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Background and Objectives: Tobacco use is known to affect incidence and postoperative outcome for several neurosurgical disorders, but its relationship to trigeminal neuralgia (TN) is not known. We sought to identify unique population characteristics that correlate with tobacco use in a cohort of patients with TN who underwent microvascular decompression (MVD), including effect on long-term postoperative outcome., Methods: Data about 171 patients with classic TN treated with MVD were obtained from a prospectively maintained registry. Patients were classified as smokers or nonsmokers based on the use of tobacco within the 6 months before surgery. Analysis of clinical characteristics and postoperative outcome was performed., Results: Compared with nonsmokers with TN, MVD patients using tobacco were significantly younger (53 vs 62 years, P < .01) and less likely to report pain in a single distribution of the trigeminal nerve (36% vs 65%, P < .01). There was no difference between smokers and nonsmokers in the presence of some degree of continuous pain, severity of neurovascular compression, sex, race, obesity, pain duration before presentation, immediate postoperative outcome, length of stay, or postoperative complication profile. Among 128 patients followed for at least 6 months, smokers were significantly less likely to be pain-free off medications at the last follow-up (36% vs 57%, P < .05)., Conclusion: In patients undergoing MVD for TN, smoking is associated with younger age of TN onset, more widespread facial pain, and worse long-term postoperative outcome after MVD. These features suggest that TN in smokers may represent a more severe disease form compared with TN in nonsmokers with different responses to treatment., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background Cervical facet dislocation is a serious injury that can result in permanent neurologic damage. Current guidelines recommend immediate closed reduction of cervical dislocations, though the efficacy of this practice remains a debate. This study aims to evaluate whether immediate open reduction and fixation of cervical dislocations offer equal or better outcomes for patients and limit the need for follow-up operations. Methods This is a retrospective study including patients who presented to the emergency department of a single institution from 2008 to 2023 with cervical facet dislocation. Patients were divided into groups based on initial treatment: either open or closed reduction. Time to surgery was calculated as the time between arrival to the ED and incision time in the OR. Primary outcomes were improvement in motor and sensory deficits at six-week post-operative follow-up. Results There were 31 patients who met the inclusion criteria. Time to treatment did not differ significantly between the open versus closed reduction groups. There were no differences between groups in improvement in motor function, sensory function, or pain at the six-week follow-up. All patients treated with initial closed reduction ultimately required surgical stabilization. Conclusions Open reduction as a first-line treatment did not increase the time to treatment for patients with cervical facet dislocations. Patients had equivalent functional outcomes in both treatment groups. The findings suggest that current practice guidelines may delay definitive treatment without improving patient safety or outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of University Hospitals Cleveland Medical Center, Cleveland, USA issued approval 20231238. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yaffe et al.)

Background: Bedside procedures represent a substantial proportion of the neurosurgical resident's responsibilities. Although music interventions in healthcare have classically been employed for the benefit of the patient, there is evidence in support of its positive effects on healthcare workers as well., Objectives: We aimed to create a novel framework-the shared music experience (SME)-which allows for patient and provider to discuss and mutually select a musical playlist during bedside procedural interventions., Methods: A single-center prospective pilot study with nested design was carried out during a 6-month period. One sample was neurosurgery residents at our institution, while the other was patients undergoing nonemergent bedside procedures. Primary endpoints included change in neurosurgery residents' and patients' perception of patient-provider alliance. Secondary endpoints include quantitative and qualitative analysis of feedback from residents and patients about the SME framework., Results: Twelve out of 13 (92.3%) eligible neurosurgery residents were enrolled. Twenty-eight SMEs were carried out. Twenty-six of 28 patients (92.9%) replied that they did enjoy the SME. Patients who partook in SMEs had a significant increase in metrics of patient-clinician alliance as measured by the mARM-5. All 7 residents who participated in at least 1 SME reported having enjoyed performing procedures within the framework and affirmed they would either ''often'' (2/7, 28.6%) or ''always'' (5/7, 71.4%) implement SME in future practice., Conclusions: The SME is a novel intervention that can be employed to help patients and providers find common ground through music and foster the patient-clinician relationship during bedside procedures., (Copyright © 2024. Published by Elsevier Inc.)

