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INTRODUCTION Timing of intervention and complication profiles in surgical repair of craniosynostosis have been widely debated. Early intervention is frequently promoted as a means of decreasing morbidity while maintaining favorable outcomes via minimally invasive techniques such as endoscopic strip craniectomy. Immediate postoperative morbidity due to complications of early vs late intervention remains a key element in comparing timing and technique for craniosynostosis repair. In addition, concurrent fronto-orbital advancement with open cranial vault remodeling may increase the risk of postoperative complications. We present an evaluation of surgical timing and the presence of fronto-orbital advancement as independent predictors of in-hospital complications after craniosynostosis repair. METHODS Retrospective analysis was performed in the National Inpatient Sample database from 1998 to 2009. Patients younger than 3 years having undergone elective surgical repair for craniosynostosis were identified. Comorbidities, demographics, transfusion status, and syndromic diagnosis were included as covariates. A multivariate regression model was used to characterize the association between age at the time of surgery and in-hospital complications. A subgroup analysis using the variable of concurrent fronto-orbital advancement was restricted to patients 8 to 24 months of age to exclude endoscopic craniosynostosis repair, which is traditionally repaired less than 6 months of age. Multivariate logistic regression was used to assess the impact of concurrent fronto-orbital advancement on postoperative complications. RESULTS A total of 6010 craniosynostosis surgery cases (42.9%, age 0-7 months; 29.5%, age 8-12 months; and 27.6%, age 13-36 months) were included. Patients in the 7-to 12-month age group were more likely to experience complications when compared with the 0- to 6-month age group (odds ratio [OR],1.32; P < 0.05) and 13-to 36-month age group (OR, 1.32; P = 0.056). Syndromic patients (OR, 1.92; P < 0.001) and patients receiving an intraoperative blood transfusion (OR, 1.60; P < 0.05) demonstrated an increased risk for complications. In the subanalysis of 2936 patients aged 8 to 24 months, 15.1% of patients received frontoorbital advancement, which was associated with a significantly increased risk of complications (OR, 1.43; P < 0.05). CONCLUSIONS Intermediate age (7-12 months) and concurrent fronto-orbital repair were independent risk factors for immediate postoperative complications. These findings may better inform the decision-making process for craniosynostosis repair in terms of timing and need for concurrent fronto-orbital reconstruction.

Safety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival. The National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized. Overall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p

OBJECTIVEThe available evidence suggests that the clinical benefits of extended resection are limited for chemosensitive tumors, such as primary CNS lymphoma. Oligodendroglioma is generally believed to be more sensitive to chemotherapy than astrocytoma of comparable grades. In this study the authors compare the survival benefit of gross-total resection (GTR) in patients with oligodendroglioma relative to patients with astrocytoma.METHODSUsing the Surveillance, Epidemiology, and End Results (SEER) Program (1999–2010) database, the authors identified 2378 patients with WHO Grade II oligodendroglioma (O2 group) and 1028 patients with WHO Grade III oligodendroglioma (O3 group). Resection was defined as GTR, subtotal resection, biopsy only, or no resection. Kaplan-Meier and multivariate Cox regression survival analyses were used to assess survival with respect to extent of resection.RESULTSCox multivariate analysis revealed that the hazard of dying from O2 and O3 was comparable between patients who underwent biopsy only and GTR (O2: hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.73–1.53; O3: HR 1.18, 95% CI 0.80–1.72). A comprehensive search of the published literature identified 8 articles without compelling evidence that GTR is associated with improved overall survival in patients with oligodendroglioma.CONCLUSIONSThis SEER-based analysis and review of the literature suggest that GTR is not associated with improved survival in patients with oligodendroglioma. This finding contrasts with the documented association between GTR and overall survival in anaplastic astrocytoma and glioblastoma. The authors suggest that this difference may reflect the sensitivity of oligodendroglioma to chemotherapy as compared with astrocytomas.

Although foreign medical graduates (FMGs) have been essential to the US physician workforce, the increasing competitiveness has made it progressively challenging for FMGs to match in US neurosurgery programs. We describe geographic origins and characteristics associated with successful match into US neurosurgery training programs.Retrospective review of AANS membership data (2007-2017). Scopus was used to collect bibliometrics.From 2009 neurosurgical residents, 165 (8.2%) were FMGs. Most were male (n = 148; 89.6%) with a median age of 34.0 years. Top six feeder countries (TFC) included India (13.9%; n = 23), Lebanon and Pakistan (9.1%; n = 15), Caribbean Region (7.2%; n = 12), Mexico (6.67%; n = 11), and Greece (3.6%; n = 6). Compared to FMGs from non-top feeder countries (NTFC), TFC FMGs had higher H-indices (2 vs 4, p = 0.049), greater number of publications (2 vs 5, p = 0.04), were more likely to have an MBBS/MBBCh (n = 38 vs n = 17, p = 0.03), and had twice as many candidates from major feeder medical schools that successfully matched into a US neurosurgery program (n = 43 vs NTFC = 20, p 0.001). NTFC FMGs were almost 3-times more likely to match at an affiliated neurosurgery program (8 vs TFC = 3, p = 0.03), while TFC FMGs were 1.5-times more likely to match at an NIH Top-40 program (33 vs NTFC = 21, p = 0.03).TFC graduates have higher bibliometrics, frequently come from major feeder schools, and have greater match success at a broader selection of programs and NIH top-40 programs. Future studies characterizing FMG country and medical school origins may enable foreign students to geographically target institutions of interest and could allow US programs to better evaluate foreign training environments.

Objective We used the SEER (Surveillance Epidemiology and End Results) database (1999–2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum. Methods We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival. Results Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18–50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005–2010) relative to those treated in the pre-temozolomide era (1999–2004) (median survival, 9 and 4 months, respectively; P = 0.005). Conclusions In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention.

Introduction Truly informed consent is an elusive goal, seldom attained in medical or surgical practice. Patients often do not fully understand procedures and therapies they undergo or the associated sequelae. Historically, informed consent and patient education have been limited to physician discussions, sometimes with the addition of simple visual aids. More recently, there is a growing body of decision aids available, including interactive multimedia patient educational modules that review preoperative through postoperative care, risks, benefits, alternatives, different surgical options, as well as commonly asked questions. We hypothesized that the addition of a Web-based educational tool would positively impact attainment of informed consent and satisfaction in plastic surgery patients. Methods We performed a prospective randomized controlled study comparing patients who presented in consultation for breast reconstruction, breast reduction, and abdominoplasty. Patients received standard patient education along with a procedure-specific (study) or general patient safety (control) Web-based educational module. Informed consent was measured using a surgical-focused, modified version of the Shared Decision-making 25 index tool. Patient demographic information as well as surrogate markers of familiarity with technology were recorded preoperatively and postoperatively. Comparisons were made between study and control groups, procedure subgroups, and preoperative and postoperative time points. Demographic factors and consent variables were compared among experimental and procedure groups. Results Data were collected from 65 patients preoperatively and 48 patients postoperatively. Thirty patients competed both surveys. Overall, no differences in patient characteristics or familiarity with technology were observed between experimental groups. Demographic characteristics were also similar between groups. No meaningful differences were identified in comparisons between experimental groups on either cross-sectional or longitudinal analyses. Nearly all patient responses were consistent with being well informed and satisfied with the educational process. Conclusions Overall, patients undergoing plastic surgery procedures are adequately informed and have a high degree of satisfaction regarding their patient education. The addition of a Web-based informed consent tool did not make a demonstrable difference in informed consent.

