Faculty Bibliography

Human papillomavirus (HPV) was recently identified as a risk factor for oropharyngeal squamous cell carcinoma (SCC) independent of tobacco and alcohol use. The prognosis of patients with HPV-related oropharyngeal carcinomas is better than that for patients with non-HPV-related cancers. Researchers and clinicians can test for HPV infection in cancer by (1) testing directly for HPV DNA and (2) testing for overexpression of the downstream p16 protein; there is currently no consensus regarding which is the better test. The chances of developing a reliable oropharyngeal HPV screening test for high-risk populations are promising. Such a test would allow for secondary prevention by identifying individuals with precursor or early-stage cancerous lesions that are more amenable to treatment. HPV testing has particular significance in SCC of an unknown primary site in head and neck cancer. Successful HPV testing of nodal metastasis can localize cancer specifically to the oropharynx. The optimal evaluation for SCC of an unknown primary in the head and neck has yet to be determined. Some studies have shown that the tonsillar fossa is the most probable primary site, followed closely by the base of the tongue. Biopsies often miss tonsillar carcinoma in the deep crypts of the lymph tissue, as well as in those rare cases in which the primary tumor is located contralateral to the metastatic lymph node. Recently, there has been an increase in the number of reports of diagnosed synchronous bilateral HPV-related tonsillar carcinomas. This increase has profound implications for the surgical approach of SCC of an unknown primary site in the head and neck and in tonsillar carcinoma, and it supports the need for bilateral tonsillectomy. We present 2 cases of incidentally discovered synchronous bilateral tonsillar carcinoma, and we review the literature.

BACKGROUND: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). METHODS: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. RESULTS: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. CONCLUSION: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

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.].

OBJECTIVE: To evaluate the role of tension on the genioglossus muscle in the performance of genioglossus advancement on sleep-disordered breathing in patients undergoing multilevel obstructive sleep apnea (OSA) surgery. STUDY DESIGN: Prospective study. SETTING: Academic practice. SUBJECTS AND METHODS: Twenty-three subjects underwent genioglossus advancement with uvulopalatopharyngoplasty for OSA. Subjects underwent pre- and postoperative polysomnography, cephalometry, and subjective assessment questionnaires. Eighteen subjects completed the study. The tension force of the mandible and the bicortical width of the genial tubercle were measured and surgical response determined. RESULTS: Improvement in apnea-hypopnea index (AHI) was seen in 15 of 18 subjects (83.3%). Eleven subjects were classified as responders and 7 as nonresponders (61.1% success), with responders exhibiting a statistically significant reduction in mean delta AHI as compared with nonresponders: 28.3 +/- 26.2 versus 2.0 +/- 22.0 events per hour (95% confidence interval, 1.8-50.8; P = .037). The Epworth Sleepiness Scale improved from 13.2 +/- 4.5 to 7.6 +/- 3.4 (P = .002). There was no significant difference in body mass index, neck circumference, overall tension, or mandibular width between responders and nonresponders. However, there was a significant difference in the tension:width ratio between responders (53.9 +/- 6.38 g/mm) and nonresponders (65.4 +/- 11.2 g/mm; 95% confidence interval, 0.92-22.1; P = .036). CONCLUSION: This article describes a novel approach to determine the force applied to the genioglossus during advancement and its correlation to postoperative outcomes. The tension:width ratio may be an indicator for postoperative success and delta AHI improvement in OSA patients.

BACKGROUND: The effect of many contemporary chemotherapeutic drugs on pregnancy and livebirth is not well established. We aimed to establish the effects of these drugs on pregnancy in male and female survivors of childhood cancer not exposed to pelvic or cranial radiotherapy. METHODS: We used data from a subset of the Childhood Cancer Survivor Study cohort, which followed 5-year survivors of the most common types of childhood cancer who were diagnosed before age 21 years and treated at 27 institutions in the USA and Canada between 1970 and 1999. We extracted doses of 14 alkylating and similar DNA interstrand crosslinking drugs from medical records. We used sex-specific Cox models to establish the independent effects of each drug and the cumulative cyclophosphamide equivalent dose of all drugs in relation to pregnancies and livebirths occurring between ages 15 years and 44 years. We included siblings of survivors as a comparison group. FINDINGS: We included 10 938 survivors and 3949 siblings. After a median follow-up of 8 years (IQR 4-12) from cohort entry or at age 15 years, whichever was later, 4149 (38%) survivors reported having or siring a pregnancy, of whom 3453 (83%) individuals reported at least one livebirth. After a median follow-up of 10 years (IQR 6-15), 2445 (62%) siblings reported having or siring a pregnancy, of whom 2201 (90%) individuals reported at least one livebirth. In multivariable analysis, survivors had a decreased likelihood of siring or having a pregnancy versus siblings (male survivors: hazard ratio [HR] 0.63, 95% CI 0.58-0.68; p<0.0001; female survivors: 0.87, 0.81-0.94; p<0.0001) or of having a livebirth (male survivors: 0.63, 0.58-0.69; p<0.0001; female survivors: 0.82, 0.76-0.89; p<0.0001). In male survivors, reduced likelihood of pregnancy was associated with upper tertile doses of cyclophosphamide (HR 0.60, 95% CI 0.51-0.71; p<0.0001), ifosfamide (0.42, 0.23-0.79; p=0.0069), procarbazine (0.30, 0.20-0.46; p<0.0001) and cisplatin (0.56, 0.39-0.82; p=0.0023). Cyclophosphamide equivalent dose in male survivors was significantly associated with a decreased likelihood of siring a pregnancy (per 5000 mg/m(2) increments: HR 0.82, 95% CI 0.79-0.86; p<0.0001). However, in female survivors, only busulfan (<450 mg/m(2) HR 0.22, 95% CI 0.06-0.79; p=0.020; >/=450 mg/m(2) 0.14, 0.03-0.55; p=0.0051) and doses of lomustine equal to or greater than 411 mg/m(2) (0.41, 0.17-0.98; p=0.046) were significantly associated with reduced pregnancy; cyclophosphamide equivalent dose was associated with risk only at the highest doses in analyses categorised by quartile (upper quartile vs no exposure: HR 0.85, 95% CI 0.74-0.98; p=0.023). Results for livebirth were similar to those for pregnancy. INTERPRETATION: Greater doses of contemporary alkylating drugs and cisplatin were associated with a decreased likelihood of siring a pregnancy in male survivors of childhood cancer. However, our findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few. Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer. FUNDING: National Cancer Institute, National Institutes of Health, and the American Lebanese-Syrian Associated Charities.

Altered communication (hoarseness, dysphonia, and breathy voice) that can result from vocal fold paralysis, secondary to numerous etiologies, may be amenable to surgical restoration. In this article, both traditional and cutting-edge phonosurgical procedures targeting the symptoms resulting from vocal fold paralysis are reviewed, with emphasis on the characteristic imaging appearances of various injectable materials, implants, and augmentation procedures used in the treatment of vocal fold paralysis. In addition, complications of injection laryngoplasty and medialization laryngoplasty are illustrated. Familiarity with the expected imaging changes following treatment of vocal fold paralysis may prevent the misinterpretation of posttreatment changes as pathology. Identifying common complications related to injection laryngoplasty and localization of displaced implants is crucial in determining specific management in patients who have undergone phonosurgical procedures for the management of vocal fold paralysis.

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.

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.