Advancements in chimeric antigen receptor-expressing T-cell therapy for glioblastoma multiforme: Literature review and future directions.

Glioblastoma multiforme (GBM) is an aggressive cancer that has been difficult to treat and often requires multimodal therapy consisting of surgery, radiotherapy, and chemotherapy. Chimeric antigen receptor-expressing (CAR-T) cells have been efficacious in treating hematological malignancies, resulting in several FDA-approved therapies. CAR-T cells have been more recently studied for the treatment of GBM, with some promising preclinical and clinical results. The purpose of this literature review is to highlight the commonly targeted antigens, results of clinical trials, novel modifications, and potential solutions for challenges that exist for CAR-T cells to become more widely implemented and effective in eradicating GBM.

Academic accomplishments of Black neurosurgeons in the United States.

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding. METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites. RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts. CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

The Safety and Efficacy of Concurrent Immune Checkpoint Blockade and Stereotactic Radiosurgery Therapy with Practitioner and Researcher Recommendations.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown growing promise in the treatment of brain metastases, especially combined with stereotactic radiosurgery (SRS). The combination of ICIs with SRS has been studied for efficacy as well as increasing radiation necrosis risks. In this review, we compare clinical outcomes of radiation necrosis, intracranial control, and overall survival between patients with brain metastases treated with either SRS alone or SRS-ICI combination therapy. METHODS: A literature search of PubMed, Scopus, Embase, Web of Science, and Cochrane was performed in May 2023 for articles comparing the safety and efficacy of SRS/ICI versus SRS-alone for treating brain metastases. RESULTS: The search criteria identified 1961 articles, of which 48 met inclusion criteria. Combination therapy with SRS and ICI does not lead to significant increases in incidence of radiation necrosis either radiographically or symptomatically. Overall, no difference was found in intracranial control between SRS-alone and SRS-ICI combination therapy. Combination therapy is associated with increased median overall survival. Notably, some comparative studies observed decreased neurologic deaths, challenging presumptions that improved survival is due to greater systemic control. The literature supports SRS-ICI administration within 4 weeks of another for survival but remains inconclusive, requiring further study for other outcome measures. CONCLUSIONS: Combination SRS-ICI therapy is associated with significant overall survival benefit for patients with brain metastases without significantly increasing radiation necrosis risks compared to SRS alone. Although intracranial control rates appear to be similar between the 2 groups, timing of treatment delivery may improve control rates and demands further study attention.

Oncolytic viral therapy: a review and promising future directions.

Oncolytic viral therapy is quickly emerging as a promising subset of immunotherapy, which theoretically can target tumor cells while sparing surrounding healthy cells by harnessing the replication machinery of viruses with tropism for tumor cells, resulting in direct oncolysis, and by transforming immunologically "cold" tumor into areas that elicit the host's immune response. This review provides an overview of oncolytic viral therapy until the present day, starting with the original concept in 1912. The general mechanism of oncolytic viruses (OVs) depends on selectively integrating them into tumor cells based on genetic engineering of viral genomic material, inducing oncolysis and eliciting the host's innate immune response. Moreover, a major component of oncolytic viral therapy has been herpes simplex virus, with talimogene laherparepvec being the only FDA-approved oncolytic viral therapy for the treatment of melanomas. This review explores the characteristics, advantages, disadvantages, and therapeutic uses of several DNA and RNA viral families. A snapshot of the oncolytic viral treatments used in the most recent and advanced clinical trials is also provided. Lastly, the challenges of implementing oncolytic viral therapy are explored, both at a molecular and clinical level, with a highlight of promising future directions. In particular, the lack of an optimal delivery method based on tumor type for oncolytic viral therapy poses a significant obstacle, even in clinical studies. Intrathecal continuous delivery of OVs is a promising prospect, potentially by adapting the novel continuous irrigation and drainage IRRAflow catheter. Further exploration and testing of the IRRAflow catheter should be undertaken.