There is limited information on the management strategies and survival trends for oligodendroglioma patients. Here we used the Surveillance, Epidemiology and End Results (SEER, 1999–2012) database to analyze the historical trends of oligodendroglioma patient survival and correlate these trends to evolving clinical practice of radiation therapy (RT) use and surgical practice of gross total resection (GTR). We identified 2689 World Health Organization (WHO) grade II oligodendroglioma (abbreviated as O2) and 1191 WHO grade III oligodendroglioma (abbreviated as O3). Time-trend analyses were performed for overall survival, radiation treatment (RT) use, and extent of surgical resection (EOR). In multivariable Cox models that accounted for age, race, sex, tumor size, tumor location, EOR, and RT status, the hazard of dying from O3 has significantly decreased over the study period (p

It is well established that traumatic brain injury (TBI) is associated with the development of psychiatric disorders. However, the impact of psychiatric disorders on TBI outcome is less well understood. We examined the outcomes of patients who experienced a traumatic subdural hemorrhage and whether a comorbid psychiatric disorder was associated with a change in outcome. A retrospective observational study was performed in the California Office of Statewide Health Planning and Development (OSHPD) and the Nationwide Inpatient Sample (NIS). Patients hospitalized for acute subdural hemorrhage were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Patients with coexisting psychiatric diagnoses were identified. Outcomes studied included mortality and adverse discharge disposition. In OSPHD, diagnoses of depression (OR = 0.64, p 0.001), bipolar disorder (OR = 0.45, p 0.05), and anxiety (OR = 0.37, p 0.001) were associated with reduced mortality during hospitalization for TBI, with a trend toward psychosis (OR = 0.56, p = 0.08). Schizophrenia had no effect. Diagnoses of psychosis (OR = 2.12, p 0.001) and schizophrenia (OR = 2.60, p 0.001) were associated with increased adverse discharge. Depression and bipolar disorder had no effect, and anxiety was associated with reduced adverse discharge (OR = 0.73, p = 0.01). Results were confirmed using the NIS. Analysis revealed novel associations between coexisting psychiatric diagnoses and TBI outcomes, with some subgroups having decreased mortality and increased adverse discharge. Potential mechanisms include pharmacological effects of frequently prescribed psychiatric medications, the pathophysiology of individual psychiatric disorders, or under-coding of psychiatric illness in the most severely injured patients. Because pharmacological mechanisms, if validated, might lead to improved outcome in TBI patients, further studies may provide significant public health benefit.

Background Prior investigations of microsurgical breast reconstruction have not distinguished the effects of surgeon versus hospital volume and failed to address the effect of patient clustering. Our data-driven analysis aims to determine the impacts of surgeon and hospital volume on outcomes of microsurgical breast reconstruction. Methods Nationwide Inpatient Sample (NIS) data from 2008 to 2011 was analyzed for patients who underwent microsurgical breast reconstruction. Volume-outcome relationships were analyzed with restricted cubic spline analysis. A multivariable mixed-effects logistic regression was used to account for patient clustering effect. Results A total of 5,404 NIS patients met inclusion criteria. High-volume (HV) surgeons had a 59% decrease in the risk of inpatient complications, which became non-significant after clustering correction. For HV hospitals, there was a 47% decrease in the risk of inpatient complications (odds ratio = 0.53; 95% confidence intervals 0.30, 0.91; p = 0.021) that was statistically significant with the clustering adjustment. Neither the volume-cost relationship for surgeons nor hospitals remained statistically significant after accounting for clustering. Conclusions Hospital volume plays a significant impact on outcomes in microsurgical breast reconstruction, while surgeon volume has comparatively not shown to be similarly impactful. The complexity of care related to microsurgical breast reconstruction warrants equally complex and engineered health systems.

Objective Although stroke guidelines recommend antiplatelets be started 24 hours after tissue plasminogen activator (tPA), select mechanical thrombectomy (MT) patients with luminal irregularities or underlying intracranial atherosclerotic disease may benefit from earlier antiplatelet administration. Methods We explore the safety of early (

BACKGROUND Calculation of intracranial volume from neuroimaging can be complex and time consuming. In the adult population, there is evidence suggesting that owing to its strong correlation, head circumference (HC) may be used as a surrogate for intracranial volume (ICV). We were interested in studying the correlation between HC and ICV in patients with craniosynostosis. METHODS After institutional review board approval, a retrospective review was performed on patients with craniosynostosis. GE Healthcare AdW 4.3 volume assessment software was used to calculate ICV and HC based on preoperative computed tomographic scans. Pearson correlation was used to estimate correlation coefficients between ICV and HC for this patient population, with 0 to 0.3 considered a weak correlation, 0.4 to 0.6 considered a moderate correlation, 0.7 to 1 considered a strong correlation, and P < 0.05 was considered statistically significant. RESULTS A total of 196 craniosynostosis patients were included in this study. There were 121 male and 75 female patients. Seventy-nine patients had metopic, 45 had coronal, 64 had sagittal, and 8 had lambdoid synostosis. Mean age was 8.2 months. Mean HC and ICV were 42.9 cm and 829 cm, respectively. Overall, there was a strong correlation between HC and ICV (r = 0.81). Patients were further categorized by craniosynostosis type. Very strong correlation was obtained for patients with coronal (0.89), metopic (0.98), and lambdoid craniosynostosis (0.97). Strong correlation was obtained for patients with sagittal synostosis (0.73). When categorized by sex, a stronger correlation was obtained for female patients (0.84) compared with male patients (0.80). Statistical significance was reached for all reported correlations. CONCLUSION Our preliminary data suggest that a very strong correlation exists between HC and ICV for male and female patients with all types of craniosynostosis, making HC a useful surrogate for ICV in this patient population.

