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Study Design: Retrospective cohort study., Objective: To analyze national trends in the management of acute traumatic central cord syndrome., Summary of Background Data: Acute traumatic central cord syndrome (ATCCS) is the most common incomplete spinal cord injury. Initial management involves decompression and stabilization of the cervical spinal cord. On the basis of mixed literature regarding operative timing for ATCCS, we aimed to evaluate trends in early, late, and delayed surgery over the last 5-10 years and compare their respective outcomes., Methods: Data were obtained from the National Inpatient Sample (NIS) using specific ICD-10 codes. Baseline demographics, comorbidities, and outcomes were evaluated. These patients were grouped based on whether central cord syndrome (CCS) operative treatment was early (within 24h of admission), late (between 24 and 48h of admission), or delayed (after 48h of admission)., Results: A total of 21,265 patients underwent operative management for ATCCS; 16.7% received early operative management, 35.6% received late operative management, and 47.6% received delayed operative management. Compared with the total cohort, the delayed operative management group was more likely to contain patients with obesity (7.1% vs. 6.3%, P<0.001), chronic obstructive pulmonary disease (COPD) (12.9% vs. 11.1%, P<0.001), and diabetes mellitus (28.1% vs. 26.1%, P<0.001). Early operative management was more likely in patients with plegia (24.7% vs. 17%, P<0.001) and bowel/bladder dysfunction (14.6% vs. 9.5%, P<0.001) and was independently associated with lower rates of prolonged length of stay (LOS) (OR=0.71) and acute kidney injury (AKI) (OR=0.696)., Conclusions: Our analysis of the trends in operative timing for ATCCS demonstrated an overall increase in the rate of early operative management and a decrease in the rate of delayed operative management. These findings mirror the current evolution of the literature on the topic. Nuances in early versus late outcomes should be used to help decision making related to operative timing in ATCCS., Level of Evidence: Level III., Competing Interests: M.K. discloses honorarium and stock in Globus Medical Inc. The remaining authors declare no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cerebral venous thrombosis (CVT) is a rare condition that presents with significant treatment challenges and has traditionally been managed with anticoagulation. However, for patients who fail anticoagulation or present with severe symptoms, endovascular thrombectomy (EVT) has emerged as a favorable treatment modality. This study examines the outcomes, complications, and comorbidities associated with EVT in patients with CVT., Methods: A query of the 2015-2019 National (Nationwide) Inpatient Sample was performed for patients admitted to hospitals with ICD-10 diagnosis codes for CVT and ICD-10 procedure codes for usage of EVT. Demographic information, baseline comorbidities, complications, and discharge dispositions were compared between patients who underwent EVT and those who were managed medically., Results: A total of 36,005 patients diagnosed with CVT were identified from 2015(Q4) to 2019. Of these patients, 325 (0.9%) received EVT. Patients who underwent EVT were older (<0.001), more likely to be female (p = 0.016), and had higher rates of diabetes mellitus (p = 0.012), hypertension (p < 0.001), and obesity (p < 0.001). These patients also presented with more severe neurological symptoms, including higher National Institutes of Health Stroke Scale scores (p < 0.001), coma (p < 0.001), and cerebral edema (p < 0.001). Patients undergoing EVT had a higher incidence of in-hospital mortality (p = 0.007) and were less likely to be discharged routinely (p < 0.001)., Conclusions: This study found that patients with CVT who underwent EVT were older, more likely to be female, and presented with more severe neurological conditions. After controlling for severity, EVT in patients with CVT was associated with significant risks, including higher rates of complications and inpatient mortality. Although EVT is associated with significant risks, the findings of this study suggest that its outcomes may reflect the severity of the underlying condition rather than the procedure itself. Careful patient selection and individualized management strategies are essential for optimizing outcomes in this high-risk population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Gliomas are the most common primary tumor in the central nervous system (CNS), with low-grade gliomas (LGG) comprising more than 5 percent of all adult primary CNS tumors. While glioblastoma, the most malignant glioma subtype, is known to present with hemorrhage, LGGs rarely present with hemorrhage. This systematic review investigates LGGs that present as hemorrhage and provides an illustrative case presentation in order to evaluate trends and outcomes for this pathology., Methods: A systematic review of the literature was performed to evaluate presentation, treatment, and outcomes for patients with LGG that present as intracranial hemorrhage. Articles included were case series describing surgical approach; literature reviews were excluded. Variables evaluated included presenting symptoms, imaging results, and postoperative outcomes., Results: The initial screen yielded 1373 articles. Fourteen articles, published between 1977 and 2023, met inclusion criteria. Sixteen (16) patients were identified with LGG that presented initially as hemorrhage. The most common tumors were pilocytic astrocytoma (6/16), subependymoma (4/16), and ependymoma (2/16). The most common presenting symptoms were headaches (9/11) and impaired consciousness (9/11). Eleven patients underwent gross total resection of the tumor, while four patients received partial resection. Outcomes included two mortalities and one recurrence after six months; the thirteen remaining patients had no recurrence at final reported follow-up., Conclusion: LGGs presenting with hemorrhage are associated with more severe initial symptoms. Though very uncommon, it is imperative to recognize the possibility of an underlying low-grade neoplasm in the setting of hemorrhage. Such early identification can lead to expeditious surgical intervention which can alleviate symptoms, lead to diagnosis, and ultimately trigger adjuvant treatment that has the potential to prolong survival. Continued research on the underlying pathophysiology of these hemorrhagic low-grade tumors is needed to further stratify risk in these populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background and Objective: Due to the potential debilitating sequelae following pediatric mTBI, the CDC published the Guideline on the Diagnosis and Management of mTBI Among Children in 2018. However, the guideline identified several key gaps in our clinical knowledge to support several clinical recommendations. The objective of this review is to evaluate if subsequent research has addressed these gaps in clinical practice recommendations., Methods: A literature review was conducted in PubMed using keywords from the CDC guidelines for the years of July 2015-January 2021. Articles were screened by title and abstract so only studies with children < 18 years of age and those focusing on mTBI were included., Results: A total of 531 articles were identified after screening. Forty-three percent was prospective; 24% were case reports, literature reviews, comments, or protocols; 19% were retrospective, 7% were cross-sectional, 4% were RCTs, and 4% were systematic reviews/meta-analyses. Forty-nine percent focused on diagnosis, 17% on prognosis, and 34% on treatment. The four most published topics were neuropsychological tools (28%), risk factors for intracranial injury and computed tomography (11%), cognitive/physical rest (11%), and return to school (10%)., Conclusion: Since the release of the 2018 CDC guidelines, the majority of publications addressing pediatric mTBI have been prospective studies evaluating the clinical application of neuropsychological tools in concussion management. While these studies do address several of the clinical gaps noted by the CDC regarding the diagnosis and prognosis of pediatric mTBI, there remains a lack of high-quality studies focused on improving pediatric concussion treatment and outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/objectives: Recent studies reveal an "obesity paradox", suggesting better clinical outcomes after intracranial hemorrhage for obese patients compared to patients with a healthy BMI. While this paradox indicates improved survival rates for obese individuals in stroke cases, it is unknown whether this trend remains true across all forms of intracranial hemorrhage. Therefore, the objective of our study was to investigate the incidence, characteristics, and outcomes of hospitalized obese patients with intracranial hemorrhage., Methods: The National Inpatient Sample (NIS) database was queried for data from 2015 to 2019 to identify adult patients aged 18 years and older with a primary diagnosis of non-traumatic intracranial hemorrhage. Using International Classification of Disease 10th Edition codes, patients were stratified by BMI categories: healthy weight, overweight, class I-II obesity, and class III obesity. The cohorts were examined for demographic characteristics, comorbidities, stroke severity, inpatient complications, interventions, and clinical outcomes, including length of stay (LOS), discharge disposition, and inpatient mortality., Results: Of 41,960 intracranial hemorrhage patients identified, 13,380 (33.0%) also had an obese BMI. Class I-II obese intracranial hemorrhage patients were more likely to be of white race (OR: 1.101, 95% CI: 1.052, 1.152, p < 0.001), less likely to be female (OR: 0.773, 95% CI: 0.740, 0.808, p < 0.001), and more likely to have diabetes mellitus (OR: 1.545, 95% CI: 1.477, 1.616, p < 0.001) and hypertension (OR: 1.828, 95% CI: 1.721, 1.943, p < 0.001) in comparison to healthy-weight patients. In a matched cohort analysis adjusting for demographics and severity, intracranial hemorrhage patients with class I-II obesity had a shorter length of stay (LOS) (OR 0.402, 95% CI: 0.118, 0.705, p < 0.001), reduced inpatient mortality (OR 0.847, 95% CI: 0.798, 0.898, p < 0.001), and more favorable discharge disposition (OR 1.395, 95% CI: 1.321, 1.474, p < 0.001) compared to their healthy-weight counterparts. Furthermore, these patients were less likely to require decompressive hemicraniectomy (OR 0.697, 95% CI: 0.593, 0.820, p < 0.001). Following an analysis of individual ICH subtypes, obese subarachnoid hemorrhage (SAH) patients demonstrated reduced mortality (OR: 0.692, 95% CI: 0.577-0.831, p < 0.001) and LOS (OR: 0.070, 95% CI: 0.466-0.660, p = 0.039), with no differences in discharge disposition. Similarly, intracerebral hemorrhage patients demonstrated reduced mortality (OR: 0.891, 95% CI: 0.827-0.959, p = 0.002) and LOS (OR: 0.480, 95% CI: 0.216-0.743, p < 0.001). Other ICH subtypes showed improved discharge outcomes (OR: 1.504, 95% CI: 1.368-1.654, p < 0.001), along with decreased mortality (OR: 0.805, 95% CI: 0.715-0.907, p < 0.001) and LOS (OR: -10.313, 95% CI: -3.599 to -2.449, p < 0.001)., Conclusions: Intracranial hemorrhage patients with class I-II obesity exhibited more favorable clinical outcomes than those who were of a healthy weight or overweight. Despite its association with risk factors contributing to intracranial hemorrhage, class I-II obesity was associated with improved outcomes, lending support to the existence of the obesity paradox in stroke.

