The epidemiology of crib-related head injuries: A ten-year nationwide analysis.

INTRODUCTION: Falls from cribs resulting in head injury are understudied and poorly characterized. The purpose of this study was to advance current understanding of the prevalence, descriptive characteristics of injury victims, and the types of crib fall-related head injuries (CFHI) using queried patient cases from the National Electronic Injury Surveillance System (NEISS) database. METHODS: Using the US Consumer Product Safety Commission's System NEISS database, we queried all CFHIs among children from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of the incident, diagnoses, ED disposition, and sequelae were analyzed. The number of CFHI from all US EDs during each year was also collected from the database. RESULTS: There were an estimated 54,799 (95% CI: 30,228-79,369) total visits to EDs for CFHIs between 2012 and 2021, with a decrease in incidence of approximately 20% during the onset of the COVID-19 pandemic (2019: 5616 cases, 2020: 4459 cases). The annual incidence of injuries showed no significant trend over the 10-year study period. An available subset of 1782 cases of head injuries from approximately 100 EDs was analyzed, and 1442 cases were included in final analysis. Injuries were sorted into three primary categories: unspecified closed head injury (e.g., closed head injury, blunt head trauma, or traumatic brain injury), concussion, or open head injury and skull fracture. Unspecified closed head injuries were the most common of all head injuries (95.4%, 1376/1442). Open head injuries (14/1442, 0.97%) and concussions 3.6% (52/1442, 3.6%) were rare. Most injuries involved children under the age of 1 (42.6%) compared to children who were 1, 2, 3, or 4-years old. About a fourth of patients had other diagnoses in addition to their primary injury including scalp/forehead hematomas, emesis, and contusions. Female patients were more likely to present with other diagnoses in addition to their primary head injury (Difference: 12.3%, 95% CI: 9.87%-15.4%, p < .0001). CONCLUSION: Despite minimum rail height requirements set by the Consumer Safety Product Commission (CPSC), head injuries associated with crib falls are prevalent in the United States. However, most injuries were minor with a vast majority of patients being released following examination and treatment.

Barriers to overcoming immunotherapy resistance in glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma.

Chitinase 3-like 1 (Chi3l1) is a secreted protein that is highly expressed in glioblastoma. Here, we show that Chi3l1 alters the state of glioma stem cells (GSC) to support tumor growth. Exposure of patient-derived GSCs to Chi3l1 reduced the frequency of CD133+SOX2+ cells and increased the CD44+Chi3l1+ cells. Chi3l1 bound to CD44 and induced phosphorylation and nuclear translocation of ß-catenin, Akt, and STAT3. Single-cell RNA sequencing and RNA velocity following incubation of GSCs with Chi3l1 showed significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq revealed that Chi3l1 increases accessibility of promoters containing a Myc-associated zinc finger protein (MAZ) transcription factor footprint. Inhibition of MAZ downregulated a set of genes with high expression in cellular clusters that exhibit significant cell state transitions after treatment with Chi3l1, and MAZ deficiency rescued the Chi3L-induced increase of GSC self-renewal. Finally, targeting Chi3l1 in vivo with a blocking antibody inhibited tumor growth and increased the probability of survival. Overall, this work suggests that Chi3l1 interacts with CD44 on the surface of GSCs to induce Akt/ß-catenin signaling and MAZ transcriptional activity, which in turn upregulates CD44 expression in a pro-mesenchymal feed-forward loop. The role of Chi3l1 in regulating cellular plasticity confers a targetable vulnerability to glioblastoma. SIGNIFICANCE: Chi3l1 is a modulator of glioma stem cell states that can be targeted to promote differentiation and suppress growth of glioblastoma.

Pediatric all-terrain vehicle (ATV) related head injury rates and patterns: A 10-year nationwide analysis.

