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Objective: The objective of this study is to assess disparities in adherence to swallowing therapy for clinically diagnosed oropharyngeal dysphagia (OD) patients. Methods: Analysis was conducted on data from 600 patients with OD and confirmed impairments in swallowing safety and/or efficiency on a videofluoroscopic swallow study. Patients were classified based on their adherence to treatment sessions, defined as the number of swallow treatment sessions attended. The outcome of treatment adherence was categorized into two groups: those who attended fewer than 50% of the prescribed treatment sessions and those who attended 50% or more of the sessions. Continuous variables were presented as mean ± standard deviation or median ± interquartile range. Categorical variables were compared using Pearson chi‐square tests and Fisher's exact test when appropriate. Univariable and multivariable binary logistic regression models were employed to identify factors associated with successful adherence. Results: Approximately 79% adhered to swallowing treatment. We found no significant relationship between adherence and age, sex, race, ethnicity, primary language, marital status, insurance status, occupation, median income, distance, education, OD severity, and diagnosis year (p > 0.05). We found no covariables to be significant predictors to swallowing treatment nonadherence in both univariable and multivariable binary regression models (p > 0.05). Conclusion: The variables analyzed in this study were not significantly associated with nonadherence to swallow therapy. Nevertheless, our study still addressed an important knowledge gap and future studies would benefit from exploring other relevant socioeconomic and disease‐related factors. Level of evidence: Level 4. [ABSTRACT FROM AUTHOR]

The geometry of hydrogen sulfide was studied by calculating potential energy surface (PES) with over 1800 configurations. The calculations were performed at very accurate CCSD(T)/aug‐cc‐pvz5 level. The most stable geometry on the PES has bond angle (H−S−H) of 92.40° and bond length (S−H) of 1.338 Å. The PES shows that hydrogen sulfide is a quite flexible molecule. Namely, it can change the bonding angle (H−S−H) in the range of 15.6° (from 84.6° to 100.2°) and the bond lengths (S−H) in the range of 0.082 Å (from 1.299 Å to 1.381 Å) with an energy increase of only 1.0 kcal/mol. An influence of hydrogen sulfide geometry on its hydrogen bonds was studied on several hydrogen sulfide/hydrogen sulfide and water/hydrogen sulfide dimers. It showed that the change of hydrogen sulfide geometry does not influence the strength of hydrogen bond. Fully optimized geometries in gas and water solution phases revealed structural differences of both monomers and dimers in gas phase and water phase. SAPT analysis of the optimized dimer geometries showed that in all the dimers electrostatic is the most dominant contribution, while, in the dimers with hydrogen sulfide, the influence of dispersion contribution becomes quite pronounced. [ABSTRACT FROM AUTHOR]

A procedure is developed for producing basic electronic components utilizing materials sourced from discarded orange, grapefruit, lemon, apple, banana, potato, and carrot peels. Initially, these materials undergo dehydration, followed by a meticulous pulverization process to obtain fine powder. Natural adhesives like water, honey, sugar, starch, and gelatin are employed to interconnect the materials. Formed substrates are characterized using Scanning Electron Microscopy, Energy Dispersive X‐ray Spectroscopy, and an optical profilometer. Furthermore, the relative permittivity of the materials is determined. Three distinct types of substrates, derived from the aforementioned peels, are crafted in varying dimensions. Substrates measuring 4 cm × 2.5 cm host interdigital capacitive sensors, whereas larger 6 cm × 3.5 cm substrates accommodate inductor‐capacitor (LC) sensors. Each of the six samples undergoes individual dry testing, while LC sensors are additionally tested with the post‐application of artificial saliva and mouthwash liquids. The sensor's characterization involves measurement of impedance and phase angle for all samples. Capacitance is additionally measured for capacitors, and inductance for LC circuits. These assessments are carried out within the frequency range spanning from 1 MHz to 400 MHz. The objective is the development of fully functional electronic components, derived from discarded edible items, fostering sustainable practices, and finding applications in biomedicine. [ABSTRACT FROM AUTHOR]

