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Cognitive impairment has a profound deleterious impact on long-term outcomes of glioma surgery. The human insula, a deep cortical structure covered by the operculum, plays a role in a wide range of cognitive functions including interceptive thoughts and salience processing. Both low-grade (LGG) and high-grade gliomas (HGG) involve the insula, representing up to 25% of LGG and 10% of HGG. Surgical series from the past 30 years support the role of primary cytoreductive surgery for insular glioma patients; however, reported cognitive outcomes are often limited to speech and language function. The breath of recent neuroscience literature demonstrates that the insula plays a broader role in cognition including interoceptive thoughts and salience processing. This article summarizes the vast functional role of the healthy human insula highlighting how this knowledge can be leveraged to improve the care of patients with insular gliomas.

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFB-driven GBM cells induce the expression of the potent proinflammatory cytokine IL-1β in MDM, which engages IL-1R1 in tumor cells, activates the NF-κB pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1β/IL-1R1 between tumors and MDM creates an interdependence driving PDGFB-driven GBM progression. Genetic loss or locally antagonizing IL-1β/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, and reduced exhausted CD8+ T cells and thereby extends the survival of tumor-bearing mice. In contrast to IL-1β, IL-1α exhibits antitumor effects. Genetic deletion of Il1a/b is associated with decreased recruitment of lymphoid cells and loss-of-interferon signaling in various immune populations and subsets of malignant cells and is associated with decreased survival time of PDGFB-driven tumor-bearing mice. In contrast to PDGFB-driven GBM, Nf1-silenced tumors have a constitutively active NF-κB pathway, which drives the expression of MCPs to recruit monocytes into tumors. These results indicate local antagonism of IL-1β could be considered as an effective therapy specifically for proneural GBM.

INTRODUCTION Intracranial electrode monitoring is fundamentally important for epilepsy surgery evaluations. Currently, there is an emerging debate over the optimal approach between subdural grids and stereoelectroencephalography (SEEG). Our institution utilizes two strategies for intracranial EEG ictal recordings: 1) a “hybrid” approach, whereby patients receive combined subdural grid and intraoperative neuronavigation-based depth electrode implantations, and 2) SEEG. METHODS A retrospective review was performed on consecutive patients that underwent hybrid or SEEG implantation from July 2012 to July 2019. Intracranial recordings were utilized in patients with putative seizure onset regions that were MR-negative, poorly localized, and/or abutting eloquent cortex. Hemorrhagic and non-hemorrhagic complications, neurological deficit at discharge, success of localizing seizure focus, one-year Engel I outcomes, and electrode locations. RESULTS 99 hybrid and 44 SEEG procedures were performed. Hemorrhagic complication rates were similar (SEEG: 8%; hybrid: 7.1%, P = .96). SEEG hemorrhages were all intra-axial, whereas hybrid hemorrhages were all extra-axial. Neurological deficits from hybrid cases were quickly reversed with prompt hematoma evacuation, while SEEG was associated with more severe deficits at discharge (P < .01). There was no difference in non-hemorrhagic complications (P = .24). Hybrid cases had higher density of electrode contacts (hybrid: 122.1±28.5, SEEG: 89.8±34.2, P < .01), with more sampling of eloquent cortices. SEEG electrodes were more likely to be located in white matter (SEEG: 34.0%, hybrid: 9.2%, P < .01). CONCLUSION The hybrid and SEEG approaches resulted in similar, relatively low hemorrhage rates in our institutional series. An important difference, however, is that SEEG-related hemorrhages in eloquent brain regions resulted in lasting neurological deficits. Grid-related subdural hemorrhages did not lead to any long-standing injury. The decision to use hybrid or SEEG should tailor the characteristics of either approach to the localization question(s) for a given patien.

