 met the inclusion criteria. Patient educational interventions were text-based (2 studies), multimedia/video-based (3), mobile/tablet-based (5), or used virtual reality (2) or three-dimensional printing (3). Interventions were disease-specific for cerebrovascular lesions (5), degenerative spine disease (2), concussion/traumatic brain injury (2), movement disorders (1), brain tumor (1), adolescent epilepsy (1), and other cranial/spinal elective procedures (3). Eleven studies (n = 18–175) documented patient knowledge acquisition using self-reported knowledge questionnaires (5) or more objective assessments based on true/false or multiple-choice questions (6). Most studies (10/11) reported statistically significant increases in patient knowledge after implementation of the intervention. Ten studies (n = 14–600) documented patient satisfaction using validated satisfaction surveys (2), Likert scale surveys (6), or other questionnaires (2). Although all studies reported increases in patient satisfaction after the intervention, only 4 were statistically significant. Conclusions Patient educational interventions using various modalities are broadly applicable within neurosurgery and ubiquitously enhance patient knowledge and satisfaction. Interventions should be implemented when possible.

Objective Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort Methods The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS. Results 1,605,723 patients with AIS were identified from 2010–2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p Conclusion AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight.

Delayed cerebral ischemia (DCI) represents a devastating complication of aneurysmal subarachnoid hemorrhage (aSAH) and is a significant predictor of morbidity and mortality. Recent studies have implicated inflammatory processes in the pathogenesis of DCI.aSAH patient data were retrospectively obtained from the eICU Collaborative Research Database (eICU CRD). Multivariable logistic regression models and receiver operating characteristic (ROC) curve analyses were employed to assess the association between low serum albumin (3.4 g/dL) and clinical endpoints: DCI and in-hospital mortality.Among 276 aSAH patients included in the analysis, 35.5% (n=98) presented with low serum albumin levels and demonstrated a higher incidence of DCI (18.4% vs. 8.4%, OR=2.45, 95% CI 1.17, 5.10; p=0.017) and in-hospital mortality (27.6% vs. 16.3%, OR=1.95, 95% CI 1.08, 3.54; p=0.027) compared to patients with normal admission albumin values. In a multivariable model controlling for age and World Federation of Neurosurgical Societies grade, low serum albumin remained significantly associated with DCI (OR=2.52, 95% CI 1.18, 5.36; p=0.017), but not with in-hospital mortality. A combined model for prediction of DCI, encompassing known risk factors in addition to low serum albumin, achieved an area under the curve of 0.65 (sensitivity=0.55, specificity=0.75).Serum albumin, a routine and inexpensive laboratory measurement, can may potentially aid in the identification of patients with aSAH at risk for the development of DCI.

Introduction Acute kidney injury (AKI) is associated with poor outcome in aneurysmal subarachnoid hemorrhage patients (aSAH). Frailty has recently been demonstrated to correlate with elevated mortality and morbidity; its impact on predicting AKI and mortality in aSAH patients has not been investigated. Objective Evaluating risk factors and predictors for AKI in aSAH patients. Methods aSAH patients from a single-center's prospectively maintained database were retrospectively evaluated for development of AKI within 14 days of admission. Baseline demographic and clinical characteristics were collected. The effect of frailty and other risk factors were evaluated. Results Of 213 aSAH patients, 53 (33.1%) were frail and 12 (5.6%) developed AKI. Admission serum creatinine (sCr) and peak sCr within 48 h were higher in frail patients. AKI patients showed a trend towards higher frailty. Mortality was significantly higher in AKI than non-AKI aSAH patients. Frailty was a poor predictor of AKI when controlling for Hunt and Hess (HH) grade or age. HH grade ≥ 4 strongly predicted AKI when controlling for frailty. Conclusion AKI in aSAH patients carries a poor prognosis. The HH grade appears to have superior utility as a predictor of AKI in aSAH patients than mFI.