Objective: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. Methods: Forty‐eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. Results: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non‐specific laryngeal and extra‐laryngeal symptoms and signs that can be evaluated with validated patient‐reported outcome questionnaires and clinical instruments. The hypopharyngeal–esophageal multichannel intraluminal impedance–pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. Conclusion: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. Level of Evidence: 5 Laryngoscope, 134:1614–1624, 2024 [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of disinfection protocols utilizing a ultraviolet (UV) Smart D60 light system with Impelux™ technology with a standard Cidex ortho‐phthalaldehyde (OPA) disinfection protocol for cleaning flexible fiberoptic laryngoscopes (FFLs). Methods: Two hundred FFLs were tested for bacterial contamination after routine use, and another 200 FFLs were tested after disinfection with one of four methods: enzymatic detergent plus Cidex OPA (standard), enzymatic detergent plus UV Smart D60, microfiber cloth plus UV Smart D60, and nonsterile wipe plus UV Smart D60. Pre‐ and post‐disinfection microbial burden levels and positive culture rates were compared using Kruskal‐Wallis ANOVA and Fisher's two‐sided exact, respectively. Results: After routine use, approximately 56% (112/200) of FFLs were contaminated, with an average contamination level of 9,973.7 ± 70,136.3 CFU/mL. The standard reprocessing method showed no positive cultures. The enzymatic plus UV, microfiber plus UV, and nonsterile wipe plus UV methods yielded contamination rates of 4% (2/50), 6% (3/50), and 12% (6/50), respectively, with no significant differences among the treatment groups (p > 0.05). The pre‐disinfection microbial burden levels decreased significantly after each disinfection technique (p < 0.001). The average microbial burden recovered after enzymatic plus UV, microfiber plus UV, and nonsterile wipe plus UV were 0.40 CFU/mL ± 2, 0.60 CFU/mL ± 2.4, and 12.2 CFU/mL ± 69.5, respectively, with no significant difference among the treatment groups (p > 0.05). Micrococcus species (53.8%) were most frequently isolated, and no high‐concern organisms were recovered. Conclusion: Disinfection protocols utilizing UV Smart D60 were as effective as the standard chemical disinfection protocol using Cidex OPA. Level of Evidence: NA Laryngoscope, 133:3512–3519, 2023 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety, immunogenicity, and efficacy of INO‐3107, a DNA immunotherapy designed to elicit targeted T‐cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). Methods: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO‐3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment‐emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post‐INO‐3107 and cellular immune responses. Results: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO‐3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO‐3107 induced durable cellular responses against HPV‐6 and HPV‐11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. Conclusion: The data suggest that INO‐3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. Level of Evidence: 3 Laryngoscope, 133:3087–3093, 2023 [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes between two standard‐of‐care anesthesia regimens for operative laryngoscopy: general anesthesia with a neuromuscular blocking agent (NMBA) versus remifentanil and propofol (non‐NMBA). Methods: This was a prospective, single‐blinded, randomized controlled trial at a tertiary care center. Patients were randomized to either anesthesia using rocuronium (NMBA) or with remifentanil/propofol infusion alone (non‐NMBA). Intraoperative impressions, anesthesia data, and post‐operative patient surveys were collected. Results: Sixty‐one patients who underwent suspension laryngoscopy from 2020 to 2022 were included (25 female, 36 male, ranging 20–81 years). Thirty patients were enrolled in the NMBA arm and 31 patients in the non‐NMBA arm. Heart rate and mean arterial pressure were higher in the NMBA (p < 0.01). Patients in the non‐NMBA group were more likely to require vasopressors (p = 0.04, RR = 3.08 [0.86–11.05]). Surgeons were more frequently satisfied with conditions in the NMBA group (86.7%) compared to the non‐NMBA group (58.1%, p < 0.01). Procedures were more likely to be paused due to movement in the non‐NMBA group (45.1%) compared to the NMBA group (16.6%, p < 0.03, RR = 2.26 [1.02–4.99]). Patients in the non‐NMBA group were more likely to endorse myalgia the week after surgery (44%) compared to the NMBA group (8.3%, p < 0.01) and reported higher average pain levels on a 0–10 pain scale (3.7) compared to the paralysis group (2.0). Conclusions: Anesthesia with rocuronium was associated with better intraoperative conditions and postoperative pain compared to anesthesia with remifentanil/propofol. Remifentanil/propofol were associated with lower blood pressure and suppression of laryngoscopy‐associated tachycardia. Level of Evidence: 2 Laryngoscope, 133:2654–2664, 2023 [ABSTRACT FROM AUTHOR]

Objectives: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi‐institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea. Methods: Post‐hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence. Results: Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5‐year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ2 = 0.09, p = 0.77). Conclusion: Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most. Level of Evidence: 3 Laryngoscope, 133:2255–2263, 2023 [ABSTRACT FROM AUTHOR]

Background/Objectives: Base of tongue (BOT) dysfunction is common following oropharyngeal concurrent chemoradiation therapy (CCRT). We present a clinically relevant animal model quantifying the effects of CCRT on tongue strength and elasticity over time. Methods: Fifty‐three male and 53 female Sprague–Dawley rats were randomized to control or experimental groups. Experimental animals received cisplatin, 5‐fluorouracil, and 5 fractions of 7 Gy directed to the BOT. Controls received no intervention. At 2 weeks, 5 months, or 10 months after CCRT, animals underwent non‐survival surgery to measure twitch and tetanic tongue strength, which were analyzed using multivariate linear mixed effects models. Tongue displacement, a surrogate for tongue elasticity, was also determined via stress–strain testing and analyzed via a multivariate linear mixed effects model. Results: Reporting the combined results of both sexes, the estimated experimental group mean peak twitch forces became more divergent over time compared to controls, being 8.3% lower than controls at 2 weeks post‐CCRT, 15.7% lower at 5 months, and 31.6% lower at 10 months. Estimated experimental group mean peak tetanic forces followed a similar course and were 2.9% lower than controls at 2 weeks post CCRT, 20.7% lower at 5 months, and 27.0% lower at 10 months. Stress–strain testing did not find CCRT to have a significant effect on tongue displacement across experimental timepoints. Conclusions: This study demonstrates an increasing difference in tongue strength over time between controls and animals exposed to CCRT. Tongue elasticity was not significantly affected by CCRT, suggesting that changes in strength may not be caused by fibrosis. Level of Evidence: NA Laryngoscope, 133:1455–1461, 2023 [ABSTRACT FROM AUTHOR]

The North American Airway Collaborative (NoAAC) previously published a 3‐year multi‐institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re‐enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision‐making. Level of evidence: 2—prospective cohort study. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP). Study Design: Prospective, multi-institutional cohort study. Methods: Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence. Results: The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76–59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66–14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites. Conclusions: RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location. [ABSTRACT FROM AUTHOR]

The present paper proposes a flexible and efficient methodology for constructing norm‐bounded optimal receding horizon control laws for a group of agents, each one of which is described as a repeated integrator of an arbitrary order and with a common input delay. The goal of each agent is to track the given target, while simultaneously avoiding other agents in the group. Polynomial expansion, together with appropriate subspace projection, is utilized in order to derive receding control law in the closed form. Properties of this control law have been investigated, and its link to a well‐known control strategy based on avoidance functions, which ensures collision avoidance in the case of first‐order integrator agents, has been derived. [ABSTRACT FROM AUTHOR]