Developing a computable phenotype for glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor, and thus it is important to be able to identify patients with this diagnosis for population studies. However, this can be challenging as diagnostic codes are non-specific. The aim of this study was to create a computable phenotype (CP) for GBM from structured and unstructured data to identify patients with this condition in a large electronic health record (EHR). METHODS: We used the UF Health Integrated Data Repository, a centralized clinical data warehouse that stores clinical and research data from various sources within the UF Health system, including the EHR system. We performed multiple iterations to refine the GBM-relevant diagnosis codes, procedure codes, medication codes, and keywords through manual chart review of patient data. We then evaluated the performances of various possible proposed CPs constructed from the relevant codes and keywords. RESULTS: We underwent six rounds of manual chart reviews to refine the CP elements. The final CP algorithm for identifying GBM patients was selected based on the best F1-score. Overall, the CP rule "if the patient had at least 1 relevant diagnosis code and at least 1 relevant keyword" demonstrated the highest F1-score using both structured and unstructured data. Thus, it was selected as the best-performing CP rule. CONCLUSIONS: We developed a CP algorithm for identifying patients with GBM using both structured and unstructured EHR data from a large tertiary care center. The final algorithm achieved an F1-score of 0.817, indicating a high performance which minimizes possible biases from misclassification errors.

A Retrospective Cohort Study Evaluating the Safety and Efficacy of Sequential versus Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection.

Methods: We conducted a retrospective review of patients with pleural infection requiring intrapleural therapy at two tertiary referral centres. Results: We included 84 (62.2%) and 51 (37.8%) patients who received sequential and concurrent intrapleural therapy, respectively. Patient demographics and clinical characteristics, including age, RAPID score, and percentage of pleural opacity on radiographs before intrapleural therapy, were similar in both groups. Treatment failure rates (defined by either in-hospital mortality, surgical intervention, or 30-day readmission for pleural infection) were 9.5% and 5.9% with sequential and concurrent intrapleural therapy, respectively (p = 0.534). This translates to a treatment success rate of 90.5% and 94.1% for sequential and concurrent intrapleural therapy, respectively. There was no significant difference in the decrease in percentage of pleural effusion size on chest radiographs (15.1% [IQR 6-35.7] versus 26.6% [IQR 9.9-38.7], p = 0.143) between sequential and concurrent therapy, respectively. There were also no significant differences in the rate of pleural bleeding (4.8% versus 9.8%, p = 0.298) and chest pain (13.1% versus 9.8%, p = 0.566) between sequential and concurrent therapy, respectively. Conclusion: Our study adds to the growing literature on the safety and efficacy of concurrent intrapleural therapy in pleural infection.

Patterns and predictors of anxiety and depression symptom trajectories in patients diagnosed with primary brain tumors.

BACKGROUND: Patients with primary brain tumors (pPBTs) often exhibit heightened distress. This study assesses how symptoms of anxiety and depression change over time in pPBTs and identifies factors that may predict patients' symptom trajectories. METHODS: Ninety-nine adult pPBTs completed psychosocial assessments at neuro-oncology appointments over 6-18 months. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain; symptoms of anxiety and depression were assessed with the Patient-Reported Outcomes Measurement Information System short forms. The prevalence of patients with clinically elevated symptoms and those who experienced clinically meaningful changes in symptoms throughout follow-up were examined. Linear mixed-effects models evaluated changes in symptoms over time at the group level, and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level. RESULTS: At enrollment, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with follow-up data (n = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. There were no significant changes in anxiety or depression scores over time, but better physical, functional, and brain-cancer well-being predicted lower levels of anxiety and depression (p < 0.001). Five sub-groups of patients with distinct symptom trajectories emerged via LCGA. CONCLUSIONS: pPBTs commonly experience elevated symptoms of anxiety and depression that may fluctuate in clinically meaningful manners throughout the disease. Routine screening for elevated symptoms is needed to capture clinically meaningful changes and identify factors affecting symptoms to intervene on.

The Enhanced Recovery After Surgery pathway for posterior cervical surgery: a retrospective propensity-matched cohort study.