BACKGROUND The aims of the current analysis were to study the change in ventricular volume (VV) obtained with cranial distraction in patients with craniosynostosis and compare it with the change in total intracranial volume (ICV) and brain volume. METHODS After institutional review board approval, a retrospective review was performed on patients undergoing cranial distraction over a 5-year period. GE Healthcare AdW 4.3 volume assessment software was utilized to calculate preoperative and postdistraction ICV, VV, and whole-brain volume. Data were also collected on patient demographics, age at the time of distraction, time spent in distraction and consolidation, and length of stay. t Tests were used for comparison. RESULTS Twenty-three patients met our inclusion criteria. Forty-eight percent of patients (n = 11) had right-sided cranial distraction, 30% (n = 7) had bilateral distraction, and 22% of patients (n = 5) had left-sided distraction. At the preoperative stage, mean head circumference was 42.5 ± 4.7 cm, mean ICV was 810.1 ± 27 cm, mean non-VV (NVV) was 796.2 ± 268 cm, and mean VV was 13.9 ± 9 cm. After a mean of 27.4 mm of distraction, occurring over a mean of 26 days and consolidation period of 149 days, a second computed tomography scan was obtained. Mean postdistraction head circumference was 49.1 ± 3.9 cm, mean ICV was 1074.1 ± 203 cm, mean NVV was 1053.5 ± 197 cm, and VV was 20.6 ± 14 cm. Mean % increase in ICV at this stage was 47.4%; mean % NVV increase was 48.5% as opposed to 60.3% increase in VV. CONCLUSIONS Cranial distraction is known to effectively increase ICV. Our study suggests that the effect of this volumetric increase is much more pronounced on the VV compared with the brain volume. Further studies are underway to investigate whether this short-term marked increase in VV is sustained over a long-term period.

BACKGROUND Although mechanical thrombectomy has become the standard of care for large-vessel occlusion, the role of conscious sedation versus general anesthesia (GA) with intubation during thrombectomy remains controversial. Aphasia may increase patient agitation or apparent uncooperativeness/confusion and thereby lead to higher use of GA. The purpose of this study was to identify risk factors for GA and determine if the side of vessel occlusion potentially impacts GA rates. MATERIALS AND METHODS Patients who underwent mechanical thrombectomy of the middle cerebral artery (MCA) for acute ischemic stroke at our institution between April 2014 and July 2017 were retrospectively reviewed. Patient characteristics, procedural factors, and outcomes were assessed using multivariate regression analyses. Mediation analysis was utilized to investigate whether aphasia lies on the causal pathway between left-sided MCA stroke and GA. RESULTS Overall, 112 patients were included: 62 with left-sided and 50 with right-sided MCA occlusion. Patients with left-sided MCA occlusion presented with aphasia significantly more often those with right-sided occlusion (90.3% vs. 32.0%; P

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

OBJECT: High-grade gliomas (HGGs) have poor survival and high treatment costs. Intraoperative MRI (ioMRI) improves gross-total resection (GTR) rates and prolongs progression-free survival (PFS) in HGGs, but questions regarding its cost-effectiveness persist. To date, no clinical decision analysis models assessing ioMRI in the treatment of HGG exist. METHODS: An integrated 5-state microsimulation model was constructed to follow patients with HGG. Patients treated with ioMRI were compared to those without ioMRI from initial resection/debulking until death. Following surgery and treatment of complications, patients existed in one of 3 health states: PFS, progressive disease, or dead. Patients with recurrence were offered up to two repeat resections. PFS, health utility values, probabilities, and costs were obtained from randomized-controlled trials whenever possible. Otherwise, national databases, registries, and non-randomized trials were used. Uncertainty in model inputs was assessed using deterministic and probabilistic sensitivity analyses. A healthcare perspective was taken for this analysis. A willingness to pay (WTP) threshold of $100,000/QALY gained was used to determine cost-efficacy. RESULTS: IoMRI yielded an incremental benefit of 0.18 QALYs (1.16 QALYs without ioMRI vs. 1.34 with) at an incremental cost of $13,447 ($157,000 without vs. $170,447 with) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio (ICER) of $76,442 per QALY. Given our parameter distributions, probabilistic sensitivity analysis demonstrated that ioMRI had a 99.5% chance of cost-effectiveness at a WTP threshold of $100,000/QALY. CONCLUSION: Intra-operative MRI is likely a cost-effective modality in the treatment of HGGs.

Brainstem tumors represent formidable lesions for neurosurgical intervention. They should be approached with a thorough understanding of the anatomy and clear sense of surgical goals. A 14-year-old previously healthy girl presented with 2 weeks of nausea, headaches, diplopia, and gait instability. Workup revealed a 3.5 x 2.5 x 2.5 cm contrast-enhancing mass within the right midbrain. The patient consented to the surgical procedure. Preoperative imaging demonstrated superior displacement of the deep venous system because of the tumor, as well as inferior displacement of the fourth cranial nerve exit zone and posterior bowing of the entire tectal region. This allowed a safe corridor from a supracerebellar infratentorial approach. The three quarters lateral position was chosen to optimize surgeon ergonomics and allow for gravity to drain blood from the operative field. Near total resection was obtained without any new neurologic deficit. Final pathology was consistent with pilocytic astrocytoma, World Health Organization grade I. The video demonstrates the surgical approach in addition to techniques for brainstem tumor resection (Video 1).

Background The thalamus has a demonstrated role in language, particularly through its connectivity to frontal language cortices. Case Description A 59-year-old man with transient mixed aphasia following resection of a left-sided thalamic cavernous malformation is reported. No operative complications were encountered, and there was no surgical contact with cortical language areas. The patient recovered full language function within a week postoperatively. Conclusions The role of thalamic nuclei in language processes and other reports of transient thalamic aphasia are reviewed.

OBJECTIVELesions of the foramen magnum, inferolateral-to-midclival areas, and ventral pons and medulla are often treated using a far-lateral or extreme-lateral infrajugular transcondylar–transtubercular exposure (ELITE) approach. The development and surgical relevance of critical posterior skull base bony structures encountered during these approaches, including the occipital condyle (OC), hypoglossal canal (HGC), and jugular tubercle (JT), are nonetheless poorly defined in the pediatric population.METHODSMeasurements from high-resolution CT scans were made of the relevant posterior skull base anatomy (HGC depth from posterior edge of the OC, OC and JT dimensions) from 60 patients (evenly distributed among ages 0–3, 4–7, 8–11, 12–15, 16–18, and > 18 years), and compared between laterality, sex, and age groups by using t-tests and linear regression.RESULTSThere were no significant differences in posterior skull base parameters by laterality, and HGC depth and JT size did not differ by sex. The OC area was significantly larger in males versus females (174.3 vs 152.2 mm2; p = 0.01). From ages 0–3 years to adult, the mean HGC depth increased 27% (from 9.0 to 11.4 mm) and the OC area increased 52% (from 121.4 to 184.0 mm2). The majority of growth for these parameters occurred between the 0–3 year and 4–7 year age groups. Conversely, JT volume increased nearly 3-fold (281%) from 97.4 to 370.9 mm3 from ages 0–3 years to adult, with two periods of substantial growth seen between the 0–3 to 4–7 year and the 12–15 to 16–18 year age groups. Overall, JT growth during pediatric development was significantly greater than increases in HGC depth and OC area (p < 0.05). JT volume remained < 65% of adult size up to age 16.CONCLUSIONSWhen considering a far-lateral or ELITE approach in pediatric patients, standard OC drilling is likely to be needed due to the relative stability of OC and HGC anatomy during development. The JT significantly increases in size with development, yet is only likely to need to be drilled in older children (> 16 years) and adults.