Background: Patients with thoracic metastatic epidural spinal cord compression (MESCC) often undergo extensive surgical decompression to avoid functional decline. Though limited in scope, scales including the revised cardiac risk index (RCRI) are used to stratify surgical risk to predict perioperative morbidity. This study uses the 5-item modified frailty index (mFI-5) to predict outcomes following transpedicular decompression/fusion for high-grade MESCC., Methods: A retrospective chart review was conducted on patients who underwent transpedicular decompression and fusion for MESCC (baseline demographics, spinal instability neoplastic score, preoperative and postoperative Bilsky scores, primary cancer type, and RCRI). Primary outcomes included length of stay (LOS), intraoperative estimated blood loss, readmission/reoperation within 90 days of index surgery, 90-day mortality, and posthospitalization disposition., Results: One hundred twenty-seven patients were included in our study. Ninety percent of patients' lesions were Bilsky 2 or greater. Increasing frailty, measured by mFI-5, was a significant predictor of increased LOS (P < 0.01) and 90-day mortality (P < 0.05). Multivariate analysis adjusting for sex, body mass index , and age still showed statistical significance (P < 0.05). MFI-5 was not a significant predictor of readmission/reoperation within 90 days or estimated blood loss. Age - not mFI-5 or RCRI - was a significant predictor for posthospitalization nonhome disposition (P = 0.001)., Conclusions: The mFI-5 can serve as a useful predictor of outcomes after transpedicular decompression and fusion for thoracic MESCC as it can account for the patient's frailty. Our study demonstrated the mFI-5 as a predictor of LOS and 90-day mortality. These results provide a background to both understanding and integrating frailty into decision-making in MESCC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years' follow-up., Methods: We searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits., Results: Following propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35-0.85; P = 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6)., Conclusions: This study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture., Registration: Open Science Framework ( https://osf.io/vgrwz )., (© 2024. The Author(s).)

Background: While the indication for Anterior Cervical Discectomy and Fusion (ACDF) may influence the expected postoperative course, there is limited data comparing how length of stay (LOS) and disposition for patients with myelopathy differ from those with radiculopathy. This study aimed to compare LOS and discharge disposition, in patients undergoing ACDF for cervical radiculopathy versus those for myelopathy., Methods: A retrospective review of all adult ACDF cases between 2013 and 2019 was conducted analyzing sex, age, race, comorbidities, level of surgery, myelopathy measures when applicable, complications, dysphagia, hospital LOS, and discharge disposition., Results: A total of 157 patients were included in the study with 73 patients undergoing an ACDF for radiculopathy and 84 for myelopathy. Univariate analysis determined older age (p < 0.01), male sex (p = 0.03), presence of CKD (p < 0.01) or COPD (p = 0.01), surgery at C3/4 level (p = 0.01), and indication (p < 0.01) as predictors for a discharge to either acute rehabilitation or a skilled nursing facility rather than to home. Multivariate logistic regression demonstrated age and indication as the only independent predictors of disposition, with home disposition being more likely with decreased age (OR 0.92, 95 % CI 0.86-0.98) and radiculopathy as the diagnosis (OR 6.72, 95 % CI 1.22- 37.02)., Conclusions: Myelopathic patients, as compared to those with radiculopathy at presentation, had significantly longer LOS, increased dysphagia, and were more often discharged to a facility. Understanding these two distinct populations as separate entities will streamline the pre and post-surgical care as the current DRG codes and ICD 10 PCS do not differentiate the expected post-operative course in patients undergoing ACDF for myelopathy versus radiculopathy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Anemia has been reported in nearly 40% of acute ischemic stroke (AIS) patients and is linked to significant morbidity and disability. The presence of anemia is associated with worse outcomes in AIS, specifically in the presence of large vessel occlusion (LVO). An optimal hemoglobin (Hb) target specific to this pathology has not yet been established. The goal of this review is to systematically review literature that observes the association that exists between AIS outcomes and hemoglobin (Hb) levels., Methods: A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies from 2008-2022. The following inclusion and exclusion criteria were used: studies of adult patients with AIS; must describe outcomes with regard to Hb levels in AIS (not limited to LVO); must be written in English. The clinical variables extracted included Length of Stay (LOS), modified rankin score (mRS), Hb levels, and mortality., Results: A total of 1,154 studies were gathered, with 116 undergoing full text review. 31 studies were included in this review. The age of patients ranged from 61.4 to 77.8. The presence of anemia in AIS increased LOS by 1.7 days on average and these patients also have a 15.2% higher rate of mortality at one year, on average., Discussion: This data suggests that the contemporary thresholds for treating anemia in AIS patients may be inadequate because anemia is strongly associated with poor outcomes (e.g., mRS>2 or mortality) and increased LOS in AIS patients. The current generalized Hb threshold for transfusion (7 g/dL) is also used in AIS patients, however, a more aggressive transfusion parameter should be further explored based on these findings. Further studies are required to confirm these findings and to determine if a more liberal RBCT threshold will result in clinical benefits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Desai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Stereotactic radiosurgery (SRS) has recently emerged as a minimally invasive alternative to resection for treating multiple brain metastases. Given the lack of consensus regarding the application of SRS versus resection for multiple brain metastases, the authors aimed to conduct a systematic literature review of all published work on the topic., Methods: The PubMed, OVID, Cochrane, Web of Science, and Scopus databases were used to identify studies that examined clinical outcomes after resection or SRS was performed in patients with multiple brain metastases. Radiological studies, case series with fewer than 3 patients, pediatric studies, or national database studies were excluded. Data extracted included patient demographics and mean overall survival (OS). Weighted t-tests and ANOVA were performed., Results: A total of 1300 abstracts were screened, 450 articles underwent full-text review, and 129 studies met inclusion criteria, encompassing 20,177 patients (18,852 treated with SRS and 1325 who underwent resection). The OS for the SRS group was 10.2 ± 6 months, and for the resection group it was 6.5 ± 3.8 months. A weighted ANOVA test comparing OS with covariates of age, sex, and publication year revealed that the treatment group (p = 0.045), age (p = 0.034), and publication year (0.0078) were all independently associated with OS (with SRS, younger age, and later publication year being associated with longer survival), whereas sex (p = 0.95) was not., Conclusions: For patients with multiple brain metastases, SRS and resection are effective treatments to prolong OS, with published data suggesting that SRS may have a trend toward lengthened survival outcomes. The authors encourage additional work examining outcomes of treatments for multiple brain metastases.