INTRODUCTION: The use of all-terrain vehicles (ATVs) carries significant risk of permanent injury and death, disproportionately affecting children. These injuries commonly affect the head and are especially severe among children as they are often unhelmeted and more likely than adults to experience rollover injuries. Many studies examining patients with ATV-related injuries are single-center cohort studies, with few focusing specifically on head injuries. In the present study, we aimed to characterize the annual incidence of ATV-related head injuries between 2012 and 2021, classify and compare head injury types, and identify descriptive characteristics of ATV-related head injury victims. METHODS: Using the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) database, we queried all head injuries associated with operating or riding an ATV in children under 18 years-old from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of incident, diagnoses, and sequelae were analyzed. We also collected the estimated number of ATV-related head injuries from all US EDs using the NEISS algorithm provided by the database. RESULTS: Using the NEISS algorithm we identified 67,957 (95% CI: 43,608 - 92,305) total pediatric ATV-related head injuries between 2012 and 2021. The annual incidence of ATV-related head injury was similar throughout this study period except for a 20% increase during the COVID-19 pandemic period of 2019-2021 (2019: 6382 injuries, 2020: 6757 injuries, 2021: 7600 injuries). A subset of 1890 cases from approximately 100 EDs were then analyzed. Unspecified closed head injuries were the prevailing type of injury (38%, 900/1890), followed by concussions (27%, 510/1890). More severe injuries included intracranial hemorrhages in 91 children (3.8%, 91/1890). Injuries of all types were predominantly seen in 14-17 year-old's (780/1890, 41%) and in males (64.1%, 1211/1890). In addition, ATV-associated injuries were significantly more common in those coded as white (58.0%, 1096/1890) than any other racial group. ATV-associated accidents among children younger than 9 more commonly occurred at the home compared to accidents involving children older than 9 (57% vs. 32%, p < 0.0001). CONCLUSION: ATV-related head injuries cause a significant annual burden among children, with growing incidence in recent years. Further research may wish to explore potential benefits of helmet use and supervision of younger children in possible prevention of these accidents and their associated economic and non-economic costs.

The burden of unhelmeted motorcycle injury: A nationwide scoring-based analysis of helmet safety legislation.

INTRODUCTION: Motorcycle collisions comprise a large portion of motor vehicle injuries and fatalities with over 80,000 injuries and 5,500 fatalities per year in the United States. Unhelmeted riders have poor medical outcomes and generate billions in costs. Despite helmet use having been shown to lower the risk of neurological injury and death, helmet compliance is not universal, and legislation concerning helmet use also varies widely across the United States. METHODS: In this study, we systematically reviewed helmet-related statutes from all US jurisdictions. We evaluated the stringency of these statutes using a legislative scoring system termed the Helmet Safety Score (HSS) ranging from 0-7 points, with higher scores denoting more stringent statutes. Regression modeling was used to predict unhelmeted mortality using our safety scores. RESULTS: The mean score across all jurisdictions was 4.73. We found jurisdictions with higher HSS's generally had lower percentages of unhelmeted fatalities in terms of total fatalities as well as per 100,000 people and 100,000 registered motorcycles. In contrast, some lower-scoring jurisdictions had over 100 times more unhelmeted fatalities than higher-scoring jurisdictions. Our HSS significantly predicted unhelmeted motorcycle fatalities per 100,000 people (ß = -0.228 per 1-point increase, 95% CI: -0.288 to -0.169, p < .0001) and per 100,000 registered motorcycles (ß = -6.17 per 1-point increase, 95% CI: -8.37 to -3.98, p < .0001) in each state. Aspects of our score concerning helmet exemptions for riders and motorcycle-type vehicles independently predicted higher fatalities (p < .0001). Higher safety scores predicted lower unhelmeted fatalities. CONCLUSION: Stringent helmet laws may be an effective mechanism for decreasing unhelmeted mortality. Therefore, universal helmet laws may be one such mechanism to decrease motorcycle-related neurological injury and fatality burden. In states with existing helmet laws, elimination of exemptions for certain riders and motorcycle-type vehicles may also decrease fatalities.

Time of Discharge and 30-Day Re-Presentation to an Acute Care Setting After Elective Lumbar Decompression Surgery.