OBJECTIVE: The Enhanced Recovery After Surgery (ERAS) protocol is a comprehensive, multifaceted approach aimed at improving postoperative outcomes. It incorporates a range of strategies to promote early and more effective recovery, including reducing pain, complications, and length of stay, without increasing readmission rate. To date, ERAS for spine surgery patients has been primarily limited to lumbar surgery and anterior cervical decompression and fusion (ACDF). ERAS has not been previously studied for posterior cervical surgery, which may present a greater opportunity for improvement in patient outcomes with ERAS than ACDF. This single-institution, multi-surgeon study assessed the impact of an ERAS protocol in patients undergoing posterior cervical decompression surgery. METHODS: This study included a retrospective consecutive patient cohort with controls that were propensity matched for age, body mass index, sex, home opioid use, surgical levels, Nurick grade, and smoking status. In addition, consecutive patients who underwent posterior cervical decompression surgery for degenerative disease from December 2014 to December 2021 were included. ERAS was implemented in December 2018. Demographic, perioperative, clinical, and radiographic information was gathered. Regression models were created to evaluate length of stay, physiological function, pain levels, and opioid use. The primary focus was length of stay, with secondary outcomes including timing of ambulation, bowel movement, and voiding; daily pain scores; opioid consumption; discharge status; 30-day readmission rates; and reoperation rates. RESULTS: There were 366 patients included in the study, all of whom were included in multivariate models, and 254 (127 in each cohort) were included on the basis of matching. After propensity matching, patient characteristics, operative procedures, and operative duration were similar between groups. The ERAS cohort had a significantly improved length of stay (3.2 vs 4.7 days, p < 0.0001) and home discharge rate (80% vs 50%, p < 0.001) without an increase in readmission rate. The ERAS cohort had an earlier day of the first ambulation (p = 0.003), bowel movement (p = 0.014), and voiding (p = 0.001). ERAS demonstrated a significantly lower composite complication rate (1.1 vs 1.8, p < 0.0001). ERAS resulted in better maximum pain scores (p = 0.043) and trended toward improved mean pain scores (p = 0.072), although total opioid use was similar. CONCLUSIONS: Implementing a novel ERAS protocol significantly improved length of stay, return of physiological function, home discharge, complications, and maximum pain score after posterior cervical surgery.

Review of spinal dural arteriovenous fistulas: Challenges, diagnostics, management, and pathophysiology.

Spinal dural arteriovenous fistulae are rare, spinal vascular malformations that commonly present with progressive myelopathy in a specific demographic and are treatable with surgery (preferred) and/or endovascular embolization. PubMed and Google Scholar were searched with terms including but not limited to "spinal dural arteriovenous fistula", "imaging", "management" "surgery vs embolization", "outcomes", "pathogenesis" to find relevant studies, including emerging research. The purpose of this literature review is to highlight presentation, imaging characteristics, management strategies, pathophysiology, and future directions for these rare but distinct entities.

Secondary Mechanisms of Neurotrauma: A Closer Look at the Evidence.

Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma is a potential cause of cell death, oxidative stress, and neuroinflammation. These secondary injuries lack defined therapy. The major causes of secondary injury in neurotrauma include endoplasmic reticular stress, mitochondrial dysfunction, and the buildup of reactive oxygen or nitrogenous species. Stress to the endoplasmic reticulum in neurotrauma results in the overactivation of the unfolded protein response with subsequent cell apoptosis. Mitochondrial dysfunction can lead to the release of caspases and the buildup of reactive oxygen species; several characteristics make the central nervous system particularly susceptible to oxidative damage. Together, endoplasmic reticulum, mitochondrial, and oxidative stress can have detrimental consequences, beginning moments and lasting days to months after the primary injury. Understanding these causative pathways has led to the proposal of various potential treatment options.

Enhanced recovery after surgery (ERAS) improves return of physiological function in frail patients undergoing one- to two-level TLIFs: an observational retrospective cohort study.

