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CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8(+) and CD4(+) T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host's ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.

Purpose The Woven EndoBridge (WEB) can be used to treat wide-necked aneurysms without antiplatelet medications, suggesting it may have advantages in the setting of aneurysmal subarachnoid hemorrhage (aSAH). The goal was assessment of safety and efficacy of WEB in aSAH given the delayed nature of aneurysmal thrombosis. Methods An international retrospective analysis of patients with aSAH treated with WEB was conducted at 7 tertiary centers from 2016 to 2020. Outcomes included rates of rebleeding, retreatment, complications, and complete occlusion. Furthermore, a systematic review and meta-analysis was conducted from 2011 to 2020 assessing the same outcomes. All pooled event rates were calculated using a random effect model. Results Consecutive patients with aSAH harbored 25 aneurysms that were treated with 29 WEB devices. The mean age was 53 years, and 65% were female. Zero experienced rebleeding, 2 were retreated, 2 experienced complications, 16 were completely occluded at 3 months, and 21 were completed occluded at 9–12 months. Meta-analysis of 309 WEB treatments for aSAH from 7 case series revealed 2.5% (95% CI 1–5%) had rebleeding, 9% (95% CI 4–17%) were retreated, 17% (95% CI 10–30%) had complications, and 61% (95% CI 51–71%) were completely occluded at 3–6 months. Conclusion WEB embolization in the setting of aSAH provides similar protection against rebleeding with comparable retreatment rates to traditional approaches. However, there is a higher rate of incomplete radiographic occlusion and operative complications compared to WEB embolization of unruptured aneurysms. Long-term prospective studies are needed to fully delineate the role of WEB embolization in aSAH.

PurposeWe aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO).MethodsPubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted.ResultsForty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05).ConclusionSBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.

The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors. Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID) with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD) or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor. In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL) for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers. Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally inhibit HER receptors. NCT00359190.

For the past three decades, neurosurgeons have utilized cranial neuro-navigation systems, bringing millimetric accuracy to operating rooms worldwide. These systems require an operating room team, anesthesia, and, most critically, cranial fixation. As a result, treatments for acute neurosurgical conditions, performed urgently in emergency rooms or intensive care units on awake and non-immobilized patients, have not benefited from traditional neuro-navigation. These emergent procedures are performed freehand, guided only by anatomical landmarks with no navigation, resulting in inaccurate catheter placement and neurological deficits. A rapidly deployable image-guidance technology that offers highly accurate, real-time registration and is capable of tracking awake, moving patients is needed to improve patient safety. The Zeta Cranial Navigation System is currently the only non-fiducial-based, FDA-approved neuro-navigation device that performs real-time registration and continuous patient tracking. To assess this system’s performance, we performed registration and tracking of phantoms and human cadaver heads during controlled motions and various adverse surgical test conditions. As a result, we obtained millimetric or sub-millimetric target and surface registration accuracy. This rapid and accurate frameless neuro-navigation system for mobile subjects can enhance bedside procedure safety and expand the range of interventions performed with high levels of accuracy outside of an operating room.

Background Robotic-assisted surgery is used with increasing frequency in general surgery for a variety of applications. In spite of this increase in usage, the learning curve is not yet defined. This study reviews the literature on the learning curve in robotic general surgery to inform adopters of the technology. Methods PubMed and EMBASE searches yielded 3690 abstracts published between July 1986 and March 2016. The abstracts were evaluated based on the following inclusion criteria: written in English, reporting original work, focus on general surgery operations, and with explicit statistical methods. Results Twenty-six full-length articles were included in final analysis. The articles described the learning curves in colorectal (9 articles, 35%), foregut/bariatric (8, 31%), biliary (5, 19%), and solid organ (4, 15%) surgery. Eighteen of 26 (69%) articles report single-surgeon experiences. Time was used as a measure of the learning curve in all studies (100%); outcomes were examined in 10 (38%). In 12 studies (46%), the authors identified three phases of the learning curve. Numbers of cases needed to achieve plateau performance were wide-ranging but overlapping for different kinds of operations: 19–128 cases for colorectal, 8–95 for foregut/bariatric, 20–48 for biliary, and 10–80 for solid organ surgery. Conclusion Although robotic surgery is increasingly utilized in general surgery, the literature provides few guidelines on the learning curve for adoption. In this heterogeneous sample of reviewed articles, the number of cases needed to achieve plateau performance varies by case type and the learning curve may have multiple phases as surgeons add more complex cases to their case mix with growing experience. Time is the most common determinant for the learning curve. The literature lacks a uniform assessment of outcomes and complications, which would arguably reflect expertise in a more meaningful way than time to perform the operation alone.

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide and many patients with TBI require intensive care unit (ICU) management. When facing a life-threatening illness, such as TBI, a palliative care approach that focuses on noncurative aspects of care should always be considered in the ICU. Research shows that neurosurgical patients in the ICU receive palliative care less frequently than the medical patients in the ICU, which is a missed opportunity for these patients. However, providing appropriate palliative care to neurotrauma patients in an ICU can be difficult, particularly for young adult patients. The patients’ prognoses are often unclear, the likelihood of advance directives is small, and the bereaved families must act as decision-makers. This article highlights the different aspects of the palliative care approach as well as barriers and challenges that accompany the TBI patient population, with a particular focus on young adult patients with TBI and the role of their family members. The article concludes with recommendations for physicians for effective and adequate communication to successfully implement the palliative care approach into standard ICU care and to improve quality of care for patients with TBI and their families.