BACKGROUND: Evidence regarding the consequence of efforts to increase patient throughput and decrease length of stay in the context of elective spine surgery is limited. OBJECTIVE: To evaluate whether early time of discharge results in increased rates of hospital readmission or return to emergency department for patients admitted after elective, posterior, lumbar decompression surgery. METHODS: We conducted a retrospective cohort study of 779 patients admitted to hospital after undergoing elective, posterior, lumbar decompression surgery. Multiple logistic regression evaluated the relationship between time of discharge and the primary outcome of return to acute care within 30 days, while controlling for sociodemographic, procedural, and discharge characteristics. RESULTS: In multiple logistic regression, time of discharge earlier in the day was not associated with increased odds of return to acute care within 30 days (odds ratio [OR] 1.18, 95% CI 0.92-1.52, P = .19). Weekend discharge (OR 1.99, 95% CI 1.04-3.79, P = .04) increased the likelihood of return to acute care. Surgeon experience (<1 year of attending practice, OR 0.43, 95% CI 0.19-1.00, P = .05 and 2-5 years of attending practice, OR 0.50, 95% CI 0.25-1.01, P = .054), weekend discharge (OR 0.49, 95% CI 0.27-0.89, P = .02), and physical therapy evaluation (OR 0.20, 95% CI 0.12-0.33, P < .001) decreased the likelihood of discharge before noon. CONCLUSION: Time of discharge is not associated with risk of readmission or presentation to the emergency department after elective lumbar decompression. Weekend discharge is independently associated with increased risk of readmission and decreased likelihood of prenoon discharge.

Neighborhood-level socioeconomic status, extended length of stay, and discharge disposition following elective lumbar spine surgery.

Background: In the context of increased attention afforded to hospital efficiency and improved but safe patient throughput, decreasing unnecessary hospital length of stay (LOS) is imperative. Given that lumbar spine procedures may be among a hospital's most profitable services, identifying patients at risk of increased healthcare resource utilization prior to surgery is a valuable opportunity to develop targeted pre- and peri-operative intervention and quality improvement initiatives. The purpose of the present investigation was to examine patient factors that predict prolonged LOS as well as discharge disposition following elective, posterior, lumbar spine surgery. Methods: We employed a retrospective cohort analysis on 779 consecutive patients treated with lumbar surgery without fusion. Our primary outcome measures were extended LOS (three or more midnights) and discharge disposition. Patient sociodemographic, procedural, and discharge characteristics were adjusted for in our analysis. Sociodemographic variables included Area of Deprivation Index (ADI), a comprehensive metric of socioeconomic status, utilizing income, education, employment, and housing quality based on patient zip code. Multivariable logistic regression and ordinal logistic regression analyses were performed to assess whether covariates were independently predictive of extended LOS and discharge disposition, respectively. Results: 779 patients were studied, with a median age of 66 years (±15) and a median LOS of 1 midnight (range, 1-10 midnights). Patients in the most disadvantaged ADI quintile (adjusted odds ratio, aOR 2.48 95% CI 1.15-5.47), those who underwent a minimally-invasive or tubular retractor surgery (aOR 3.03 95% CI 1.02-8.56), those who had an intra-operative drain placed (aOR 4.46 95% CI 2.53-7.26), who had a cerebrospinal fluid leak (aOR 3.46 95% CI 1.55-7.58), who were discharged anywhere but home (aOR 17.11 95% CI 9.24-33.00), and those who were evaluated by physical therapy (aOR 7.23 95% CI 2.13-45.30) or OT (aOR 2.20 95% CI 1.13-4.22) had a significantly increased chance of an extended LOS. Preoperative opioid use was not associated with an increased LOS following surgery (aOR 1.12 95% CI 0.56-1.46). Extended LOS was not associated with post-discharge emergency department representation or unplanned readmission within 90 days following discharge (p=0.148). Patients who were older (aOR 1.99 95% CI 1.62-2.48), in higher quintiles on ADI (3rd quintile; aOR 1.90 95% CI 1.12-3.23, 4th quintile; aOR 1.79, 95% CI 1.05-3.05, 5th quintile; aOR 2.16 95% CI 1.26-3.75), who had a CSF leak (aOR 2.18 95% CI 1.22-3.86), or who had a longer procedure duration (aOR 1.38 95% CI 1.17-1.62) were more likely to require additional services or be sent to a subacute facility upon discharge. Conclusions: Patient sociodemographics, along with procedural factors, and discharge disposition were all associated with an increased likelihood of prolonged LOS and resource intensive discharges following elective lumbar spine surgery. Several of these factors could be reliably identified pre-operatively and may be amenable to targeted preoperative intervention. Improving discharge disposition planning in the peri-operative period may allow for more efficient use of hospitalization and inpatient and post-acute resources.