In an effort to determine the thermochemistry of established organometallic transformation, the well documented reaction of alkynes with a palladacycle was investigated by isothermal titration calorimetry (ITC). Although the mechanism of the insertion of unsaturated substrates into the Pd−C bond of cyclopalladated compounds is known, no information is available so far about their thermochemistry. The enthalpies of the reactions of Ph−C≡C−Ph and MeOC(O)−C≡C(O)COMe with the bisacetonitrilo salt of the N,N‐benzylamine palladacycle were determined by ITC in chlorobenzene after having optimized the conditions to ensure that only the double and a single insertion of alkynes were occurring respectively. The reaction energy profile established by DFT for the double insertion process involving Ph−C≡C−Ph confirmed earlier conclusions on the rate determining character of the first insertion. Further computations of reaction enthalpies reveal significant discrepancies between ITC and DFT‐D/continuum solvation enthalpies, that are suspected to arise from an unexpected explicit noncovalent interaction of PhCl with the components of the reaction. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long‐term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence. Study Design: International, prospective, 3‐year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS. Methods: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS1000 cohort recorded PEF data on a mobile smartphone app. Cox regression tested the associations between the magnitude of postoperative PEF improvement and longitudinal 90‐day PEF decline with the risk of disease recurrence. Results: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3‐year prospective study comparing surgical treatment efficacy and 385 had appropriate PEF measurements and follow‐up data. Of those patients, 42% (161/385) required at least one operation during study follow‐up. The mean PEF preceding operative intervention was 241 L/min (95% confidence interval [CI]: 120–380) corresponding to a predicted PEF of 52%. The mean increase in PEF following a procedure was 111 L/min (95% CI: 96–125 L/min). Interestingly, the magnitude of immediate PEF improvement was not predictive of disease recurrence (hazard ratio [HR] for 100 L/min increase = 0.90, 95% CI: 0.60–1.00). However, recurrence was associated with the magnitude of PEF decline over 90 days (30% vs. 10% decline, HR = 2.2, 95% CI: 1.5–3.0). Conclusions: We provide normative PEF data on a large iSGS patient cohort. The degree of PEF improvement immediately after surgery was not associated with a longer procedure‐free interval. However, a 30% decline in PEF over 90 days was associated with elevated risk of disease recurrence. Level of Evidence: 2 Laryngoscope, 131:E2841–E2848, 2021 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Adjuvant medications including proton pump inhibitors (PPI), antibiotics (trimethoprim/sulfamethoxazole [TMP‐SMX]), and inhaled corticosteroids (ICS) may be prescribed for patients with idiopathic subglottic stenosis (iSGS). We describe medication use with endoscopic dilation (ED) or endoscopic resection with medical treatment (ERMT) and evaluate impact on outcomes. Study Design: International, prospective, 3‐year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS. Methods: Post hoc secondary analysis of prospectively collected North American Airway Collaborative data on outcomes linked with adjuvant medication utilization. Primary outcome was time to recurrent operation, evaluated using Kaplan–Meier curves and Cox regression analysis. Secondary outcomes of change in peak expiratory flow (PEF) and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score over 12 months were compared. Results: Sixty‐one of 129 patients undergoing ED received PPI (47%), and 10/143 patients undergoing ED received ICS (7%). TMP‐SMX was used by 87/115 patients (76%) undergoing EMRT. PPI use in the ED group did not affect time to recurrence (hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.53–1.88; P =.99) or 12‐month change in PEF (L/min) (median [interquartile range], 12.0 [10.7–12.2] vs. 8.7 [−5.1 to 24.9]; P =.59), but was associated with 12‐month change in CCQ (−0.05 [−0.97 to 0.75] vs. −0.50 [−1.60 to 0.20]; P =.04). ICS did not affect outcome measures. TMP‐SMX use in ERMT did not affect time to recurrence (HR = 0.842, 95% CI: 0.2345–3.023; P =.79), PEF at 12 months (75 [68–89] vs. 81 [68–89]; P =.92), or 12‐month change in CCQ (0.20 [−1.05 to 0.47] vs. −0.30 [−1.00 to 0.10]; P =.45). Conclusion: There is no standard practice for prescribing adjuvant medications. These data do not support that adjuvant medications prolong time to recurrence or increase PEF. Patients with iSGS and gastroesophageal reflux disease may experience some symptom benefit with PPI. Level of Evidence: 3 Laryngoscope, 131:E2880–E2886, 2021 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Singers have high vocal demands and are at increased risk of developing voice disorders. Different singing genres place different technical demands on the voice. However, differences in laryngeal pathology based on genre have not been well‐researched. The purpose of this study was to determine the prevalence of laryngeal pathology in different genres of professional and amateur singers who present with a voice complaint. Study Design: Retrospective review. Methods: Retrospective review of patients seen at a tertiary laryngology practice. Self‐identified singers who reported their primary singing genre and categorized their singing as a full‐time job, part‐time job, or amateur involvement were included. Type and prevalence of pathology were calculated based on genre and professional status. Results: Of the 302 self‐identified singers, 54% (n = 164) had laryngeal pathology. Among those with pathology, the most common finding was fibrotic lesion (38.4%, 63/164). Genres in which a majority of singers had pathology were other (69.2%, 9/13), choral (64.7%, 11/17), pop (63.2%, 12/19), musical theater (61.4%, 43/70), country (100%, 4/4), and Latin (100%, 2/2). The highest prevalence of pathology was seen in part‐time professional singers (62.2%, 41/66) and full‐time professionals (60.8%, 62/102), compared to amateurs (45.1%, 60/133). Conclusions: Laryngeal pathology is prevalent in singers presenting with a voice complaint. Regardless of genre or professional status, fibrotic lesions were the most common pathological finding. This study provides preliminary data on the prevalence of different laryngeal pathologies found in singers by genre and degree of professional involvement. Level of Evidence: 4 Laryngoscope, 131:2076–2080, 2021 [ABSTRACT FROM AUTHOR]

The magnetic properties of the 2D anisotropic antiferromagnetic spin‐1/2 Heisenberg model with Dzyaloshinskii–Moriya interaction and in‐plane frustration are studied. The method of spin Green's functions within the framework of Tyablikov's random‐phase‐approximation decoupling scheme is used to derive expressions for the spin‐wave spectrum, sublattice magnetization, and transition temperature. Based on these expressions, a detailed analysis of the influence of varying values of model parameters on their magnetic properties is conducted. The model is also applied to the high‐Tc superconducting parent compound La2CuO4 and the results compared with available experimental data. [ABSTRACT FROM AUTHOR]