Glioblastoma (GBM) is categorized by the World Health Organization (WHO) as a grade 4 glioma and is a uniformly fatal tumor of the central nervous system. With the discovery of specific gene anomalies, GBM classification has been modified several times to provide better diagnostic and prognostic accuracy. Survival outcomes remain dismal despite the current therapeutic modalities, which include a combination of surgical resection, adjuvant chemotherapy, and radiotherapies, providing brief control of tumor progression. GBM remains aggressive and reoccurs primarily due to the presence of a unique population of untreatable glioblastoma stem cells (GSC). The presence of high mutation rates and a dysregulated transcriptional landscape increase GSC resistance to conventional chemotherapy and radiation therapy, contributing to poor outcomes seen in GBM patients. Accordingly, GSCs have emerged as targets of interest in new GBM treatment paradigms. Consequently, it is important to understand their distinct properties, such as GSC interactions with the hypoxic microenvironment, enhancing their growth. The epigenomic regulators and fundamental molecular components of the signaling pathways represent potential targets for GBM therapies. In this review, we aimed to describe the evolution of GBM classification and highlight the current therapeutic modalities, including gene and immunotherapies, and mammalian target of rapamycin (mTOR) inhibitors to target GBM. Furthermore, we explored the molecular pathway of GSCs and the ongoing investigation of circulating tumor cells (CTC), along with precision therapeutics, which aim to provide novel discoveries and effective treatments for GBM with improved survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Study Design: Systematic review., Objective: To systematically review the use of intraoperative methadone in spine surgery and examine its effects on postoperative opioid use, pain, length of stay, and operative time., Summary of Background Data: Spine surgery patients commonly have a history of chronic pain and opioid use, and as a result, they are at an increased risk of severe postoperative pain. While pure mu opioids remain the standard for acute surgical pain management, they are associated with significant short-term and long-term adverse events. Methadone presents an alternative to pure mu opioids which may improve postoperative management of pain following intraoperative use., Methods: A systematic review of MEDLINE, Embase, and Web of Science databases was conducted to review existing literature detailing operating time, postoperative pain, opioid usage, and hospital length of stay (LOS) following intraoperative methadone administration in spine surgery., Results: Following screening of 994 articles and application of inclusion criteria, 8 articles were included, 4 of which were retrospective. Conventional spine surgery intraoperative analgesic strategies used as comparators for intraoperative methadone included hydromorphone, ketamine, and sufentanil. Considering patient outcomes, included studies observed that patients treated with intraoperative methadone had statistically similar or significantly reduced pain scores, opioid usage, and LOS compared with comparator analgesics. However, one study observed that intraoperative methadone used in a multimodal analgesia regimen strategy with ketamine resulted in a shortened LOS compared with the use of intraoperative methadone alone. Differences in operating time between cases that used intraoperative methadone and cases that used comparator analgesics were not statistically significant among included studies., Conclusion: Methadone may present an alternative option for both intraoperative and postoperative analgesia in spine surgery recovery protocols and may reduce postoperative pain, opioid use, and LOS while maintaining consistent operating time and reduced side effects of pure mu opioids., Level of Evidence: Level II., Competing Interests: M.K. reports stock and honorarium with Globus Medical Inc., and is a consultant for Sanara MedTech. The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There has been growing data about the association between D-dimer levels and thrombectomy outcomes in acute ischemic stroke patients (AIS) with no cumulative evidence. This systematic review and meta-analysis aim to discuss and analyze the findings of the current studies to provide more robust evidence in this regard., Methods: A systematic search was conducted through PubMed, Web of Science, Embase, and Scopus to retrieve all relevant investigations. A meta-analysis was conducted, and the results were presented in odds ratio (ORs) for binary variables and ratio of means (ROM) for continuous variables, each accompanied by its respective 95% confidence intervals (CIs)., Results: After searching and screening, 14 studies were included. The analysis showed that the low D-dimer group had significantly higher rates of favorable functional outcome (OR: 4.40; 95%CI: 2.65-7.30; p  < 0.001, n = 3) and recanalization (OR: 4.13; 95%CI: 1.57-10.84; p  = 0.004, n = 3) than the high one. The association between D-dimer levels and first-pass effect and re-occlusion risk was also demonstrated. Eventually, two studies also demonstrated a significant association between high D-dimer levels and deep venous thrombosis and symptomatic intracranial hemorrhage as post-thrombectomy complications., Conclusion: Current evidence indicates a significant association between D-dimer levels and post-thrombectomy outcomes in AIS patients. However, current data are remarkably heterogeneous, and additional comparative investigations are needed., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications., Methods: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model., Results: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe., Significance: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [SW, CRM & PM reported personal fees (speakers bureau) from LivaNova outside the submitted work. R.M. is the cofounder/owner of Seizure Tracker, LLC, which has received funding from Courtagen, Engage Therapeutics, Greenwich Biosciences, Neurelis, UCB, Xenon Pharmaceuticals, and grants from TuberousSclerosis Alliance. SC is the co-founder/owner of EpilepsyAI, LLC, which has received funding from Neurelis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential Competing Interest.]., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Although ventriculoperitoneal (VP) shunts are a common treatment for hydrocephalus, there are complication risks including infections. Late complications such as ventriculitis from ascending abdominal infections can have severe consequences. However, the incidence of central nervous system (CNS) infections in VP shunt patients with abdominal infections is not well understood. We aimed to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections., Methods: Using the National Inpatient Sample, we studied patients from 2016 to 2019 to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. Results were compared with VP shunt patients admitted for primary pneumonia., Results: Among 725 VP shunt patients presenting with abdominal infections, 20 (2.8%) had CNS infections. Chronic obstructive pulmonary disease, hypertension, older age, and a smoking history were more common in patients with CNS infections and primary abdominal infection (P < .05). Patients who developed CNS infection had a significantly higher likelihood of both blood transfusion and coma but a lower likelihood of seizures. VP shunt patients with CNS infections were more likely to undergo shunt removal (odds ratio [OR] = 23.167, P < .001). 4.1% of VP shunt patients with primary abdominal infections died during admission. In a population of primary abdominal infection and pneumonia patients with VP shunts, a multivariate logistic regression analysis controlling for age, sex, and comorbidities identified abdominal infection as an independent risk factor for both CNS infection (OR = 51.208, P < .001) and inpatient death (OR = 3.417, P < .001). Among 6620 VP shunt patients admitted with primary pneumonia, only 5 (0.1%) had CNS infection compared with 20 (2.8%) in those with a primary abdominal infection (OR = 37.532, P < .001), and mortality was 1.6% vs 4.1% for those with a primary abdominal infection (P < .05)., Conclusion: CNS infections in VP-shunted patients with abdominal infections are relatively rare but may lead to increased risks of death and other serious adverse outcomes., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Purpose: Cerebral venous thrombosis (CVT) is associated with a high degree of morbidity and mortality. Our objective is to elucidate characteristics, treatments, and outcomes of patients with cancer and CVT (CA-CVT)., Methods: The 2016-2019 National Inpatient Sample (NIS) database was queried for patients with a primary diagnosis of CVT. Patients with a currently active diagnosis of malignancy (CA-CVT) were then identified. Demographics and comorbidities were compared between CA-CVT and CVT patients. Subgroup analyses explored patients with hematopoietic cancer and non-hematopoietic cancers. Stroke severity and treatment were explored. Inpatient outcomes studied were discharge disposition, length of stay, and mortality., Results: Between 2016 and 2019, 6,140 patients had a primary diagnosis code of CVT, and 370 (6.0%) patients had a coexisting malignancy. The most common malignancy was hematopoietic (n=195, 52.7%), followed by central nervous system (n=40, 10.8%), respiratory (n=40, 10.8%), and breast (n=40, 10.8%). These patients tended to be older than non-CA-CVT and were more likely to have coexisting comorbidities. CA-CVT patients had higher severity scores on the International Study of Cerebral Vein and Dural Sinus Thrombosis Risk Score (ISCVT-RS) and increased complications. In a propensity-score matched cohort, there were no differences in inpatient outcomes., Conclusion: Malignancy occurs in 6% of patients presenting with CVT and should be considered a potential comorbidity in instances where clear causes of hypercoagulabilty have not been identified. Malignancy was linked to higher mortality rates. Nonetheless, after adjusting for the severity of CVT, the outcomes for inpatients with cancer-associated CVT were comparable to those without cancer, indicating that the increased mortality associated with malignancy is probably due to more severe CVT conditions.