Introduction: Cauda equina syndrome (CES) is most caused by lumbar disc herniation, and the associated treatment involves prompt surgical decompression. Rarer causes of CES include perineural (Tarlov) cysts., Clinical Presentation: A 62-year-old female with history of rheumatoid arthritis, hip and knee replacements, and chronic low back pain presented with worsening back pain, left leg weakness and pain for 6 weeks, and bowel/bladder incontinence with diminished sensation in the perianal region for 24 h prior to presentation. MRI demonstrated severe spinal stenosis at L4-S1, central disc herniation at L5-S1, and compression of the cauda equina, consistent with CES. A lumbar decompression was performed. Patient did well at 2-week follow up, but presented 5 weeks post-discharge with increased left leg pain/weakness and genitalia anesthesia. Imaging was unremarkable. Two months later, the patient presented with diminished sensation in the buttocks and bilateral lower extremities and bowel/bladder incontinence. Imaging demonstrated a large cystic presacral mass with involvement of the left sciatic foramen and S3 neural foramen. A team of plastic, orthopedic, and neurological surgeons performed an S3 sacral laminectomy, foraminotomy, partial sacrectomy, and S3 rhizotomy, and excision of the large left hemorrhagic pudendal mass. Final pathology demonstrated a perineural cyst with organizing hemorrhage. On follow-up, the patient's pain and weakness improved., Conclusion: CES-like symptoms were initially attributed to a herniated disk. However, lumbar decompression did not resolve symptoms, prompting further radiographic evaluation at two separate presentations. This represents the first reported case of a pudendal tumor causing symptoms initially attributed to a herniated disc., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