Increasing patient age has been associated with worse outcomes after pituitary adenoma resection in previous studies, but the prognostic value of frailty compared with advancing age on pituitary adenoma resection outcomes has not been clearly evaluated.The National Surgical Quality Improvement Program from 2015 to 2019 was queried for data for patients aged18 years who underwent pituitary adenoma resection (n = 1454 identified patients). Univariate and multivariate analyses of age and frailty (5-factor modified frailty index [mFI-5]) were performed on 30-day mortality, major complications, extended length of stay (eLOS), discharge destination, and readmission and reoperation. The receiver operating characteristic curve analysis was performed to compare effect of age and mFI-5.On univariate analysis, increasing frailty was significantly associated with greater risk of unplanned readmission (frail: odds ratio [OR], 1.9; 95% confidence interval [CI], 1.2-3.2; severely frail: OR, 6.9; 95% CI, 2.4-19.8) and a major complication (frail: OR, 3.6; 95% CI, 2.1-6.1). Severe frailty was also associated with nonhome discharge (OR, 10.6; 95% CI, 3.2-35.8) and eLOS (OR, 4.5; 95% CI, 1.5-13.4). Increasing age was not associated with any of these outcome measures. Multivariate analysis also demonstrated similar trends. In receiver operating characteristic curve analysis, the mFI-5 score showed higher discrimination for major complications compared with age (area under the curve: 0.624 vs. 0.503; P0.001).Increasing frailty, and not advancing age, was an independent predictor for major complications, unplanned readmissions, eLOS, and nonhome discharge after pituitary adenoma resection, suggesting frailty to be superior to age in preoperative risk stratification in this patient population.

Literature evaluating frailty in traumatic spinal cord injury (tSCI) is limited.To evaluate the prognostic significance of baseline frailty status in tSCI.Patients with tSCI were identified in the National Inpatient Sample from 2015 to 2018 and stratified according to frailty status, which was quantified using the 11-point modified frailty index (mFI).Among 8825 operatively managed patients with tSCI identified (mean age 57.9 years, 27.6% female), 3125 (35.4%) were robust (mFI = 0), 2530 (28.7%) were prefrail (mFI = 1), 1670 (18.9%) were frail (mFI = 2), and 1500 (17.0%) were severely frail (mFI ≥ 3). One thousand four-hundred forty-five patients (16.4%) were routinely discharged (to home), and 320 (3.6%) died during hospitalization, while 2050 (23.3%) developed a severe complication, and 2175 (24.6%) experienced an extended length of stay. After multivariable analysis adjusting for age, illness severity, trauma burden, and other baseline covariates, frailty (by mFI-11) was independently associated with lower likelihood of routine discharge [adjusted odds ratio (aOR) 0.82, 95% CI 0.77-0.87; Plt; .001] and development of a severe complication (aOR 1.17, 95% CI 1.12-1.23; Plt; .001), but not with in-hospital mortality or extended length of stay. Subgroup analysis by age demonstrated robust associations of frailty with routine discharge in advanced age groups (aOR 0.71 in patients 60-80 years and aOR 0.69 in those older than 80 years), which was not present in younger age groups.Frailty is an independent predictor of clinical outcomes after tSCI, especially among patients of advanced age. Our large-scale analysis contributes novel insights into limited existing literature on this topic.

Background: Previous literature has identified a survival advantage in acute ischemic stroke (AIS) patients with elevated body mass indices (BMIs), a phenomenon termed the “obesity paradox.” Objective: The aim of this study was to evaluate the independent association between obesity and clinical outcomes following AIS. Methods: Weighted discharge data from the National Inpatient Sample were queried to identify AIS patients from 2015 to 2018. Multivariable logistic regression and Cox proportional hazards modeling were performed to evaluate associations between obesity (BMI ≥ 30) and clinical endpoints following adjustment for acute stroke severity and comorbidity burden. Results: Among 1,687,805 AIS patients, 216,775 (12.8%) were obese. Compared to nonobese individuals, these patients were younger (64 vs. 72 mean years), had lower baseline NIHSS scores (6.9 vs. 7.9 mean score), and a higher comorbidity burden. Multivariable analysis demonstrated independent associations between obesity and lower likelihood of mortality (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI]: 0.71, 0.82, p < 0.001; hazard ratio 0.84, 95% CI: 0.73, 0.97, p = 0.015), intracranial hemorrhage (aOR 0.87, 95% CI: 0.82, 0.93, p < 0.001), and routine discharge to home (aOR 0.97, 95% CI: 0.95, 0.99; p = 0.015). Mortality rates between obese and nonobese patients were significantly lower across stroke severity thresholds, but this difference was attenuated among high severity (NIHSS > 20) strokes (21.6% vs. 23.2%, p = 0.358). Further stratification of the cohort into BMI categories demonstrated a “U-shaped” association with mortality (underweight aOR 1.58, 95% CI: 1.39, 1.79; p < 0.001, overweight aOR 0.64, 95% CI: 0.42, 0.99; p = 0.046, obese aOR 0.77, 95% CI: 0.71, 0.83; p < 0.001, severely obese aOR 1.18, 95% CI: 0.74, 1.87; p = 0.485). Sub-cohort assessment of thrombectomy-treated patients demonstrated an independent association of obesity (BMI 30–40) with lower mortality (aOR 0.79, 95% CI: 0.65, 0.96; p = 0.015), but not with routine discharge. Conclusion: This cross-sectional analysis demonstrates a lower likelihood of discharge to home as well as in-hospital mortality in obese patients following AIS, suggestive of a protective effect of obesity against mortality but not against all poststroke neurological deficits in the short term which would necessitate placement in acute rehabilitation and long-term care facilities.