Objectives: Subarachnoid hemorrhage (SAH) from spontaneous aneurysm rupture is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in SAH patients., Materials and Methods: International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28., Results: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89 %) had a comorbid diagnosis of AKI. SAH patients with AKI were older (p < 0.01) and more often obese (p < 0.01) compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p < 0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities., Conclusions: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to improve their chances of recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

As the incidence of subdural hematoma is increasing, it is important to understand symptomatology and clinical variables associated with treatment outcomes and mortality in this population; patients with subdural hematoma were selected from the National Inpatient Sample (NIS) Database between 2016 and 2020 using International Classification of Disease 10th Edition (ICD10) codes. Moderate-to-severe subdural hematoma patients were identified using the Glasgow Coma Scale (GCS). Multivariate regression was first used to identify predictors of in-hospital mortality and then beta coefficients were used to create a weighted mortality score. Of 29,915 patients admitted with moderate-to-severe subdural hematomas, 12,135 (40.6%) died within the same hospital admission. In a multivariate model of relevant demographic and clinical covariates, age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were independent predictors of mortality ( p < 0.001 for all). Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were assigned a "1" in a weighted mortality score. The ROC curve for our model showed an area under the curve of 0.64. Age greater than 70, diabetes mellitus, mechanical ventilation, hydrocephalus, and herniation were predictive of mortality. We created the first clinically relevant weighted mortality score that can be used to stratify risk, guide prognosis, and inform family discussions.

Background: Traumatic spinal injury (TSI) can lead to severe morbidity and significant health care resource utilization. Intraoperative navigation (ION) systems have been shown to improve outcomes in some populations. However, controversy about the benefit of ION remains. To our knowledge, there is no large database analysis studying the outcomes of ION on TSI patients. Here we hope to compare complications and outcomes in patients with TSI undergoing spinal fusion of 3 or more levels with or without the use of ION., Methods: The 2015-2019 National Surgical Quality Improvement Program (NSQIP) database was queried for cases of posterior spinal instrumentation of 3 or more levels. This population was then selected for postoperative diagnosis consistent with TSI. The effect of prolonged operative time was analyzed for all patients. Propensity score matching analysis was performed to create ION case and non-ION control groups. Baseline demographic characteristics, complications, and outcome data were collected and compared between ION and non-ION groups., Results: A total of 1,034 patients were included in the propensity matched analysis. Among comorbidities, only obesity was significantly more likely in the non-ION group. There was no difference in case complexity between the two groups. ION was associated with higher incidence of prolonged operative time but was a negative independent predictor for sepsis. Prolonged operative time was a significant independent predictor for pulmonary embolism and requirement of transfusion in all patients. Discharge to home, readmission, and reoperation rates did not differ between TSI patients with or without ION., Conclusions: Use of ION during posterior spinal fusion of 3 or more levels in TSI patients is not associated with worse outcomes. Prolonged operative time, rather than ION, appears to have a higher influence on the rate of complications in this population. Evaluation of ION in the context of specific populations and pathology is warranted to optimize its use.

Study Design: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks., Objective: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs., Summary of Background Data: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate., Methods: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used., Results: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies ( P =0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies., Conclusions: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted., Level of Evidence: Level 3., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intracranial abscess (IA) causes significant morbidity and mortality. The impact of baseline frailty status on post-operative outcomes of IA patients remains largely unknown. The present study evaluated if frailty status can be used to prognosticate outcomes in IA patients., Methods: We retrospectively reviewed all IA patients undergoing craniotomy at our institution from 2011 to 2018 (N.=18). These IA patients were age and gender matched with patients undergoing craniotomy for intracranial tumor (IT), an internal control for comparison. Demographic and clinical data were collected to measure frailty, using the modified frailty index-11 (mFI-11) and pre-operative American Society of Anesthesiologists Physical Status Classification System (ASA). Post-operative complications were measured by the Clavien-Dindo Grade (CDG)., Results: No significant difference in mFI-11 or ASA score was observed between the IA and IT groups (P=0.058 and P=0.131, respectively). IA patients had significantly higher CDG as compared with the control IT patients (P<0.001). There was a trend towards increasing LOS in the IA group as compared to the IT group (P=0.053). Increasing mFI and ASA were significant predictors of LOS by multiple linear regression in the IA group (P=0.006 and P=0.001, respectively), but not in the control IT group. Neither mFI-11 nor ASA were found to be predictors for CDG in either group. Within this case-control group of patients, we found an increase for odds of having IA with increasing mFI (OR=1.838, 95% CI: 1.016-3.362, P=0.044)., Conclusions: Frail IA patients tend to have more severe postoperative complications. The mFI-11 seems to predict increased resource utilization in the form of LOS. This study provides the initial retrospective data of another neurosurgical pathology where frailty leads to significantly worse outcomes. We also found that mFI may serve as a potential risk factor for severe disease.

Background: Improved outcomes in surgical patients have been associated with increasing volume of cases. This has led to the development of centers that facilitate care for a specific patient population. This study aimed to evaluate associations of outcomes with hospital characteristics in patients undergoing resection of malignant brain tumors., Methods: The 2016-2020 National Inpatient Sample was queried for patients undergoing resection of malignant brain tumors. Teaching hospitals with caseloads >2 standard deviations above the mean (140 cases) were categorized as high-volume centers (HVCs). Value of care was evaluated by adding one point for each of the following: short length of stay, low total charges, favorable discharge disposition, and lack of major comorbidity or complication., Results: In 3009 hospitals, 118,390 patients underwent resection of malignant brain tumors. HVC criteria were met by 91 (3%) hospitals. HVCs were more likely to treat patients of younger age or higher socioeconomic status (P < 0.01 for all). The Mid-Atlantic and South Atlantic regions had the highest percentage of cases and number of HVCs. Value of care was higher at HVCs (P < 0.01). Care at HVCs was associated with decreased complications (P < 0.01 for all) and improved patient outcomes (P < 0.01 for all)., Conclusions: Patients undergoing craniotomy for malignant brain neoplasms have superior outcomes in HVCs. Trends of centralization may reflect the benefits of multidisciplinary treatment, geographic preferences, publicity, and cultural impact. Improvement of access to care is an important consideration as this trend continues., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: Retrospective case series and systemic literature meta-analysis., Background: Thoracolumbar junction region stenosis produces spinal cord compression just above the conus and may manifest with symptoms that are not typical of either thoracic myelopathy or neurogenic claudication from lumbar stenosis., Objective: As few studies describe its specific pattern of presenting symptoms and neurological deficits, this investigation was designed to improve understanding of this pathology., Methods: A retrospective review assessed surgically treated cases of T10-L1 degenerative stenosis. Clinical outcomes were evaluated with the thoracic Japanese Orthopedic Association score. In addition, a systematic review and meta-analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)., Results: Of 1069 patients undergoing laminectomy at 1477 levels, 31 patients (16M/15F) were treated at T10-L1 a mean age 64.4 (SD=11.8). Patients complained of lower extremity numbness in 29/31 (94%), urinary dysfunction 11/31 (35%), and back pain 11/31 (35%). All complained about gait difficulty and objective motor deficits were detected in 24 of 31 (77%). Weakness was most often seen in foot dorsiflexion 22/31 (71%). Deep tendon reflexes were increased in 10 (32%), decreased in 11 (35%), and normal 10 (32%); the Babinski sign was present 8/31 (26%). Mean thoracic Japanese Orthopedic Association scores improved from 6.4 (SD=1.8) to 8.4 (SD=1.8) ( P <0.00001). Gait subjectively improved in 27/31 (87%) numbness improved in 26/30 (87%); but urinary function improved in only 4/11 (45%)., Conclusions: Thoracolumbar junction stenosis produces distinctive neurological findings characterized by lower extremity numbness, weakness particularly in foot dorsiflexion, urinary dysfunction, and inconsistent reflex changes, a neurological pattern stemming from epiconus level compression and the myelomeres for the L5 roots. Surgery results in significant clinical improvement, with numbness and gait improving more than urinary dysfunction. Many patients with thoracolumbar junction stenosis are initially misdiagnosed as being symptomatic from lumbar stenosis, thus delaying definitive surgery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions via its discrete binding partners to form two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin-sensitive mTORC1, which regulates protein synthesis and cell growth, is tightly controlled by PI3K/Akt and is nutrient-/growth factor-sensitive. In the brain, mTORC1 is also sensitive to neurotransmitter signaling. mTORC2, which is modulated by growth factor signaling, is associated with ribosomes and is insensitive to rapamycin. mTOR regulates stem cell and cancer stem cell characteristics. Aberrant Akt/mTOR activation is involved in multistep tumorigenesis in a variety of cancers, thereby suggesting that the inhibition of mTOR may have therapeutic potential. Rapamycin and its analogues, known as rapalogues, suppress mTOR activity through an allosteric mechanism that only suppresses mTORC1, albeit incompletely. ATP-catalytic binding site inhibitors are designed to inhibit both complexes. This review describes the regulation of mTOR and the targeting of its complexes in the treatment of cancers, such as glioblastoma, and their stem cells.

