Faculty Bibliography

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.

PURPOSE/OBJECTIVE:Preoperative localization of a parathyroid adenoma is usually obtained by the combination of ultrasound and scintigraphy with technetium-99m methoxyisobutylisonitrile. We evaluated the role of F18-fluorocholine in neck positron emission tomography/magnetic resonance imaging as a novel tool for localizing parathyroid adenomas. METHODS:Patients with primary hyperparathyroidism were recruited from February 2016 to August 2017 and F18-fluorocholine positron emission tomography/magnetic resonance imaging was performed to localize the parathyroid adenoma prior to surgery. We compared sensitivity and accuracy of this modality with ultrasound and technetium-99m methoxyisobutylisonitrile scintigraphy using the verified location of the diseased parathyroid as found in surgery. RESULTS:Nineteen patients were included in our study (15 women and 4 men, mean age 60.5 ± 9.8 years). Positron emission tomography/magnetic resonance imaging precisely localized the pathologic parathyroid gland in 16/19 cases (84.2%) and predicted the diseased side in 19/19 cases (100%). Ultrasound and technetium 99 m methoxyisobutylisonitrile sestamibi scintigraphy predicted the location of the parathyroid adenoma in 16/19 (84.2%) and 14/19 (74%), respectively. In 3/19 patients, positron emission tomography/magnetic resonance imaging localized the parathyroid adenoma where as other modalities failed. Positron emission tomography/magnetic resonance imaging was more accurate when compared to each modality separately (p < 0.001, p = 0.017), however, when comparing the three modalities all together no differences were found (p = 0.506). CONCLUSIONS:Localizing parathyroid adenomas with F18-fluorocholine positron emission tomography/magnetic resonance imaging may be a promising secondary imaging modality.

OBJECTIVE:To assess the impact of implementing a dedicated Patient Safety and Quality Improvement (PSQI) curriculum for otolaryngology residents. METHODS:Residents in two otolaryngology residency programs were recruited to participate in the study. Residents at institution A (intervention group) participated in a formal, newly developed, year-long PSQI curriculum. Residents at institution B (control group) participated in traditional, morbidity, and mortality conference-based PSQI education, with no formal curriculum in place. Curriculum participants completed anonymous surveys to assess learner satisfaction. Validated instruments were administered to assess for changes in resident confidence in the ability to develop PSQI projects, their attitudes toward patient safety, and PSQI-related knowledge. The number and quality of PSQI-related resident projects were also assessed. RESULTS:Survey responses demonstrated excellent learner satisfaction with the curriculum. Based on validated instrument-based responses, both programs demonstrated similar confidence scores (P = 0.05), safety attitudes (P = 0.82), and PSQI knowledge (P = 0.29) at the beginning of the year. The residents of institution A demonstrated significant improvement in confidence (P = 0.00009) and knowledge (P = 0.0006) after completing the curriculum, with no improvement noted for residents at institution B in either confidence (P = 0.06) or knowledge (P = 0.79). Neither program demonstrated improvement in attitudes toward patient safety at the end of the year-long curriculum. CONCLUSION/CONCLUSIONS:Implementing a formal curriculum dedicated to PSQI led to an improvement in PSQI-related project development confidence and PSQI knowledge. Attitudes toward safety did not improve over the course of a year. Longer-term studies involving multiple institutions and other interventions are needed to evaluate the impact and duration of changes that occur. LEVEL OF EVIDENCE/METHODS:1b. Laryngoscope, 2018.