The physiologic processes underlying MRI contrast enhancement in glioblastoma patients remain poorly understood. MRIs of 148 glioblastoma subjects from The Cancer Imaging Archive were segmented using Iterative Probabilistic Voxel Labeling (IPVL). Three aspects of contrast enhancement (CE) were parametrized: the mean intensity of all CE voxels (CEi), the intensity heterogeneity in CE (CEh), and volumetric ratio of CE to necrosis (CEr). Associations between these parameters and patterns of gene expression were analyzed using DAVID functional enrichment analysis. Glioma CpG island methylator phenotype (G-CIMP) glioblastomas were poorly enhancing. Otherwise, no differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. High CEi was associated with expression of genes that mediate inflammatory responses. High CEh was associated with increased expression of genes that regulate remodeling of extracellular matrix (ECM) and endothelial permeability. High CEr was associated with increased expression of genes that mediate cellular response to stressful metabolic states, including hypoxia and starvation. Our results indicate that CE in glioblastoma is associated with distinct biological processes involved in inflammatory response and tissue hypoxia. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.

Background and importance Flow diversion for the treatment of aneurysm-induced hemifacial spasm (HFS) has not been previously described. Clinical presentation The authors present the case of a 60-yr-old woman who presented with 1 yr of progressive left HFS secondary to a vertebral artery aneurysm compressing the root entry zone of cranial nerve VII. The patient's aneurysm was successfully treated with a flow diverting stent. Conclusion In the immediate postoperative period, the patient had near complete resolution of her HFS symptoms. At her 6-mo follow-up the patient had no angiographic filling of the aneurysm and her HFS symptoms had completely resolved.

OBJECTIVEIn this paper the authors review their 16-year single-institution consecutive patient experience in the endoscopic treatment of nonsyndromic craniosynostosis with an emphasis on careful review of any associated treatment-related complications and methods of complication avoidance, including preoperative planning, intraoperative management, and postoperative care and follow-up.METHODSA retrospective chart review was conducted on all patients undergoing endoscopic, minimally invasive surgery for nonsyndromic craniosynostosis at Rady Children’s Hospital from 2000 to 2015. All patients were operated on by a single neurosurgeon in collaboration with two plastic and reconstructive surgeons as part of the institution’s craniofacial team.RESULTSTwo hundred thirty-five patients underwent minimally invasive endoscopic surgery for nonsyndromic craniosynostosis from 2000 to 2015. The median age at surgery was 3.8 months. The median operative and anesthesia times were 55 and 105 minutes, respectively. The median estimated blood loss (EBL) was 25 ml (median percentage EBL 4.2%). There were no identified episodes of air embolism or operative deaths. One patient suffered an intraoperative sagittal sinus injury, 2 patients underwent intraoperative conversion of planned endoscopic to open procedures, 1 patient experienced a dural tear, and 1 patient had an immediate reexploration for a developing subgaleal hematoma. Two hundred twenty-five patients (96%) were admitted directly to the standard surgical ward where the median length of stay was 1 day. Eight patients were admitted to the intensive care unit (ICU) postoperatively, 7 of whom had preexisting medical conditions that the team had identified preoperatively as necessitating a planned ICU admission. The 30-day readmission rate was 1.7% (4 patients), only 1 of whom had a diagnosis (surgical site infection) related to their initial admission. Average length of follow-up was 2.8 years (range < 1 year to 13.4 years). Six children (< 3%) had subsequent open procedures for perceived suboptimal aesthetic results, 4 of whom (> 66%) had either coronal or metopic craniosynostosis. No patient in this series either presented with or subsequently developed signs or symptoms of intracranial hypertension.CONCLUSIONSIn this large single-center consecutive patient series in the endoscopic treatment of nonsyndromic craniosynostosis, significant complications were avoided, allowing for postoperative care for the vast majority of infants on a standard surgical ward. No deaths, catastrophic postoperative morbidity, or evidence of the development of symptomatic intracranial hypertension was observed.

Background Today, patients can access a myriad of information sources regarding plastic surgery procedures prior to meeting with a surgeon. Despite their widespread use, the role of these sources in a patient’s decision-making remains undefined. We hypothesized that the physician remains the key information source for patients making surgical decisions in plastic surgery, but that other sources may deliver important insights and prove helpful to varying degrees. We also explored motivations for this outside information search and any differences in perceived value among patients. Methods We administered a survey regarding various information sources to our breast reconstruction, reduction, and abdominoplasty patients. Responses were compared between surgery groups and demographic groups. Ordinal logistic regression analysis was used to determine the impact of patient characteristics on helpfulness rank of different sources. Results Survey results were obtained from 58 patients, of whom 10 (17.2%) had abdominoplasty, 35 (60.3%) breast reconstruction, and 13 (22.4%) breast reduction. The most popular information sources prior to the first surgical appointment were Internet searches (56.9%) and family/friends/other patients (39.7%). After the initial appointment, the most useful sources were plastic surgeons (84.5%), and the Internet (36.2%). Most patients (73.5%) still sought outside information after their appointment. On a Likert-type scale of helpfulness, plastic surgeons ranked 4.28/5, followed by the web-based patient education platform, 3.73 and the Internet, 3.6. A total of 63% of participants listed plastic surgeons as their single most important source of information. In ordinal logistic regression analysis, non-white race was significantly associated with higher rank of surgeon helpfulness (p < 0.05). Relative to low-income patients, income $50-100k (p < 0.05) and $100k+ (p < 0.05) were associated with lower rank of surgeon helpfulness. Conclusions Most patients seek outside information prior to visiting with a surgeon from the Internet, social media, or family and friends. Patients consider plastic surgeons their most valuable information source overall, though still in need of supplementation for varying reasons. Additionally, certain demographic differences affect patient perception of information sources, and this is an important factor for surgeons to consider as they approach educating patients.