Background: Pediatric non-accidental trauma often necessitates the involvement of protective services. However, the subjectivity and lack of standardization of referral infrastructure may result in some discrepancies between referral patterns and instances of child abuse., Methods: An institutional retrospective chart review was conducted between 2015 and 2021, in which all cases of patients under the age of 14 who suffered a burn injury and received a child protective service (CPS) consult were reviewed. Baseline demographics and characteristics were defined. Multivariate analysis was utilized to identify predictors of CPS involvement, while the regression analysis was employed to parse associations between burn injuries and CPS involvement., Results: Between July 2015 and December 2021, 340 patients (median age two years, IQR: 1-6 years) under the age of 14 who experienced a burn injury were evaluated. Forty-four (12.9%) of the patients' cases received a CPS referral, of which three (0.9%) resulted in a CPS intervention. The most common mechanism of burn within the cohort was scald (241 patients, 70.9%). The median total body surface area (TBSA) was 3.0% (IQR: 1.0%-6.0%), and 76 (22.4%) suffered a high TBSA (>75 th percentile). Caucasian race (p < 0.001) and scald mechanisms (p = 0.014) were associated with higher TBSA. When considering how such injuries translated to CPS referrals, increasing age was found to be associated with a decreased likelihood of CPS involvement. Meanwhile, the Black race (p = 0.027) and increasing area deprivation index (ADI) (p = 0.038) were associated with CPS involvement. Those with CPS involvement experienced a greater length of hospital stay (p = 0.001). Black race and intensive care unit level of care were found to be positive predictors of CPS involvement. In total, three (6.82%) of the 44 cases with CPS involvement were found to be substantiated. The three children who required CPS intervention were discharged to foster care settings., Conclusion: Hospitalized pediatric burn injuries must be investigated due to concern of child abuse, yet external factors such as race and socioeconomic status may play a role in the involvement of CPS. Such referrals may not always be substantiated and could lead to further injurious sequelae for children and their families., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Vazquez et al.)

Background/aim: Brain metastasis (BM) is a complex multi-step process involving various immune checkpoint proteins. Mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3) are implicated in tumorigenesis and are critical upstream regulators of Programmed Death Ligand 1 (PD-L1), an immunotherapy target. Tumor suppressor p53, dysregulated in cancers, regulates STAT3 and ERK1/2 signaling. This study examined the roles of STAT3, MAPK and p53 status in BM initiation and maintenance., Materials and Methods: Twenty-six BM, with various primary malignancies, were used (IRB-approved) to determine mutant p53 (p53 mt ), pSTAT3 Tyr705 , pERK1/2 Thr202/Tyr204 , and PD-L1 expression using immunohistochemistry. cDNA microarray was used for gene expression analysis. Brain-metastatic breast cancer cells (MDA-MB-231) were treated with STAT3 (NSC74859) or MAPK/ERK1/2 (U0126) inhibitors in regular or astrocytic media. ERK1/2 pathway was assessed using western blotting, and cell proliferation and migration were determined using MTT and scratch-wound assays, respectively., Results: pSTAT3 Tyr705 and pERK1/2 Thr202/Tyr204 were expressed at tumor margins, whereas p53 mt and PD-L1 were uniformly expressed, with significant overlap between expression of these proteins. Gene expression analysis identified alterations in 18 p53- and 32 STAT3- or MAPK-associated genes contributing to dysregulated immune responses and cell cycle regulation. U0126 and NSC74859 reduced pERK1/2 Thr202/Tyr204 expression. Cell proliferation decreased following each treatment (p≤0.01). Migration stagnated following U0126 treatment in astrocytic media (p≤0.01)., Conclusion: Activation of STAT3 and ERK1/2 promotes BM and provides compelling evidence for use of STAT3, ERK1/2 and p53 status as potential immunotherapeutic targets in BM., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT., Methods: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay., Results: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002)., Conclusion: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interests to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Dexamethasone, a long-acting potent glucocorticoid, is one of the most widely used medications in neurosurgery. In this paper, the authors recount the history of dexamethasone's rise in neurosurgery and discuss its use in brain tumors in the context of emerging neuro-oncological immunotherapies. In 1958, Glen E. Arth synthesized a 16-alpha-methylated analog of cortisone (dexamethasone) for treatment of rheumatoid arthritis. Joseph Galicich, a neurosurgery resident at the time, applied the rheumatological drug to neurosurgery. He gave doses to patients who had undergone craniotomy for tumor removal and saw their paresis improve, midline shift resolve, and mortality rates decrease. He advocated for clinical trials and the drug became a mainstay in neurosurgery. As neuro-oncological treatments evolve to include immunotherapy, the immunosuppressive effects of dexamethasone are becoming an unwanted effect. The question then becomes: how does one treat the patient's symptoms if the only drug that has been used throughout history may become a detriment to their oncological treatment? Since its discovery, dexamethasone has maintained an impressive staying power in the field, acting as a standard drug for cerebral edema for more than 60 years. However, with the advent of immunotherapy, research is warranted to evaluate ways of treating symptomatic edema in the context of modern neuro-oncological therapies.

Background: Burn injuries play a significant role in pediatric injury-related mortality and morbidity. In this study, we aim to explore the relationship between patient demographics, socioeconomic factos and burn severity in pediatric patients., Methods: Patients under age 14 hospitalized at Westchester Medical Center for burn injury between 2015 and 2021 were reviewed. Demographic variables including mechanism of burn, total body surface area (TBSA) involvement, surgical intervention, hospital length of stay (LOS), and LOS per TBSA burn were extracted. The Area Deprivation Index (ADI) was calculated to further assess socioeconomic factors., Results: We included 399 patients under the age of 14 hospitalized for burn injuries at our institution between 2015 and 2021. The median age was 2 (IQR 1-6) years old, and 42.6% were female. High ADI (p = 0.018), Caucasian race (p = 0.001), and flame mechanism (p < 0.001) were independently associated with burn TBSA> 5%. LOS per TBSA was shorter in the Caucasian population (p = 0.022)., Conclusion: In burn injury patients, further research is necessary to investigate modifiable risk factors in individuals of Caucasian race or lower socioeconomic status to target effective prevention campaigns., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd and ISBI. All rights reserved.)

Background: The systemic inflammatory response syndrome (SIRS) is a clinical reaction that can occur due to a variety of stimuli. Reamed intramedullary femoral nailing is a common orthopedic surgery that has been shown to induce SIRS. To date, no nationwide analyses have been performed to evaluate the incidence, risk factors, and economic burdens of SIRS following intramedullary femoral nailing for femoral shaft fractures. The objective of this study is to investigate the independent predictors, incidence, post-operative, and economic burden of SIRS among patients treated with intramedullary nailing for femoral shaft fractures., Methods: We utilized the 2016-2019 National Inpatient Sample (NIS) to identify patients who underwent intramedullary femoral nailing and were diagnosed with non-infectious SIRS (NI-SIRS) based on ICD-10-CM coding. Identified patients who underwent intramedullary femoral nailing were dichotomized into SIRS and Non-SIRS groups to assess independent predictors of SIRS development, and to compare post-operative complications and costs., Results: A total of 65,240 patients with femur shaft fractures underwent IMFN, of which 665 (1.0 %) developed NI-SIRS. Patients with NI-SIRS had a higher incidence of laparotomy (OR = 13.97, p < 0.001), initial treatment with external fixation (OR = 1.845, p < 0.001), and late application of external fixation (OR = 4.884, p = 0.005). Routine discharge (OR = 0.491, p < 0.001) was less likely in patients with NI-SIRS. Length of stay (12.38 days vs 7.16 days, p < 0.001) and total charges ($278, 590 vs $145,118, p < 0.001) were both increased in patients with NI-SIRS., Conclusion: NI-SIRS is associated with increasing injury severity and post-operative complications. Those that developed NI-SIRS experienced higher healthcare resource utilization. Risk factors associated with development of NI-SIRS warrant further investigation., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Acute neurological manifestations in patients with Behcet's syndrome are rare yet may lead to devastating outcomes. Distinguishing primary neurological deficits from spontaneous hemorrhagic insults is of particular importance for the prognosis of patients with Behcet's syndrome. Here, we investigate the clinical characteristics, management, and outcomes of nontraumatic hemorrhagic injury in patients with Bechet's syndrome. Following the case presentation, a systematic review of the literature identified cases of spontaneous hemorrhage among patients with Behcet's syndrome. Variables of interest were collected from each article to characterize patient demographics, clinical manifestations, management, and reported outcomes. Additionally, a rare case of nontraumatic intramedullary spinal bleeding in a young male with Behcet's syndrome is presented. Including our case, we analyzed 12 cases of spontaneous bleeding associated with Behcet's syndrome in 12 articles. Patient age ranged from 16 to 71 (median = 36), with a male predominance (n = 11, 91.7%). Involvement of cardiothoracic structures (n = 3, 25%), pulmonary (n = 4, 33.3%), and gastrointestinal or genitourinary vasculature (n = 3, 25%) was most common, followed by extracranial (n = 2, 16.7%) and central nervous system vasculature (n = 1, 8.3%). Clinical presentation varied depending on which specific systems or anatomical structures were involved. Anticoagulation or antiplatelet therapy was mentioned in three cases (27.3%). Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) were noted to be elevated in six cases (54.5%). Most cases were managed surgically (n = 8, 66.7%); four cases were managed conservatively (33.3%). In our case, the patient's intramedullary bleed was allowed to dissolve without further manipulation. Of the reported outcomes, major recovery was achieved in 10 patients (83.3%), and two patients died from aneurysm or pseudoaneurysm rupture (16.7%). New-onset neurological findings in patients with Behcet's syndrome should raise suspicion for possible spontaneous hemorrhage. Our case presents the first reported instance of an abrupt onset of neurological injury secondary to intramedullary spinal cord bleed in Behcet's syndrome. A systematic review of the literature demonstrates no difference in mortality for patients managed conservatively compared to those who undergo surgical treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Das et al.)