Cranial Irradiation for Childhood Cancers and Adult Risk of Meningioma.

INTRODUCTION: Following cranial irradiation, there is an increased risk of developing secondary neoplasms, especially meningiomas. Despite childhood cancer survivors who have undergone cranial irradiation having an increased risk of acquiring radiation-induced meningioma (RIM), there is no widely used standard guideline for meningioma screening. METHODS: At a single institution, we reviewed three adult survivors of childhood cancer who were treated for RIM between 2010 and 2020. We recorded age at diagnosis for the primary lesion, the radiation dose, age at RIM diagnosis, and tumor characteristics including treatment, pathology, and outcome. Two had had T-cell acute lymphocytic leukemia and one a rhabdomyosarcoma. The age of diagnosis of the RIM ranged from 20 to 40 years, with latencies ranging from 18 to 33 years. All lesions were classified as WHO Grade I meningiomas, and only 1 patient had a subsequent recurrence. A literature search identified articles that address RIM: a total of 684 cases were identified in 36 publications. RESULTS: Mean radiation doses ranged from 1.4 gray to 70 gray. Mean age of diagnosis for secondary meningioma ranged from 8 to 53.4 years old, with latency periods ranging from 2.8 to 44 years. Given variability in the way that investigators have published their results, it is difficult to make a single recommendation for RIM screening. Using our experience and the literature, we devised two different screening protocols and calculated their expense. CONCLUSIONS: We recommend that data be standardized in a registry to provide greater insight into the clinical and resource allocation questions, especially as long-term survival of children with pediatric cancer into full adulthood becomes more commonplace worldwide.

Continued underrepresentation of historically excluded groups in the neurosurgery pipeline: an analysis of racial and ethnic trends across stages of medical training from 2012 to 2020.

OBJECTIVE: US allopathic medical schools have experienced improvements in racial and ethnic diversity among matriculants in the past decade. It is not clear, however, whether better representation of historically excluded racial and ethnic groups at medical school entry impacts subsequent stages of the medical training pipeline leading into a specific field. The aim of this study was to examine these trends as they relate to the neurosurgical medical education pipeline and consider the drivers that sustain barriers for underrepresented groups. METHODS: Race and ethnicity reports from the American Association of Medical Colleges were obtained on allopathic medical school applicants, acceptees, and graduates and applicants to US neurosurgical residency programs from 2012 to 2020. The representation of groups categorized by self-reported race and ethnicity was compared with their US population counterparts to determine the representation quotient (RQ) for each group. Annual racial composition differences and changes in representation over time at each stage of medical training were evaluated by estimating incidence rate ratios (IRRs) and 95% confidence intervals (CIs) using non-Hispanic Whites as the reference group. RESULTS: On average, Asian and White individuals most frequently applied and were accepted to medical school, had the highest graduation rates, and applied to neurosurgery residency programs more often than other racial groups. The medical school application and acceptance rates for Black individuals increased from 2012 to 2020 relative to Whites by 30% (95% CI 1.23-1.36) and 42% (95% CI 1.31-1.53), respectively. During this same period, however, inequities in neurosurgical residency applications grew across all non-Asian racialized groups relative to Whites. While the incidence of active Black neurosurgery residents increased from 2012 to 2020 (0.6 to 0.7/100,000 Black US inhabitants), the prevalence of White neurosurgery residents grew in the active neurosurgery resident population by 16% more. CONCLUSIONS: The increased racial diversity of medical school students in recent years is not yet reflected in racial representation among neurosurgery applicants. Disproportionately fewer Black relative to White US medical students apply to neurosurgery residency, which contributes to declining racial representation among all active neurosurgery resident physicians. Hispanic individuals are becoming increasingly represented in neurosurgery residency but continue to remain underrepresented relative to the US population. Ongoing efforts to recruit medical students into neurosurgery who more accurately reflect the diversity of the general US population are necessary to ensure equitable patient care.