Traumatic subdural hematomas (tSDHs) have high morbidity and mortality and often require neurosurgical intervention. The risk of venous thromboembolism (VTE) after tSDH ranges from 1%-20%, yet a consensus chemoprophylaxis protocol does not exist. An increased understanding of VTE risk factors following tSDH may inform development of prophylaxis guidelines.Retrospective analysis of a prospective, single-institution Level I trauma center database identified the incidence and risk factors for deep venous thrombosis (DVT) and pulmonary embolism (PE) in consecutive tSDH patients from 1990-2015. Univariate and multivariate analyses were used.Of 3024 tSDH patients, 682 (22.6%) required neurosurgical intervention in the form of an intracranial pressure monitor, external ventricular drain (EVD), or craniotomy/craniectomy. Overall, 129 (4.3%) and 20 (0.7%) patients were diagnosed with a DVT or PE. Risk factors for DVT included age =60 (odds ratio [OR]=1.5, P=0.039), preexisting endocrine disorder (OR=4.1, P=0.001), hospital length of stay =7 days (OR=4.7, P0.001), intensive care unit length of stay =7 days (OR=3.6, P0.001), and lower extremity fracture (OR=2.1, P=0.004); GCS3 was associated with a reduced DVT risk (OR=0.6, P=0.020). Risk factors for PE included intensive care unit length of stay =7 days (OR=9.7, P0.001) and lower extremity fracture (OR=4.7, P=0.002). Neurosurgical intervention did not independently increase VTE risk but was associated with increased hospital length of stay (P0.001).While overall VTE risk is low following tSDH, elderly patients and those with severe injuries requiring prolonged hospitalizations have increased thrombotic risk. Development of tiered VTE prophylaxis regimens based on early postinjury thrombotic risk profiles warrants future study.

OBJECTIVEPreoperative embolization of meningiomas can facilitate their resection when they are difficult to remove. The optimal use and timing of such a procedure remains controversial given the risk of embolization-linked morbidity in select clinical settings. In this work, the authors used a large national database to study the impact of immediate preoperative embolization on the immediate outcomes of meningioma resection.METHODSMeningioma patients who had undergone elective resection were identified in the National (Nationwide) Inpatient Sample (NIS) for the period 2002–2014. Patients who had undergone preoperative embolization were propensity score matched to those who had not, adjusting for patient and hospital characteristics. Associations between preoperative embolization and morbidity, mortality, and nonroutine discharge were investigated.RESULTSOverall, 27,008 admissions met the inclusion criteria, and 633 patients (2.34%) had undergone preoperative embolization and 26,375 (97.66%) had not. The embolization group was younger (55.17 vs 57.69 years, p < 0.001) with a lower proportion of females (63.5% vs 69.1%, p = 0.003), higher Charlson Comorbidity Index (p = 0.002), and higher disease severity (p < 0.001). Propensity score matching retained 413 embolization and 413 nonembolization patients. In the matched cohort, preoperative embolization was associated with increased rates of cerebral edema (25.2% vs 17.7%, p = 0.009), posthemorrhagic anemia or transfusion (21.8% vs 13.8%, p = 0.003), and nonroutine discharge (42.8% vs 35.7%, p = 0.039). There was no difference in mortality (≤ 2.4% vs ≤ 2.4%, p = 0.82). Among the embolization patients, the mean interval from embolization to resection was 1.49 days. On multivariate analysis, a longer interval was significantly associated with nonroutine discharge (OR 1.33, p = 0.004) but not with complications or mortality.CONCLUSIONSRelative to meningioma patients who do not undergo preoperative embolization in the same admission, those who do have higher rates of cerebral edema and nonroutine discharge but not higher rates of stroke or death. Thus, meningiomas requiring preoperative embolization represent a distinct clinical entity that requires prolonged, more complex care. Further, among embolization patients, the timing of resection did not affect the risk of in-hospital complications, suggesting that the timing of surgery can be determined according to surgeon discretion.

Introduction: Delays in door to groin puncture time (DGPT) for patients with ischemic stroke caused by acute large vessel occlusions (LVO) are associated with worse clinical outcomes. We present the results of a quality improvement protocol for endovascular stroke treatment at the University of California, San Diego (UCSD) that aimed to minimize DGPT. Materials and Methods: Our stroke team implemented a series of quality improvement measures to decrease DGPT, with a target of 90 minutes or less. Sixty-three patients treated at our center were retrospectively divided into three groups based on the date of their intervention as a proxy for the implementation of process improvement protocols: 23 patients treated from July to December 2015, 24 patients treated from January to July 2016, and 16 patients treated from July 2016 to December 2016. Multivariate log-linear and logistic regression analyses were used to assess the predictors of prolonged DGPT and compliance with target DGPT (

BACKGROUND High-quality physician communication is the foundation for achieving high patient satisfaction. Increasing importance is placed on eliciting feedback from patients. However, there have been few studies looking at the impact of resident involvement on patient satisfaction. Our hospital system values the patient's likelihood to recommend the practice as the top marker for patient satisfaction. METHODS Between May 2016 and December 2016 at University of California, San Diego, all outpatient appointments were randomly mailed Press-Ganey surveys or an eSurvey regarding their experience. The surveys were filtered based on resident participation, and an χ test was performed to assess the impact of residents. An additional aim was to determine the degree to which the impact of resident involvement differed between surgical specialties. Binomial probability was calculated for each specialty using the 'no resident' group as the reference percentage. RESULTS A total of 73,834 surveys were mailed or sent electronically, and 17,653 surveys were returned (23.9% response rate). Overall, patients expressed high levels of satisfaction with the quality of physician communication. Patients who had residents involved in their care reported a decrease in satisfaction with physician communication and a decrease in the likelihood to recommend the practice (88.7% vs 90.4%, P < 0.001). In the analysis of resident impact by surgical specialty, 9 specialties qualified for analysis. Resident involvement was associated with lower physician communication scores in orthopedic surgery (P = 0.032), otolaryngology (P = 0.015), and vascular surgery (P = 0.01). In all other surgical subspecialties, there was no statistically significant difference between groups. CONCLUSIONS Overall, patients expressed high levels of satisfaction with the quality of physician communication with and without resident involvement. Resident physician involvement in surgical clinic visits was associated with lower overall patient satisfaction and decreased likelihood of recommending the practice. In addition, we observed that resident involvement was not associated with lower communication scores in most surgical specialties, including Plastic Surgery.