BACKGROUND CONTEXT: The enhanced recovery after surgery (ERAS) protocol is a multimodal approach which has been shown to facilitate recovery of physiological function, and reduce early post-operative pain, complications, and length of stay (LOS) in open one- to two-level TLIF. The benefit of ERAS in specifically frail patients undergoing TLIF has not been demonstrated. Frailty is clinically defined as a syndrome of physiological decline that can predispose patients undergoing surgery to poor outcomes. PURPOSE: This study primarily evaluated the benefit of an ERAS protocol in frail patients undergoing one- or two-level open TLIF compared to frail patients without ERAS. Secondarily, we assessed whether outcomes in frail patients with ERAS approximated those seen in nonfrail patients with ERAS. STUDY DESIGN: Retrospective consecutive patient cohort with controls propensity-matched for age, body mass index, sex, and smoking status. PATIENT SAMPLE: Consecutive patients that underwent one- or two-level open TLIF for degenerative disease from August, 2015 to July, 2021 by a single surgeon. ERAS was implemented in December 2018. OUTCOME MEASURES: Primary outcome measure was return of postoperative physiological function defined as the summation of first day to ambulate, first day to bowel movement, and first day to void. Additional outcome measures included LOS, daily average pain scores, opioid use, discharge disposition, 30-day readmission rate, and reoperation. METHODS: A retrospective analysis of frail patients > 65 years of age undergoing one- to two-level open TLIF post-ERAS were compared to propensity matched frail pre-ERAS patients. Frailty was assessed using the Fried phenotype classification (score >1). Patient demographics, LOS, first-day-to-ambulate (A1), first-day-to-bowel movement (B1), first-day-to-void (V1) were collected. Return of physiological function was defined as A1+B1+V1. Primary analysis was a comparison of frail patients pre-ERAS versus post-ERAS to determine effect of ERAS on return of physiologic function with frailty. Secondary analysis was a comparison of post-ERAS frail versus post-ERAS nonfrail patients to determine if return of physiologic function in frail patients with ERAS approximates that of nonfrail patients. RESULTS: In the primary analysis, 32 frail patients were included with mean age ± standard deviation of 72.8±4.4 years, mean BMI 28.8±5.5, 65.6% were male, 15 pre-ERAS and 17 post-ERAS. Patient characteristics were similar between groups. After ERAS implementation, return of physiological function improved by a mean 3.2 days overall (post-ERAS 3.4 vs. pre-ERAS 6.7 days) (p<.0001), indicating a positive effect of ERAS in frail patients. Additionally, length of stay improved by 1 day (4.8±1.6 vs. 3.8±1.9 days, p<.0001). Total daily intravenous morphine milligram equivalent (MME) as well as average daily pain scores were similar between groups. Secondarily, 26 nonfrail patients post ERAS were used as a comparison group with the 17 post-ERAS frail cohort. Mean age of this cohort was 73.4±4.6 years, mean BMI 27.4±4.9, and 61.9% were male. Return of physiologic function was similar between cohorts (post-ERAS nonfrail 3.5 vs. post-ERAS frail 3.4 days) (p=.938), indicating the benefit with ERAS in frail patients approximates that of nonfrail patients. CONCLUSIONS: ERAS significantly improves return of physiologic function and length of stay in patients with frailty after one- to two-level TLIF, and approximates improved outcomes seen in non-frail patients.

Personal recovery in the postdischarge period for individuals with schizophrenia spectrum diagnoses: The role of community integration and social support.