Predicting access to postoperative treatment after glioblastoma resection: an analysis of neighborhood-level disadvantage using the Area Deprivation Index (ADI).

PURPOSE: Social determinants of health (SDoH)-socioeconomic and environmental factors-impact outcomes. The Area Deprivation Index (ADI), a composite of seventeen SDoH factors, has been correlated with poorer outcomes. We aimed to compare outcomes and treatment access for glioblastoma, a universally fatal malignant brain tumor, in patients more (ADI 34-100%) versus less disadvantaged (ADI 0-33%). METHODS: A 5-year retrospective study of Rhode Island Hospital and Mayo Clinic databases was conducted from 2012 to 2017 for patients ≥ 18 years with glioblastoma. Patient addresses were matched to ADI percentiles and grouped into more (top 66% ADI) and less disadvantaged. Adjusted multivariable regressions were used to compare outcomes between groups. RESULTS: A total of 434 patients met inclusion; 92.9% were insured, 56.2% were more disadvantaged (n = 244), and the more disadvantaged cohort was younger on average (62 years). After adjustment, the more disadvantaged group had decreased odds of receiving gross total resection (adjusted odds ratio (aOR) 0.43, 95% CI [0.27-0.68]; p < 0.001). This cohort also had decreased odds of undergoing chemotherapy (aOR 0.51[0.26-0.98]), radiation (aOR 0.39[0.20-0.77]), chemoradiation (aOR 0.42[0.23-0.77]), tumor-treating fields (aOR 0.39[0.16-0.93]), and clinical trial participation (aOR 0.47[0.25-0.91]). No differences in length of survival or postoperative Karnofsky Performance Status Scale were observed. CONCLUSION: More disadvantaged glioblastoma patients had decreased odds of receiving gross total resection. They also exhibited decreased odds of receiving standard of care like chemoradiation as well as participating in a clinical trial, compared to the less disadvantaged group. More research is needed to identify modifiable SDoH barriers to post-operative treatment in disadvantaged patients with glioblastoma.

Predicting the Impact of Race and Socioeconomic Status on Cranioplasty Materials and Outcomes.

BACKGROUND: Cranioplasty can be performed with either autologous or synthetic materials. No clear consensus has been reached regarding which material is superior and which social factors might influence the choice of treatment modality and the outcomes. We investigated the effects of race and socioeconomic status on the implant choice and outcomes. METHODS: We conducted a cross-sectional study of adult cranioplasty patients from 2002 to 2017 using the National Inpatient Sample. Autologous implant use, admission costs, length of stay (LOS), and home discharge were analyzed by race, income quartile, and insurance type using multivariable regression models. RESULTS: A total of 105,714 admissions met the inclusion criteria. Most of the patients were women (50.3%) and White (73.7%). Black, other race, and Medicaid patients had greater odds of autologous graft usage, and patients in the 76th-100th income quartile had lower usage. Higher income patients (51th-75th and 76th-100th) had had significantly higher hospitalization costs, amounting to a $1547.2 increase, compared with the bottom quartile. The Medicaid patients had a longer LOS (odds ratio, 1.06; P = 0.008) and decreased rates of home discharge (odds ratio, 0.41; P < 0.001). CONCLUSIONS: We found increased autologous cranioplasty usage for non-White and Medicaid patients and increased use of higher cost synthetic implants for high-income patients. Non-White patients and those from higher income quartiles incurred higher admission costs. Medicaid patients had a longer LOS and decreased rates of home discharge.

Influence of Time of Discharge and Length of Stay on 30-Day Outcomes After Elective Anterior Cervical Spine Surgery.