The objective of this study was observation of the adhesive interface on original tooth samples, as well as their epoxy replicas, under SEM. A light‐cure flowable composite was incrementally placed and light‐polymerized in previously prepared cylindrical dentinal cavities on the buccal surfaces of extracted human third molars. After finishing procedures, impressions of the composite/dentin margin were made using polyvinylsiloxane in order to obtain accurate epoxy replicas for SEM analysis. Ultrastructural morphology of the adhesive surface was observed at high magnifications (≥1,000×) on original tooth samples, which were previously prepared to expose the part of the dentin surface, which participates in the formation of adhesive bond. SEM micrographs showed that marginal adaptation was mostly of acceptable quality. In some of the SEM micrographs of original tooth samples, marginal gap formation, and resin tag breakdown were noted, which were ascribed to polymerization shrinkage. Profound understanding of ultrastructural morphology is necessary for achieving more predictable and durable margin between composite restorations and surrounding tooth structures, and SEM analysis can serve that purpose. [ABSTRACT FROM AUTHOR]

Objective: Race predicts overall mortality (OM) of laryngeal squamous cell carcinoma (LSCC) in the United States (US). We assessed whether racial disparities affect cancer‐specific mortality (CSM) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Adults with LSCC from 2004 to 2015 were selected. Univariable and multivariable Cox proportional hazards and Fine‐Gray competing‐risks regression analysis adjusted for clinicodemographic factors defined hazard ratios (aHR). Results: We identified 14,506 patients. The median age was 63 years. Most were male (11,725, 80.8%) and white (11,653, 80.3%), followed by Black (2294, 15.8%). Most had early‐stage disease (7544, 52.0%) and received radiotherapy only (4107, 28.3%), followed by chemoradiation (3748, 25.8%). With median follow‐up of 60 months, overall 3‐ and 5‐year OM were 34.0% and 43.2%; CSM were 16.0% and 18.9%, respectively. Black patients had higher OM than white patients on univariable (HR 1.35, 95% CI, 1.26–1.44, P <.001) and multivariable (aHR 1.10, 95% CI, 1.02–1.18, P =.011) analyses. Black patients had higher CSM on univariable analysis (HR 1.22, 95% CI, 1.09–1.35, P <.001) but not on multivariable CSM analysis (aHR 1.01, 95% CI, 0.90–1.13, P =.864). On multivariable analysis, year of diagnosis, age, disease site, stage, treatment, nodal metastasis, marital status, education, and geography significantly predicted CSM. Conclusion: On multivariable analyses controlling for sociodemographic, clinical, and treatment characteristics, Black and white patients differed in OM but not in CSM. However, Black patients presented with greater proportions of higher stage cancers and sociodemographic factors such as income and marital status that were associated with worse outcomes. Efforts to target sociodemographic disparities may contribute to the mitigation of racial disparities in LSCC. Level of Evidence: 4 Laryngoscope, 131:E1147–E1155, 2021 [ABSTRACT FROM AUTHOR]

The magnetic properties of the 2D anisotropic antiferromagnetic spin‐1/2 Heisenberg model with Dzyaloshinskii–Moriya interaction and in‐plane frustration are studied. The method of spin Green's functions within the framework of Tyablikov's random‐phase‐approximation decoupling scheme is used to derive expressions for the spin‐wave spectrum, sublattice magnetization, and transition temperature. Based on these expressions, a detailed analysis of the influence of varying values of model parameters on their magnetic properties is conducted. The model is also applied to the high‐Tc superconducting parent compound La2CuO4 and the results compared with available experimental data. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To assess the safety and efficacy of autologous cultured fibroblasts (ACFs) to treat dysphonia related to vocal fold scar and age-related vocal atrophy (ARVA).Study Design: Randomized, double-blinded, placebo-controlled, multi-institutional, phase II trial.Methods: ACFs were expanded from punch biopsies of the postauricular skin in each subject; randomization was 2:1 (treatment vs. placebo). Three injections of 1-2 × 107 cells or placebo saline was performed at 4-week intervals for each vocal fold. Follow-up was performed at 4, 8, and 12 months. The primary outcome was improved mucosal waves. Secondary outcomes included Voice Handicap Index (VHI)-30, patient reported voice quality outcomes, and perceptual analysis of voice.Results: Fifteen subjects received ACF and six received saline injections. At 4, 8, and 12 months after ACF treatments, a significant improvement in mucosal wave grade relative to baseline was observed in both vocal scar and ARVA groups. Relative to control group, mucosal waves were significantly improved in the ARVA group at 4 and 8 months. Perceptual analysis significantly improved in the vocal scar group 12 months after ACF treatments compared to controls. Vocal scar group reported significantly improved vocal quality from baseline. VHI and expert rater voice grade improved in both groups, but did not achieve significance. No adverse events related to fibroblast injections were observed.Conclusions: In this cohort, injection of ACFs into the vocal fold lamina propria (LP) was safe and significantly improved mucosal waves in patients with vocal scar and ARVA. ACF may hold promise to reconstruct the LP.Level Of Evidence: 1 Laryngoscope, 130:2650-2658, 2020. [ABSTRACT FROM AUTHOR]