OBJECTIVE: The experience of personal recovery from mental health has been theorized to occur through several pathways. CHIME is a seminal theoretical framework of personal recovery that is widely endorsed by the existing literature. Few studies have examined the utility of the CHIME framework with those experiencing acute challenges in their engagement in the recovery process. The purpose of the present study was to examine part of the CHIME framework for individuals with schizophrenia spectrum diagnoses in the period immediately following hospitalization. Specifically, the impact of social support and community integration on personal recovery was examined. METHODS: The present study involved a secondary analysis of a Phase 2 clinical trial. Assessment measures were administered to participants 1-month (n = 82) and 6-months (n = 72) postdischarge from a psychiatric hospital. Hierarchical regression and mediation analyses were conducted to assess the relationship between social support, community integration, and 1-month and 6-month personal recovery. RESULTS: Hierarchical regression analysis indicated that community integration and social support significantly predicted personal recovery. Mediation analyses indicated social support partially accounts for the relationship between community integration and personal recovery at 1- and 6-months postdischarge, providing evidence for social support as a mechanism of personal recovery during this time. CONCLUSION AND IMPLICATIONS FOR PRACTICE: This quantitative investigation of CHIME highlights the mechanism of social support for individuals who are experiencing acute challenges in their recovery. These findings point to the need for interventions that enhance community integration and social support postdischarge. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A 37-Year-Old Woman Presenting With Hemoptysis, Dyspnea and Fever.

CASE PRESENTATION: A 37-year-old woman presented to the ED in Singapore with a 6-month history of chronic cough and dyspnea that was associated with small volume hemoptysis, night sweats and occasional fever. Of note, she had no sick contacts or recent travel. Systemic review revealed no loss of weight or appetite and no autoimmune features. She had no other medical history and was a lifelong nonsmoker and was not an alcoholic.

Recurrent pneumothoraces with diffuse small ground-glass and solid nodules.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is the lesser known pulmonary manifestation of tuberous sclerosis. It manifests radiologically as diffuse small ground-glass and solid nodules. Accurate diagnosis is essential as it can be mistaken for miliary tuberculosis or malignant lesions which necessitates specific treatment. Constellation of radiological features such as multicentric disease at onset and stability over time can help to distinguish MMPH from its differentials. Histologically, MMPH is characterized by hamartomatous proliferation of type II pneumocytes with a lack of high nuclear to cytoplasmic ratio. MMPH confers a benign prognosis unlike its differentials. Therefore, accurate diagnosis is paramount in ensuring appropriate care is delivered. Here, we describe the radiological and histological features of MMPH in a patient with genetically proven tuberous sclerosis complex and co-existing lymphangioleiomyomatosis.

Randomized trial of a brief peer support intervention for individuals with schizophrenia transitioning from hospital to community.

This phase 2 randomized trial examined the outcomes of a brief, transitional, peer support intervention designed to address the poor outcomes that are common for individuals with schizophrenia spectrum illnesses in the period immediately following hospitalization. In the context of treatment-as-usual, participants were provided with a peer support intervention, 'the Welcome Basket,' in which participants received 1-2 sessions of peer support in the two weeks before discharge and met weekly for a month post-discharge. The study also piloted a brief version of this intervention with only one community session post-discharge with the same pre-discharge process. It was hypothesized that the full intervention would improve community transition outcomes, with community functioning (Multnomah Community Ability Scale) being the primary measure and secondary measures including symptomatology, community integration, personal recovery, quality of life, and social support. The examination of the brief intervention was exploratory. Measures were completed at baseline, 1-month post-discharge, and follow-up at 6 months. A total of 110 participants were randomized to one of three interventions, with outcome data obtained from 82 and follow-up from 74. While feasible, we did not find that the Welcome Basket intervention was superior to treatment as usual for any of our primary or secondary outcome measures. Future work is needed to determine whether a more extended intervention is required and whether specific subgroups of patients may benefit (e.g. those without access to immediate psychiatric care or those better able to engage with a peer).

Plasma PrPC and ADAM-10 as novel biomarkers for traumatic brain injury and concussion: a pilot study.