Background: Intracerebral hemorrhage (ICH) carries significant morbidity and mortality. Previous single-center retrospective analysis suggests that end-stage renal disease (ESRD) is a risk factor for severe ICH and worse outcomes. This investigation aims to examine the impact of ESRD on ICH severity, complications, and outcomes using a multicenter national database., Methods: The International Classification of Disease, Ninth and Tenth Revision Clinical Modification codes were used to query the National Inpatient Sample for patients with ICH and ESRD between 2010 and 2019. Primary endpoints were the functional outcome, length of stay (LOS), and in-hospital mortality. Multivariate variable regression models and a propensity-score matched analysis were established to analyze patient outcomes associated with baseline patient characteristics., Results: We identified 211,266 patients with ICH, and among them, 7,864 (3.77%) patients had a concurrent diagnosis of ESRD. Patients with ESRD were younger (60.85 vs. 67.64, P < 0.01) and demonstrated increased ICH severity (0.78 vs. 0.77, P < 0.01). ESRD patients experienced higher rates of sepsis (15.9% vs. 6.15%, P < 0.01), acute myocardial infarction (8.05% vs. 3.65%, P < 0.01), and cardiac arrest (5.94% vs. 2.4%, P < 0.01). In addition, ESRD predicted poor discharge disposition (odds ratio [OR]: 2.385, 95% confidence interval [CI]: 2.227-2.555, P < 0.01), longer hospital LOS (OR: 1.629, 95% CI: 1.553-1.709, P < 0.01), and in-hospital mortality (OR: 2.786, 95% CI: 2.647-2.932, P < 0.01)., Conclusions: This study utilizes a multicenter database to analyze the effect of ESRD on ICH outcomes. ESRD is a significant predictor of poor functional outcomes, in-hospital mortality, and prolonged stay in the ICH population., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Brain Circulation.)

Background: Traumatic spondyloptosis (TS) with complete spinal cord transection and unrepairable durotomy is particularly rare and can lead to a difficult-to-manage cerebrospinal fluid (CSF) leak., Methods: We performed a systematic review of the literature on TS and discuss the management strategies and outcomes of TS with cord transection and significant dural tear. We also report a novel case of a 26-year-old female who presented with thoracic TS with complete spinal cord transection and unrepairable durotomy with high-flow CSF leak., Results: Of 93 articles that resulted in the search query, 13 described cases of TS with complete cord transection. The approach to dural repair was only described in 8 ( n = 20) of the 13 articles. The dura was not repaired in two (20%) of the cases. Ligation of the proximal end of the dural defect was done in 15 (75%) of the cases, all at the same institution. One (5%) case report describes ligation of the distal end; one (5%) case describes the repair of the dura with duraplasty; and another (5%) case describes repair using muscle graft to partially reconstruct the defect., Conclusion: Suture ligation of the thecal sac in the setting of traumatic complete spinal cord transection with significant dural disruption has been described in the international literature and is a safe and successful technique to prevent complications associated with persisting high-flow CSF leakage. To the best of our knowledge, this is the first report of thecal sac ligation of the proximal end of the defect from the United States., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)

Objective: The objective of this paper was to compare the predictive ability of the recalibrated Risk Analysis Index (RAI-rev) with the 5-item modified frailty index-5 (mFI-5) for postoperative outcomes of anterior cervical discectomy and fusion (ACDF)., Methods: This study was performed using data of adult (age > 18 years) ACDF patients obtained from the National Surgical Quality Improvement Program database during the years 2015-2019. Multivariate modeling and receiver operating characteristic (ROC) curve analysis, including area under the curve/C-statistic calculation with the DeLong test, were performed to evaluate the comparative discriminative ability of the RAI-rev and mFI-5 for 5 postoperative outcomes., Results: Both the RAI-rev and mFI-5 were independent predictors of increased postoperative mortality and morbidity in a cohort of 61,441 ACDF patients. In the ROC analysis for 30-day mortality prediction, C-statistics indicated a significantly better performance of the RAI-rev (C-statistic = 0.855, 95% CI 0.852-0.858) compared with the mFI-5 (C-statistic = 0.684, 95% CI 0.680-0.688) (p < 0.001, DeLong test). The results were similar for postoperative ACDF morbidity, Clavien-Dindo grade IV complications, nonhome discharge, and reoperation, demonstrating the superior discriminative ability of the RAI-rev compared with the mFI-5., Conclusions: The RAI-rev demonstrates superior discrimination to the mFI-5 in predicting postoperative ACDF mortality and morbidity. To the authors' knowledge, this is the first study to document frailty as an independent risk factor for postoperative mortality after ACDF. The RAI-rev has conceptual fidelity to the frailty phenotype and may be more useful than the mFI-5 in preoperative ACDF risk stratification. Prospective validation of these findings is necessary, but patients with high RAI-rev scores may benefit from knowing that they might have an increased surgical risk for ACDF morbidity and mortality.

Study Design: Systematic review., Objective: Evaluate characteristics of patients with thoracolumbar injury classification and severity (TLICS) score of 4 (To4) severity traumatic thoracolumbar injury., Summary of Background Data: The TLICS score is used to predict the need for operative versus nonoperative management in adult patients with traumatic thoracolumbar injury. Ambiguity exists in its application and score categorization., Methods: A systematic review of the literature was performed. The databases of MEDLINE, Embase, Web of Science, and Cochrane Review were queried. Studies included adults with traumatic thoracolumbar injury with assigned TLICS score and description of management strategy., Results: A total of 16 studies met inclusion criteria representing 1911 adult patients with traumatic thoracolumbar injury. There were 503 (26.32%) patients with To4, of which 298 (59.24%) were operative. Studies focusing on the thoracolumbar junction and AO Type A fracture morphology had To4 patient incidences of 11.15% and 52.94%, respectively. Multiple studies describe better quality of life, pain scores, and radiographic outcomes in To4 who underwent operative treatment patients., Conclusion: To4 injuries are more commonly AO Type A and located in the thoracolumbar junction in adult patients with traumatic thoracolumbar injury. Despite ambiguous recommendations regarding treatment provided by TLICS, outcomes favor operative intervention in this subset of traumatic thoracolumbar injury patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Spinal cord stimulation (SCS) is an effective treatment modality for chronic pain conditions for which other treatment modalities have failed to provide relief. Ample prospective studies exist supporting its indications for use and overall efficacy. However, less is known about how SCS is used at the population level. Our objective is to understand the demographics, clinical characteristics, and utilization patterns of open and percutaneous SCS procedures., Materials and Methods: The Nationwide Inpatient Sample data base of 2016-2019 was queried for cases of percutaneous or open placement (through laminotomy/laminectomy) of SCS (excluding SCS trials) using International Classification of Disease (ICD), 10th revision, procedure coding system. Baseline demographic characteristics, complications, ICD-Clinical Modification, Diagnosis Related Group, length of stay (LOS), and yearly implementation data were collected. Complications and outcomes were evaluated in total and between the open and percutaneous SCS groups., Results: A total of 2455 inpatients had an SCS placed, of whom 1970 (80.2%) received SCS through open placement. Placement of open SCS was associated with Caucasian race (odds ratio [OR] = 1.671, p < 0.001), private insurance (OR = 1.332, p = 0.02), and age more than 65 years (OR = 1.25, p = 0.034). The most common diagnosis was failed back surgery syndrome (23.8%). Patients with percutaneous SCS were more likely to have a hospital stay of < 1 day (OR = 2.318; 95% CI, 1.586-3.387; p < 0.001). Implant complications during the inpatient stay were positively associated with open SCS placement and reported in 9.4% of these cases (OR = 3.247, p < 0.001)., Conclusions: Patients who underwent open SCS placement were more likely to be older, Caucasian, and privately insured. Open SCS placement showed greater LOS and implant-related complications during their hospital stay. These findings highlight both potential socioeconomic disparities in health care access for chronic pain relief and the importance of increasing age and medical comorbidities as important factors that can influence SCS implants in the inpatient setting., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

