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Objective: Neck metastases are a poor prognostic factor in olfactory neuroblastoma (ONB). Pathologic dural invasion (pathDI) may increase the risk of neck metastases due to invasion of dural lymphatics. We aim to evaluate the prognostic value of pathDI in predicting rates of neck metastases and recurrence using a large, multicenter database of ONB patients., Data Sources: Retrospective review of a prospective, multicenter database of electronic health records of all patients who presented with ONB between 2005 and 2021 at nine tertiary academic care centers within North America., Review Methods: Clinicopathologic features including modified Kadish staging systems, margin status, treatment modalities, Hyams grading, follow-up time, and survival., Results: Of 258 ONB patients, 189 patients met the inclusion criteria. The 10-year neck recurrence-free survival (neck-RFS) rates were 85.7% (75.6‒97.3) and 61.8% (47.9‒79.8) for patients without and with pathDI, respectively (p = 0.018). Time-to-event multivariable regression analysis found pathDI to have an odds ratios of 9.7 (95% confidence interval [CI] 1.2-80.4, p = 0.04) for neck-RFS and 9.5 for RFS at any site (95% CI 1.1-83.3, p = 0.04)., Conclusion: In multivariable analysis, the presence of pathDI appears to be the strongest predictor of neck recurrence and recurrence at any site. Future studies exploring the benefit of elective neck dissection or radiation for patients with pathDI may impact disease management., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background and Objective: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated., Methods: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses., Results: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm 3 vs 0.49 ± 1.17 cm 3 , P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis., Conclusion: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Aim: To assess the knowledge, attitudes and practices of Registered Nurses working in residential aged care facilities pertaining to pain management for residents living with dementia., Background: Sub-optimal pain management continues for people living with dementia in residential aged care. Registered Nurses are the pivotal staff responsible for complex assessment and management of people residing in residential aged care facilities., Design and Methods: :This integrative literature review was informed by Whittemore (2005). Searching and screening followed the PRISMA guidelines., Results: Thirteen papers were identified, the major themes identified were gaps in knowledge and skills, uncertainty of assessment, and delays in treatment., Conclusion: Registered Nurses require education on pain management for people living with dementia in residential aged care. Broader issues in residential aged care contribute to the problem and require examination. Research pertaining to Registered Nurses' roles pain management for residents living with dementia is required.

Background: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence., Methods: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses., Results: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence., Conclusions: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning., (© 2024 ARS‐AAOA, LLC.)

This paper presents a novel adaptation of the conventional approximate Bayesian computation sequential Monte Carlo (ABC-SMC) sampling algorithm for parameter estimation in the presence of uncertainties, coined combinatorial ABC-SMC. Inference of this type is used in situations where there does not exist a closed form of the associated likelihood function, which is replaced by a simulating model capable of producing artificial data. In the literature, conventional ABC-SMC is utilised to perform inference on continuous parameters. The novel scheme presented here has been developed to perform inference on parameters that are high-dimensional binary, rather than continuous. By altering the form of the proposal distribution from which to sample candidates in subsequent iterations (referred to as waves), high-dimensional binary variables may be targeted and inferred by the scheme. The efficacy of the proposed scheme is demonstrated through application to vibration data obtained in a structural dynamics experiment on a fibre-optic sensor simulated as a finite plate with uncertain boundary conditions at its edges. Results indicate that the method provides sound inference on the plate boundary conditions, which is validated through subsequent application of the method to multiple vibration datasets. Comparisons between appropriate forms of the metric function used in the scheme are also developed to highlight the effect of this element in the schemes convergence.

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II-VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures., (© 2024. The Author(s).)

Importance: Current olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence., Objective: The primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence., Design, Setting, and Participants: This retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers., Intervention: Standard-of-care ONB treatment., Main Outcome and Measures: The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction., Results: A total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18)., Conclusions and Relevance: The study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.

Objective  The aim of this work was the development of an augmented reality system including the functionality of conventional surgical navigation systems. Methods  An application software for the Augmented Reality System HoloLens 2 from Microsoft was developed. It detects the position of the patient as well as position of surgical instruments in real time and displays it within the two-dimensional (2D) magnetic resonance imaging or computed tomography (CT) images. The surgical pointer instrument, including a pattern that is recognized by the HoloLens 2 sensors, was created with three-dimensional (3D) printing. The technical concept was demonstrated at a cadaver skull to identify anatomical landmarks. Results  With the help of the HoloLens 2 and its sensors, the real-time position of the surgical pointer instrument could be shown. The position of the 3D-printed pointer with colored pattern could be recognized within 2D-CT images when stationary and in motion at a cadaver skull. Feasibility could be demonstrated for the clinical application of transsphenoidal pituitary surgery. Conclusion  The HoloLens 2 has a high potential for use as a surgical navigation system. With subsequent studies, a further accuracy evaluation will be performed receiving valid data for comparison with conventional surgical navigation systems. In addition to transsphenoidal pituitary surgery, it could be also applied for other surgical disciplines., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Skull base chordoma is a rare and locally destructive malignancy which presents unique therapeutic challenges. While achieving gross total resection (GTR) confers the greatest survival advantage, the role of adjuvant radiotherapy (RT) for patients who receive GTR remains unclear in the absence of prospective trials. Here, we aim to assess the effect of RT on survival outcomes in skull base chordoma patients who receive GTR by utilizing the Surveillance, Epidemiology, and End Results (SEER) database., Methods: Patients with diagnostic, primary site, and resection codes specific for chordoma, skull base, and GTR, respectively, were queried in the SEER database (2000-2018). Kaplan-Meier curves (log-rank test) were constructed and Cox proportional hazards models were used to assess survival outcomes., Results: A total of 115 skull base chordomas undergoing GTR were identified, of which 37 (32%) received no RT and 78 (68%) received RT. Median follow-up was 55.00 months (range: 0.00-227.00). Overall survival (OS) of patients with GTR was 85% and 70% at 5 and 10 years, respectively. Multivariate Cox proportional hazard analysis among chordoma patients undergoing GTR found age ≥65 (P < 0.01) was associated with poorer OS outcomes. RT appeared to trend toward offering benefit in terms of OS in patients after GTR, however this did not achieve statistical significance in the adjusted model (HR = 0.51, CI = 0.23-1.16, P = 0.09). When comparing, disease-specific survival was also not improved in patients undergoing RT (HR = 0.58, CI = 0.23-1.46, P = 0.25)., Conclusions: It remains unclear whether RT after GTR of chordoma improved survival outcomes among SEER database patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives  Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. Design  The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. Methods  The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. Setting/Participants  RAPID was formed by 11 academic U.S. pituitary centers. Results  A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. Conclusion  The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Embedded soft sensors can significantly impact the design and control of soft-bodied robots. Although there have been considerable advances in technology behind these novel sensing materials, their application in real-world tasks, especially in closed-loop control tasks, has been severely limited. This is mainly because of the challenge involved with modeling a nonlinear time-variant sensor embedded in a complex soft-bodied system. This article presents a learning-based approach for closed-loop force control with embedded soft sensors and recurrent neural networks (RNNs). We present learning protocols for training a class of RNNs called long short-term memory (LSTM) that allows us to develop accurate and robust state estimation models of these complex dynamical systems within a short period of time. Using this model, we develop a simple feedback force controller for a soft anthropomorphic finger even with significant drift and hysteresis in our feedback signal. Simulation and experimental studies are conducted to analyze the capabilities and generalizability of the control architecture. Experimentally, we are able to develop a closed-loop controller with a control frequency of 25 Hz and an average accuracy of 0.17 N. Our results indicate that current soft sensing technologies can already be used in real-world applications with the aid of machine learning techniques and an appropriate training methodology.