BACKGROUND: Cellular prion protein (PrPC) is a lipid raft protein abundant within CNS. It is regulated by a disintegrin and metalloproteinase domain containing protein 10 (ADAM10). PrPC has previously been implicated as a biomarker for TBI. ADAM10 has not been investigated as a TBI biomarker. OBJECTIVE: We evaluated PrPC and ADAM10 as candidate biomarkers for TBI. METHODS: We performed ELISA for ADAM10 and PrPC on plasma samples of patients with TBI admitted to Brigham and Women's Hospital. Plasma samples from 20 patients admitted for isolated TBI were acquired from a biobank with clinical information. Control plasma (37 samples) was acquired from a commercial source. GraphPad was used to conduct statistical analysis. RESULTS: 37 controls and 20 TBI samples were collected. Of the patients with TBI, eight were mild, three were moderate, and nine were severe. Both PrPC and ADAM10 were elevated in patients with TBI compared with control (p < .001). ADAM10 exhibited greater expression in patients with worse clinical grade. There was no significant association of either PrPC or ADAM10 with time after injury. CONCLUSIONS: Our results indicate that PrPC and ADAM10 appear to be useful potential tools for screening of TBI. ADAM10 is closely associated with clinical grade.

Subdural Pneumocephalus Aspiration Reduces Recurrence of Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma (cSDH) is a common neurosurgical condition, with symptoms ranging from headaches to coma. Operative evacuation is the treatment of choice. Subdural reaccumulation leading to reoperation is a vexing postoperative complication. OBJECTIVE: To present a novel technique for intraoperative aspiration of pneumocephalus via a subdural drain following SDH evacuation as a method of reducing potential subdural space and promoting cerebral expansion, thereby decreasing SDH recurrence. METHODS: In this retrospective study, 15 patients who underwent operative evacuation of cSDH between 2008 and 2015 were assessed. Six patients underwent a small craniotomy with intraoperative pneumocephalus aspiration. These patients were matched by age, gender, and anticoagulation status to 9 patients who underwent evacuation of SDH without pneumocephalus aspiration. Quantitative volumetric analysis was performed on the preoperative, postoperative, and 1-mo follow-up computed tomography scan to assess the subdural volume. RESULTS: In the immediate postoperative period, there was no difference in the percentage of residual subdural fluid between the aspiration and control groups (0.291 vs 0.251; P = 1.00). There was a decrease in amount of pneumocephalus present when the aspiration technique was applied (0.182 vs 0.386; P = .041). At 1-mo follow-up, there was a decrease in the residual cSDH volume between the aspiration and the control groups (28.7 mL vs 60.8 mL; P = .011). The long-term evacuation rate was greater in the aspiration group (75.4% vs 51.6%; P = .015). CONCLUSION: Intraoperative aspiration of cSDH cavity is a safe technique that may enhance cerebral expansion and reduce likelihood of cSDH recurrence.

Variance Reduction in Neurosurgical Practice: The Case for Analytics-Driven Decision Support in the Era of Big Data.

OBJECTIVE: Variance between providers in neurosurgery can lead to inefficiencies and poor patient outcomes. Evidence-based guidelines (EBGs) have been developed; however, they have not been well implemented into the clinician workflow. Therefore, clinicians have been left to make decisions with incomplete information. Equally underused are the electronic health records (EHRs), which house enormous amounts of health data, but the power of that "big data" has failed to be capitalized on. METHODS: Early attempts at EBGs were rigid and nonadaptive; however, with the current advances in data informatics and machine learning algorithms, it is now possible to integrate "big data" and rapid data processing into clinical decision support tools. We have presented an overview of the background of EHRs and EBGs in neurosurgery and explored the possibility of integrating them to reduce unwanted variance. RESULTS: As we strive toward variance reduction in healthcare, the integration of "big data" and EBGs for decision-making will be key. We have proposed that EHRs are an ideal platform for integrating EBGs into the clinician workflow and have presented as an example of a successful early generation model, Neurocore. With this approach, it will be possible to build EBGs into the EHR software, to continuously update and optimize EBGs according to the flow of patient data into the EHR, and to present data-driven clinical decision support at the point of care. CONCLUSIONS: Variance reduction in neurosurgery through the integration of evidence-based decision support in EHRs will lead to improved patient safety, a reduction in medical errors, maximization of the use of the available data, and enhanced decision-making power for clinicians.