OBJECTIVES/OBJECTIVE:To develop and validate an algorithm to predict occult nodal metastasis in clinically node negative oral cavity squamous cell carcinoma (OCSCC) using machine learning. To compare algorithm performance to a model based on tumor depth of invasion (DOI). MATERIALS AND METHODS/METHODS:Patients who underwent primary tumor extirpation and elective neck dissection from 2007 to 2013 for clinical T1-2N0 OCSCC were identified from the National Cancer Database (NCDB). Multiple machine learning algorithms were developed to predict pathologic nodal metastasis using clinicopathologic data from 782 patients.The algorithm was internally validated using test data from 654 patients in NCDB and was then externally validated using data from 71 patients treated at a single academic institution. Performance was measured using area under the receiver operating characteristic (ROC) curve (AUC). Machine learning and DOI model performance were compared using Delong's test for two correlated ROC curves. RESULTS:The best classification performance was achieved with a decision forest algorithm (AUC = 0.840). When applied to the single-institution data, the predictive performance of machine learning exceeded that of the DOI model (AUC = 0.657, p = 0.007). Compared to the DOI model, machine learning reduced the number of neck dissections recommended while simultaneously improving sensitivity and specificity. CONCLUSION/CONCLUSIONS:Machine learning improves prediction of pathologic nodal metastasis in patients with clinical T1-2N0 OCSCC compared to methods based on DOI. Improved predictive algorithms are needed to ensure that patients with occult nodal disease are adequately treated while avoiding the cost and morbidity of neck dissection in patients without pathologic nodal disease.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Direct glucocorticoid (GC) injection for vocal fold (VF) scarring has evolved as a therapeutic strategy, but the mechanisms underlying the antifibrotic effects remain unclear. GCs act via the glucocorticoid receptor (GR), which is phosphorylated at multiple serine residues in a hormone-dependent manner to affect bioactivity. We hypothesize that GCs regulate SMAD signaling via GR phosphorylation in vocal fold fibroblasts (VFFs). STUDY DESIGN/METHODS:In vitro. METHODS:phosphorylation was examined via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunocytochemistry. Quantitative polymerase chain reaction was employed to determine GR-mediated effects of DM on genes related to fibrosis. RESULTS:phosphorylation increased. RU486 limited the effects of DM. SMAD3 and SMAD7 mRNA expression significantly decreased 4 hours after DM administration (P < 0.05); this response was negated by RU486. COL1A1 remained unchanged, and ACTA2 significantly increased following 24 hours of DM treatment (P < 0.05). CONCLUSION/CONCLUSIONS:DM regulated TGF-β1 signaling via altered SMAD3 and SMAD7 expression. This response was associated with altered GR phosphorylation. These findings provide insight into the mechanisms of steroidal effects on vocal fold repair; ultimately, we seek to enhance therapeutic strategies for these challenging patients. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVES/OBJECTIVE:(1) To determine the effect of hearing aid (HA) bandwidth on bimodal speech perception in a group of unilateral cochlear implant (CI) patients with diverse degrees and configurations of hearing loss in the nonimplanted ear, (2) to determine whether there are demographic and audiometric characteristics that would help to determine the appropriate HA bandwidth for a bimodal patient. DESIGN/METHODS:Participants were 33 experienced bimodal device users with postlingual hearing loss. Twenty three of them had better speech perception with the CI than the HA (CI>HA group) and 10 had better speech perception with the HA than the CI (HA>CI group). Word recognition in sentences (AzBio sentences at +10 dB signal to noise ratio presented at 0° azimuth) and in isolation [CNC (consonant-nucleus-consonant) words] was measured in unimodal conditions [CI alone or HAWB, which indicates HA alone in the wideband (WB) condition] and in bimodal conditions (BMWB, BM2k, BM1k, and BM500) as the bandwidth of an actual HA was reduced from WB to 2 kHz, 1 kHz, and 500 Hz. Linear mixed-effect modeling was used to quantify the relationship between speech recognition and listening condition and to assess how audiometric or demographic covariates might influence this relationship in each group. RESULTS:For the CI>HA group, AzBio scores were significantly higher (on average) in all bimodal conditions than in the best unimodal condition (CI alone) and were highest at the BMWB condition. For CNC scores, on the other hand, there was no significant improvement over the CI-alone condition in any of the bimodal conditions. The opposite pattern was observed in the HA>CI group. CNC word scores were significantly higher in the BM2k and BMWB conditions than in the best unimodal condition (HAWB), but none of the bimodal conditions were significantly better than the best unimodal condition for AzBio sentences (and some of the restricted bandwidth conditions were actually worse). Demographic covariates did not interact significantly with bimodal outcomes, but some of the audiometric variables did. For CI>HA participants with a flatter audiometric configuration and better mid-frequency hearing, bimodal AzBio scores were significantly higher than the CI-alone score with the WB setting (BMWB) but not with other bandwidths. In contrast, CI>HA participants with more steeply sloping hearing loss and poorer mid-frequency thresholds (≥82.5 dB) had significantly higher bimodal AzBio scores in all bimodal conditions, and the BMWB did not differ significantly from the restricted bandwidth conditions. HA>CI participants with mild low-frequency hearing loss showed the highest levels of bimodal improvement over the best unimodal condition on CNC words. They were also less affected by HA bandwidth reduction compared with HA>CI participants with poorer low-frequency thresholds. CONCLUSIONS:The pattern of bimodal performance as a function of the HA bandwidth was found to be consistent with the degree and configuration of hearing loss for both patients with CI>HA performance and for those with HA>CI performance. Our results support fitting the HA for all bimodal patients with the widest bandwidth consistent with effective audibility.