Objective: Admission to the hospital for an acute cerebrovascular condition such as stroke or brain hemorrhage can be a traumatic and disorienting experience for patients and their family members. The COVID-19 pandemic has further intensified this experience in addition to exacerbating clinician and resident burnout. To ameliorate some of these concerns, a team of resident and medical student trainees implemented a virtual shared medical appointment (vSMA) program for inpatients with acute cerebrovascular disorders and their caregivers. The authors hypothesized that an early intervention in the form of a vSMA improves patient and caregiver health literacy and preparedness while simultaneously educating clinical trainees on effective communication skills and reducing clinician burnout., Methods: Patients and caregivers of admitted patients were identified through a census of neurosurgery, neurocritical care, and neurology electronic medical records. A weekly 60-minute secure virtual session consisted of introductions and a 10-minute standardized presentation on cerebrovascular disease management, followed by participant-guided discussion. Participants completed presession and postsession surveys. Through this small feasibility study data were obtained regarding present challenges, both expected and unforeseen., Results: A total of 170 patients were screened, and 13 patients and 26 caregivers participated in at least 1 vSMA session. A total of 6 different healthcare providers facilitated sessions. The vSMA program received overwhelmingly positive feedback from caregivers. Survey responses demonstrated that 96.4% of caregivers and 75% of patients were satisfied with the session, 96.4% of caregivers and 87.5% of patients would recommend this type of appointment to a friend or family member, and 88.8% of providers reported feeling validated by conducting the session. The participant group had a 20% greater percentage of patients discharged home without home needs compared to the nonparticipant group. The primary obstacles encountered included technological frustrations with the consent process and the sessions themselves., Conclusions: Implementation of a vSMA program at a tertiary care center during a pandemic was feasible. Themes caregivers expressed on the postsession survey included better understanding of caring for a stroke patient and coping with the unpredictability of a patient's prognosis. The pandemic has precipitated shifts toward telehealth, but this study highlights the importance of avoiding marginalization of elderly and less technologically inclined populations.

Aneurysmal subarachnoid hemorrhage is a disease with high mortality and morbidity due in large part to delayed effects of the hemorrhage, including vasospasm, and delayed cerebral ischemia. These two are now recognized as overlapping yet distinct entities, and supportive therapies for delayed cerebral ischemia are predicated on identifying DCI as quickly as possible. The purpose of this overview is to highlight diagnostic tools that are being used in the identification of DCI in the neurocritical care settings., Competing Interests: The 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., (Copyright © 2022 Labak, Shammassian, Zhou and Alkhachroum.)

Background: Centers of excellence (COEs) are interdisciplinary healthcare organizations created with the goal of improving health/economic outcomes in medical treatment for both individuals and health systems, compared to traditionally structured counterparts. Multiple studies have highlighted both societal/individual burdens associated with back pain, underscoring the importance of identifying new avenues for improving both cost/clinical outcomes for this patient population. Here, we utilize available literature to better characterize the features of a spine COE at a tertiary care center and determine the impact of COEs on patient satisfaction and outcomes., Methods: A systematic review describing spine COEs was performed. PubMed, OVID, Cochrane, Web of Science, and Scopus were utilized for electronic literature search. Data including institution, department, pathologies treated, patient satisfaction scores, patient outcomes, and descriptions of the COE, were extracted and analyzed by two reviewers per full-text article. Inclusion criteria consisted of literature describing the organization, purpose, or outcomes of a spine COE, all publication types (except technical/operative report), adult or pediatric patients, publication from inception through September 2021. Exclusion criteria consisted of articles that do not discuss spinal COEs, technical/operative reports, studies unavailable in English language, unavailable full text, or non-human subjects. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included studies., Results: Five hundred and sixty-seven unique publications were obtained from the literature search. Of these articles, 20 were included and 547 were excluded based on inclusion and exclusion criteria. Following full-text review of the 20 publications, 6 contained pertinent data. Quantitative data comparing COE versus non-COE was contradictory in comparing complication rates and episodic costs. Qualitative data included descriptions of spine COE features and cited improved patient care, technical advancements, and individualized care paths as positive aspects of the COE model. Mean risk of bias assessment was 3.67., Discussion: There is little evidence regarding if spine COEs provide an advantage over traditionally organized facilities. The current number and heterogeneity of publications, and lack of standardized metrics used to define a spinal COE are limiting factors. Spinal COE may offer higher value care, reduced complication rates and advancements in knowledge and technical skill., 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-21-46/coif). GS presently receives consulting fees as a Stryker consultant. The other authors have no conflicts of interest to declare., (2022 Journal of Spine Surgery. All rights reserved.)