Objective: We conducted a quality improvement project to increase the rate of discharges before noon (DBN) in the otolaryngology department at a tertiary care center.Methods: Based on a Plan-Do-Study-Act framework, monthly discharge data and observed-to-expected (O:E) length of stay were collected and shared with the department members monthly. A target of 43% DBN was predetermined by the center (Plan). The following interventions were implemented (Do): discharge planning starting at the time of admission, focus on early attending-to-resident team communication, placement of discharge order prior to rounding, and weekly reminders to the entire department.Results: Discharges were monitored for 3 years. For the year prior to this study, a minority of patients were discharged before noon (12 months: 75 of 190, 36%). During the first 6 months of monitoring (Study), no significant improvement was identified (34 of 95, 36%). After interventions, performance significantly improved (31 months: 250 of 548, 68%). The performance was consistently above the predetermined target of 43%. During the study time, O:E length of stay remained below the predetermined target (O:E ratio, 0.90; hospital target, 0.93).Discussion: Comprehensive discharge planning beginning at the time of admission, weekly reminders, and improved communication (Act) can help to prioritize DBN and increase the percentage of discharges before noon.Implications For Practice: By utilizing a quality improvement framework, significant improvements in timely discharge can be achieved and sustained with changes in workflow and departmental culture. These changes can be achieved without increases in resources or prolonging the length of stay. [ABSTRACT FROM AUTHOR]

When dealing with fractional order systems, perturbations in differentiation orders arise frequently due to issues with floating point arithmetics, or due to imprecisions of various order estimation algorithms. This study establishes new results regarding stability/instability of fractional systems with perturbed differentiation orders, knowing the related properties of their unperturbed counterparts. First of all, starting from a point in the space of differentiation orders, sufficient stability/instability conditions of all systems with differentiation orders varying along a line segment with a prescribed direction are established. Then, a continuation procedure is developed allowing computation of the maximum perturbation (along some given direction) which guarantees that the number of zeros in the closed right‐half plane of the characteristic function remain unchanged. Finally, sufficient conditions are established guaranteeing stability/instability of all systems having differentiation orders within a domain. The established results allow concluding on the stability of incommensurate fractional transfer functions. They are illustrated by a number of examples, including an experimental one. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To describe recurrence patterns in patients with recurrent respiratory papillomatosis (RRP) following surgical intervention.Study Design: Single-center, retrospective, longitudinal case series.Methods: Initial and follow-up laryngoscopic examinations of seven previously untreated adult-onset RRP patients were reviewed. Patients were followed longitudinally for periods ranging from 3 months to 7 years. Lesion locations were recorded using a twenty-one region laryngeal schematic, and maps were generated to illustrate the distribution of disease before and after cold-knife or potassium-titanyl-phosphate laser intervention. Univariate and multivariate analyses were employed to examine variables affecting recurrence patterns.Results: Across all patients, a statistically significant correlation between initial distribution and primary recurrence was observed. Seventy-five percent of new lesions were adjacent to regions with preexisting disease; 83% of new glottic lesions were adjacent to preexisting glottic lesions, and 66% of supraglottic lesions were adjacent to preexisting supraglottic regions. No statistically significant differences in recurrence rate were observed across sites.Conclusions: In previously untreated patients with adult-onset recurrent respiratory papillomatosis, lesions tended to recur either in the same regions or regions adjacent to those affected at the time of initial surgery.Level Of Evidence: 4 Laryngoscope, 129:1993-1997, 2019. [ABSTRACT FROM AUTHOR]

Objectives: (1) To determine the short-term effectiveness of oral steroids in women with benign vocal fold lesions and (2) to determine the effectiveness of adjuvant oral steroids in women undergoing voice therapy for benign vocal fold lesions.Study Design: Randomized, double-blind, placebo-controlled clinical trial.Setting: Tertiary voice care center.Subjects and Methods: Thirty-six patients undergoing voice therapy for the treatment of phonotraumatic vocal fold lesions randomly received either a 4-day course of oral steroids or a placebo prior to initiating voice therapy. Voice Handicap Index-10 (VHI-10) scores, video and audioperceptual analyses, acoustic and aerodynamic analyses at baseline, and patient perception of improvement after a short course of steroids or a placebo and at the conclusion of voice therapy were collected.Results: Thirty patients completed the study, of whom 27 (only female) were analyzed. The primary outcome measure, VHI-10, did not improve after the 4-day course of steroids or placebo. Secondary measures similarly showed no improvement with steroids relative to placebo. Voice therapy demonstrated a positive effect on both VHI-10 and patient-perceived improvement of voice in all subjects.Conclusion: A short course of oral steroids did not benefit women with phonotraumatic vocal fold lesions. In addition, steroids had little beneficial effect when used adjunctively with voice therapy in this patient cohort. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species.Study Design: Ex vivo animal model.Methods: Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2-mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two-dimensional maps of the free VF edge through the conus elasticus were created for these characterizations.Results: Structural stiffness was 7.79 gf/mm (0.15-74.55) for leporine, 2.48 gf/mm (0.20-41.75) for canine, and 1.45 gf (0.56-4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine.Conclusions: Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed.Level Of Evidence: NA Laryngoscope, 129:E26-E31, 2019. [ABSTRACT FROM AUTHOR]

Psoriasis is a complex immune-mediated systemic disease affecting 1% to 2% of the North American population.1 Although observational studies have reported an increased risk of depression with psoriasis severity when compared to the general population, the literature remains scarce with regard to the risk of suicide in psoriasis.2-4 Two recent meta-analyses of observational studies reported conflicting results, one showed no association between psoriasis and suicidality,4 while the second showed an increased risk of suicidal ideation and behaviour individuals with psoriasis when compared to the general population.3 As psoriasis severity may change over the life course of the disease, we aimed to establish if the risk of suicidal behaviour (hospital admission for suicide attempt and suicide death) in individuals with psoriasis increases with the severity of the disease. Individuals with a psoriasis diagnosis in the prior three years, psoriasis treatment in the prior year or a hospitalization for a suicide attempt in the prior two years were excluded. When hospital admission for suicide attempt and suicide death were examined separately, similar results were observed for the association between psoriasis severity and death by suicide (severe psoriasis: 3.34, 1.39-8.08). [Extracted from the article]