BACKGROUND: Encouraging early time of discharge (TOD) for medical inpatients is commonplace and may potentially improve patient throughput. It is unclear, however, whether early TOD after elective spine surgery achieves this goal without a consequent increase in re-presentations to the hospital. OBJECTIVE: To evaluate whether early TOD results in increased rates of hospital readmission or return to the emergency department after elective anterior cervical spine surgery. METHODS: We analyzed 686 patients who underwent elective uncomplicated anterior cervical spine surgery at a single institution. Logistic regression was used to evaluate the relationship between sociodemographic, procedural, and discharge characteristics, and the outcomes of readmission or return to the emergency department and TOD. RESULTS: In multiple logistic regression, TOD was not associated with increased risk of readmission or return to the emergency department within 30 days of surgery. Weekend discharge (odds ratio [OR] 0.33, 95% CI 0.21-0.53), physical therapy evaluation (OR 0.44, 95% CI 0.28-0.71), and occupational therapy evaluation (OR 0.32, 95% CI 0.17-0.63) were all significantly associated with decreased odds of discharge before noon. Disadvantaged status, as measured by area of deprivation index, was associated with increased odds of readmission or re-presentation (OR 1.86, 95% CI 0.95-3.66), although this result did not achieve statistical significance. CONCLUSION: There does not appear to be an association between readmission or return to the emergency department and early TOD after elective spine surgery. Overuse of inpatient physical and occupational therapy consultations may contribute to decreased patient throughput in surgical admissions.

Neighborhood-Level Socioeconomic Status Predicts Extended Length of Stay After Elective Anterior Cervical Spine Surgery.

BACKGROUND: A significant portion of health care spending is driven by a small percentage of the overall population. Understanding risk factors predisposing patients to disproportionate use of health care resources is critical. Our objective was to identify risk factors leading to a prolonged length of stay (LOS) after cervical spine surgery. METHODS: A single-center cohort analysis was performed on patients who underwent elective anterior spine surgery from 2015 to 2021. Multivariate logistic regression evaluated the effects of sociodemographic factors including Area of Deprivation Index (quantifies income, education, employment, and housing quality), procedural, and discharge characteristics on postoperative LOS. Extended LOS was defined as greater than the 90th percentile in midnights for the study population (≥3 midnights). RESULTS: A total of 686 patients were included in the study, with a mean age of 57 years (range, 26-92 years), median of 1 level (1-4) fused, and median LOS of 1 midnight (interquartile range, 1-2). After adjusting for confounders, patients had increased odds of extended LOS if they were highly disadvantaged on the Area of Deprivation Index (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.04-4.82; P = 0.039); had surgery on Thursday or Friday (OR, 1.94; 95% CI, 1.01-3.72; P = 0.046); had a corpectomy performed (OR, 2.81; 95% CI, 1.26-6.28; P = 0.012); or discharged not to home (OR, 8.24; 95% CI, 2.88-23.56; P < 0.001). Patients with extended LOS were more likely to present to the emergency department or be readmitted within 30 days after discharge (P = 0.024). CONCLUSIONS: After adjusting for potential cofounders, patients most disadvantaged on Area of Deprivation Index were more likely to have an extended LOS.

The National Inpatient Sample: A Primer for Neurosurgical Big Data Research and Systematic Review.

OBJECTIVE: The National Inpatient Sample (NIS) (the largest all-payer inpatient database in the United States) is an important instrument for big data analysis of neurosurgical inquiries. However, earlier research has determined that many NIS studies are limited by common methodological pitfalls. In this study, we provide the first primer of NIS methodological procedures in the setting of neurosurgical research and review all reported neurosurgical studies using the NIS. METHODS: We designed a protocol for neurosurgical big data research using the NIS, based on our subject matter expertise, NIS documentation, and input and verification from the Healthcare Cost and Utilization Project. We subsequently used a comprehensive search strategy to identify all neurosurgical studies using the NIS in the PubMed and MEDLINE, Embase, and Web of Science databases from inception to August 2021. Studies underwent qualitative categorization (years of NIS studied, neurosurgical subspecialty, age group, and thematic focus of study objective) and analysis of longitudinal trends. RESULTS: We identified a canonical, 4-step protocol for NIS analysis: study population selection; defining additional clinical variables; identification and coding of outcomes; and statistical analysis. Methodological nuances discussed include identifying neurosurgery-specific admissions, addressing missing data, calculating additional severity and hospital-specific metrics, coding perioperative complications, and applying survey weights to make nationwide estimates. Inherent database limitations and common pitfalls of NIS studies discussed include lack of disease process-specific variables and data after the index admission, inability to calculate certain hospital-specific variables after 2011, performing state-level analyses, conflating hospitalization charges and costs, and not following proper statistical methodology for performing survey-weighted regression. In a systematic review, we identified 647 neurosurgical studies using the NIS. Although almost 60% of studies were reported after 2015, <10% of studies analyzed NIS data after 2015. The average sample size of studies was 507,352 patients (standard deviation = 2,739,900). Most studies analyzed cranial procedures (58.1%) and adults (68.1%). The most prevalent topic areas analyzed were surgical outcome trends (35.7%) and health policy and economics (17.8%), whereas patient disparities (9.4%) and surgeon or hospital volume (6.6%) were the least studied. CONCLUSIONS: We present a standardized methodology to analyze the NIS, systematically review the state of the NIS neurosurgical literature, suggest potential future directions for neurosurgical big data inquiries, and outline recommendations to improve the design of future neurosurgical data instruments.