Reducing or eliminating persistent disparities in lung cancer incidence and survival has been challenging because our current understanding of lung cancer biology is derived primarily from populations of European descent. Here we show results from a targeted sequencing panel using NCI-MD Case Control Study patient samples and reveal a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. This increase in mutation frequency was validated with independent WES data from the NCI-MD Case Control Study and TCGA. We find that patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. Together, these findings suggest the identification of these potentially actionable mutations could have clinical significance for targeted therapy and the enrollment of minority populations in clinical trials. Lung cancer etiology has largely been studied in homogenous populations of European descent. Here, targeted sequencing in African American lung adenocarcinomas finds significantly higher prevalence of PTPRT and JAK2 mutations, validated independently by whole exome sequencing, highlighting potentially clinically actionable mutations in this population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Abstract BACKGROUND Prescription opioid use and opioid-related deaths have become an epidemic in the United States, leading to devastating economic and health ramifications. Opioids are the most commonly prescribed drug class to treat low back pain, despite the limited body of evidence supporting their efficacy. Furthermore, preoperative opioid use prior to spine surgery has been reported to range from 20% to over 70%, with nearly 20% of this population being opioid dependent. OBJECTIVE To review the medical literature on the effect of preoperative opioid use in outcomes in spine surgery. METHODS We reviewed manuscripts published prior to February 1, 2019, exploring the effect of preoperative opioid use on outcomes in spine surgery. We identified 45 articles that analyzed independently the effect of preoperative opioid use on outcomes (n = 32 lumbar surgery, n = 19 cervical surgery, n = 7 spinal deformity, n = 5 “other”). RESULTS Preoperative opioid use is overwhelmingly associated with negative surgical and functional outcomes, including postoperative opioid use, hospitalization duration, healthcare costs, risk of surgical revision, and several other negative outcomes. CONCLUSION There is an urgent and unmet need to find and apply extensive perioperative solutions to combat opioid use, particularly in patients undergoing spine surgery. Further investigations are necessary to determine the optimal method to treat such patients and to develop opioid-combative strategies in patients undergoing spine surgery.

Purpose We demonstrate the complexities of managing pediatric patients on extracorporeal membrane oxygenation (ECMO) therapy requiring neurosurgery, focusing on systemic anticoagulation, cardiac function, and medically refractory intracranial pressure (ICP). Methods A 3.5-year-old female with Tetralogy of Fallot developed severe ischemic cerebral edema following post-operative cardiac arrest and required ECMO. This case, along with four additional cases of children requiring neurosurgery while on ECMO, was examined. Results Emergency neurosurgical intervention in the primary case led to significant improvement, highlighting the delicate balance between managing ECMO-induced anticoagulation and urgent neurosurgical needs. The additional cases had variable outcomes, emphasizing the challenges of caring for these critically ill patients. Conclusion Successful management of children requiring ECMO support and neurosurgical intervention requires thoughtful multidisciplinary care. This report illustrates some of the nuances in such decision-making, and demonstrates one potential path to a good outcome.

Monocytes and monocyte-derived macrophages (MDMs) from blood circulation infiltrate glioblastoma (GBM) and promote growth. Here, we show that PDGFS-driven GBM cells induce the expression of the potent proinflammatory cytokine IL- 1[beta] in MDM, which engages IL-1R1 in tumor cells, activates the NF-[kappa]B pathway, and subsequently leads to induction of monocyte chemoattractant proteins (MCPs). Thus, a feedforward paracrine circuit of IL-1[beta]/IL-1R1 between tumors and MDM creates an interdependence driving PDGFS-driven GBM progression. Genetic loss or locally antagonizing IL-1[beta]/IL-1R1 leads to reduced MDM infiltration, diminished tumor growth, and reduced exhausted [CD8.sup.+] T cells and thereby extends the survival of tumor-bearing mice. In contrast to IL-1[beta], IL-1[alpha] exhibits antitumor effects. Genetic deletion of ll1a/b is associated with decreased recruitment of lymphoid cells and loss-of-interferon signaling in various immune populations and subsets of malignant cells and is associated with decreased survival time of PDGFS-driven tumor-bearing mice. In contrast to PDGFB-driven GBM, Nf1-silenced tumors have a constitutively active NF-[kappa]B pathway, which drives the expression of MCPs to recruit monocytes into tumors. These results indicate local antagonism of IL-1[beta] could be considered as an effective therapy specifically for proneural GBM.

Purpose African Americans, especially men, have a higher incidence of lung cancer compared with all other racial and ethnic groups in the US. Self-reported race is frequently used in genomic research studies to capture an individual’s race or ethnicity. However, it is clear from studies of genetic admixture that human genetic variation does not segregate into the same biologically discrete categories as socially defined categories of race. Previous studies have suggested that the degree of West African ancestry among African Americans can contribute to cancer risk in this population, though few studies have addressed this question in lung cancer. Methods Using a genetic ancestry panel of 100 SNPs, we estimated West African, European, and Native American ancestry in 1,407 self-described African Americans and 2,413 European Americans. Results We found that increasing West African ancestry was associated with increased risk of lung cancer among African American men (OR Q5 vs Q1  = 2.55 (1.45–4.48), p  = 0.001), while no association was observed in African American women (OR Q5 vs Q1  = 0.90 (0.51–1.59), p  = 0.56). This relationship diminished following adjustment for income and education. Conclusions Genetic ancestry is not a major contributor to lung cancer risk or survival disparities.