One of the major obstacles to the widespread uptake of data-based Structural Health Monitoring so far, has been the lack of damage-state data for the (mostly high-value) structures of interest. To address this issue, a methodology for sharing data and models between structures has been developed- Population-Based Structural Health Monitoring (PBSHM). PBSHM works on the principle that, if populations of structures are sufficiently similar, or share sections which can be considered similar, then data and models can be shared between them for use in diagnostic inference. The PBSHM methodology therefore relies on two key components: firstly, identifying whether structures are sufficiently similar for successful transfer of diagnostics; this is achieved by the use of an abstract representation of structures. Secondly, machine learning techniques are exploited to effectively transfer information between the structures in a way that improves damage detection and classification across the whole population. Although PBSHM has been conceived to deal with large and general classes of structures, much of the detailed developments presented so far have concerned bridges; the aim of this paper is to provide similarly detailed discussions in the aerospace context. The overview here will examine data transfer between aircraft components, as well as illustrating how one might construct an abstract representation of a full aircraft., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brennan, Gosliga, Gardner, Mills and Worden.)

Objective: Prealbumin levels correlate with overall nutritional status, and low values are associated with poor wound healing. We investigated whether low preoperative prealbumin levels predict risk of endoscopic endonasal skull base surgery (EESBS) reconstruction failure, as demonstrated by postoperative cerebrospinal fluid (CSF) leak and/or infection., Methods: Between October 2018 and February 2020, 98 patients with documented preoperative prealbumin levels were prospectively followed. The incidence of CSF leak and infection in patients with low prealbumin levels (≤20 mg/dL) was compared with those with normal prealbumin levels (>20 mg/dL). Numerous factors previously shown to influence CSF leak rates were assessed. Both univariate and multivariable analyses were performed to identify independent predictive factors., Results: Within this prospectively gathered patient cohort composed of >95% "high-risk" expanded EESBS, 14 of 98 patients (14.3%) experienced a postoperative CSF leak. Factors univariately associated with postoperative complications at the 0.2 level of significance were used in a multivariable model. Low prealbumin levels (≤20 mg/dL) proved to be a strong independent predictive factor associated with a 5-fold increased risk of postoperative CSF leak (odds ratio 5.01, P = 0.01), and postoperative surgical-site infection (P = 0.0009). These associations remained after controlling for multiple other factors, including body mass index, surgical pathology, previous EESBS, risk assessment index, and high- versus low-flow intraoperative CSF leaks., Conclusions: Preoperative prealbumin levels are an independent predictor of EESBS associated CSF leak and infection. Future studies are needed to investigate the utility of screening and correcting prealbumin levels to limit postoperative complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Patients taking a medicinal product in a homecare setting typically use a medical device to facilitate the injection process. Reductions in wireless connectivity costs, combined with the rapid adoption of smartphones with connectivity to cloud-based services, are enabling these drug delivery devices to now be connected to a digital ecosystem as connected combined products (CCPs). The purposes of this article are to identify the challenges in developing and releasing these products when they straddle different regulatory frameworks and standards and to highlight gaps in the European Union regulations., Methods: Industry subject matter experts from pharmaceutical, medical device, and consultancy companies, who are members of the Medtech & Pharma Platform Association, formed 4 working groups to address current best practice for developing and releasing CCPs and the different relevant regulatory frameworks. The 4 areas studied were clinical and regulatory, usability and human factors engineering, development and life cycle management, and cybersecurity., Findings: Development teams require new skills to create innovative products that have a good safety profile and are simple to use, such as design thinking to understand user needs and systems engineering to manage complexity and ensure interoperability. Risk management process should integrate cybersecurity, data privacy, and data integrity, whereas design control processes should enable asynchronous development cycles for hardware and software components. Regulatory frameworks exist for individual components within the CCP. However, for a complex product, regulatory guidance is needed when combining components with different risk and safety profiles and to ensure that the responsibilities and liabilities of companies contributing components are clear. The efficient management of software changes and product updates, as well as dealing with end-of-life hardware and backward compatibility to older software versions, needs agile approaches when it comes to regulatory updates., Implications: The regulatory uncertainties and development processes outlined in this article need to be addressed. We call for joint discussions among the various stakeholders in the fields of medicinal products, medical devices, and in vitro diagnostics, as well as standalone software, data protection, and cybersecurity experts, together with regulators and lawmakers in the European Union to meet in focused discussion groups with the aim of devising pragmatic solutions and regulations for the benefit of the sector and hence the patients it serves., Competing Interests: Declaration of Interest All authors hold positions in commercial companies, but they have not received any grant, honoraria, or other compensation to author this article. The study was conceived of, executed on, and written during the authors’ day job. Authors may hold shares and/or stock options in their respective companies. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2022. Published by Elsevier Inc.)