Outcomes for Adults with Metabolic Syndrome Undergoing Elective Carotid Endarterectomy.

BACKGROUND: Metabolic syndrome (MetS) is a disorder characterized by a constellation of cardiometabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and glucose intolerance that has been associated with adverse perioperative outcomes. We evaluated outcomes for patients with MetS after carotid endarterectomy (CEA) in the largest population to date. METHODS: We performed a matched cohort analysis using clinical data from 2012 to 2018 in the American College of Surgeons National Surgical Quality Improvement Program. We used propensity scores to match patients to attain covariate balance and used logistic regression to assess odds of unfavorable outcomes, including a predefined primary outcome of composite cardiovascular incident. RESULTS: We identified 50,423 eligible adult patients, of whom 14.2% qualified for MetS (n = 7156). Patients with MetS tended to have CEA at an earlier age, more functional dependence, and longer operative durations. After matching, MetS remained associated with the primary outcome of combined cardiovascular incident (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.18-1.72; P < 0.001), stroke (OR, 1.44; 95% CI, 1.12-1.85; P = 0.004), prolonged length of stay (OR, 1.31; 95% CI, 1.18-1.44; P < 0.001), and discharge to facility (OR, 1.32; 95% CI, 1.08-1.61; P = 0.007). We also found that obesity alone is protective against combined cardiovascular incident, whereas hypertension with diabetes and MetS increase odds of a cardiovascular complication. CONCLUSIONS: Metabolic syndrome is associated with adverse outcomes for adult patients undergoing elective CEA.

An Instructive Case of Cerebral Mucormycosis.

BACKGROUND: Mucormycosis can lead to fatal rhinocerebral infection. CASE: A 53-year-old male with diabetes presented with altered mental status. He had been recently discharged from an admission for COVID-19 pneumonia treated with remdesivir and methylprednisolone. Imaging demonstrated a large left frontal mass with midline shift suspicious for a primary brain neoplasm. His neurologic exam rapidly declined and the patient was taken to the operating room for decompressive hemicraniectomy. Post-operatively, the patient remained comatose and failed to improve. Autopsy revealed a cerebral mucormycosis infection. DISCUSSION: Despite concern for a primary brain neoplasm the patient was diagnosed postmortem with a mucormycosis infection. Other features supporting this diagnosis included nasal sinusitis on initial scans, his fulminant clinical decline, rapidly progressive imaging findings, and persistent hyperglycemia throughout his clinical course. CONCLUSION: In an era of high steroid usage to treat COVID-19, mucormycosis infection must be considered in high-risk patients demonstrating disproportionate clinical decline.

Brain tumor craniotomy outcomes for dual-eligible medicare and medicaid patients: a 10-year nationwide analysis.

