Faculty Bibliography

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.

The orbit is contained within a complex bony architecture with overlying soft tissue that involves many important anatomical structures. Orbital trauma is a frequent cause of damage to these structures. The authors review the literature on reconstructive techniques focusing on fractures of the orbital rim, orbital roof, orbital floor, medial orbital wall, and naso-orbito-ethmoid complex. A thorough literature review was conducted using PubMed analyzing articles relevant to the subject matter. Various search terms were used to identify articles regarding orbital trauma presentation, diagnosis, management, as well as postoperative complications. Articles were examined by all authors and pertinent information was gleaned for the purpose of generating this review. Orbital trauma can result in a wide variety of complications in form and function. Not all orbital fractures require operative repair. However, bony disruption can cause enophthalmos, hypophthalmos, telecanthus, epiphora, cerebrospinal fluid leaks, orbital hematoma, and even blindness to name a few. Timing of operative repair as well as reconstructive method is dictated by the patient's individual presentation. Successful fracture management requires a detailed understanding of the anatomy and pathophysiology to ensure restoration of the patients' preoperative state. Orbital trauma encompasses a wide variety of mechanisms of injury and resulting fracture patterns. A variety of surgical approaches to the orbit exist as has been discussed allowing the surgeon access to all area of interest. Regardless of the fracture complexity, the principles of atraumatic technique, anatomic reduction, and stable fixation apply in all cases.

The Mongolian gerbil (Meriones unguiculatus) is a member of the rodent family that displays several features not found in mice or rats, including sensory specializations and social patterns more similar to those in humans. These features have made gerbils a valuable animal for research studies of auditory and visual processing, brain development, learning and memory, and neurological disorders. Here, we report the whole gerbil annotated genome sequence, and identify important similarities and differences to the human and mouse genomes. We further analyze the chromosomal structure of eight genes with high relevance for controlling neural signaling and demonstrate a high degree of homology between these genes in mouse and gerbil. This homology increases the likelihood that individual genes can be rapidly identified in gerbil and used for genetic manipulations. The availability of the gerbil genome provides a foundation for advancing our knowledge towards understanding evolution, behavior and neural function in mammals.

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.

BACKGROUND:No head to head comparison is available between surgical lip lifting and upper lip filler injections to decide which technique yields the best results in patients. Despite the growing popularity of upper lip augmentation, its effect on societal perceptions of attractiveness, successfulness and overall health in woman is unknown. METHODS:Blinded casual observers viewed three versions of independent images of 15 unique patient lower faces for a total of 45 images. Observers rated the attractiveness, perceived success, and perceived overall health for each patient image. Facial perception questions were answered on a visual analog scale from 0 to 100, where higher scores corresponded to more positive responses. RESULTS:Two hundred and seventeen random observers with an average age of 47 years (standard deviation, 15.9) rated the images. The majority of observers were females (n=183, 84%) of white race (n=174, 80%) and had at least some college education (n=202, 93%). The marginal mean score for perceived attractiveness from the natural condition was 1.5 points (95% confidence interval [CI], 0.9-2.18) higher than perceived attractiveness from the simulated upper lip filler injection condition, and 2.6 points higher (95% CI, 1.95-3.24) than the simulated upper lip lift condition. There was a moderate to strong correlation between the scores of the same observer. CONCLUSIONS:Simulated upper lip augmentation is amenable to social perception analysis. Scores of the same observer for attractiveness, successfulness, and overall health are strongly correlated. Overall, the natural condition had the highest scores in all categories, followed by simulated upper lip filler, and lastly simulated upper lip lift.

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.

Understanding the cellular interactions during oral carcinogenesis has the potential to identify novel prognostic and therapeutic targets. This study aimed at investigating the cancer stem cell (CSC)-fibroblast niche interactions using in-vitro dysplastic cell line models developed from different stages of 4NQO-induced oral carcinogenic mice model. The spontaneously transformed epithelial cells (DysMSCTR6, 14 and 16) were developed from three time points (mild/moderate/severe), while two fibroblast cell lines (FibroMSCTR12, 16) were developed from moderate and severe dysplastic tissue. The epithelial (Epcam+/Ck+) and the fibroblast cell lines (Vimentin+/α-SMA+/Ck-) were authenticated and assessment of cells representing progressive grades of dysplastic severity indicated a significant increase in dysplastic marker profile (P < 0.05). Evaluation of the CSC characteristics showed that an increase in expression of Cd133, Cd44, Aldh1a1, Notch1, and Sox2 was accompanied by an increase in migratory (P > 0.05) and colony formation capacity (P > 0.005). Targeting Notch1 (GSI inhibitor PZ0187; 30 μM), showed a significant reduction in cell proliferation capacity (P < 0.05) and in the dysplastic marker profile. Further, Notch1 inhibition resulted in down regulation of Cd133 and Aldh1a 1 (P < 0.05) and a complete abrogation of colony formation ability (P < 0.0001). The effect of niche interactions evaluated using FibroMSCTR12-conditioned media studies, revealed an enrichment of ALDH1A1+ cells (P < 0.05), induction of spheroid formation ability (P < 0.0001) and increased proliferation capacity (3.7 fold; P < 0.005). Although PZ0187 reduced cell viability by ∼40%, was unable to abrogate the conditioned-media induced increase in proliferation capacity completely. This study reports a Notch-1 dependent enrichment of CSC properties during dysplastic progression and a Notch-1 independent dysplastic cell-fibroblast interaction during oral carcinogenesis.

PURPOSE/OBJECTIVE:Medical error in the United States carries substantial economic and safety costs, which manifest in a large number of malpractice suits filed each year. The aim of this study was to characterize the various sociologic and medical factors that influence malpractice suits occurring from cases of facial trauma. MATERIALS AND METHODS/METHODS:test, and Fisher t test were performed using SPSS. RESULTS:Of the 69 defendants (76.8% men and 23.2% women; age range, 17 to 57 yr), which resulted from 53 claims, 12 (17.4%) involved plastic surgeons and 10 (14.5%) involved emergency physicians. Most complaints consisted of inadequate care that deviated from treatment standards (32 [46.4%]) and delayed diagnosis (24 [34.8%]). Of delayed diagnosis cases, 14 patients had radiographic imaging performed. Geographic location of the claim was statistically significant-the Midwest upheld 40% of complaints (P = .007) and the South dismissed 91.4% (P = .027). CONCLUSIONS:The impact of sociologic factors, including geographic region, informed consent, and cosmesis, and medical factors, such as delayed diagnosis and deviation from standard of care, in facial trauma litigation were found to be incongruent with previous studies describing the medicolegal influences in facial plastic procedures. This analysis provides greater insight to surgical practitioners across subspecialty disciplines regarding the potential legal implications of malpractice.

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.

BACKGROUND:Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. METHODS:A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions. RESULTS:WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time. CONCLUSION/CONCLUSIONS:These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.