Competing Interests: Declaration of competing interest The authors report no conflicts of interest.

Study Design: Retrospective review at a single institution of all adult patients who underwent elective lumbar fusion surgery for degenerative spinal disease from 2013 to 2018. Reoperation rates and change in clinical management due to routine imaging findings were the primary outcomes., Objective: To investigate what effects immediate routine postoperative imaging has on the clinical management of patients following lumbar fusion surgery., Summary of Background Data: The clinical utility of routine postoperative imaging following lumbar fusion surgery remains uncertain. Existing studies on the clinical utility of postoperative imaging in lumbar fusion patients have largely focused on imaging obtained post-discharge. We present a retrospective analysis that to our knowledge is the first study reporting on the clinical utility of routine imaging in lumbar fusion patients during the immediate postoperative period., Methods: The medical records of patients who had undergone elective lumbar instrumented fusion for degenerative disease from 2013 to 2018 by neurosurgeons across one regional healthcare system were retrospectively analyzed. Inpatient records and imaging orders for patients were reviewed. Routine immediate postoperative imaging was defined by any lumbar spine imaging prior to discharge in the absence of specific indications., Results: Analysis identified 115 patients who underwent elective lumbar instrumented fusion for degenerative disease. One-hundred-twelve patients received routine postoperative imaging. Routine imaging was abnormal in four patients (4%). There was one instance (<1%) where routine immediate postoperative imaging led to change in clinical management. Abnormal routine imaging was not associated with either reoperation or development of neurological symptoms postoperatively (P = 0.10), however, new or worsening neurologic deficits did predict reoperation (P < 0.01)., Conclusion: New neurologic deficit was the only significant predictor of reoperation. Routine imaging, whether normal or abnormal, was not found to be associated with reoperation. The practice of routine imaging prior to discharge following elective lumbar fusion surgery appears to provide little utility to clinical management.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cranial surgical site infections (cSSIs) are associated with significant morbidity. Measures to reduce cSSI are necessary to reduce patient morbidity as well as hospital costs and resource utilization., Objective: To identify and characterize interventions or bundled interventions aimed at reduction of the incidence of cranial surgical site infections., Methods: A systematic review of the literature was conducted according to the PRISMA guidelines. The search strategy included randomized trials, quasi-experimental studies, cohort studies, and case series published between 2000 and 2020 that evaluated interventions implemented to reduce cSSI. Bias assessments and data extraction were performed on included studies., Results: The initial search generated 1249 studies. Application of inclusion and exclusion criteria and review of references yielded 15 single-intervention and 6 bundled-intervention studies. The single interventions included handwashing protocols, use of vancomycin powder, hair washing and clipping practices, and incision closure techniques. Bundled interventions addressed a variety of preoperative, intraoperative, and postoperative changes. Despite a lack of strong evidence to support the adoption of statistically significant interventions, the use of vancomycin powder may be effective in reducing cSSI. In addition, bundled interventions that involved cultural changes, such as increased teaching/education, personal accountability, direct observation, and feedback, showed some success in decreasing SSI rates., Conclusions: The strength of the conclusions is limited by small sample sizes, study heterogeneity, relatively low cSSI incidence, and high case variability. Some evidence supports the use of intraoperative vancomycin powder in adult noncranioplasty cases and the application of accountability, teaching, and surveillance of faculty, particularly those early in training., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to explore racial/ethnic factors that may be associated with survival in patients with glioblastoma by querying the National Cancer Database (NCDB)., Methods: The NCDB was queried for patients diagnosed with glioblastoma between 2004 and 2014. Patient demographic variables included age at diagnosis, sex, race, ethnicity, Charlson-Deyo score, insurance status, and rural/urban/metropolitan location of zip code. Treatment variables included surgical treatment, extent of resection, chemotherapy, radiation therapy, type of radiation, and treatment facility type. Outcomes included 30-day readmission, 30- and 90-day mortality, and overall survival. Multivariable Cox regression analyses were performed to evaluate variables associated with race and overall survival., Results: A total of 103 652 glioblastoma patients were identified. There was a difference in the proportion of patients for whom surgery was performed, as well as the proportion receiving radiation, when stratified by race ( P < .001). Black non-Hispanics had the highest rates of unplanned readmission (7.6%) within 30 days (odds ratio [OR]: 1.39 compared to White non-Hispanics, P < .001). Asian non-Hispanics had the lowest 30- (3.2%) and 90-day mortality (9.8%) when compared to other races (OR: 0.52 compared to White non-Hispanics, P = .031). Compared to White non-Hispanics, we found Black non-Hispanics (hazard ratio [HR]: 0.88, P < .001), Asian non-Hispanics (HR: 0.72, P < .001), and Hispanics (HR: 0.69, P < .001) had longer overall survival., Conclusions: Differences in treatment and outcomes exist between races. Further studies are needed to elucidate the etiology of these race-related disparities and to improve outcomes for all patients., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objectives: Prone positioning has been shown to be a beneficial adjunctive supportive measure for patients who develop acute respiratory distress syndrome. Studies have excluded patients with reduced intracranial compliance, whereby patients with concomitant neurologic diagnoses and acute respiratory distress syndrome have no defined treatment algorithm or recommendations for management. In this study, we aim to determine the safety and feasibility of prone positioning in the neurologically ill patients., Design and Setting: A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses 2009 guidelines, yielded 10 articles for analysis. Using consensus from these articles, in combination with review of multi-institutional proning protocols for patients with nonneurologic conditions, a proning protocol for patients with intracranial pathology and concomitant acute respiratory distress syndrome was developed., Measurements and Main Results: Among 10 studies included in the final analysis, we found that prone positioning is safe and feasible in the neurologically ill patients with acute respiratory distress syndrome. Increased intracranial pressure and compromised cerebral perfusion pressure may occur with prone positioning. We propose a prone positioning protocol for the neurologically ill patients who require frequent neurologic examinations and intracranial monitoring., Conclusions: Although elevations in intracranial pressure and reductions in cerebral perfusion pressure do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with acute respiratory distress syndrome and concomitant neurologic diagnoses. In cases where intracranial pressure, cerebral perfusion pressure, and brain tissue oxygenation can be monitored, prone position ventilation should be considered a safe and viable therapy., Competing Interests: Dr. Alkhachroum received funding from National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under the Miami Clinical and Translational Science Institute KL2 Career Development Award UL1TR002736. Dr. Sedney’s institution received funding from NIH/National Institute on Aging, and she received funding from Arbeitsgemeinschaft für Osteosynthesefragen Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor's shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma's and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1's binding with fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 however, TUBB4 expression is unaltered upon fasentin treatment. Using human pluripotent stem cell antibody array, we demonstrate reduced levels of Oct3/4, Nanog, Sox2, Sox17, Snail and VEGFR2 (Vascular endothelial growth factor receptor 2) upon CR-42-24 treatment. Overall, our data confirm that silencing TUBB4 or GLUT1 reduce GSC tumorsphere formation, self-renewal and proliferation in vitro. These findings suggest GLUT1 and its binding partner TUBB4 as druggable targets that warrant further investigation in GBM.