INTRODUCTION: Dual-eligible (DE) patients, simultaneous Medicare and Medicaid beneficiaries, have been shown to have poorer clinical outcomes while incurring higher resource utilization. However, neurosurgical oncology outcomes for DE patients are poorly characterized. Accordingly, we examined the impact of DE status on perioperative outcomes following glioma, meningioma, or metastasis resection. METHODS: We identified all admissions undergoing a craniotomy for glioma, meningioma, or metastasis resection in the National Inpatient Sample from 2002 to 2011. Assessed outcomes included inpatient mortality, complications, discharge disposition, length of stay (LOS), and hospital costs. Multivariable regression adjusting for 13 patient, severity, and hospital characteristics assessed the association between DE status and outcomes, relative to four reference insurance groups (Medicare-only, Medicaid-only, private insurance, self-pay). RESULTS: Of 195,725 total admissions analyzed, 3.0% were dual-eligible beneficiaries (n = 5933). DEs were younger than Medicare admissions (P < 0.001) but older than Medicaid, private, and self-pay admissions (P < 0.001). Relative to other insurance groups, DEs also exhibited higher severity of illness, risk of mortality, and Charlson Comorbidity Index scores as well as treatment at low-volume hospitals (all P < 0.001). DEs had lower mortality than self-pay admissions (odds ratio [OR] 0.47, P = 0.017). Compared to Medicare, Medicaid, private, and self-pay admissions, DEs had lower rates of discharge disposition (OR 0.53, 0.50, 0.34, and 0.27, respectively, all P < 0.001). DEs also had higher complications (OR 1.23 and 1.20, respectively, both P < 0.05) and LOS (ß = 1.06 and 1.13, respectively, both P < 0.01) than Medicare and private insurance beneficiaries. Differences in discharge disposition remained significant for all three tumor subtypes, but only glioma DE admissions continued to exhibit higher complications and LOS. CONCLUSIONS: DEs undergoing definitive craniotomy for brain tumor had higher rates of unfavorable discharge disposition compared to all other insurance groups and, especially for glioma surgery, had higher inpatient complication rates and LOS. Practice and policy reforms to improve outcomes for this vulnerable clinical population are warranted.

The effect of levetiracetam treatment on survival in patients with glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O6-methylguanine-DNA methyltransferase (MGMT) expression. Adding LEV to the standard of care (SOC) for GBM may improve TMZ efficacy. This study aimed to pool the existing evidence in the literature to quantify LEV's effect on GBM survival and characterize its safety profile to determine whether incorporating LEV into the SOC is warranted. METHOD: A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence. RESULTS: From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I2 = 75%, p < 0.01). Meta-regression determined that LEV treatment effect decreased with greater rates of MGMT methylation (RC = 0.03, p = 0.02) and increased with greater proportions of female patients (RC = - 0.05, p = 0.002). Concurrent LEV with the SOC for GBM did not increase odds of adverse events relative to other AEDs. CONCLUSIONS: Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.

Dimorphic glioblastoma with glial and epithelioid phenotypes: Clonal evolution and immune selection.

Purpose: Epithelioid glioblastoma is an unusual histologic variant of malignant glioma. The present study investigates both the genomic and transcriptomic determinants that may promote the development of this tumor. Methods: Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on an epithelioid glioblastoma, along with a specific bioinformatic pipeline to generate electronic karyotyping and investigate the tumor immune microenvironment. Microdissected sections containing typical glioblastoma features and epithelioid morphology were analyzed separately using the same methodologies. Results: An epithelioid glioblastoma, with immunopositivity for GFAP, Olig-2, and ATRX but negative for IDH-1 and p53, was identified. The tumor cell content from microdissection was estimated to be 85-90% for both histologic tumor components. WES revealed that both glioma and epithelioid sections contained identical point mutations in PTEN, RB1, TERT promoter, and TP53. Electronic karyotype analysis also revealed similar chromosomal copy number alterations, but the epithelioid component showed additional abnormalities that were not found in the glioblastoma component. The tumor immune microenvironments were strikingly different and WTS revealed high levels of transcripts from myeloid cells as well as M1 and M2 macrophages in the glioma section, while transcripts from CD4+ lymphocytes and NK cells predominated in the epithelioid section. Conclusion: Epithelioid glioblastoma may be genomically more unstable and oncogenically more advanced, harboring an increased number of mutations and karyotype abnormalities, compared to typical glioblastomas. The tumor immune microenvironment is also different.