Objective  The endoscopic endonasal approach (EEA) is commonly employed in skull base surgery for neoplasm resection. While nasal deformity following EEA is described, this study aimed to perform a detailed qualitative and quantitative assessment of the associated saddle nose deformity (SND) in particular. Setting/Participants  This is a retrospective review of 20 adult patients with SND after EEA for resection of skull base tumors over a 5-year period at the University of Pittsburgh Medical Center. Main Outcome Measures  Fifteen measurements related to SND were obtained on pre- and postoperative imaging. Statistical analyses were performed to evaluate differences between pre- and postoperative anatomies. Results  The most common EEA was transsellar. Reconstruction techniques included nine free mucosal grafts alone, eight vascularized nasoseptal flaps (NSFs), one combined free mucosal graft/abdominal fat graft, and one combined NSF/fascia lata graft. Imaging analysis showed a trend toward loss of mean nasal height, nasal tip projection, and nasolabial angle postoperatively. Subgroup analysis showed that patients with NSF reconstruction had a significantly decreased nasal tip projection (1.2 mm, p  = 0.039) and increased alar base width (1.2 mm, p  = 0.046) postoperatively. Patients without functional pituitary microadenomas demonstrated significantly increased nasofrontal angle and decreased nasal tip projection on postoperative imaging, in contrast to those with functional adenomas who had no measurable significant changes. Conclusion  Clinically evident SND does not always lead to significant radiographic changes. This analysis suggests that patients who undergo surgery for indications other than functional pituitary microadenomas or who receive NSF reconstruction develop more marked SND on standard imaging tests., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: In the present study, we investigated the role of intraoperative neuromonitoring (IONM) in internal carotid artery (ICA) injury during endoscopic endonasal skull base surgery (EESBS)., Methods: The study group included all 13 patients who had experienced an ICA injury during EESBS with IONM from 2004 to 2017. The medical records were reviewed for the perioperative data. The IONM reports were reviewed to evaluate the baseline somatosensory evoked potentials (SSEP), electroencephalography (EEG), and brainstem auditory evoked potentials (BAEP) and their significant changes related to ICA injury and/or the subsequent surgical/endovascular interventions., Results: All 13 patients had undergone SSEP and 7 patients had BAEP monitoring during surgery. EEG was added during emergent angiography following the surgery for 5 patients. Two patients showed significant SSEP changes, and one showed significant SSEP and EEG changes, indicating cerebral hypoperfusion. Of these 3 patients, patient 1 had experienced irreversible SSEP loss with postoperative stroke. Patients 2 and 3 had SSEP and/or EEG changes that had recovered to baseline after interventions without postoperative deficits. Despite ICA injury, 10 patients showed no significant SSEP and/or EEG changes, and all 7 patients with BAEP monitoring showed no significant BAEP changes, indicating adequate cerebral and brainstem perfusion, respectively. The injured ICA was sacrificed in 4 patients, of whom 3 showed stable SSEP and 1 had experienced irreversible SSEP loss. IONM correlated with the postoperative neurologic examination findings in all cases, adequately predicting the neurologic outcomes after ICA injury., Conclusion: SSEP and EEG monitoring can accurately detect cerebral hypoperfusion and provide real-time feedback during surgery. SSEP and EEG changes predicted for neurologic outcomes and guide surgical decisions regarding the preservation or sacrifice of the ICA. Comprehensive multimodality monitoring according to the surgical risks can serve to detect and guide the management of ICA injury in EESBS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective  Though microvascular free tissue transfer is well established for open skull base reconstruction, normative data regarding flap design and inset after endoscopic endonasal skull base surgery (ESBS) is lacking. We aim to describe anatomical considerations of endoscopic endonasal inset of free tissue transfer of transclival (TC) and anterior cranial base resection (ACBR) defects. Design and Setting  Radial forearm free tissue transfer (RFFTT) model. Participants  Six cadaveric specimens. Main Outcome Measures  Pedicle orientation, pedicle length, and recipient vessel intraluminal diameter. Results  TC and ACBR defects averaged 17.2 and 11.7 cm 2 , respectively. Anterior and lateral maxillotomies and endoscopic medial maxillectomies were prepared as corridors for flap and pedicle passage. Premasseteric space tunnels were created for pedicle tunneling to recipient facial vessels. For TC defects, the RFFTT pedicle was oriented cranially with the flap placed against the clival defect (mean pedicle length 13.1 ± 0.6 cm). For ACBR defects, the RFFTT pedicle was examined in three orientations with respect to anterior-posterior axis of the RFFTT: anteriorly, posteriorly, and laterally. Lateral orientation offered the shortest average pedicle length required for anastomosis in the neck (11.6 ± 1.29 cm), followed by posterior (13.4 ± 0.7cm) and anterior orientations (14.4 ± 1.1cm) ( p  < 0.00001, analysis of variance). Conclusions  In ACBR reconstruction using RFFTT, our data suggests lateral pedicle orientation shortens the length required to safely anastomose facial vessels and protects the frontal sinus outflow anteriorly while limiting pedicle exposure through a maxillary corridor within the nasal cavity. With greater understanding of anatomical factors related to successful preoperative flap planning, free tissue transfer may be added to the ESBS reconstruction ladder., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Purpose: The skull base inventory (SBI) was developed to better assess health-related quality of life (HR-QOL) in patients with anterior and central skull base neoplasms treated by endoscopic and open approaches. The primary objective of this study was to prospectively assess the psychometric properties of the SBI., Methods: This study is part of a multi-center study of patients undergoing endoscopic and open procedures completed between 2012 and 2018. Participants were eligible if they were over 18 years of age; had benign or malignant anterior, antero-lateral, or central skull base tumors; and required either an open or endoscopic skull base surgical approach. In order to assess the psychometric properties of the SBI, patients completed the instrument at six time points (preoperative, 2 weeks, 3 months, 6 months, 12 months postoperative). Patients also completed the Anterior Skull Base (ASB) questionnaire and the Sinonasal Outcome Test (SNOT-22) to allow comparison to the SBI., Results: One hundred and eighty-seven patients were included across five centers, with 121 having an endoscopic procedure. Internal consistency (Cronbach's alpha = 0.95) and test-retest at 12 months and 12 months plus 2 weeks (intraclass correlation > 0.90) were excellent. Concurrent validity was demonstrated by very strong correlation between total SBI scores and ASB scores (r = 0.810 to 0.869, p < 0.001) and moderate correlation between nasal domain SBI scores and SNOT-22 scores (r = - 0.616 to - 0.738, p < 0.001). Convergent validity was demonstrated by moderate correlation between change in SBI scores and global QOL change (r s  = 0.4942, p < 0.001). The minimally important clinical difference (global HR-QOL change of "a little better" or "a little worse") was 6.0., Conclusion: The SBI questionnaire is reliable and valid for patients treated by both endoscopic and open approaches and can be used for assessment of HR-QOL in these settings.

Objectives/hypothesis: Surgical management of nasopharyngeal tumors has evolved in the endoscopic era. Lateral exposure remains difficult especially near the petrous internal carotid artery and bony Eustachian tube (ET). Our study examines the need to sacrifice the vidian and greater palatine nerves in order to successfully perform en bloc endoscopic nasopharyngectomy., Methods: Four cadaveric specimens (eight sides) were dissected bilaterally using a binarial, extended, endoscopic endonasal approach (EEA). Nasopharyngectomy was completed including an extended transptyergoid approach for resection of the cartilaginous ET at its junction with the bony ET. Dissection was attempted without sacrifice of the vidian or palatine nerves., Results: Successful en bloc nasopharyngectomy combined with a nerve-sparing transpterygoid approach was achieved in all specimens with successful preservation of the palatine and vidian nerves. The approach provided exposure of foramen lacerum, the petrous carotid, foramen spinosum, and foramen ovale as well as all segments of the cartilaginous Eustachian tube, Meckel's cave and the parapharyngeal carotid. There was no inadvertent exposure or injury of the internal carotid artery., Conclusion: Endoscopic nasopharyngectomy combined with a nerve-sparing transpterygoid approach allows for en bloc resection of the cartilaginous Eustachian tube and nasopharyngeal contents with broad skull base exposure and preservation of the internal carotid artery, vidian and palatine nerves., Level of Evidence: VI Laryngoscope, 130:2343-2348, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea-dwelling species will allow several pending evolutionary questions to be unlocked., Findings: We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome., Conclusions: This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments., (© The Author(s) 2020. Published by Oxford University Press.)