Background: Primary central nervous system lymphomas (PCNSLs) account for 1%-2% of primary central nervous system tumors. Until recently, treatment has centered on biopsy, radiotherapy, and high-dose methotrexate, without a clear role for cytoreductive surgery. The objective of this article is to compare the impact of biopsy versus cytoreductive surgery in outcomes of patients with PCNSL, including postoperative complications and survival., Methods: We performed a systematic review of literature published from January 1, 1968 to May 2, 2018 related to PCNSL treatment in patients undergoing biopsy or resection. Data on morbidity, progression-free survival, and overall survival were extracted and analyzed., Results: A total of 1291 nonduplicate citations were identified, with 244 articles selected for full-text review. Twenty-four articles were included for data abstraction including 2 level IIb studies, 4 level IIIb studies, and the remaining 18 articles representing level IVb studies. Of these articles, 15 failed to show benefit with cytoreductive surgery; most of these articles included relatively small sample sizes and predated standardization of high-dose systemic methotrexate treatment. Larger, more recent series included 9 articles providing evidence in support of cytoreductive surgery. Patient age, functional status, and treatment with chemotherapy and/or radiation were associated with improved survival across studies., Conclusions: The treatment of PCNSL is challenging and ever-evolving. Earlier, smaller studies failed to show the benefit of cytoreductive surgery over biopsy in patients with PCNSL. Larger, more recent series seem to show the possible benefit of cytoreductive surgery in PCNSL. Future well-designed prospective studies may help further elucidate the role of resection in the modern treatment of PCNSL., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immune checkpoints are known to contribute to tumor progression by enhancing cancer's ability to evade the immune system and metastasize. Immunotherapies, including monoclonal antibodies, have been developed to target specific immunosuppressive molecules on the membranes of cancer cells and have proven revolutionary in the field of oncology. Recently, small molecule inhibitors (SMIs) have gained increased attention in cancer research with potential applications in immunotherapy. SMIs have desirable benefits over large-molecule inhibitors, such as monoclonal antibodies, including greater cell permeability, organ specificity, longer half-lives, cheaper production costs, and the possibility for oral administration. This paper will review the mechanisms by which noteworthy and novel immune checkpoints contribute to tumor progression, and how they may be targeted by SMIs and epigenetic modifiers to offer possible adjuvants to established therapeutic regimens. SMIs target immune checkpoints in several ways, such as blocking signaling between tumorigenic factors, building immune tolerance, and direct inhibition via epigenetic repression of immune inhibitory molecules. Further investigation into combination therapies utilizing SMIs and conventional cancer therapies will uncover new treatment options that may provide better patient outcomes across a range of cancers., Competing Interests: None.