Mass effect has demonstrated prognostic significance for glioblastoma, but is poorly quantified. Here we define and characterize a novel neuroimaging parameter, lateral ventricle displacement (LVd), which quantifies mass effect in glioblastoma patients. LVd is defined as the magnitude of displacement from the center of mass of the lateral ventricle volume in glioblastoma patients relative to that a normal reference brain. Pre-operative MR images from 214 glioblastoma patients from The Cancer Imaging Archive (TCIA) were segmented using iterative probabilistic voxel labeling (IPVL). LVd, contrast enhancing volumes (CEV) and FLAIR hyper-intensity volumes (FHV) were determined. Associations with patient survival and tumor genomics were investigated using data from The Cancer Genome Atlas (TCGA). Glioblastoma patients had significantly higher LVd relative to patients without brain tumors. The variance of LVd was not explained by tumor volume, as defined by CEV or FLAIR. LVd was robustly associated with glioblastoma survival in Cox models which accounted for both age and Karnofsky’s Performance Scale (KPS) (p = 0.006). Glioblastomas with higher LVd demonstrated increased expression of genes associated with tumor proliferation and decreased expression of genes associated with tumor invasion. Our results suggest LVd is a quantitative measure of glioblastoma mass effect and a prognostic imaging biomarker.

Background: Quality improvement protocols (QI) aim to reduce in-hospital delays that result in prolonged door-to-groin-puncture time (DGPT) for the endovascular treatment of ischemic stroke. At our institution, we implemented a comprehensive QI protocol to reduce DGPT from June 2015 to December 2016. Here we discuss the QI protocol on DGPT across diverse modes of arrival to our interventional suite. Methods: 61 patients underwent mechanical thrombectomy for ischemic stroke during our QI period. Independent samples t-tests were used to investigate differences in DGPT early in the QI protocol (July 2015 to February 2016, n=30) versus late in the QI protocol (March 2016 to December 2016, n=31) for patients that presented via emergency medical services (EMS), inpatient, and hospital transfers. Results: Each mode of arrival demonstrated reductions in DGPT (Figure 1). The greatest reduction in DGPT was for the 23 patients within the emergency medical services (EMS) group with a mean reduction of 39 minutes which approached, but didn’t achieve, statistical significance (138 vs. 99; p=0.06). Discussion: QI interventions impact DGPT across different patient arrival methods. QI protocols accounting for patient presentation allow tailored approaches to institutional measures to reduce DGPT.

OBJECTIVESafety-net hospitals deliver care to a substantial share of vulnerable patient populations and are disproportionately impacted by hospital payment reform policies. Complex elective procedures performed at safety-net facilities are associated with worse outcomes and higher costs. The effects of hospital safety-net burden on highly specialized, emergent, and resource-intensive conditions are poorly understood. The authors examined the effects of hospital safety-net burden on outcomes and costs after emergent neurosurgical intervention for ruptured cerebral aneurysms.METHODSThe authors conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) from 2002 to 2011. Patients ≥ 18 years old who underwent emergent surgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage (SAH) were included. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital included in the NIS database. Hospitals that performed clipping and coiling were stratified as low-burden (LBH), medium-burden (MBH), and high-burden (HBH) hospitals.RESULTSA total of 34,647 patients with ruptured cerebral aneurysms underwent clipping and 23,687 underwent coiling. Compared to LBHs, HBHs were more likely to treat black, Hispanic, Medicaid, and uninsured patients (p < 0.001). HBHs were also more likely to be associated with teaching hospitals (p < 0.001). No significant differences were observed among the burden groups in the severity of subarachnoid hemorrhage. After adjusting for patient demographics and hospital characteristics, treatment at an HBH did not predict in-hospital mortality, poor outcome, length of stay, costs, or likelihood of a hospital-acquired condition.CONCLUSIONSDespite their financial burden, safety-net hospitals provide equitable care after surgical clipping and endovascular coiling for ruptured cerebral aneurysms and do not incur higher hospital costs. Safety-net hospitals may have the capacity to provide equitable surgical care for highly specialized emergent neurosurgical conditions.

Several innovative surgical options for the management of trigeminal neuralgia have emerged over the past 40 years. In addition to microvascular decompression, other techniques have been introduced for the treatment of trigeminal neuralgia and facial nerve pain. This chapter describes the following novel therapeutic modalities: endoscopic microvascular decompression, radiosurgery, radiofrequency, thermocoagulation, glycerol rhizotomoy, balloon compression, Gasserian ganglion stimulation, and subcutaneous trigeminal nerve stimulation. For each of these techniques, this chapter provides a description of the procedure, criteria for patient selection, and discusses published data regarding patient outcomes.

Trigeminal neuralgia is a rare syndrome classically described as brief paroxysms of severe, lancinating facial pain along a unilateral trigeminal nerve distribution. Numerous clinical presentations of trigeminal neuralgia exist, with various distinct etiologies. Several classification schemes have been designed for clinical and research purposes. However, varying terminology and inconsistent utilization of these systems can lead to diagnostic confusion and ungeneralizable research findings. Similarly, multiple pain scales have been used for trigeminal neuralgia with differing degrees of granularity, validity, and reliability. This chapter provides an overview of the commonly used classification systems and pain scales in the context of their evolution and utilization. Furthermore, the authors provide recommendations for application of these systems to clinical and research practice.

Primary repair of cleft lip and palate occurs early in life, but ideal timing of these interventions remains controversial. Prior research has indicated that a later palate repair may improve patients' midfacial growth long term, whereas optimal timing of lip repair to maximize midfacial growth has not been identified.The purpose of this study is to analyze a large, diverse cohort of patients with cleft lip and palate to determine whether timing of primary palate repair and primary lip repair contributed significantly to subsequent orthognathic surgery. Methods Seventy-one nonsyndromic patients with cleft lip and/or palate were followed until age 23 years, and data regarding original diagnosis, surgical procedures, and dates were collected. Within our patient cohort, 12 patients (16.9%) underwent orthognathic surgery. Binary logistic regressions, Fisher exact tests, and Mann-Whitney U tests were used to determine whether timing of primary palate repair and primary lip repair contributed significantly to subsequent orthognathic surgery. Results In our cohort, the association of early lip repair with later orthognathic surgery trended toward significance (P = 0.080). Timing of primary palate repair was not significantly associated with later orthognathic surgery (P= 0.291). When correcting for sex, race, diagnosis, location of care, incidence of lip adhesions, and incidence of lip revisions, patient age at primary lip procedure was a significant predictor of later orthognathic surgery (P = 0.041). Conclusions Inconsistent with prior research, age at primary palate repair in our cohort was not correlated with incidence of orthognathic surgery. Delayed primary lip repair was associated with a significant decrease in the rate of subsequent orthognathic surgery.