This 25-year-old woman presented after a second hemorrhage from a mesencephalic cavernous malformation. High-definition fiber tracking demonstrated lateral displacement of the corticospinal tracts, making a midline approach ideal. The lesion appeared to present to the third ventricle, but a transcallosal approach was abandoned due to the posterior third ventricular location and after FIESTA imaging revealed a superior and medial rim of normal parenchyma that would have to be transgressed to access the malformation. An endoscopic endonasal approach with interdural pituitary hemitransposition was performed. The interpeduncular cistern was accessed and the thalamoperforating arteries dissected to access the cavernous malformation that was completely removed in a piecemeal fashion. The patient's preexisting internuclear ocular palsies and hemiparesis were slightly worsened after surgery as predicted by a drop in anterior tibialis motor evoked potentials. Postoperative MRI showed no infarct, and the hemiparesis was back to baseline at 1-month follow-up. The video can be found here: https://youtu.be/e6203R9HHmk., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2019, Ezequiel Goldschmidt, Andrew S. Venteicher, Maximiliano Nuñez, Eric Wang, Carl Snyderman, and Paul Gardner.)

Competing Interests: Competing interests: None declared.

Near-infrared (NIR) light is commonly used to map venous anatomy in the upper extremities to gain intravenous access for line placement. In this report, the authors describe the use of a common and commercially available NIR vein finder to delineate the cortical venous anatomy prior to dural opening.During a variety of cranial approaches, the dura was directly visualized using an NIR vein finder. The NIR light source allowed for recognition of the underlying cortical venous anatomy, dural sinuses, and underlying pathology before the dura was opened. This information was considered when tailoring the dural opening. When the dura was illuminated with the NIR vein finder, the underlying cortical and sinus venous anatomy was evident and correlated with the observed cortical anatomy. The vein finder was also accurate in locating superficial lesions and pathological dural veins. A complete accordance in the findings on the pre- and post-dural opening images was observed in all cases.This simple, inexpensive procedure is readily compatible with operative room workflow, necessitates no head fixation, and offers a real-time image independent of brain shift.

Background: Many studies have explored molecular markers of carotid plaque development and vulnerability to rupture, usually having examined whole carotid plaques. However, there are regional differences in plaque morphology and known shear-related mechanisms in areas surrounding the lipid core., Objective: To determine whether there are regional differences in protein expression along the long axis of the carotid plaque and how that might produce gaps in our understanding of the carotid plaque molecular signature., Methods: Levels of 7 inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 p70, IFN-γ, and TNF-α) and caspase-3 were analyzed in prebifurcation, bifurcation, and postbifurcation segments of internal carotid plaques surgically removed from symptomatic and asymptomatic patients. Expression profiles of miRNAs and mRNAs were determined with microarrays for the rupture-prone postbifurcation segment for comparison with published whole plaque results., Results: Expression levels of all proteins examined, except IL-10, were lowest in the prebifurcation segment and significantly higher in the postbifurcation segment. Patient group differences in protein expression were observed for the prebifurcation segment; however, no significant differences were observed in the postbifurcation segment between symptomatic and asymptomatic patients. Expression profiles from postbifurcation carotid plaques identified 4 novel high priority miRNAs differentially expressed between patient groups (miR-214, miR-484, miR-942, and miR-1287) and 3 high-confidence miRNA:mRNA targets, including miR-214:APOD, miR-484:DACH1, and miR-942:GPR56., Conclusion: The results demonstrate regional differences in protein expression for the first time and show that focus on the rupture-prone postbifurcation region leads to prioritization for further study of novel miRNA gene regulation mechanisms., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Objective: Diffusion imaging tractography has allowed the in vivo description of brain white matter. One of its applications is preoperative planning for brain tumor resection. Due to a limited spatial and angular resolution, it is difficult for fiber tracking to delineate fiber crossing areas and small-scale structures, in particular brainstem tracts and cranial nerves. New methods are being developed but these involve extensive multistep tractography pipelines including the patient-specific design of multiple regions of interest (ROIs). The authors propose a new practical full tractography method that could be implemented in routine presurgical planning for skull base surgery., Methods: A Philips MRI machine provided diffusion-weighted and anatomical sequences for 2 healthy volunteers and 2 skull base tumor patients. Tractography of the full brainstem, the cerebellum, and cranial nerves was performed using the software DSI Studio, generalized-q-sampling reconstruction, orientation distribution function (ODF) of fibers, and a quantitative anisotropy-based generalized deterministic algorithm. No ROI or extensive manual filtering of spurious fibers was used. Tractography rendering was displayed in a tridimensional space with directional color code. This approach was also tested on diffusion data from the Human Connectome Project (HCP) database., Results: The brainstem, the cerebellum, and the cisternal segments of most cranial nerves were depicted in all participants. In cases of skull base tumors, the tridimensional rendering permitted the visualization of the whole anatomical environment and cranial nerve displacement, thus helping the surgical strategy., Conclusions: As opposed to classical ROI-based methods, this novel full tractography approach could enable routine enhanced surgical planning or brain imaging for skull base tumors.

Background: Vascularized intranasal flaps are the primary reconstructive option for endoscopic skull base defects. Flap vascularity may be compromised by injury to the pedicle or prior endonasal surgery. There is currently no validated technique for intraoperative evaluation of intranasal flap viability., Objective: To evaluate the efficacy of indocyanine green (ICG) near-infrared angiography in predicting the viability of pedicled intranasal flaps during endoscopic skull base surgery through a pilot study., Methods: ICG near-infrared fluorescence endoscopy was performed during endoscopic endonasal surgery for skull base tumors. Intraoperative and postoperative data were collected regarding enhancement of the flap body and pedicle. Fluorescence was rated qualitatively. Postoperatively, flap perfusion was evaluated via MRI-contrast enhancement in addition to clinical outcomes (cerebrospinal fluid leak and endoscopic flap appearance)., Results: Thirty-eight patients underwent ICG fluorescence angiography. Both the body and pedicle enhanced in 20 patients (53%), while the pedicle only enhanced for 12 patients (32%), the body only for 3 (8%), and neither for 3 (8%). When both the pedicle and body enhanced with ICG, the rate of postoperative MRI contrast enhancement was 100% and the rate of flap necrosis was 0%. The sensitivity and specificity of flap pedicle ICG enhancement for predicting postoperative flap MRI enhancement were 97% and 67%, respectively. Two of 3 patients without enhancement developed flap necrosis., Conclusion: ICG fluorescence angiography of intraoperative flap perfusion is feasible and correlates well with outcomes of postoperative MRI flap enhancement and flap necrosis. Additional study is needed to further refine the imaging technique and optimally characterize the clinical utility.