(1) Background: Celiac disease (CD) can cause long-term inflammation and endothelial dysfunction and has been cited as a risk factor for acute ischemic stroke (AIS) in pediatric patients. However, the rate and outcomes of AIS in pediatric patients with CD has not been explored in a large population. Our objective is to explore the rate, severity, and outcomes of CD amongst pediatric AIS patients on a nationwide level. (2) Methods: The National Inpatient Sample (NIS) database was queried from 2016 to 2020 for pediatric patients with a principal diagnosis of AIS. Patients with a concurrent diagnosis of CD (AIS-CD) were compared to those without (AIS). Baseline demographics and comorbidities, clinical variables of severity, hospital complications, and the rates of tissue plasminogen activator (tPA) and mechanical thrombectomy were compared between the two groups. The main outcomes studied were mortality, discharge disposition, length of stay (LOS), and total hospital charges. (3) Results: Of 12,755 pediatric patients with a principal diagnosis of AIS, 75 (0.6%) had concurrent CD. There were no differences in the severity, discharge disposition, or mortality between the AIS-CD and AIS patients. Patients with AIS-CD were more likely to receive tPA at an outside hospital within 24 h of admission ( p < 0.01) and more likely to undergo mechanical thrombectomy ( p < 0.01) compared to the AIS patients. (4) Conclusions: CD patients made up only 0.6% of all pediatric AIS patients. No differences in the severity, mortality, or discharge disposition suggests a minimal to absent role of CD in the etiology of stroke. The CD-AIS patients were more likely to receive a tPA or undergo a mechanical thrombectomy; studies are needed to confirm the safety and efficacy of these interventions in pediatric patients.

Frailty is a measure of physiological reserve that has been demonstrated to be a discriminative predictor of worse outcomes across multiple surgical subspecialties. Anterior cervical discectomy and fusion (ACDF) is one of the most common neurosurgical procedures in the United States and has a high incidence of postoperative dysphagia. To determine the association between frailty and dysphagia after ACDF and compare the predictive value of frailty and age. 155,300 patients with cervical stenosis (CS) who received ACDF were selected from the 2016-2019 National Inpatient Sample (NIS) utilizing International Classification of Disease, tenth edition (ICD-10) codes. The 11-point modified frailty index (mFI-11) was used to stratify patients based on frailty: mFI-11 = 0 was robust, mFI-11 = 1 was prefrail, mFI-11 = 2 was frail, and mFI-11 = 3 + was characterized as severely frail. Demographics, complications, and outcomes were compared between frailty groups. A total of 155,300 patients undergoing ACDF for CS were identified, 33,475 (21.6%) of whom were frail. Dysphagia occurred in 11,065 (7.1%) of all patients, and its incidence was significantly higher for frail patients (OR 1.569, p < 0.001). Frailty was a risk factor for postoperative complications (OR 1.681, p < 0.001). Increasing frailty and undergoing multilevel ACDF were significant independent predictors of negative postoperative outcomes, including dysphagia, surgically placed feeding tube (SPFT), prolonged LOS, non-home discharge, inpatient death, and increased total charges (p < 0.001 for all). Increasing mFI-11 score has better prognostic value than patient age in predicting postoperative dysphagia and SPFT after ACDF., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The pleiotropic cytokine IL-9 signals to target cells by binding to a heterodimeric receptor consisting of the unique subunit IL-9R and the common subunit γ-chain shared by multiple cytokines of the γ-chain family. In the current study, we found that the expression of IL-9R was strikingly upregulated in mouse naive follicular B cells genetically deficient in TNFR-associated factor 3 (TRAF3), a critical regulator of B cell survival and function. The highly upregulated IL-9R on Traf3-/- follicular B cells conferred responsiveness to IL-9, including IgM production and STAT3 phosphorylation. Interestingly, IL-9 significantly enhanced class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells, which was not observed in littermate control B cells. We further demonstrated that blocking the JAK-STAT3 signaling pathway abrogated the enhancing effect of IL-9 on class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells. Our study thus revealed, to our knowledge, a novel pathway that TRAF3 suppresses B cell activation and Ig isotype switching by inhibiting IL-9R-JAK-STAT3 signaling. Taken together, our findings provide (to our knowledge) new insights into the TRAF3-IL-9R axis in B cell function and have significant implications for the understanding and treatment of a variety of human diseases involving aberrant B cell activation such as autoimmune disorders., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Background: Disparities in neurosurgical care have emerged as an area of interest when considering the impact of social determinants on access to health care. Decompression via anterior cervical discectomy and fusion (ACDF) for cervical stenosis (CS) may prevent progression towards debilitating complications that may severely compromise one's quality of life. This retrospective database analysis aims to elucidate demographic and socioeconomic trends in ACDF provision and outcomes of CS-related pathologies., Methods: The Healthcare Cost and Utilization Project National Inpatient Sample database was queried between 2016 and 2019 using International Classification of Diseases 10th edition codes for patients undergoing ACDF as a treatment for spinal cord and nerve root compression. Baseline demographics and inpatient stay measures were analyzed., Results: Patients of White race were significantly less likely to present with manifestations of CS such as myelopathy, plegia, and bowel-bladder dysfunction. Meanwhile, Black patients and Hispanic patients were significantly more likely to experience these impairments representative of the more severe stages of the degenerative spine disease process. White race conferred a lesser risk of complications such as tracheostomy, pneumonia, and acute kidney injury in comparison to non-white race. Insurance by Medicaid and Medicare conferred significant risks in terms of more advanced disease prior to intervention and negative inpatient. Patients in the highest quartile of median income consistently fared better than patients in the lowest quartile across almost every aspect ranging from degree of progression at initial presentation to incidence of complications to healthcare resource utilization. All outcomes for patients age > 65 were worse than patients who were younger at the time of the intervention., Conclusions: Significant disparities exist in the trajectory of CS and the risks associated with ACDF amongst various demographic cohorts. The differences between patient populations may be reflective of a larger additive burden for certain populations, especially when considering patients' intersectionality., Competing Interests: None of the authors report any relevant disclosures or conflicts of interest., (© 2023 The Authors.)

Objective: The aim of this study was to assess the safety and efficacy of combined active responsive neurostimulation (RNS) and vagus nerve stimulation (VNS) therapies in pediatric patients with drug-resistant epilepsy., Methods: A single-center retrospective chart review was conducted on pediatric patients implanted with the RNS System with a concomitant active VNS System (VNS+RNS) between 2015 and 2021. Patients with at least 1 month of overlapping concomitant VNS and RNS treatment were included. Patients who had an RNS device implanted after 21 years of age, those who had responsive neurostimulators implanted after their VNS was inactivated, or those in whom the VNS battery died and was not replaced before RNS System implantation were excluded., Results: Seven pediatric VNS+RNS patients were identified, and their courses of treatment were evaluated. All patients tolerated concurrent VNS and RNS treatment well, no device-device interactions were identified, and no major treatment-related adverse effects were noted. The median follow-up after RNS System implantation was 1.2 years. By electroclinical criteria, all 7 patients achieved 75%-99% reductions in the frequency of disabling seizures after RNS System implantation. By patient and caregiver report, 2 patients (28.6%) had 75%-99% reductions in the frequency of their disabling seizures, 2 patients (28.6%) achieved 50%-74% reductions, 2 patients achieved 1%-24% reduction in frequency of disabling seizures, and 1 patient (14.3%) experienced a 1%-24% increase in seizure frequency. The available VNS magnet swipe data identified 2 patients with 75%-99% reductions in seizure frequency as measured by magnet swipes, one with 25%-49% reductions and the other with 1%-24% increases in seizure frequency as measured by magnet swipes., Conclusions: This study demonstrated that RNS and VNS therapies can safely be used simultaneously in pediatric patients. RNS may potentially augment the therapeutic effects of VNS treatment. Patients in whom a response to VNS has been suboptimal should still be considered for RNS therapy.

Objective: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Decompressive hemicraniectomy (DHC) is a treatment option for severe pediatric TBI (pTBI) not amenable to medical management of intracranial pressure. Posttraumatic hydrocephalus (PTH) is a known sequela of DHC that may lead to further injury and decreased capacity for recovery if not identified and treated. The goal of this study was to characterize risk factors for PTH after DHC in patients with pTBI by using the Kids' Inpatient Database (KID)., Methods: The records collected in the KID from 2016 to 2019 were queried for patients with TBI using International Classification of Diseases, 10th Revision codes. Data defining demographics, complications, procedures, and outcomes were extracted. Multivariate regression was used to identify risk factors associated with PTH. The authors also investigated length of stay and hospital charges., Results: Of 68,793 patients with pTBI, 848 (1.2%) patients underwent DHC. Prolonged mechanical ventilation (PMV) was required in 475 (56.0%) patients with pTBI undergoing DHC. Three hundred (35.4%) patients received an external ventricular drain (EVD) prior to DHC. PTH was seen in 105 (12.4%), and 50 (5.9%) received a ventriculoperitoneal shunt. DHC before hospital day 2 was negatively associated with PTH (OR 0.464, 95% CI 0.267-0.804; p = 0.006), whereas PMV (OR 2.204, 95% CI 1.344-3.615; p = 0.002) and EVD placement prior to DHC (OR 6.362, 95% CI 3.667-11.037; p < 0.001) were positively associated with PTH. PMV (OR 7.919, 95% CI 2.793-22.454; p < 0.001), TBI with subdural hematoma (OR 2.606, 95% CI 1.119-6.072; p = 0.026), and EVD placement prior to DHC (OR 4.575, 95% CI 2.253-9.291; p < 0.001) were independent predictors of ventriculoperitoneal shunt insertion. The mean length of stay and total hospital charges were significantly increased in patients with PMV and in those with PTH., Conclusions: PMV, presence of subdural hematoma, and EVD placement prior to DHC are risk factors for PTH in patients with pTBI who underwent DHC. Higher healthcare resource utilization was seen in patients with PTH. Identifying risk factors for PTH may improve early diagnosis and efficient resource utilization.