Flexible laryngoscopy, the gold-standard evaluation of the larynx and the pharynx, is one of the most commonly performed procedures in otolaryngology. During the coronavirus disease 2019 (COVID-19) pandemic, flexible laryngoscopy represents a risk for patients and an occupational hazard for otolaryngologists and any clinic staff involved with the procedure or endoscope reprocessing. Here we present a set of recommendations on flexible laryngoscopy performance during the pandemic, including patient selection, personal protective equipment, and endoscope disinfection, based on a consensus reached during a virtual webinar on March 24, 2020, attended by approximately 300 participants from the American laryngology community. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To develop a clinically relevant model of oropharyngeal concurrent chemoradiation therapy (CCRT) in order to quantify the effects of CCRT on tongue function and structure. CCRT for advanced oropharyngeal cancer commonly leads to tongue base dysfunction and dysphagia. However, no preclinical models currently exist to study the pathophysiology of CCRT-related morbidity, thereby inhibiting the development of targeted therapeutics.Study Design: Animal model.Methods: Twenty-one male Sprague-Dawley rats were randomized into three groups: 2 week (2W), 5 month (5M), and control (C). The 2W and 5M animals received cisplatin, 5-fluorouracil, and five fractions of 7 Gy to the tongue base; the C animals received no intervention. In vivo tongue strength and displacement, as well as hyoglossus muscle collagen content, were assessed. Analyses were conducted 2 weeks or 5 months following completion of CCRT in the 2W and 5M groups, respectively.Results: Peak tetanic and twitch tongue forces were significantly reduced in both 2W and 5M animals compared to controls (tetanic: P = .0041, P = .0089, respectively; twitch: P = .0201, P = .0020, respectively). Twitch half-decay time was prolonged in 2W animals compared to controls (P = .0247). Tongue displacement was significantly reduced across all testing parameters in 5M animals compared to both the C and 2W groups. No differences in collagen content were observed between experimental groups.Conclusions: The current study is the first to describe a preclinical model of CCRT to the head and neck with an emphasis on clinical relevance. Tongue strength decreased at 2 weeks and 5 months post-CCRT. Tongue displacement increased only at 5 months post-CCRT. Fibrosis was not detected, implicating alternative causative factors for these findings.Level Of Evidence: NA Laryngoscope, 1783-1790, 2018. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Our laboratory and others hypothesized that Smad3 is a principle mediator of the fibrotic phenotype in the vocal folds (VFs), and we further posited that alteration of Smad3 expression through short interfering (si)RNA holds therapeutic promise, yet delivery remains challenging. To address this issue, we employed a novel synthetic oligomer, lipitoid, complexed with siRNA to improve stability and cellular uptake with the goal of increased efficiency of RNA-based therapeutics.Study Design: In vitro study and in vivo animal model.Methods: In vitro, lipitoid cytotoxicity was quantified via colorimetric and LIVE/DEAD assays in immortalized human VF fibroblasts and primary rabbit VF fibroblasts. In addition, optimal incubation interval and solution for binding siRNA to lipitoid for intracellular delivery were determined. In vivo, a rabbit model of VF injury was employed to evaluate Smad3 knockdown following locally injected lipitoid-complexed siRNA.Results: In vitro, lipitoid did not confer additional toxicity compared to commercially available reagents. In addition, 20-minute incubation in 1× phosphate-buffered saline resulted in maximal Smad3 knockdown. In vivo, Smad3 expression increased following VF injury. This response was significantly reduced in injured VFs at 4 and 24 hours following injection (P = .035 and .034, respectively).Conclusions: The current study is the first to demonstrate targeted gene manipulation in the VFs as well as the potential utility of lipitoid for localized delivery of genetic material in vivo. Ideally, these data will serve as a platform for future investigation regarding the functional implications of therapeutic gene manipulation in the VFs.Level Of Evidence: NA. Laryngoscope, 128:E178-E183, 2018. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Although the primary goal of medialization laryngoplasty is to improve glottic closure, implant placement is also likely to alter the biomechanical properties of the vocal fold (VF). We sought to employ novel, nanoscale technology to quantify these properties following medialization based on the hypothesis that different medialization materials will likely yield differential biomechanical effects.Study Design: Ex vivo.Methods: Nine pig larynges were divided into three groups: control, Silastic (Dow Corning, Midland, Michigan, U.S.A.) block medialization, or Gore-Tex (W.L. Gore & Associates, Newark, Delaware) medialization. Laryngoplasty was performed on excised, intact larynges. The larynges were then bisected in the sagittal plane and each subjected to dynamic nanomechanical analysis (nano-DMA) at nine locations using a 250-μm flat-tip punch and frequency sweep-load profile across the free edge of the VF and inferiorly along the conus elasticus.Results: Silastic block and Gore-Tex implant introduced increased storage and loss moduli. Overall, storage moduli mean (maximum) increased from 38 kilopascals (kPa) (119) to 72 kPa (422) and 129 kPa (978) in control, Gore-Tex, and Silastic implants, respectively. Similarly, loss moduli increased from 13 kPa (43) to 22 kPa (201) and 31 kPa (165), respectively. Moduli values varied widely by location in the Silastic block and Gore-Tex groups. At the free VF edge, mean (maximum) storage moduli were lowest in the Gore-Tex group, 20 kPa (44); compared to control, 34.5 kPa (86); and Silastic, 157.9 kPa (978), with similar loss and complex moduli trends.Conclusion: Medialization laryngoplasty altered VF structure biomechanical properties; Silastic and Gore-Tex implants differentially impact these properties.Level Of Evidence: NA. Laryngoscope, 128:1163-1169, 2018. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: A secure airway is critical to study obstructive disorders of the larynx and trachea in preclinical models. Tracheostomy has been described in rabbits, swine, canines, and other mammals using tracheostomy tubes or permanent stomas. No studies specifically evaluated morbidity and mortality associated with these models, and existing studies using tracheostomy make little mention of tracheostomy-related complications. We assessed the management, complications, and mortality associated with tracheostomy in a rabbit model that has recently gained significant attention.Study Design: In vivo.Methods: Twenty-two female rabbits underwent tubeless tracheotomy. Rabbits were monitored hourly for the first 8 hours, with progressively increasing intervals between evaluations up to 7 days. A suctioning and tracheal moisture protocol was employed, and animals with signs of crusting or impending airway compromise underwent therapeutic bronchoscopy.Results: Nine of 22 (41%) rabbits succumbed to tracheostomy-related complications, ranging from 1 to 7 days after tracheotomy. The experiment consisted of two study groups. The preliminary group of 10 rabbits studied over a 4-day period had 40% mortality. After implementing modified preventive therapy guidelines and a new humidification system, the second group of 12 rabbits studied over a 7-day period had 42% mortality. Average time to unrecoverable complication was 2.2 days (median = 2 days). Cause of death was airway obstruction in four animals and respiratory depression in three animals, and two animals were found unresponsive.Conclusion: Tracheostomy in preclinical rabbit models should be temporally limited, and investigators should anticipate tracheostomy-related complications during study design.Level Of Evidence: NA. Laryngoscope, 128:E68-E71, 2018. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the interfacial micromorphology of total-etch adhesives and dentin structures different locations by using SEM. Standardized cylindrical cavities (3mm in diameter, 2mm deep) with all margins in dentin were prepared on occlusal and buccal surfaces of twenty extracted human third molars. A total-etch dentin adhesive system and a light-cure flowable composite (Filtek Ultimate Flowable, 3M ESPE, St. Paul, MN, USA) were used in this study. Micro-morphological SEM analysis of the marginal seal of the original tooth specimens was performed using high magnification of up to 1000×. In this study, we found the difference in interfacial micromorphology in dentin different locations. Also, marginal gap was found in both observed dentin area. Better understanding of complexity and three- dimensional variations of the tooth structure is important for prevention of clinical challenges such as postoperative sensitivity, marginal discoloration and secondary caries, which could be prevented by achieving of predictable and long-lasting adhesive bond. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP.Study Design: Multi-institutional, retrospective case series.Methods: Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease.Results: In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P < .0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P < .0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P = .005) and were more likely to have lesions in any laryngeal subsite (P < .0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P = .0037, OR: 1.62), particularly in the posterior and subglottic regions (P = .0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution.Conclusions: In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution warrants further investigation.Level Of Evidence: 4. Laryngoscope, 128:138-143, 2018. [ABSTRACT FROM AUTHOR]