GOALS/PURPOSE Plastic surgery residents often desire additional training in rhinoplasty than what is provided by their residency program. The goal of this study was to define and evaluate a specific process used to structure preoperative, intraoperative, and postoperative protocols for rhinoplasty patients in the resident aesthetic clinic (RAC) to enhance qualitative and quantitative experience. Complication rates and patient/resident satisfaction scores were also examined. METHODS Resident clinic rhinoplasty patients underwent a well-defined and established process that included patient education and informed consent, preoperative planning in a conference-based session, specific adherence to established surgical techniques, and structured postoperative management and follow-up. This process also included supervision criteria for residents in the operating room and clinical setting. Patient and resident satisfaction at the RAC was evaluated by a Web-based survey. A database of procedural complications and methods was compiled and evaluated. RESULTS Between June 2012 and June 2015, 146 aesthetic resident cases were completed through the University of California, San Diego Residency Aesthetic Surgery Program. Of these cases, 34 (17%) were rhinoplasty procedures. Residents at our institution assisted on an average of 55 rhinoplasty procedures with the faculty and performed an average of 12 rhinoplasty procedures as primary surgeons. The residents surveyed felt that they had a good autonomous experience (P < 0.001), and 90% reported confidence with rhinoplasty. Postoperative complications were recorded and included asymmetry (n = 4, 10.5%), septal perforation (n = 1, 2.6%), and difficulty in breathing (n = 6, 15.8%). There were no patients who experienced infections, and the complication rate requiring revision in the operating room was 0%. CONCLUSIONS Optimizing protocols in rhinoplasty in an RAC has allowed for the RAC to flourish in the breadth and complexity of rhinoplasty operations. This has enabled residents to gain a structured and autonomous exposure to rhinoplasty cases. Cases were done with an acceptable complication rate and with good patient and resident satisfaction. This is a unique report in that it provides a structured process for preoperative, intraoperative, and postoperative care in rhinoplasty operations.

BACKGROUND Ventral hernia repair is a common procedure and is undertaken by surgeons with varying training backgrounds. Outcomes after hernia repair depend on numerous factors, some being patient or surgeon specific. It remains unclear what the ideal roles are for general and plastic surgeons in open ventral hernia repair. We hypothesized that open ventral hernia repair by plastic surgeons is safe and comparable with general surgeons. METHODS We performed a retrospective observational study using data from the National Surgical Quality Improvement Program database from 2007 to 2013. Patients with a primary diagnosis of ventral hernia undergoing open repair were identified. Multivariate regression modeling was performed, adjusting for surgeon specialty, patient characteristics, common concurrent procedures, and the total number of concurrent procedures. Outcomes studied were major and minor 30-day complications, operation time, readmission, unplanned reoperation, and length of hospital stay. RESULTS We identified 53,746 patients who underwent open repair, 53,282 (99.1%) by general surgeons (GS) and 464 (0.9%) by plastic surgeons (PS). There were significantly different rates of concurrent panniculectomy (12.1% PS vs 2.4% GS) and component separation (24.8% PS vs 5.3% GS), representing increased PS case complexity. 52.3% of GS and 92.9% of PS performed panniculectomy without an alternate specialty surgeon. 81.3% of GS and 97.4% of PS performed component separation without an alternate specialty surgeon. The PS patients had a significantly longer uncorrected length of stay and operation time than GS patients (all P < 0.001). Similarly, PS was positively associated with uncorrected major and minor complications (P < 0.001). However, these relationships did not persist on multivariate analysis after adjusting for demographic characteristics, medical comorbidities, concurrent procedures, and total procedure load. Furthermore, PS was associated with lower odds of major complications (operating room, 0.49; P = 0.05) compared with GS. CONCLUSIONS Outcomes of hernia repair by plastic surgeons are comparable with general surgeons, despite plastic surgeons being involved in many complex cases. Interestingly, we identified that general surgeons are performing adjunctive procedures to ventral hernia previously handled by plastic surgeons. Although further study is warranted, we conclude that for open ventral hernia repair, plastic surgeons provide a comparable alternative to general surgeons.

The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in polygenic diseases is generally challenging. However, hiPSCs from BPD patients responsive to lithium offered unique opportunities to discern lithium's target and hence gain molecular insight into BPD. By profiling the proteomics of BDP-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2). Active non-phosphorylated CRMP2, which binds cytoskeleton, is present throughout the neuron; inactive phosphorylated CRMP2, which dissociates from cytoskeleton, exits dendritic spines. CRMP2 elimination yields aberrant dendritogenesis with diminished spine density and lost lithium responsiveness (LiR). The "set-point" for the ratio of pCRMP2: CRMP2 is elevated uniquely in hiPSC-derived neurons from LiR BPD patients, but not with other psychiatric (including lithium-nonresponsive BPD) and neurological disorders. Lithium (and other pathway modulators) lowers pCRMP2, increasing spine area and density. Human BPD brains show similarly elevated ratios and diminished spine densities; lithium therapy normalizes the ratios and spines. Consistent with such "spine-opathies," human LiR BPD neurons with abnormal ratios evince abnormally steep slopes for calcium flux; lithium normalizes both. Behaviorally, transgenic mice that reproduce lithium's postulated site-of-action in dephosphorylating CRMP2 emulate LiR in BPD. These data suggest that the " lithium response pathway" in BPD governs CRMP2's phosphorylation, which regulates cytoskeletal organization, particularly in spines, modulating neural networks. Aberrations in the posttranslational regulation of this developmentally critical molecule may underlie LiR BPD pathogenesis. Instructively, examining the proteomic profile in hiPSCs of a functional agent-even one whose mechanism-of-action is unknown-might reveal otherwise inscrutable intracellular pathogenic pathways., Funding Agencies:NIH's Library of Integrated Network-based Cellular Signatures Program Viterbi Foundation Neuroscience Initiative Stanley Medical Research Institute R21MH093958 R33MH087896 R01MH095088 Tau Consortium California Institute of Regenerative Medicine training grants University of California, San Diego T32 training grant in psychiatry California Bipolar Foundation International Bipolar Foundation Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Ministry of Education, Science, Sports and Culture in Japan 42890001 RC2MH090011

The biologic processes that contribute to contrast enhancement on magnetic resonance imaging of glioblastoma patients remain poorly understood. Glioblastoma tumors from The Cancer Imaging Archive were segmented using iterative probabilistic voxel labeling. Three parameters of contrast enhancement (CE) were calculated: intensity (CE(i)), heterogeneity (CE(h)), and volumetric ratio to necrosis (CE(r)). Associations between these parameters and gene expression from The Cancer Genome Atlas were examined to gain insights into their underlying biologic process. Glioma CpG island methylator phenotype glioblastomas (G-CIMP) were poorly enhancing. No differences in CE parameters were found between proneural, neural, mesenchymal, and classical glioblastomas. Increased CE(i) was associated with expression of genes that mediate inflammatory immune responses. High CE(h) was associated with increased genes required for tumor migration and invasion, including those that modulate extracellular matrix (ECM) and endothelial vascularity. High CE(r) was associated increased gene expression associated with stressful metabolic states, including hypoxia and starvation. Our results indicate aspects of CE are associated with distinct underlying biology. Integrative analysis of these CE parameters may yield meaningful information pertaining to the biologic state of glioblastomas and guide future therapeutic paradigms.