Background and Purpose: Acute ischemic stroke (AIS) is a rare occurrence during pregnancy and the postpartum period. Existing literature evaluating endovascular mechanical thrombectomy (MT) for this patient population is limited. Methods: The National Inpatient Sample was queried from 2012 to 2018 to identify and characterize pregnant and postpartum patients (up to 6 weeks following childbirth) with AIS treated with MT. Complications and outcomes were compared with nonpregnant female patients treated with MT and to other pregnant and postpartum patients managed medically. Complex samples regression models and propensity score matching were implemented to assess adjusted associations and to address confounding by indication, respectively. Results: Among 4590 pregnant and postpartum patients with AIS, 180 (3.9%) were treated with MT, and rates of utilization increased following the MT clinical trial era (2015–2018; 1.9% versus 5.3%, P =0.011). Compared with nonpregnant patients with AIS treated with MT, they experienced lower rates of intracranial hemorrhage (11% versus 24%, P =0.069) and poor functional outcome (50% versus 72%, P =0.003) at discharge. Pregnant/postpartum status was independently associated with a lower likelihood of development of intracranial hemorrhage (adjusted odds ratio, 0.26 [95% CI, 0.09–0.70]; P =0.008) following multivariable analysis adjusting for age, illness severity, and stroke severity. Following propensity score matching, pregnant and postpartum patients treated with MT and those medically managed differed in frequency of venous thromboembolism (17% versus 0%, P =0.001) and complications related to pregnancy (44% versus 64%, P =0.034), but not in functional outcome at discharge or hospital length of stay. Pregnant and postpartum women treated with MT did not experience mortality or miscarriage during hospitalization. Conclusions: This large-scale analysis utilizing national claims data suggests that MT is a safe and efficacious therapy for AIS during pregnancy and the postpartum period. In the absence of prospective clinical trials, population-based cross-sectional analyses such as the present study provide valuable clinical insight.

The safety and efficacy of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) for large vessel occlusion stroke remains a highly contested and unanswered clinical question. We aim to characterize the clinical profile, complications, and discharge disposition of EVT patients treated with and without preceding IVT using a large, nationally-representative sample.The National Inpatient Sample was queried from 2015 to 2018 to identify adult patients with anterior circulation stroke treated with EVT with and without preceding IVT. Multivariable logistic regression analysis and propensity-score matching were employed to assess adjusted associations with clinical endpoints and to address confounding by indication for IVT, respectively.Among 48,525 patients identified, 40.7% (n = 19,735) received IVT prior to EVT. On unadjusted analysis, patients treated with IVT bridging therapy experienced higher rates of intracranial hemorrhage (26% vs. 24%, p = 0.003) and routine discharge to home with or without services (33% vs. 27%, p 0.001), a lower frequency of thromboembolic complications (3% vs. 5%, p 0.001), and lower rates of extended hospital stays (eLOS) (20% vs. 24%, p 0.001). Multivariable logistic regression analysis adjusting for demographic and baseline clinical characteristics demonstrated independent associations of IVT bridging therapy with intracranial hemorrhage (aOR 1.28, 95% CI 1.15, 1.43; p 0.001), thromboembolic complications (aOR 0.66, 95% CI 0.53, 0.83; p 0.001), routine discharge (aOR 1.27, 95% CI 1.15, 1.40; p 0.001), and eLOS (aOR 0.76, 95% CI 0.68, 0.85; p 0.001). Sensitivity testing confirmed these findings.Preceding IVT was associated with favorable functional outcomes following endovascular therapy. Prospective randomized clinical trials are warranted for further evaluation.