Background: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described., Objective: To analyze the association between frailty and outcomes in LS., Methods: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10 th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death., Results: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU., Conclusion: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) is a prevalent cause of disability and death in the pediatric population, often requiring prolonged mechanical ventilation. Patients with significant TBI or intracranial hemorrhage require advanced airway management to protect against aspiration, hypoxia, and hypercarbia, eventually necessitating tracheostomy. While tracheostomy is much less common in children compared to adults, its prevalence among pediatric populations has been steadily increasing. Although early tracheostomy has demonstrated improved outcomes in adult patients, optimal tracheostomy timing in the pediatric population with TBI remains to be definitively established., Objective: This retrospective cohort analysis aims to evaluate pediatric TBI patients who undergo tracheostomy and to investigate the impact of tracheostomy timing on outcomes., Design/methods: The Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID), collected between in 2016 and 2019, was queried using International Classification of Disease 10th edition (ICD10) codes for patients with traumatic brain injury who had received a tracheostomy. Baseline demographics, insurance status, and procedural day data were analyzed with univariate and multivariate regression analyses. Propensity score matching was performed to estimate the incidence of medical complications and mortality related to early versus late tracheostomy timing (as defined by median = 9 days)., Results: Of the 68,793 patients (mean age = 14, IQR 4-18) who suffered a TBI, 1,956 (2.8%) received a tracheostomy during their hospital stay. TBI patients who were tracheostomized were older (mean age = 16.5 vs 11.4 years), more likely to have injuries classified as severe TBIs and more likely to have accumulated more than one indicator of parenchymal injury as measured by the Composite Stroke Severity Scale (CSSS >1) than non-tracheostomized TBI patients. TBI patients with a tracheostomy were more likely to encounter serious complications such as sepsis, acute kidney injury (AKI), meningitis, or acute respiratory distress syndrome (ARDS). They were also more likely to necessitate an external ventricular drain (EVD) or decompressive hemicraniectomy (DHC) than TBI patients without a tracheostomy. Tracheostomy was also negatively associated with routine discharge. Procedural timing was assessed in 1,867 patients; older children (age >15 years) were more likely to undergo earlier placements (p < 0.001). Propensity score matching (PSM) comparing early versus late placement was completed by controlling for age, gender, and TBI severity. Those who were subjected to late tracheostomy (>9 days) were more likely to face complications such as AKI or deep vein thrombosis (DVT) as well as a host of respiratory conditions such as pulmonary embolism, aspiration pneumonitis, pneumonia, or ARDS. While the timing did not significantly impact mortality across the PSM cohorts, late tracheostomy was associated with increased length of stay (LOS) and ventilator dependence., Conclusions: Tracheostomy, while necessary for some patients who have sustained a TBI, is itself associated with several risks that should be assessed in context of each individual patient's overall condition. Additionally, the timing of the intervention may significantly impact the trajectory of the patient's recovery. Early intervention may reduce the incidence of serious complications as well as length of stay and dependence on a ventilator and facilitate a timelier recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Environment may play a role in the type, severity, and outcome of pediatric TBI (pTBI). Our objective was to characterize the impact of poor socioeconomic status (PSES) on the incidence, treatment, and outcomes of pTBI patients., Methods: The Kids' Inpatient Database (KID) was queried from 2016 to 2019 for with TBI using International Classification of Disease, 10th revision (ICD 10) codes. Data defining demographics, complications, procedures, and outcomes was extracted. PSES was defined as Medicaid insurance and Q1 median income category., Results: 26,417 patients had pTBI. 11,040 (41.8 %) of pTBI patients were on Medicaid insurance. 13,119 and 8165 (30.9 %) were in Q1 median income category. Land transport caused the majority of pTBI (41 %). Patients on Medicaid or Q1 median income were more likely to experience assault (OR 2.927, CI 95 % 2.455-3.491, p < 0.001 OR 2.033, CI 95 % 1.722-2.4000 p < 0.001 respectively). On propensity matched analysis, PSES was associated with increased mortality (OR 1.667, 95 % CI 1.322-2.100, p < 0.01), length of stay (LOS) (OR 1.369, 95 % CI 1.201-1.559, p < 0.01), and major complicated trauma (OR 1.354 95 % CI 1.090-1.682 p = 0.007). Total hospital charges were higher in pTBI patients on Medicaid ($112,101.52, +/- $203,716.35) versus non-Medicaid ($109,064.37 +/- $212,057.98) (p < 0.001)., Conclusion: PSES is correlated with increased mortality, complications, and longer LOS. Healthcare coverage and clinical training should take these disparities into account to provide improved care and optimize healthcare resource utilization., Level of Evidence: Level IV, Retrospective Database., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To determine the predictive ability of the 5-point modified frailty index relative to age in elective otology patients., Study Design: Retrospective database analysis., Setting: Multicenter, national database of surgical patients., Patients: We selected all elective surgical patients who received tympanoplasty, tympanomastoidectomy, mastoidectomy, revision mastoidectomy, and cochlear implant procedures from 2016 to 2019 from the National Surgical Quality Improvement database., Interventions: Therapeutic., Main Outcome Measures: Readmission rates, discharge disposition, reoperation rates, and extended length of hospital stay., Results: Utilizing receiver operating characteristics with area under the curve (AUC) analysis, nonrobust status was determined to be a superior predictor relative to age of readmission (AUC = 0.628 [p < 0.001] versus AUC = 0.567 [p = 0.047], respectively) and open wound infection relative to age (AUC = 0.636 [p = 0.024] versus AUC = 0.619 [p = 0.048], respectively). Nonrobust otology patients were more likely to have dyspnea at rest and an American Society of Anesthesiology score higher than 2 before surgery (odds ratios, 13.304 [95% confidence interval, 2.947-60.056; p < 0.001] and 7.841 [95% confidence interval, 7.064-8.704; p < 0.001], respectively)., Conclusion: Nonrobust status was found to be a useful predictor of readmission and prolonged length of stay in patients undergoing elective otology procedures, which generally have low complication rate. Given the aging population and corresponding increase in otology disease, it is important to use age-independent risk stratification measures. Frailty may provide a useful risk stratification tool to select surgical candidates within the aging population., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Study Design: Systematic Review., Objective: To elucidate treatment modalities and outcomes of patients with traumatic cervical spondyloptosis (TCS)., Summary: Traumatic cervical spondyloptosis (TCS) is rare and typically leads to devastating neurological injury. Management strategies vary from case to case., Methods: A systematic review of the literature identified cases of adult TCS, and data was analyzed to characterize the patient population and to assess factors that influenced clinical outcome. In addition, an illustrative case is presented in which closed reduction of a severe C7-T1 spondyloptosis injury was guided with the use of cone beam computerized tomography (O-Arm) to overcome difficulties with visualizing the cervicothoracic junction region., Results: In addition to our case, we identified 52 cases of adult TCS from 34 articles. Patient age ranged from 18 to 73 (average 45.6) with male a predominance (n = 37, 71.2%). Neurological function on presentation was most commonly ASIA E (34.6%), followed by ASIA D (21.2%) and ASIA A (19.2%). The most frequently affected levels were C7-T1 (44.2%) followed by C6-7 (33.0%). Closed reduction was attempted in 42 (80.8%) patients. A total of 49 (94.2%) patients underwent surgical treatment, with 31 (63.3%) undergoing single-approach procedures. The presence of neurological injury, cervical level of injury, and age were not significant predictors of successful closed reduction. Similarly, successful closed reduction, age, cervical level of injury, and neurological injury were not predictors of a single-approach treatment., Conclusion: TCS is rare and most frequently appears at or near the cervicothoracic junction and in males. The presentation is typically that of severe neurological injury, but partial neurological recovery occurs in many patients. No predictors of successful closed reduction or single approach surgery are identified. We postulate that the use of intraoperative multiplanar imaging technology like the O-Arm may enhance the ability to achieve a successful closed reduction given the predilection for the injury to occur at the cervicothoracic junction. Prospective study of the durability of constructs by single or combined approaches is warranted., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Spinal meningiomas are benign extra-axial tumors that can present with neurological deficits. Treatment partly depends on the degree of disability as there is no agreed-upon patient selection algorithm at present. We aimed to elucidate general patient selection patterns in patients undergoing surgery for spinal meningioma., Methods: Data for patients with spinal tumors admitted between 2016 and 2019 were extracted from the U.S. Nationwide Inpatient Sample. We identified patients with a primary diagnosis of spinal meningioma (using International Classification of Disease, 10 th revision codes) and divided them into surgical and nonsurgical treatment groups. Patient characteristics were evaluated for intergroup differences., Results: Of 6395 patients with spinal meningioma, 5845 (91.4%) underwent surgery. Advanced age, nonwhite race, obesity, diabetes mellitus, chronic renal failure, and anticoagulant/antiplatelet use were less prevalent in the surgical group (all P < 0.001). The only positive predictor of surgical treatment was elective admission status (odds ratio, 3.166; P < 0.001); negative predictors were low income, Medicaid insurance, anxiety, obesity, and plegia. Patients with bowel-bladder dysfunction, plegia, or radiculopathy were less likely to undergo surgical treatment. The surgery group was less likely to experience certain complications (deep vein thrombosis, P < 0.001; pulmonary embolism, P = 0.002). Increased total hospital charges were associated with nonwhite race, diabetes, depression, obesity, myelopathy, plegia, and surgery., Conclusions: Patients treated surgically had a decreased incidence of complications, comorbidities, and Medicaid payer status. A pattern of increased utilization of health care resources and spending was also observed in the surgery group. The results indicate a potentially underserved population of patients with spinal meningioma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Atlantoaxial rotatory subluxation (AARS) is a rare injury of the C1/C2 junction. It is often associated with trauma in adults. Treatment may depend on the duration of symptoms and clinical presentation, but there is no consensus regarding the ideal management of these injuries. Our objective is to ascertain the prevalence of neurological deficit, complications, and outcomes of patients diagnosed with AARS undergoing cervical fusion (CF) versus those treated without CF., Methods: The 2016-2019 National Inpatient Sample (NIS) was queried using International Classification of Diseases, 10th revision (ICD-10) for adult patients with C1/C2 subluxation. Patients undergoing CF were defined through ICD-10 procedure codes. Baseline health and acute illness severity was calculated using the 11-point modified frailty index (mFI-11). Presenting characteristics, treatment complications, and outcomes were evaluated of CF vs. non-CF patients., Results: Of 990 adult patients with AARS, 720 were treated without CF and 270 were treated with CF. CF patients were more often myelopathic. Patients that had undergone CF treatment were negatively associated with having had extensive trauma. Patients undergoing CF experienced significantly longer length of stay (LOS), increased healthcare resource utilization, and decreased inpatient mortality. Sepsis had a negative association with patients that underwent CF treatment while pneumonia had a positive association., Conclusions: Adult patients undergoing CF for AARS demonstrated an increase in healthcare resource utilization but also a significant decrease in mortality. Extent of acute injury appears to have a strong influence on decision making for CF. Further study of decision making for treatment of this rare injury in adults is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-22-19/coif). The authors have no conflicts of interest to declare., (2022 Journal of Spine Surgery. All rights reserved.)