Objectives: To compare robotic-assisted laparoscopic prostatectomy with conventional retropubic radical prostatectomy in maintaining pre-surgery levels of urinary and sexual functioning and to evaluate the efficacy of nerve sparing in prostatectomies in protecting urinary functioning., Material and Methods: Patients (n = 385) receiving both surgical procedures were surveyed prior to surgery. Multiple measures, including the Expanded Prostate Cancer Index Composite, the Sexual Health Inventory for Men, and the International Prostate Symptom Score, assessed sexual and urinary function at an average of 12 months post-surgery., Results: Across multiple measures, while controlling for pre-surgical sexual functioning, robotic-assisted surgery did not offer an advantage in maintaining sexual or urinary function an average of a year following the prostatectomy. Bilateral nerve sparing offered a strong and reliable advantage in the maintenance of sexual function, but not so regarding urinary function., Conclusion: While robotic-assisted prostatectomies may offer a number of medical advantages over open procedures, we found no significant effect on important quality of life outcomes associated with the technique.

Background  We evaluated a transrectus capitis posterior muscle triangle approach to the posterolateral foramen magnum, occipital condyles, jugular tubercle, and the fourth ventricle. We also assessed factors that affect the amount of bone removal required. Objective  To evaluate if the proposed approach is as effective as standard open approaches to expose the lateral portion of the foramen magnum. Methods  The proposed minimally invasive fully endoscopic approach was performed in 15 cadaveric specimens using 4-mm (0- and 45-degree) endoscopes. Results  Using a 5-cm straight paramedian incision, the rectus capitis posterior minor and major muscles were partially removed unilaterally, providing a corridor through the muscles to reach the foramen magnum region. After meticulous soft tissue dissection, key anatomical landmarks can be identified such as the greater occipital nerve, the vertebral artery that wraps around the atlanto-occipital joint, and the bony protuberance that heralds the occipital condyle. A suboccipital craniotomy associated with the transcondylar, supracondylar or paracondylar approach is performed depending on the amount of bone removal desired to maximize the surgical view. By doing so, the jugular foramen can be exposed laterally as well as the fourth ventricle medially. Conclusion  The proposed endoscopic approach can provide access through the transrectus capitis posterior muscle triangle leading directly to the occipital condyle. A stepwise approach is critical to gain a surgical corridor to the inferolateral petroclival region and the fourth ventricle.

Background: Temporary arterial occlusion (TAO) is valuable for minimizing intraoperative rupture risk during intracranial aneurysm microsurgery; however, it may be associated with ischemic injury. This study aims to identify surgical and intraoperative neurophysiologic monitoring factors that predict perioperative stroke risk after TAO., Methods: We performed a retrospective chart review of 177 intracranial aneurysm surgeries at our institution in which TAO was performed before placement of a permanent clip under monitoring with somatosensory evoked potentials (SSEPs) and electroencephalography. Perioperative stroke was defined as a new-onset neurologic deficit that developed within 24 hours postoperatively that was correlated with hypodensity on postoperative computed tomography., Results: Ten (6%) patients developed perioperative stroke in the vascular territory of TAO. SSEP changes were observed in 50% (5/10) of patients with perioperative stroke and in 14% (24/167) of patients without stroke (P = 0.003). Mean maximum single-episode TAO duration for patients who developed perioperative stroke was 12.6 minutes (95% confidence interval 8.1-17.1) and TAO duration for patients without stroke was 8.0 minutes (95% confidence interval 7.3-8.7; P = 0.026). In patients with SSEP changes, risk of stroke was particularly elevated with unruptured aneurysms (P = 0.013) compared with patients with ruptured aneurysms. Temporary clip location, number of occlusive episodes, onset and duration of intraoperative neurophysiologic monitoring changes, and rupture status were not predictive of perioperative stroke., Conclusions: SSEP changes and increased single-episode TAO duration are independently associated with increased perioperative stroke risk. SSEP changes are most predictive for perioperative stroke in unruptured cases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Silicones are inorganic compounds that have been used for the purpose of shunting ventricular fluid since the mid-20th century [1]. Complications of ventriculoperitoneal shunts have rarely been attributed to silicone allergy, with only a handful of cases reported in literature. The classic presentation of allergy to silicone ventriculoperitoneal shunt, i.e., abdominal pain with recurrent skin breakdown along the shunt tract, is nonspecific and difficult to distinguish clinically from other causes of shunt-related symptoms. It can be diagnosed by detection of antisilicone antibodies and is treated with removal of the shunt and replacement, if needed, with a polyurethane shunt system. We report the first case of suspected silicone allergy presenting as clinical peritonitis without overt colonic perforation.

Background: Onset of trigeminal neuralgia (TN) is uncommon in young adults with less favorable benefit from surgical interventions. The aim of this study was to evaluate the role of concomitant psychosomatic disorders in long-term surgical outcomes in this population., Methods: Twenty-one patients younger than 30 years of age were diagnosed initially as having medically refractory TN, and each patient underwent microvascular decompression (MVD) as initial surgical management. Correlation of clinical outcome and psychosomatic disorders (DSM-IV) was evaluated during a 15-year interval., Results: A total of 93 procedures were performed for the management of TN and subsequent iatrogenic craniofacial pain disorders. At a median of 81 months, 8 of 21 patients were free of facial pain. Fourteen patients with concomitant major depressive disorder (MDD) or other anxiety disorders underwent a higher median of procedures compared with 7 patients without known MDD or anxiety (4.5 versus 1 intervention, P = 0.038). Two of 14 patients who were diagnosed with MDD or other anxiety disorders were free of craniofacial pain, whereas 6 of 7 patients without mood or anxiety disorders were free of craniofacial pain ( P = 0.0005). Thirteen patients developed treatment-related complications that required further surgical procedures. Presence of MDD or other anxiety disorders was associated with higher rate of complications ( P = 0.026). One patient with past medical history of severe anxiety died of unknown causes., Conclusions: In young patients with TN, comorbid MDD or anxiety disorders was associated with seeking multiple invasive procedures in multiple academic centers with limited benefit and high rates of surgical induced complications.