Researchers employing Pittsburgh Compound B positron emission tomography (PIB-PET) imaging have consistently indentified old normal control (oNC) subjects with elevated tracer uptake, suggesting the presence of beta-amyloid deposition in these individuals. However, a consensus regarding the level at which PIB reveals a biologically meaningful signal does not exist (ie. an appropriate cutoff value for PIB positivity remains unclear). In this exploratory study, we sought to investigate the range of PIB distribution volume ratio (DVR) values present in our oNC cohort (N=75, age range=58-97). oNC subjects were classified based on global PIB index values (average DVR across prefrontal, parietal, lateral temporal and cingulate cortices) by employing two approaches: (1) an iterative outlier approach that revealed a cutoff value of 1.16 (IO-cutoff) and (2) an approach using data from a sample of young normal control subjects (N=11, age range=20-30) that yielded a cutoff value of 1.08 (yNC-cutoff). oNC subjects falling above the IO-cutoff had values similar to AD subjects (“PIB+”, 15%). Subjects falling between the 2 cutoffs were considered to have ambiguous PIB status (“Ambig”, 20%) and the remaining oNC were considered “PIB-“ (65%). Additional measures capturing focal DVR magnitude and extent of elevated DVR values were consistent with the classification scheme using PIB index values, and revealed evidence for elevated DVR values in a subset of PIB- oNC subjects. Furthermore, there were a greater proportion of ambiguously elevated values compared to low values, and these elevated values were present in regions known to show amyloid deposition. The analyses presented in this study, in conjunction with recently published pathological data, suggest a biological relevance of slight PIB elevations in aging.

INTRODUCTION: Surgical decisions guiding the resection of primary brain tumors need to be grounded on evidence of benefit. Using the Surveillance, Epidemiology and End Results (SEER) database, we previously demonstrated robust survival difference between patients who underwent gross total resection (GTR) and subtotal resection (STR). Here we provide an analysis of the patient population afflicted with oligodendrogliomas, anaplastic oligodendrogliomas, and oligoastrocytomas. METHODS: In the SEER database (1999-2010), we identified 2,378 low-grade oligodendrogliomas, 1,028 anaplastic oligodendrogliomas (WHO grade III), and 1,505 oligoastrocytomas (all grades). Kaplan-Meier and multivariate Cox regression were used to assess the pattern of surgical practice and overall survival. RESULTS: In contrast to findings reported for anaplastic astrocytoma and glioblastomas, there is little overall survival benefit between low-grade oligodendrogliomas, anaplastic oligodendrogliomas, and oligoastrocytomas patients who underwent GTR relative to STR. The hazard ratio of dying from low-grade oligodendroglioma in patients who underwent GTR relative to STR was 0.948, (CI: 0.709-1.269; p = 0.720). The hazard ratio of dying from anaplastic oligodendroglioma in patients who underwent GTR relative to STR was 0.866, (CI: 0.654-1.148; p = 0.317). The hazard ratio of dying from low-grade oligoastrocytoma in patients who underwent GTR relative to STR was 1.113, (CI: 0.862-1.437; p = 0.413). CONCLUSION: In contrast to patients with anaplastic astrocytoma and glioblastoma, we observed no significant survival benefit of GTR relative to STR in patients afflicted with glial tumors with an oligodendro-component. Surgical consideration should be undertaken in this context.

To investigate early effects of beta-amyloid (Aβ) on neuronal function, elderly normal controls (NCs, age range 58-97) were scanned with Pittsburgh Compound-B (PIB) positron emission tomography (a measure of Aβ) as well as functional magnetic resonance imaging (a measure of brain activation) while performing an episodic memory-encoding task of natural scenes (also performed by young NCs; age range 18-30). Relationships between Aβ and activation were assessed across task-positive (regions that activate for subsequently remembered vs. forgotten scenes) and task-negative regions (regions that deactivate for subsequently remembered vs. forgotten scenes). Significant task-related activation was present in a distributed network spanning ventrolateral prefrontal, lateral occipital, lateral parietal, posterior inferior temporal cortices, and the right parahippocampal/hippocampus, whereas deactivation was present in many default mode network regions (posteromedial, medial prefrontal, and lateral temporoparietal cortices). Task-positive activation was higher in PIB+ compared with PIB- subjects, and this activation was positively correlated with memory measures in PIB+ subjects. Although task deactivation was not impaired in PIB+ NCs, deactivation was reduced in old versus young subjects and was correlated with worse task memory performance among old subjects. Overall, these results suggest that heightened activation during episodic memory encoding is present in NC elderly subjects with high Aβ.

6567Background: Safety-net hospitals serve a vital role in treating underserved populations. These hospitals often receive less funding, which could lead to different patterns of care for patients ...

OBJECTIVEMarkov modeling is a clinical research technique that allows competing medical strategies to be mathematically assessed in order to identify the optimal allocation of health care resources. The authors present a review of the recently published neurosurgical literature that employs Markov modeling and provide a conceptual framework with which to evaluate, critique, and apply the findings generated from health economics research.METHODSThe PubMed online database was searched to identify neurosurgical literature published from January 2010 to December 2017 that had utilized Markov modeling for neurosurgical cost-effectiveness studies. Included articles were then assessed with regard to year of publication, subspecialty of neurosurgery, decision analytical techniques utilized, and source information for model inputs.RESULTSA total of 55 articles utilizing Markov models were identified across a broad range of neurosurgical subspecialties. Sixty-five percent of the papers were published within the past 3 years alone. The majority of models derived health transition probabilities, health utilities, and cost information from previously published studies or publicly available information. Only 62% of the studies incorporated indirect costs. Ninety-three percent of the studies performed a 1-way or 2-way sensitivity analysis, and 67% performed a probabilistic sensitivity analysis. A review of the conceptual framework of Markov modeling and an explanation of the different terminology and methodology are provided.CONCLUSIONSAs neurosurgeons continue to innovate and identify novel treatment strategies for patients, Markov modeling will allow for better characterization of the impact of these interventions on a patient and societal level. The aim of this work is to equip the neurosurgical readership with the tools to better understand, critique, and apply findings produced from cost-effectiveness research.