Objective: Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor β (TGF-β)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro.Study Design: In vivo and in vitro.Methods: Unilateral vocal fold injury was created in a rabbit model. SMAD3 and SMAD7 mRNA expression was quantified at 1 hour and 1, 3, 7, 14, 30, 60, and 90 days following injury. In vitro, multi-gene analysis technology was employed in our immortalized human vocal-fold fibroblast cell line following TGF-β1 stimulation ± SMAD3 knockdown across time points.Results: SMAD3 mRNA expression increased following injury; upregulation was significant at 3 and 7 days compared to control (both P < 0.001). SMAD7 mRNA was also upregulated at 3, 7, and 14 days (P = 0.02, P < 0.001, and P < 0.001, respectively). In vitro, SMAD3 knockdown reduced the expression of multiple profibrotic, TGF-β signaling, and extracellular matrix metabolism genes at 6 and 24 hours following TGF-β1 stimulation.Conclusion: Cumulatively, these data support SMAD3 as a potential master regulator of TGF-β-mediated fibrosis. SMAD3 transcription peaked 7 days following injury. Multi-gene analysis indicated that the therapeutic effectiveness of SMAD3 knockdown may be related to regulation of downstream mediators of fibroplasia and altered TGF-β signaling.Level Of Evidence: NA. Laryngoscope, 127:E308-E316, 2017. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Quantification of clinical outcomes after vocal fold (VF) interventions is challenging with current technology. High-speed digital imaging and optical coherence tomography (OCT) of excised larynges assess intact laryngeal function, but do not provide critical biomechanical information. We developed a protocol to quantify tissue properties in intact, excised VFs using dynamic nanomechanical analysis (nano-DMA) to obtain precise biomechanical properties in the micrometer scale.Study Design: Experimental animal study.Methods: Three pig larynges were bisected in the sagittal plane, maintaining an intact anterior commissure, and subjected to nano-DMA at nine locations with a 250-μm flat-tip punch and frequency sweep load profile (10-105 Hz, 1,000 μN peak force) across the free edge of the VF and inferiorly along the conus elasticus.Results: Storage, loss, and complex moduli increased inferiorly from the free edge. Storage moduli increased from a mean of 32.3 kPa (range, 6.5-55.38 kPa) at the free edge to 46.3kPa (range, 7.4-71.6) 5 mm below the free edge, and 71.4 kPa (range, 33.7-112 kPa) 1 cm below the free edge. Comparable values were 11.6 kPa (range, 5.0-20.0 kPa), 16.7 kPa (range, 5.7-26.8 kPa), and 22.6 kPa (range, 9.7-38.0 kPa) for loss modulus, and 35.7 kPa (range, 14.4-56.4 kPa), 50.1 kPa (range, 18.7-72.8 kPa), and 75.4 kPa (range, 42.0-116.0 kPa) for complex modulus. Another larynx repeatedly frozen and thawed during technique development had similarly increased storage, loss, and complex modulus trends across locations.Conclusions: Nano-DMA of the intact hemilarynx provides a platform for quantification of biomechanical responses to a myriad of therapeutic interventions to complement data from high-speed imaging and OCT.Level Of Evidence: NA Laryngoscope, 127:E225-E230, 2017. [ABSTRACT FROM AUTHOR]