Introduction Preservation of the temporal branches of the facial nerve during anterolateral craniotomies is important. Damaging it can inflict undesirable cosmetic defects to the patient. The supraorbital trans-eyebrow approach (SOTE) is a versatile keyhole craniotomy but still has a high rate of frontalis muscle (FM) palsy. Objective Anatomical study to implement the interfascial dissection during the SOTE to preserve the nerves to the FM. Methods Slight modification of the standard technique of the SOTE was performed in 6 cadaveric specimens (12 sides). Results Distal rami to the FM were exposed. The standard "u-shape" incision of the FM can cross over the nerves. Alternatively, an "l-shape" incision was performed until the superior temporal line (STL). An interfascial dissection was performed near to the STL and the interfascial fat pad was used as a protective layer for the nerves. Conclusion Various pathologies can be addressed with the SOTE. In the majority of the cases the cosmetic results are good, but FM palsy remains a drawback of this approach. The interfascial dissection may be used in an attempt to prevent frontalis rami palsy.

OBJECT The aim of this study was to evaluate the value of intraoperative neurophysiological monitoring (IONM) using electromyography (EMG), brainstem auditory evoked potentials (BAEPs), and somatosensory evoked potentials (SSEPs) to predict and/or prevent postoperative neurological deficits in pediatric patients undergoing endoscopic endonasal surgery (EES) for skull base tumors. METHODS All consecutive pediatric patients with skull base tumors who underwent EES with at least 1 modality of IONM (BAEP, SSEP, and/or EMG) at our institution between 1999 and 2013 were retrospectively reviewed. Staged procedures and repeat procedures were identified and analyzed separately. To evaluate the diagnostic accuracy of significant free-run EMG activity, the prevalence of cranial nerve (CN) deficits and the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS A total of 129 patients underwent 159 procedures; 6 patients had a total of 9 CN deficits. The incidences of CN deficits based on the total number of nerves monitored in the groups with and without significant free-run EMG activity were 9% and 1.5%, respectively. The incidences of CN deficits in the groups with 1 staged and more than 1 staged EES were 1.5% and 29%, respectively. The sensitivity, specificity, and negative predictive values (with 95% confidence intervals) of significant EMG to detect CN deficits in repeat procedures were 0.55 (0.22-0.84), 0.86 (0.79-0.9), and 0.97 (0.92-0.99), respectively. Two patients had significant changes in their BAEPs that were reversible with an increase in mean arterial pressure. CONCLUSIONS IONM can be applied effectively and reliably during EES in children. EMG monitoring is specific for detecting CN deficits and can be an effective guide for dissecting these procedures. Triggered EMG should be elicited intraoperatively to check the integrity of the CNs during and after tumor resection. Given the anatomical complexity of pediatric EES and the unique challenges encountered, multimodal IONM can be a valuable adjunct to these procedures.

We present a rare case of skull-base hemorrhagic chondrosarcoma in a patient with Ollier disease. Chondrosarcomas complicated by intracranial hemorrhage are very uncommon, with few reported cases in the literature. To our knowledge, this is the first such reported case.

Objectives To evaluate the incidence and discuss the pathogenesis of early postoperative conductive hearing loss (CHL) after microvascular decompression (MVD) for hemifacial spasm (HFS). Design Pre- and postoperative audiogram data and brainstem auditory evoked potentials (BAEPs) from patients who had underwent MVD for HFS were analyzed. Setting The study was conducted at the University of Pittsburgh Medical Center. Participants MVD for HFS patients who had pre- and postoperative audiogram data, BAEP data, and normal structure of the external and middle ear were included in the study. Main Outcome Measures CHL was diagnosed if there was an air-bone gap in pure tone audiometry of at least 10 dB at 0.5, 1, 2, or 4 kHz. Results The incidence of early postoperative CHL in the ipsilateral ear was 18.7% postoperatively. No CHL was observed in the contralateral side. No significant relationship between CHL and intraoperative BAEP changes was found. Demographic parameters were not significantly different between groups with and without CHL. Conclusions Early postoperative CHL is a significant complication after MVD. Fluid entering the mastoid air cells and/or bone-dust deposition during craniotomy may result in CHL. Long-term audiograms will be needed to evaluate the risk factors that lead to permanent CHL.

Background: Increasing use of endoscopic endonasal surgery for suprasellar lesions with extension into the optic canal (OC) has necessitated a better endonasal description of the OC., Objective: To identify the osseous OC transcranially and then investigate its anatomic relationship to the key endonasal intrasphenoidal landmarks. We also aimed to determine and describe the technical nuances for safely opening the falciform ligament and intracanalicular dura (surrounding the optic nerve [ON]) endonasally., Methods: Ten fresh human head silicon-injected specimens underwent an endoscopic transtuberculum/transplanum approach followed by 2-piece orbitozygomatic craniotomy to allow identification of 20 OCs. After completing up to 270° of endonasal bony decompression of the OC, a dural incision started at the sella and continued superiorly across the superior intercavernous sinus. Subsequently the dural opening was extended anterolaterally across the dura of the prechiasmatic sulcus, limbus sphenoidale, and planum., Results: Endonasally, the length of the osseous OC was approximately 6 mm and equivalent to the length of the lateral opticocarotid recess, as measured anteroposteriorly. The ophthalmic artery arose from the supraclinoidal carotid artery at approximately 2.5 mm from the medial osseous OC entrance. Transcranial correlation of the endonasal dural incision confirmed medial detachment of the falciform ligament and exposure of the preforaminal ON., Conclusion: The lateral opticocarotid recess allows distinction of the preforaminal ON, roofed by the falciform ligament from the intracanalicular segment in the osseous OC. This facilitates the preoperative surgical strategy regarding the extent of OC decompression and dural opening. Extensive endonasal decompression of the OC and division of the falciform ligament is feasible.

Background: The majority of chordomas show activation of the platelet-derived growth factor receptor (PDGFR). Based on in vitro intertumoral variation in response to recombinant PDGF protein and PDGFR inhibition, and variable tumor response to imatinib, we hypothesized that chordomas resistant to PDGFR inhibition may possess downstream activation of the pathway., Methods: Molecular profiling was performed on 23 consecutive chordoma primary tissue specimens. Primary cultures established from 20 of the 23 specimens, and chordoma cell lines, UCH-1 and UCH-2, were used for in vitro experiments., Results: Loss of heterozygosity (LOH) at the phosphatase and tensin homolog (PTEN) locus was observed in 6 specimens (26%). PTEN disruption statistically correlated with increased Ki-67 proliferation index, an established marker of poor outcome for chordoma. Compared to wild type, PTEN deficient chordomas displayed increased proliferative rate, and responded less favorably to PDGFR inhibition. PTEN gene restoration abrogated this growth advantage. Chordomas are characterized by intratumoral hypoxia and local invasion, and histone deacetylase (HDAC) inhibitors are capable of attenuating both hypoxic signaling and cell migration. The combination of PDGFR and HDAC inhibition effectively disrupted growth and invasion of PTEN deficient chordoma cells., Conclusions: Loss of heterozygosity of the PTEN gene seen in a subset of chordomas is associated with aggressive in vitro behavior and strongly correlates with increased Ki-67 proliferative index. Combined inhibition of PDGFR and HDAC attenuates proliferation and invasion in chordoma cells deficient for PTEN.