Background: There are known classifications that describe thoracolumbar (TL) burst type injury but it is unclear which have the most influence on management. Our objective is to investigate the association of classification publications with the quantity and type of the most influential articles on TL burst fractures., Methods: Web of Science was searched, and exclusion and inclusion criteria were used to extract the top 100 cited articles on TL burst fractures. The effects on type, number, and other variables were separated into four eras as defined by four major classification publications., Results: 30 out of the top 100 articles represent level 1 or 2 evidence. The most influential journal was Spine , accounting for 35 articles and 4,537 citations. The highest number of articles (53) was published between the years 1995-2005, culminating with the Thoracolumbar Injury Severity Classification Score (TLICS) paper. After 2005, there was an increase in average citations per year. Following 2013, the number of highly influential articles decreased, and systematic reviews (SRs) became a larger proportion of the literature. There was a statistically significant increase in the level of 1 and 2 evidence articles with time until the publication of TLICS. The predictive value of time for higher levels of evidence was only seen in the pre-2005 years (AUC: 0.717, 95% CI 0.579-0.855, p = 0.002)., Conclusions: In 1994, two articles marked the beginning of an era of highly influential TL burst fracture literature. The 2005 TLICS score was associated with a preceding increase in LOE and productivity. Following 2005, the literature saw a decrease in productivity and an increase in systematic review/meta-analysis (SR-MAs). These trends represent an increase in scholarly discussion that led to a systematic synthesis of the existing literature after publication of the 2005 TLICS article., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s). Published by Elsevier Ltd on behalf of North American Spine Society.)

Background: Responsive neurostimulation (RNS System) has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System thalamic leads is uncertain., Objective: The present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic (ECoG) analyses., Results: Anterior nucleus thalamic (ANT) leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic (CMT) leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures., Conclusion: Thalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation., Competing Interests: SW and PM reports honoraria from LivaNova, Eisai, UCB, Sunovion, Greenwich Pharmaceuticals, and participation as an investigator in clinical trials for Zogenix, GW Pharma, NeuroPace, Neurelis, UCB, Eisai. CM reports speaker fees from LivaNova, and participation as an investigator in clinical trial for NeuroPace. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GW declared a past co-authorship with the author(s) SW and PM., (Copyright © 2022 Beaudreault, Muh, Naftchi, Spirollari, Das, Vazquez, Sukul, Overby, Tobias, McGoldrick and Wolf.)

Introduction: The alar ligament is an important structure in restraining the rotational movement at the atlantoaxial joint. While bony fractures generally heal, rupture of ligaments may heal poorly in adults and often requires surgical stabilization. Atlantoaxial rotatory subluxation (AARS) is a rare injury in adults, and the prognostic importance of the presence of alar ligament injury with regard to the success of nonoperative management is unknown., Case Presentation: A 28-year-old woman presented after a traumatic Type I AARS without evidence of osseous injury, but MRI demonstrated evidence of unilateral alar ligament disruption. Initial conservative management with closed reduction and maintenance in a rigid cervical collar proved unsuccessful, with worsening pain and failure to maintain reduction. She subsequently underwent open reduction and surgical fixation of C1-C2, resulting in resolution of her pain and maintenance of alignment., Discussion: Alar ligament rupture may be a negative prognostic indicator in the success of nonoperative management of type I atlantoaxial rotatory subluxation. Additional study is warranted to better assess whether the status of the alar ligament should be considered an important factor in the management algorithm of type I AARS., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

The clinical success of the two BTK inhibitors, ibrutinib and acalabrutinib, represents a major breakthrough in the treatment of chronic lymphocytic leukemia (CLL) and has also revolutionized the treatment options for other B cell malignancies. Increasing evidence indicates that in addition to their direct effects on B lymphocytes, both BTK inhibitors also directly impact the homeostasis, phenotype and function of many other cell subsets of the immune system, which contribute to their high efficacy as well as adverse effects observed in CLL patients. In this review, we attempt to provide an overview on the overlapping and differential effects of ibrutinib and acalabrutinib on specific receptor signaling pathways in different immune cell subsets other than B cells, including T cells, NK cells, monocytes, macrophages, granulocytes, myeloid-derived suppressor cells, dendritic cells, osteoclasts, mast cells and platelets. The shared and distinct effects of ibrutinib versus acalabrutinib are mediated through BTK-dependent and BTK-independent mechanisms, respectively. Such immunomodulatory effects of the two drugs have fueled myriad explorations of their repurposing opportunities for the treatment of a wide variety of other human diseases involving immune dysregulation., Competing Interests: This study was partially supported by a research grant from Acerta Pharma, LLC., (Copyright © 2021 Zhu, Gokhale, Jung, Spirollari, Tsai, Arceo, Wu, Victor and Xie.)

Kissing spines syndrome, also known as Baastrup's disease, is a common yet underdiagnosed disorder involving close approximation of adjacent spinous processes. These painful pseudoarticulations may be secondary to the compensatory mechanisms that result from sagittal imbalance. Conventional operative correction of sagittal balance includes a wide range of procedures from facetectomies to vertebral column resection. Resection of kissing spines for the operative management of sagittal imbalance is a treatment modality not extensively discussed in the literature but may offer improved patient outcomes with shorter operative times, lower risk, and reduced length of stay. A 67-year old male with a history of degenerative disk disease and scoliosis presented with neurogenic claudication and severe back pain that worsened with walking and improved with sitting. X-ray imaging of the lumbar spine revealed straightening of the normal lumbar lordotic curvature with mild rotoscoliosis. There was also evidence of retrolisthesis of L2 on L3 that worsened with flexion. The patient had Baastrup's disease at the L3-4 and L4, 5 levels that contributed to his reduced range of motion on extension imaging. Operative treatments including long-segment fusion with interbody cages to correct sagittal balance were considered with a discussion of possible debilitating and high-risk post-surgical outcomes. Instead, the patient underwent a simple decompression surgery involving laminectomies and resection of kissing spines to correct his sagittal imbalance. Postoperative follow-up imaging demonstrated significant improvement in sagittal balance, and the patient expressed relief of back and leg pain. Although underdiagnosed, consideration of kissing spines syndrome in the surgical correction of sagittal imbalance may offer an improvement over conventional operations. Our case presents a unique surgical perspective on the treatment of spinal stenosis with kissing spines with particular regard to correcting the sagittal imbalance, avoiding debilitating procedures, and providing better immediate postoperative outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Spirollari et al.)