BACKGROUND:Intraoperative electrocorticography (ECoG) has been utilized in patients with tumor-associated seizures; however, its effectiveness for seizure control remains controversial. OBJECTIVE:To evaluate clinical outcomes in pediatric patients undergoing lesionectomy with or without ECoG. METHODS:Patients undergoing brain tumor resection at Boston Childrenʼs Hospital were examined retrospectively (2005–2014). Inclusion criteria involved diagnosis of a supratentorial tumor, ≥2 unequivocal seizures, and ≥6 mo follow-up. Patients with isolated cortical dysplasia or posterior fossa tumors were excluded. Logistic regression models evaluated predictors of ECoG use, and the impact of ECoG, gross total resection, and focal cortical dysplasia with tumors on seizure freedom by Engel Class and anti-epileptic drug use (AED). RESULTS:A total of 119 pediatric patients were included (n = 69 males, 58%; median age, 11.3 yr). Forty-one patients (34.5%) had ECoG-guided surgery. Preoperative seizure duration and number and duration of AED use were significant predictors for undergoing ECoG. There were no differences in seizure freedom (Engel Class I) or improved Engel Score (Class I-II vs III-IV) in patients who did or did not have ECoG at 30 d, 6 mo, and 1, 2, or 5 yr. Patients undergoing ECoG required a greater number of AEDs at 6 mo (P = .01), although this difference disappeared at subsequent time intervals. Gross total resection predicted seizure freedom at 30 d and 6 mo postsurgery (P = .045). CONCLUSION:This retrospective study, one of the largest evaluating the use of ECoG during tumor resection, suggests that ECoG does not provide improved seizure freedom compared to lesionectomy alone for children.

PurposeThalamic gliomas are rare neoplasms that pose significant surgical challenges. The literature is limited to single-institution retrospective case series. We systematically review the literature and describe the clinical characteristics, treatment strategies, and survival outcomes of adult thalamic gliomas.MethodsRelevant articles were identified on PubMed, Scopus, and Cochrane databases. Papers containing cases of adult thalamic gliomas with clinical outcome data were included. A comprehensive review of clinical characteristics and survival analysis was conducted.ResultsWe included 25 studies comprising 617 patients. The median age was 45 years (male = 58.6%). Glioblastoma was the most frequent histological type (47.2%), and 82 tumors were H3 K27M-mutant. Motor deficit was the most common presenting symptom (51.8%). Surgical resection was performed in 69.1% of cases while adjuvant chemotherapy and radiotherapy were administered in 56.3% and 72.6%, respectively. Other treatments included laser interstitial thermal therapy, which was performed in 15 patients (2.4%). The lesion laterality (P = 0.754) and the surgical approach (P = 0.111) did not correlate with overall survival. The median progression-free survival was 9 months, and the overall two-year survival rate was 19.7%. The two-year survival rates of low-grade and high-grade thalamic gliomas were 31.0% and 16.5%, respectively. H3 K27M-mutant gliomas showed worse overall survival (P = 0.017).ConclusionAdult thalamic gliomas are associated with poor survival. Complete surgical resection is associated with improved survival rates but is not always feasible. H3 K27M mutation is associated with worse survival and a more aggressive approach should be considered for mutant neoplasms.

Abstract BACKGROUND Transitional care programs (TCPs) coordinate care to improve safety and efficiency surrounding hospital discharge. While TCPs have the potential to reduce hospital length of stay and readmissions, their financial implications are less well understood. OBJECTIVE To perform a cost-benefit analysis of a previously published neurosurgical TCP implemented at an urban academic hospital from 2013 to 2015. METHODS Patients received intensive preoperative education and framing of expectations for hospitalization, in-hospital discharge planning and medication reconciliation with a nurse educator, and a follow-up phone call postdischarge. The cost-benefit analysis involved program costs (nurse educator salary) and total direct hospital costs within the 30-d perioperative window including readmission costs. RESULTS The average cost of the TCP was $435 per patient. The TCP was associated with an average total cost reduction of 17.2% (95% confidence interval [CI]: 7.3%-26.7%, P = .001). This decrease was driven by a 14.3% reduction in the average initial admission cost (95% CI: 6.2%-23.7%, P = .001), largely attributable to the 16.3% decrease in length of stay (95% CI: 9.93%-23.49%, P < .001). Thirty-day readmissions were significantly decreased in the TCP group, with a 5.5% readmission rate for controls and 2.4% for TCP enrollees (P = .04). The average cost of readmission was decreased by 71.3% (95% CI: 58.7%-74.7%, P < .01). CONCLUSION This neurosurgical TCP was associated with decreased costs of initial admissions, 30-d readmissions, and total costs of hospitalization alongside previously published decreased length of stay and reduced 30-d readmission rates. These results underscore the clinical and financial feasibility and impact of transitional care in a surgical setting.