Background: Skull base tumors comprise many common benign brain tumors. Treatment has advanced, allowing many survivors to return to work. However, literature is limited about the neuropsychological status of these patients prior to treatment. Literature pertaining to the relationship between neuropsychological functioning and occupational ability prior to surgical intervention is even more limited. The purpose of this analysis was to evaluate the impact of neuropsychological function on work productivity in persons with skull base tumors prior to resection., Methods: Neuropsychological function and work productivity were assessed in adults newly diagnosed with skull base tumors ( n = 45) prior to surgical intervention. Univariate analyses identified potential predictors of work limitations; variables with P < .10 were analyzed using multivariate regression analyses controlled for age, sex, tumor type, and education., Results: Poorer mental attention and flexibility (MF) and higher depressive symptoms (DS) were significantly associated with poor time management at work (MF: β = -0.59, P = .01; DS: β = 3.42, P < .01; R 2 = 0.54). Difficulty meeting physical work demands was significantly associated with poorer visuospatial ability (VA) and higher depressive symptoms (VA: β = -3.30, P = .05; DS: β = 2.29, P < .01; R 2 = 0.29). Lower learning and memory scores (LM) and higher depressive symptoms were significantly associated with difficulty meeting mental-interpersonal work demands (LM: β = -3.39, P = .04; DS: β = 3.25, P < .01; R 2 = 0.47) and overall health-related loss of work productivity (LM: β = -0.72, P = .05; DS: β = 0.659, P < .001; R 2 = 0.43)., Conclusion: Domains of neuropsychological function that predicted work productivity were identified. Future research should examine neuropsychological function, depressive symptoms, and work productivity across the care trajectory from diagnosis through long-term survivorship.

Purpose: To evaluate if adding cranial nerves (CNs) V and VI to standard intraoperative neurophysiological monitoring (IONM) of microvascular decompressions for glossopharyngeal neuralgia improve its efficacy., Methods: We reviewed all patients who received a microvascular decompression for glossopharyngeal neuralgia at our institution between January 2008 and August 2012. All received upper extremity somatosensory evoked potentials, brainstem auditory evoked potentials, and free-running electromyography of muscles innervated by ipsilateral CNs VII, IX, and X. The sample was divided into 12 patients who received additional monitoring of CNs V and VI and 15 who did not., Results: No difference on neurotonic activity presence was found on CN V (standard IONM: 0% versus additional CNs IONM: 8.33%; p = 0.423), CN VI (never present on the additional CN patients), CN VII (standard IONM: 73.33% versus additional CNs IONM: 66.64%; p = 0.973), CN IX (standard IONM: 40.0% versus additional CNs IONM: 25.0%; p = 0.683), or CN X (standard IONM: 46.67% versus additional CNs IONM: 33.33%; p = 0.701) between groups. Additionally, no differences of brainstem auditory evoked potentials wave V's delay, and amplitude at the end of the decompression, or closing of the case were found between groups., Conclusions: Monitoring free-running electromyography of additional CNs V and VI does not improve the efficacy of IONM of microvascular decompressions for glossopharyngeal neuralgia.

Background: High-definition fiber tractography (HDFT), an advanced white matter (WM) imaging technique, was evaluated in the management of supratentorial cavernous malformations., Objective: To investigate the relationship of cavernous malformations to the relevant perilesional WM tracts with HDFT and to characterize associated changes first qualitatively and then quantitatively with our novel imaging measure, quantitative anisotropy (QA)., Methods: Imaging analysis was carried out by researchers blinded to the clinical details. Contralateral WM tracts were used for comparison. Mean QA values were obtained for whole WM tracts. Qualitatively affected superior longitudinal fasciculus/arcuate fibers and corticospinal tracts were further analyzed with the use of mean QA values for the perilesional segments., Results: Of 10 patients, HDFT assisted with the decision-making process and the offer of surgical resection in 2 patients, lesion approach and removal in 7 patients, and conservative management in 1 patient. Of 17 analyzed WM tracts, HDFT demonstrated partial disruption in 2 tracts, complete disruption in 2 tracts, a combination of displacement and partial disruption in 1 tract, displacement only in 7 tracts, and no change in 5 tracts. Qualitative changes correlated with clinical symptoms. Mean QA values for the whole WM tracts were similar, with the exception of 1 case demonstrating complete disruption of 2 WM tracts. QA-based perilesional segment analysis was consistent with qualitative data in 5 assessed WM tracts., Conclusion: HDFT illustrated the precise spatial relationship of cavernous malformations to multiple WM tracts in a 3-dimensional fashion, optimizing surgical planning, and demonstrated associated disruption and/or displacement, with both occurring perilesionally. These changes were supported by our quantitative marker, which needs further validation.

Objective: To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal fluid (CSF) diversion in patients presenting with spontaneous CSF otorrhea., Study Design: Retrospective series review., Setting: Tertiary referral center., Patients: Thirty-two patients were treated surgically from 2004 to 2013 for spontaneous CSF otorrhea by the principal investigators. Patients with a history of chronic ear disease and cholesteatoma, previous mastoid surgery, head trauma, or iatrogenic injury were excluded. Average age was 56 years. Twenty-two patients (69%) were female., Intervention(s): Middle fossa repair, transmastoid repair, lumbar puncture, V-P shunt, L-P shunt, and magnetic resonance imaging., Main Outcome Measure(s): Patients underwent middle fossa or transmastoid repair of tegmen defects. Intracranial pressures were determined with lumbar puncture at time of surgical repair or shortly after surgery. CSF diversion procedures were performed in patients who were found to have elevated ICP, which was not controlled medically, presented with recurrent leak or had ICP of 25 cm or greater of H2O. Preoperative BMI was calculated., Results: Thirty-two patients underwent 37 operations. Average BMI was 35.0 kg/m2 (median, 34.7; range, 18.7-53.2 kg/m2). There were 21 repairs on the left and 16 on the right. The majority underwent a middle fossa craniotomy for repair (27/32). Two patients had bilateral repairs. Three patients (8%) underwent revision surgery, of which, 2 had untreated intracranial hypertension (ICP 24.5 and 24 cm H2O). ICP measurements were available for 29 patients. The mean ICP was 23.4 cm H2O (median, 24; range, 13-36 cm H20). Twenty-two patients (69%) had ICP of 20 cm or greater of H20; of those, 13 had an ICP of 25 cm or greater of H20. Seventeen patients (53%) underwent CSF diversion procedures., Conclusion: Our findings of elevated ICP and BMI in patients presenting with spontaneous CSF otorrhea are consistent with previous reports in the literature. The percentage of patients that underwent CSF diversion procedures was high at 53% and represents an aggressive stance in managing elevated ICP in a population that may be at risk for subsequent leaks.