BackgroundObstructive sleep apnea (OSA) portends increased morbidity and mortality following acute ischemic stroke (AIS). Evaluation of OSA in the setting of AIS treated with endovascular mechanical thrombectomy (MT) has not yet been evaluated in the literature.MethodsThe National Inpatient Sample from 2010 to 2018 was utilized to identify adult AIS patients treated with MT. Those with and without OSA were compared for clinical characteristics, complications, and discharge disposition. Multivariable logistic regression analysis and propensity score adjustment (PA) were employed to evaluate independent associations between OSA and clinical outcome.ResultsAmong 101 093 AIS patients treated with MT, 6412 (6%) had OSA. Those without OSA were older (68.5 vs 65.6 years old, pConclusionsOur findings suggest that MT is a viable and safe treatment option for AIS patients with OSA.

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.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.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.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.

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 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 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.

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.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.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 0.001) and extended length of stay (eLOS) (15.4% vs. 22.5% vs. 29.3% vs. 37.4%, p 0.001). Following multivariable analysis, increasing frailty (aOR 1.40, 95% CI 1.17, 1.68, p 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 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).Frailty may be more accurate than advanced patient age alone for prognostication of adverse events and outcomes following intracranial meningioma resection.

OBJECTIVE Studies examining the risk factors and clinical outcomes of arterial vasospasm secondary to cerebral arteriovenous malformation (cAVM) rupture are scarce in the literature. The authors used a population-based national registry to investigate this largely unexamined clinical entity. METHODS Admissions for adult patients with cAVM ruptures were identified in the National Inpatient Sample during the period from 2015 to 2019. Complex samples multivariable logistic regression and chi-square automatic interaction detection (CHAID) decision tree analyses were performed to identify significant associations between clinical covariates and the development of vasospasm, and a cAVM–vasospasm predictive model (cAVM-VPM) was generated based on the effect sizes of these parameters. RESULTS Among 7215 cAVM patients identified, 935 developed vasospasm, corresponding to an incidence rate of 13.0%; 110 of these patients (11.8%) subsequently progressed to delayed cerebral ischemia (DCI). Multivariable adjusted modeling identified the following baseline clinical covariates: decreasing age by decade (adjusted odds ratio [aOR] 0.87, 95% CI 0.83–0.92; p < 0.001), female sex (aOR 1.68, 95% CI 1.45–1.95; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.34, 95% CI 1.01–1.79; p = 0.045), intraventricular hemorrhage (aOR 1.87, 95% CI 1.17–2.98; p = 0.009), hypertension (aOR 1.77, 95% CI 1.50–2.08; p < 0.001), obesity (aOR 0.68, 95% CI 0.55–0.84; p < 0.001), congestive heart failure (aOR 1.34, 95% CI 1.01–1.78; p = 0.043), tobacco smoking (aOR 1.48, 95% CI 1.23–1.78; p < 0.019), and hospitalization events (leukocytosis [aOR 1.64, 95% CI 1.32–2.04; p < 0.001], hyponatremia [aOR 1.66, 95% CI 1.39–1.98; p < 0.001], and acute hypotension [aOR 1.67, 95% CI 1.31–2.11; p < 0.001]) independently associated with the development of vasospasm. Intraparenchymal and subarachnoid hemorrhage were not associated with the development of vasospasm following multivariable adjustment. Among significant associations, a CHAID decision tree algorithm identified age 50–59 years (parent node), hyponatremia, and leukocytosis as important determinants of vasospasm development. The cAVM-VPM achieved an area under the curve of 0.65 (sensitivity 0.70, specificity 0.53). Progression to DCI, but not vasospasm alone, was independently associated with in-hospital mortality (aOR 2.35, 95% CI 1.29–4.31; p = 0.016) and lower likelihood of routine discharge (aOR 0.62, 95% CI 0.41–0.96; p = 0.031). CONCLUSIONS This large-scale assessment of vasospasm in cAVM identifies common clinical risk factors and establishes progression to DCI as a predictor of poor neurological outcomes.

Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent neurosurgical condition associated with high morbidity and mortality. The prognostic significance of baseline frailty status in aSAH patients has not been previously evaluated in a large, nationally representative sample.Clinical outcomes data from the National Inpatient Sample from 2010-2018 were compared among sub-cohorts stratifying admissions by increasing frailty thresholds [(assessed using the 11-point modified frailty index (mFI-11)]. The previously validated NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM) were utilized. Complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess adjusted associations and discrimination of frailty for endpoints.Among 64,102 aSAH hospitalizations (mean age 55.4 years), 20.4% of admissions were classified as robust (mFI=0), 43.4% as pre-frail (mFI = 1), 24.9% as frail (mFI = 2), and 11.2% as severely frail (mFI ≥ 3). Following multivariable analysis adjusting for age and aSAH severity, increasing frailty was independently associated with NIS-SOM (OR = 1.15, 95% CI 1.09-1.21; p0.001), extended length of hospital stay (eLOS) (OR = 1.08, 1.02-1.13; p = 0.008), neurological complications (OR = 1.08, 1.03-1.13; p0.001), and medical complications (OR = 1.14, 1.08-1.21; p0.001). Based on ROC curve analysis, frailty achieved an AUC of 0.59 (0.58-0.60) and 0.54 (0.53-0.55) for NIS-SOM and eLOS, respectively. Age and NIS-SSS demonstrated significantly greater discrimination for NIS-SOM [AUC 0.69 (0.68-0.70) and 0.79 (0.78-0.80), respectively), while NIS-SSS achieved significantly greater discrimination for eLOS [(AUC 0.74 (0.73-0.75)] in comparison to both age and frailty.This national database evaluation of frailty in aSAH patients demonstrates an independent association between increasing frailty and poor functional outcome. Age and aSAH severity, however, may be more robust prognostic factors.

OBJECTIVE The authors sought to analyze a large, publicly available, nationwide hospital database to further elucidate the impact of cardiopulmonary arrest (CA) in association with subarachnoid hemorrhage (SAH) on short-term outcomes of mortality and discharge disposition. METHODS This retrospective cohort study was conducted by analyzing de-identified data from the National (Nationwide) Inpatient Sample (NIS). The publicly available NIS database represents a 20% stratified sample of all discharges and is powered to estimate 95% of all inpatient care delivered across hospitals in the US. A total of 170,869 patients were identified as having been hospitalized due to nontraumatic SAH from 2008 to 2014. RESULTS A total of 5415 patients (3.2%) were hospitalized with an admission diagnosis of CA in association with SAH. Independent risk factors for CA included a higher Charlson Comorbidity Index score, hospitalization in a small or nonteaching hospital, and a Medicaid or self-pay payor status. Compared with patients with SAH and not CA, patients with CA-SAH had a higher mean NIS Subarachnoid Severity Score (SSS) ± SD (1.67 ± 0.03 vs 1.13 ± 0.01, p < 0.0001) and a vastly higher mortality rate (82.1% vs 18.4%, p < 0.0001). In a multivariable model, age, NIS-SSS, and CA all remained significant independent predictors of mortality. Approximately 18% of patients with CA-SAH survived and were discharged to a rehabilitation facility or home with health services, outcomes that were most predicted by chronic disease processes and large teaching hospital status. CONCLUSIONS In the largest study of its kind, CA at onset was found to complicate roughly 3% of spontaneous SAH cases and was associated with extremely high mortality. Despite this, survival can still be expected in approximately 18% of patients.

OBJECTIVE Limited evidence exists characterizing the incidence, risk factors, and clinical associations of cerebral vasospasm following traumatic intracranial hemorrhage (tICH) on a large scale. Therefore, the authors sought to use data from a national inpatient registry to investigate these aspects of posttraumatic vasospasm (PTV) to further elucidate potential causes of neurological morbidity and mortality subsequent to the initial insult. METHODS Weighted discharge data from the National (Nationwide) Inpatient Sample from 2015 to 2018 were queried to identify patients with tICH who underwent diagnostic angiography in the same admission and, subsequently, those who developed angiographically confirmed cerebral vasospasm. Multivariable logistic regression analysis was performed to identify significant associations between clinical covariates and the development of vasospasm, and a tICH vasospasm predictive model (tICH-VPM) was generated based on the effect sizes of these parameters. RESULTS Among 5880 identified patients with tICH, 375 developed PTV corresponding to an incidence of 6.4%. Multivariable adjusted modeling determined that the following clinical covariates were independently associated with the development of PTV, among others: age (adjusted odds ratio [aOR] 0.98, 95% CI 0.97–0.99; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.80, 95% CI 1.12–2.90; p = 0.015), intraventricular hemorrhage (aOR 6.27, 95% CI 3.49–11.26; p < 0.001), tobacco smoking (aOR 1.36, 95% CI 1.02–1.80; p = 0.035), cocaine use (aOR 3.62, 95% CI 1.97–6.63; p < 0.001), fever (aOR 2.09, 95% CI 1.34–3.27; p = 0.001), and hypokalemia (aOR 1.62, 95% CI 1.26–2.08; p < 0.001). The tICH-VPM achieved moderately high discrimination, with an area under the curve of 0.75 (sensitivity = 0.61 and specificity = 0.81). Development of vasospasm was independently associated with a lower likelihood of routine discharge (aOR 0.60, 95% CI 0.45–0.78; p < 0.001) and an extended hospital length of stay (aOR 3.53, 95% CI 2.78–4.48; p < 0.001), but not with mortality. CONCLUSIONS This population-based analysis of vasospasm in tICH has identified common clinical risk factors for its development, and has established an independent association between the development of vasospasm and poorer neurological outcomes.