OBJECTIVES/OBJECTIVE:In-office or operative injection laryngoplasty requires needle stability for accurate material placement. To date, no reports compare injection forces based on needle gauge, bends, length, or material type or temperature. We hypothesize these factors alter injection forces and could impact clinical use. METHODS:Swine larynges were placed in a compression testing machine. Syringes were affixed to a stabilizing crossbeam. Straight needles (25G 1.5-inch; 27G 1.25-inch; or 9.8-inch malleable shaft 16G per oral with 24G tapered needle tip) were inserted into the swine vocal folds to simulate realistic tissue resistance pressure. Compressive loading was conducted at 40 mm/minute until steady-state force was achieved. Tests were completed with calcium hydroxylapatite (CaHa), carboxymethylcellulose, and hyaluronic acid at various temperatures and CaHa with various bends in the needles (n = 3 per group, comparisons performed by two-way analysis of variance (ANOVA), Tukey's post-hoc). RESULTS:Needle size, shape, and temperature altered injection force. Steady-state force was highest with the per-oral needle at a mean of 44.55N compared to 26.44N and 29.77N in the 25G and 27G percutaneous needles, respectively (P < 0.001). Stiffness rate (initial increasing force vs. distance to initiate injection) ranged from 19.75N/mm (per oral) to 22.06N/mm (25G) to 24.56N/mm (27G), (P = 0.875). Adding multiple bends to the per-oral needle increased stiffness rate to 24.99N/mm (P = 0.035), whereas the 25G needle stiffness rate remained unchanged (P = 0.941), with the stiffness rate decreasing in the 27G needle with increasing bends (P = 0.033). Increased temperature decreased injection forces across all materials. CONCLUSION/CONCLUSIONS:Needle caliber, length, and bends impact steady-state forces and stiffness rates during vocal fold injection. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2018.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:New advances in osseous microvascular mandibular rigid fixation are being employed at many institutions. These include standardized prebent/preformed reconstruction plates as well as computer-aided design/computer-aided manufacturing (CAD/CAM) custom plates that are patient specific. Our goal was to assess and compare the outcomes of both of these new technologies when utilized for mandibular microvascular reconstruction. STUDY DESIGN/METHODS:Retrospective chart review. METHODS:, Fisher exact test, and multivariable regression models. RESULTS:A total of 142 subjects underwent microvascular mandibular reconstruction in a 6-year period. Eighty-nine subjects utilized prebent/preformed plates, and 53 employed CAD/CAM custom plates. Perioperative complications occurred in 32 of 89 (35.9%) subjects with prebent/preformed plates and 11 of 53 (20.7%) subjects using CAD/CAM custom plates. Reoperation requiring hardware explantation occurred in 18 of 89 (20.2%) subjects and three of 53 (5.6%) using CAD/CAM custom plates. Statistical comparison of perioperative complications between the two groups approached significance (P = .0556), and the rate of reoperation was significant favoring CAD/CAM implants (P = .0180). CONCLUSIONS:In our experience, CAD/CAM custom plates utilized for rigid fixation during microvascular mandibular reconstruction demonstrated fewer complications and statistically lower reoperation rates when compared with prebent/preformed plates. LEVEL OF EVIDENCE/METHODS:2c Laryngoscope, 2018.

Statistical learning has been proposed as a possible mechanism by which individuals can become sensitive to the structures of language fundamental for speech perception. Since its description in human infants, statistical learning has been described in human adults and several non-human species as a general process by which animals learn about stimulus-relevant statistics. The neurobiology of statistical learning is beginning to be understood, but many questions remain about the underlying mechanisms. Why is the developing brain particularly sensitive to stimulus and environmental statistics, and what neural processes are engaged in the adult brain to enable learning from statistical regularities in the absence of external reward or instruction? This review will survey the statistical learning abilities of humans and non-human animals with a particular focus on communicative vocalizations. We discuss the neurobiological basis of statistical learning, and specifically what can be learned by exploring this process in both humans and laboratory animals. Finally, we describe advantages of studying vocal communication in rodents as a means to further our understanding of the cortical plasticity mechanisms engaged during statistical learning. We examine the use of rodents in the context of pup retrieval, which is an auditory-based and experience-dependent form of maternal behavior.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins. Within the gastrointestinal tract, GPCRs expressed by epithelial cells sense contents of the lumen, and GPCRs expressed by epithelial cells, myocytes, neurons, and immune cells participate in communication amongst cells. GPCRs control digestion, mediate digestive diseases, and coordinate repair and growth. GPCRs are the target of over one third of therapeutic drugs, including many drugs used to treat digestive diseases. Recent advances in structural, chemical, and cell biology research have revealed that GPCRs are not static binary switches that operate from the plasma membrane to control a defined set of intracellular signals. Rather, GPCRs are dynamic signaling proteins that adopt distinct conformations and subcellular distributions when associated with different ligands and intracellular effectors. An understanding of the dynamic nature of GPCRs has provided insights into the mechanism of activation and signaling of GPCRs, and has revealed opportunities for drug discovery. We review the allosteric modulation, biased agonism, oligomerization, and compartmentalized signaling of GPCRs that control digestion and digestive diseases. We highlight the implications of these concepts for the development of selective and effective drugs to treat diseases of the gastrointestinal tract.