Objective Reconstruction of large clival defects after an endoscopic endonasal procedure is challenging. The objective is to analyze the morphology, indications, and limitations of the extended nasoseptal flap, which adds the nasal floor and inferior meatus mucosa, compared with the standard nasoseptal flap, for clival reconstruction. Design Twenty-seven sides of formalin-fixed anatomical specimens and 13 computed tomography (CT) scans were used. Under 0-degree endoscopic visualization, a standard flap on one side and an extended flap on the other side were performed, as well as exposure of the sella, cavernous sinus, and clival dura mater. Coverage of both flaps was assessed, and they were incised and extracted for measurements. Results The extended flap has two parts: septal and inferior meatal. The extended flaps are 20 mm longer and add 774 mm(2) of mucosal area. They cover a clival defect from tuberculum to foramen magnum in 66.6% cases and from below the sella in 91.6%. They cover both parasellar and paraclival segments of the internal carotid arteries. The lateral inferior limits are the medial aspect of the hypoglossal canals and Eustachian tubes. CT scans can predict the need or limitation of an extended nasoseptal flap. Conclusions The nasal floor and inferior meatus mucosa adds a significant area for reconstruction of the clivus. A defect laterally beyond the hypoglossal canals is not likely covered with this variation of the flap. Preoperative CT scans are useful to guide the reconstruction techniques.

The objective of this study is to investigate late repeat microvascular decompression (MVD) with persistent or recurrent hemifacial spasm (HFS) and to compare the clinical characteristics, intraoperative findings, complications, and outcomes with first MVD. We analyzed MVDs performed at the University of Pittsburgh Medical Center between January 1, 2000 and December 31, 2007. Thirty-three patients who underwent late redo MVDs were classified as group I and 243 patients who underwent their first MVD as group II. Clinical data were collected to analyze the difference between the two groups. The mean follow-up period was 54.48 months (range, 9-102 months). There is no significant difference in preoperative clinical characteristics (gender, age, side of MVD, botox usage, facial weakness) between the two groups. In present study, we found a vein as the offending vessel in significantly more number of patients who underwent repeat MVD as compared to first MVD (P = 0.02). The lateral spread response disappeared in 66% of patients during repeat MVDs, which is not different from those undergoing their first MVD. No difference in the relief rate was found during the immediate postoperative, discharge, or follow-up stages between repeat and first MVD. Moreover, no difference was found in the incidence of complications between repeat MVD and first MVD. Late repeat MVD for HFS is an effective and safe procedure. No specific preoperative clinical characteristics were identified in patients with repeat MVD. Intraoperative monitoring with lateral spread response (LSR) is an effective tool to evaluate adequate decompression. In patients with persistent LSR at the end of the procedure, facial nerve compression from a vein should be examined. We believe that it is important to undergo a repeat MVD for failed HFS relief irrespective of the timing of the operation.

Salmonella enterica serovar Typhimurium definitive type 2 (DT2) is host restricted to Columba livia (rock or feral pigeon) but is also closely related to S. Typhimurium isolates that circulate in livestock and cause a zoonosis characterized by gastroenteritis in humans. DT2 isolates formed a distinct phylogenetic cluster within S. Typhimurium based on whole-genome-sequence polymorphisms. Comparative genome analysis of DT2 94-213 and S. Typhimurium SL1344, DT104, and D23580 identified few differences in gene content with the exception of variations within prophages. However, DT2 94-213 harbored 22 pseudogenes that were intact in other closely related S. Typhimurium strains. We report a novel in silico approach to identify single amino acid substitutions in proteins that have a high probability of a functional impact. One polymorphism identified using this method, a single-residue deletion in the Tar protein, abrogated chemotaxis to aspartate in vitro. DT2 94-213 also exhibited an altered transcriptional profile in response to culture at 42°C compared to that of SL1344. Such differentially regulated genes included a number involved in flagellum biosynthesis and motility. IMPORTANCE Whereas Salmonella enterica serovar Typhimurium can infect a wide range of animal species, some variants within this serovar exhibit a more limited host range and altered disease potential. Phylogenetic analysis based on whole-genome sequences can identify lineages associated with specific virulence traits, including host adaptation. This study represents one of the first to link pathogen-specific genetic signatures, including coding capacity, genome degradation, and transcriptional responses to host adaptation within a Salmonella serovar. We performed comparative genome analysis of reference and pigeon-adapted definitive type 2 (DT2) S. Typhimurium isolates alongside phenotypic and transcriptome analyses, to identify genetic signatures linked to host adaptation within the DT2 lineage.

Objectives: To evaluate the value of intraoperative neurophysiological monitoring (IONM) using brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SSEP) monitoring to predict and/or prevent postoperative neurological deficits during endoscopic endonasal surgery (EES)., Methods: We retrospectively identified 138 consecutive patients who had BAEP monitoring in addition to SSEP monitoring during EES at our institution. We reviewed the postoperative clinical outcomes and neurophysiological changes independently., Results: The total of number of patients with any IONM changes was 10. The incidence of BAEP changes was 3.62%. The incidence of SSEP changes was 3.62% as well. One patient had changes in both BAEPs and SSEPs. Majority of the changes were observed during changes in mean arterial pressure (MAP) without any postoperative neurological deficits. There were two postoperative neurological deficits., Discussion: BAEPs and SSEPs provide unique information about integrity of brainstem function during EES procedures involving tumors in the and around clival region. We advocate a comprehensive multimodality approach to IONM during EESs including BAEPs and SSEPs depending on the location of the neural structures at risk.

Objective To evaluate the value of free-run electromyography (f-EMG) monitoring of extraocular cranial nerves (EOCN) III, IV, and VI during expanded endonasal surgery (EES) of the skull base in reducing iatrogenic cranial nerve (CN) deficits. Design We retrospectively identified 200 patients out of 990 who had at least one EOCN monitored during EES. We further separated patients into groups according to the specific CN monitored. In each CN group, we classified patients who had significant (SG) f-EMG activity as Group I and those who did not as Group II. Results A total of 696 EOCNs were monitored. The number of muscles supplied by EOCNs that had SG f-EMG activity was 88, including CN III = 46, CN IV = 21, and CN VI = 21. There were two deficits involving CN VI in patients who had SG f-EMG activity during surgery. There were 14 deficits observed, including CN III = 3, CN IV = 2, and CN VI = 9 in patients who did not have SG f-EMG activity during surgery. Conclusions f-EMG monitoring of EOCN during EES can be useful in identifying the location of the nerve. It seems to have limited value in predicting postoperative neurological deficits. Future studies to evaluate the EMG of EOCN during EES need to be done with both f-EMG and triggered EMG.