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.

Introduction Electronic cigarettes (e-cigs) have attained common usage worldwide, yet knowledge of their physiological effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on the urge-to-cough (UTC) threshold and C5. Methods Seventeen healthy nonsmokers underwent C5 measurement employing capsaicin cough challenge at baseline, 15 minutes, and 24 hours after e-cig exposure (30 puffs 30 seconds apart). The endpoint of cough challenge is C5, the concentration of capsaicin inducing five or more coughs. The UTC threshold (Cu) is defined as the lowest concentration of capsaicin inducing UTC without an associated motor cough. Results The Cu and C5 were significantly inhibited (Cu and C5 increased) 15 minutes after e-cig use. Mean log Cu rose from -0.035±0.08 (SEM) to 0.21±0.12 (P = .005). Mean log C5 increased from 0.60±0.11 to 0.92±0.16 (P = .001). By 24 hours after e-cig exposure, Cu and C5 had returned to baseline levels. Conclusions A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of the Cu, as well as C5. Previous studies implicate nicotine as the agent responsible for suppression of C5, and we hypothesize a similar role for nicotine in the suppression of the Cu. Given our observation of the effect of a single e-cig exposure, studies of the respiratory physiologic implications of repeated or chronic e-cig use are warranted. Implications This is the first study to demonstrate that a single exposure to an e-cig significantly inhibits the Cu as measured by capsaicin cough challenge testing. These findings add to the growing body of evidence that e-cig vapor is not a physiologically benign substance, and support further investigation of the effects of repeated or chronic use of e-cigs on cough sensitivity and other respiratory parameters.

Background: Electronic cigarettes (e-cigs) have gained significant popularity worldwide yet studies evaluating their physiological effects are scarce. We recently demonstrated that a single exposure to e-cig vapor in healthy nonsmokers causes significant inhibition of cough reflex sensitivity (ATS 2015). The aim of the present study was to investigate the role of nicotine in this phenomenon by comparing the effect of nicotine- and non-nicotine-containing e-cig exposure on cough and cough reflex sensitivity. Methods: In our initial study 30 subjects underwent baseline cough reflex sensitivity measurement employing capsaicin cough challenge and again one day later 15 minutes after inhalation of 30 puffs of a nicotine-containing e-cig (Blu, Lorillard, USA) administered 30 seconds apart thus approximating the nicotine delivery of one tobacco cigarette. The number of coughs induced by e-cig inhalation was recorded. The standard endpoint of cough challenge was used: concentration of capsaicin inducing ≥5 coughs (C 5 ). Subjects with the highest degree of inhibition of cough reflex sensitivity, defined as C 5 increase of ≥2 doubling concentrations (n=8) underwent an identical protocol using a non-nicotine-containing e-cig (BlueStar, USA). Results: The 8 subjects who had experienced the largest inhibition of cough reflex sensitivity after nicotine-containing e-cig exposure demonstrated no effect after use of the non-nicotine e-cig (p=0.0078). However, nicotine e-cig inhalation acutely induced more coughs than did the nicotine-free e-cig: 8.9±8.0(SD) vs. 1.3±2.4, p=0.0156. Conclusion: Our results suggest a dual action of nicotine: an immediate peripheral protussive effect and a delayed central antitussive effect.