Faculty Bibliography

Purpose of Review: Treating malignant tumors of the anterior skull base (ASB) is a challenging task, involving complex surgery in an intricate anatomical space. The effective treatment of ASB tumors requires careful pretreatment evaluation and preoperative surgical planning by the skull base surgical team. Recent Findings: Review of the available literature demonstrates that the gradual refinement of imaging and surgical techniques, as well as improvement in reconstructive procedures, has dramatically improved patient outcomes and reduced morbidity and mortality. Furthermore, multicenter collaborations have provided higher quality evidence regarding disease behavior and treatment efficacy and safety. Summary: Current and past review of the literature continues to demonstrate the need for future investigation. High-quality evidence-based medicine is still lacking in the field of skull base surgery, and well-planned collaborative studies are needed in order to consolidate our understanding of disease behavior and treatment strategies.

HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.4 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Pharmacological Approaches for the Management of Persistent Pain in Older Adults: What Nurses Need to Know" found on pages 49-57, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until November 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe age-related barriers to pain assessment and key aspects of the assessment process. 2. Identify benefits and risks associated with commonly prescribed analgesic medications for the treatment of later life pain. DISCLOSURE STATEMENT Neither the planners nor the authors have any conflicts of interest to disclose. The current article addresses pharmacological treatment issues regarding the management of persistent pain in later life, which is a worldwide problem associated with substantial disability. Recommendations from guidelines were reviewed and data are presented regarding the benefits and risks of commonly prescribed analgesic medications. The evidence base supports a stepwise approach with acetaminophen as first-line therapy for mild-to-moderate pain. Oral nonsteroidal anti-inflammatory drugs are not recommended for long-term use. In properly selected older patients, opioid drugs should be considered if pain is not adequately controlled. Careful surveillance to monitor for benefits and harms of therapy is critical, given that advancing age increases risk for adverse effects. Key aspects of the pain care process that nurses routinely engage in are covered, including conducting pain assessments prior to initiating therapy, addressing barriers to effective pain care, educating patients and family members about the importance of reducing pain, discussing treatment-related risks and benefits, and formulating strategies to monitor for treatment outcomes. Finally, a case is presented to illustrate issues that arise in the care of affected patients. [Journal of Gerontological Nursing, 42(12), 49-57.].

OBJECTIVES/HYPOTHESIS/OBJECTIVE:The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN/METHODS:Retrospective review. METHODS:Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS:tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS:patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE/METHODS:4. Laryngoscope, 126:2733-2738, 2016.

Cochlear implants (CIs) bypass some of the mechanisms that underlie normal neural behavior as occurs in acoustic hearing. One such neural mechanism is short-term adaptation, which has been proposed to have a significant role in speech perception. Acoustically-evoked neural adaptation has been mainly attributed to the depletion of neurotransmitter in the hair-cell to auditory-nerve synapse and is therefore not fully present in CI stimulation. This study evaluated a signal processing method that integrated a physiological model of hair-cell adaptation into CI speech processing. The linear high-pass adaptation process expanded the range of rapid variations of the electrical signal generated by the clinical processing strategy. Speech perception performance with the adaptation-based processing was compared to that of the clinical strategy in seven CI users. While there was large variability across subjects, the new processing improved sentence recognition and consonant identification scores in quiet in all the tested subjects with an average improvement of 8% and 6% respectively. Consonant recognition scores in babble noise were improved at the higher signal-to-noise ratios tested (10 and 6 dB) only. Information transfer analysis of consonant features showed significant improvements for manner and place of articulation features, but not for voicing. Enhancement of within-channel envelope cues was confirmed by consonant recognition results obtained with single-channel strategies that presented the overall amplitude envelope of the signal on a single active electrode. Adaptation-inspired envelope enhancement techniques can potentially improve perception of important speech features by CI users.

Medical imaging techniques provide a wealth of information for surgical preparation, but it is still often the case that surgeons are examining three-dimensional pre-operative image data as a series of two-dimensional images. With recent advances in visual computing and interactive technologies, there is much opportunity to provide surgeons an ability to actively manipulate and interpret digital image data in a surgically meaningful way. This article describes the design and initial evaluation of a virtual surgical environment that supports patient-specific simulation of temporal bone surgery using pre-operative medical image data. Computational methods are presented that enable six degree-of-freedom haptic feedback during manipulation, and that simulate virtual dissection according to the mechanical principles of orthogonal cutting and abrasive wear. A highly efficient direct volume renderer simultaneously provides high-fidelity visual feedback during surgical manipulation of the virtual anatomy. The resulting virtual surgical environment was assessed by evaluating its ability to replicate findings in the operating room, using pre-operative imaging of the same patient. Correspondences between surgical exposure, anatomical features, and the locations of pathology were readily observed when comparing intra-operative video with the simulation, indicating the predictive ability of the virtual surgical environment.

BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.

A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species, including humans. Here we describe a novel recombinant adeno-associated virus that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABAergic function in virtually any vertebrate species.

To assess the role of abnormal transforming growth factor-beta (TGF-beta) signaling in the pathogenesis of primary myelofibrosis (PMF), the effects of the TGF-beta receptor-1 kinase inhibitor SB431542 on ex vivo expansion of hematopoietic cells in cultures from patients with JAK2V617+-polycythemia vera (PV) or PMF (JAK2V617F+, CALRpQ365f+, or unknown) and from normal sources (adult blood, AB, or cord blood, CB) were compared. In cultures of normal sources, SB431542 significantly increased by 2.5-fold the number of progenitor cells generated by days 1-2 (CD34+) and 6 (colony-forming cells) (CB) and that of precursor cells, mostly immature erythroblasts, by days 14-17 (AB and CB). In cultures of JAK2V617F+-PV, SB431542 increased by twofold the numbers of progenitor cells by day 10 and had no effect on that of precursors cells by days 12-17 ( approximately fourfold increase in all cases). In contrast, SB431542 had no effect on the number of either progenitor or precursor cells in cultures of JAK2V617F+ and CALR pQ365fs+ PMF. These ontogenetic- and disease-specific effects were associated with variegation in the ability of SB431542 to induce CD34+ cells from AB (increased), CB (decreased), or PV and PMF (unaffected) into cycle and erythroblasts in proliferation (increased for AB and PV and unaffected for CB and PMF). Differences in expansion of erythroblasts from AB, CB, and PV were associated with differences in activation of TGF-beta signaling (SHCY317, SMAD2S245/250/255, and SMAD1S/S/SMAD5S/S/SMAD8S/S) detectable in these cells by phosphoproteomic profiling. In conclusion, treatment with TGF-beta receptor-1 kinase inhibitors may reactivate normal hematopoiesis in PMF patients, providing a proliferative advantage over the unresponsive malignant clone.

Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.