Background: Transformation to glioblastoma following recurrent epidermoid cyst resection has not been reported. Chronic inflammation can underlie malignant transformation of epidermoid cysts. Astrogliosis following repeated resections may have induced the rare transformation to glioblastoma., Clinical Presentation: A patient presenting with left lower extremity weakness was found to harbor a parietal mass lesion. Histopathology demonstrated an epidermoid cyst. Following multiple re-resections, an intra-axial mass was discovered within the operative bed, confirmed as glioblastoma., Conclusion: This is the first report of glioblastoma associated with a resected epidermoid cyst. Subsequent to resection, the chronic inflammatory milieu propagated by astrogliosis is thought to have induced malignancy. The progression to glioblastoma draws attention to neoplastic transformation in the context of recurrent epidermoids.

Dysregulated metabolism in the form of aerobic glycolysis occurs in many cancers including breast carcinoma. Here, we report PDK4 (pyruvate dehydrogenase kinase 4) as key enzyme implicated in the control of glucose metabolism and mitochondrial respiration is relatively highly expressed in breast cancers, and its expression correlates with poor patient outcomes. Silencing of PDK4 and ectopic expression of miR-211 attenuates PDK4 expression in breast cancer cells. Interestingly, low miR-211 expression is significantly associated with shorter overall survival and reveals an inverse correlation between expression of miR-211 and PDK4. We have found that depletion of PDK4 by miR-211 shows an oxidative phosphorylation-dominant phenotype consisting of the reduction of glucose with increased expression of PDH and key enzymes of the TCA cycle. miR-211 expression causes alteration of mitochondrial membrane potential and induces mitochondrial apoptosis as observed via IPAD assay. Further, by inhibiting PDK4 expression, miR-211 promotes a phenotype shift towards a pro-glycolytic state evidenced by decreased extracellular acidification rate (ECAR); increased oxygen consumption rate (OCR); and increased spare respiratory capacity in breast cancer cell lines. Taken together this data establishes a molecular connection between PDK4 and miR-211 and suggests that targeting miR-211 to inhibit PDK4 could represent a novel therapeutic strategy in breast cancers., Competing Interests: None.

Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role. This paper provides a comprehensive overview of immunometabolism research and attempts to provide insight into potential immunometabolic targets in glioblastoma for the purpose of future development and study of targeted therapies.

Glioblastoma (GBM) remains one of the most lethal and difficult-to-treat cancers of the central nervous system. The poor prognosis in GBM patients is due in part to its resistance to available treatments, which calls for identifying novel molecular therapeutic targets. In this study, we identified a mediator of Notch signaling, HEY1, whose methylation status contributes to the pathogenesis of GBM. Datamining studies, immunohistochemistry and immunoblot analysis showed that HEY1 is highly expressed in GBM patient specimens. Since methylation status of HEY1 may control its expression, we conducted bisulphite sequencing on patient samples and found that the HEY1 promoter region was hypermethylated in normal brain when compared to GBM specimens. Treatment on 4910 and 5310 xenograft cell lines with sodium butyrate (NaB) significantly decreased HEY1 expression with a concomitant increase in DNMT1 expression, confirming that promoter methylation may regulate HEY1 expression in GBM. NaB treatment also induced apoptosis of GBM cells as measured by flow cytometric analysis. Further, silencing of HEY1 reduced invasion, migration and proliferation in 4910 and 5310 cells. Furthermore, immunoblot and q-PCR analysis showed the existence of a potential positive regulatory loop between HEY1 and p53. Additionally, transcription factor interaction array with HEY1 recombinant protein predicted a correlation with p53 and provided various bonafide targets of HEY1. Collectively, these studies suggest HEY1 may be an important predictive marker for GBM and potential target for future GBM therapy.

The field of immunotherapy is a continually expanding niche in cancer biology research. In the last two decades, there has been significant progress in identifying better targets and creating more specific agents for therapy in the field. B7-H3 (CD276) is an immune checkpoint from the B7 family of molecules, many of whom interact with known checkpoint markers including CTLA4, PD-1, and CD28. This is an exciting molecule that is overexpressed in many cancers, although the receptor of B7-H3 has not been characterized. Initially, B7-H3 was thought to co-stimulate the immune response, but recent studies have shown that it has a co-inhibitory role on T-cells, contributing to tumor cell immune evasion. Therefore, its overexpression has been linked to poor prognosis in human patients and to invasive and metastatic potential of tumors in in vitro models. Moreover, recent evidence has shown that B7-H3 influences cancer progression beyond the immune regulatory roles. In this review, we aim to characterize the roles of B7-H3 in different cancers, its relationship with other immune checkpoints, and its non-immunological function in cancer progression. Targeting B7-H3 in cancer treatment can reduce cell proliferation, progression, and metastasis, which may ultimately lead to improved therapeutic options and better clinical outcomes., Competing Interests: None.

Medulloblastoma is one of the most prevalent pediatric brain malignancies, accounting for approximately 20% of all primary CNS tumors in children under the age of 19. OTX2 is the member of a highly conserved family of bicoid-like homeodomain transcription factors responsible for the regulation of cerebellar development and of current investigational interest in the tumorigenesis of medulloblastoma. Recent studies have revealed that Group 3 and Group 4 medulloblastomas show marked overexpression of OTX2 with a concurrent amplification of the MYC and MYCN oncogenes, respectively, correlating with anaplasticity and unfavorable patient outcomes. More recent attempts at elucidating the mechanism of OTX2-driven oncogenesis at the cellular level has also revealed that OTX2 may confer stem-cell like properties to tumor cells via epigenetic regulation. The review seeks to define the interaction pathways and binding partners involved in OTX2 function, its usefulness as a molecular marker for risk stratification and prognosis, and the mechanism by which it drives tumor maintenance. Additionally, it will preview unpublished data by our group highlighting the unanticipated involvement of OTX2 in the control of cellular metabolism.

GLUT1, and to a lesser extent, GLUT3, appear to be interesting targets in the treatment of glioblastoma multiforme. The current review aims to give a brief history of the scientific community's understanding of these glucose transporters and to relate their importance to the metabolic changes that occur as a result of cancer. One of the primary changes that occurs in cancer, the Warburg Effect, is characterized by an extreme shift toward glycolysis from the usual reliance on oxidative phosphorylation and is currently being investigated to target the upstream and downstream factors responsible for Warburg-induced changes. Further, it aims to explain the differential expression of GLUT1 and GLUT3 in glioblastoma tissue, and how these modulations in expression can serve as targets to restore a more normal metabolism. Additionally, hypoxia-induced factor-1α's (HIF1α) role in a number of transcriptional changes typical to GBM will be discussed, including its role in GLUT upregulation. Finally, the four known subtypes of GBM [proneural, neural, mesenchymal, and classical] will be characterized in order to discuss how metabolic changes differ in each subtype. These changes have the potential to be selectively targeted in order to provide specificity to the clinical treatment options in GBM.