Objective Given the recalcitrant nature of recurrent respiratory papillomatosis, targeted therapies to reduce disease burden are fundamental to improved patient care paradigms. We seek to demonstrate the safety of imiquimod injection into vocal fold mucosa by evaluating the degree of laryngeal edema, histopathologic changes to vocal fold structure, and serologic interferon α (IFNα) levels following injection. Study Design Preclinical. Setting Academic institution. Subjects and Methods Six New Zealand White rabbits underwent unilateral injection of 100 µg of sterile imiquimod (1 µg/µL), with 100 µL of normal saline injected into the contralateral vocal fold. Direct laryngoscopy was performed on days 3, 7, and 30 following injection. Larynges from 3 rabbits were harvested on postinjection day 7 for histologic analysis. The remaining 3 rabbit larynges were harvested on day 30. Serial serum samples were drawn for IFNα quantification via immunoassay. Results No signs of respiratory distress were observed at any point. Vocal fold appearance was not clinically divergent between imiquimod and control conditions via serial direct laryngoscopic evaluation. No inflammatory lesions or scarring were identified following injection. Histology showed no signs of acute inflammatory processes or changes in the control or imiquimod injection groups. Serum IFNα increased at days 3 and 7 following imiquimod injection ( P < .0001 and P = .0368, respectively), before returning to baseline by day 14. Conclusions Vocal fold imiquimod injection did not result in notable morbidity in this preclinical model. However, serum IFNα concentrations increased transiently. These data are critical to advance the therapeutic utility of this compound, particularly in the setting of recurrent respiratory papillomatosis. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Inhalation injury significantly increases morbidity and mortality in burn patients. Approximately one in five burn patients have acute injury to the larynx, trachea, and/or lungs-and as many as 70% have long-term laryngeal abnormalities. Although inhalation injury to the lung has been studied extensively, no models exist to study these insults to the larynx. As such, we developed an in vivo rabbit model to create precise and reproducible laryngeal burn with resultant tissue damage as a foundation for interventional studies.Methods: Following tubeless tracheotomy, a custom temperature-control device was employed to apply heated air (70°C-80°C, 150°C-160°C, or 310°C-320°C) ± smoke derived from unbleached cotton to the larynx, endoscopically, minimizing adjacent tissue damage in six rabbits. Pain, nutrition, and level of activity were monitored. Direct laryngoscopy and histological examination were performed 24 hours following insult.Results: All animals survived injury with appropriate pain control; oral intake was initiated and all were adequately ventilating via tracheostomy. Burn sequelae were noted under direct visualization 24 hours after injury, and graded levels of edema and tissue damage were observed as a function of temperature. Edema obstructed true vocal fold visualization at increased temperatures. These injury patterns correlated with graded tissue damage on histology.Conclusion: We created an in vivo model of laryngeal burn injury employing a custom burn device resulting in graded tissue injury. This model is critical for investigation of the mechanisms underlying burn injury, and ultimately, the development and evaluation of therapies for this challenging population.Level Of Evidence: NA Laryngoscope, 127:186-190, 2017. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and also accuracy of the laryngopharyngeal reflux (LPR) referring diagnosis and to determine the most useful clinical tool in arriving at the final diagnosis in a tertiary laryngology practice.Study Design: Case series with planned data collection.Setting: Six tertiary academic laryngology practices.Subjects and Methods: We collected referring diagnosis and demographic information, including age, sex, ethnicity, referring physician, and whether or not patients had prior flexible laryngoscopy for 1077 patients presenting with laryngologic complaints from January 2010 and June 2013. Final diagnosis after the referred laryngologist's examination and the key diagnostic test used was then recorded.Results: Of 1077 patients, 132 had a singular referring diagnosis of LPR. Only 47 of 132 patients (35.6%) had LPR confirmed on final primary diagnosis. Transnasal flexible laryngoscopy confirmed this in 27 of 47 (57.4%) patients. Eighty-five of 132 (64.4%) had a different final diagnosis than LPR. Sixty-five of 85 (76.5%) of these alternative pathologies were diagnosed with the aid of laryngeal stroboscopy.Conclusions: LPR appears to be an overused diagnosis for laryngologic complaints. For patients who have already had transnasal flexible laryngoscopic exams prior to their referral, laryngeal stroboscopy is the key diagnostic tool in arriving at the correct diagnosis. [ABSTRACT FROM AUTHOR]

Objective Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. Methods We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Results Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). Conclusions We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To investigate the role of Smad3 as a regulator of transforming growth factor (TGF)-β1-mediated cell activities associated with fibrosis in normal human vocal fold fibroblasts. We also sought to confirm the temporal stability of Smad3 knockdown via small inhibitor ribonucleic acid (siRNA). Vocal fold fibroblasts were employed to determine the effects of Smad3 knockdown on TGF-β1-mediated migration and contraction, as well as regulation of connective tissue growth factor (CTGF). We hypothesized that Smad3 is an ideal candidate for therapeutic manipulation in vivo based on its role in fibrosis.Study Design: In vitro.Methods: Knockdown of Smad3 via siRNA was performed in our normal human vocal fold cell line. Three-dimensional collagen gel contraction and scratch assays were employed to determine the role of Smad3 on TGF-β1-mediated contraction and migration, respectively. The role Smad3 in the induction of CTGF was characterized via sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of Smad3 signaling on Smad7 messenger (m)RNA and protein were also quantified.Results: Smad3 knockdown was temporally-stable up to 72 hours (P < 0.001), diminished TGF-β1-mediated collagen gel contraction and migration, and blunted induction of CTGF, but it had no effect on TGF-β1-mediated Smad7 mRNA or protein induction.Conclusion: Transforming growth factor-β1 stimulated profibrotic cell activities in our cell line and these actions were largely reduced with Smad3 knockdown. These data provide continued support for therapeutic targeting of Smad3 for vocal fold fibrosis because it appears to regulate the fibrotic phenotype.Level Of Evidence: N/A. Laryngoscope, 126:1151-1156, 2016. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To optimize decellularization of porcine vocal folds (VF) and quantify human bone marrow-derived mesenchymal stem cell (BM-MSC) interactions with this matrix to provide a foundation for regenerative approaches to VF repair.Study Design and Methods: Vocal folds were dissected from porcine larynges and three decellularization protocols were compared, each consisting of washes and mechanical agitations with different combinations of reagents. DNA content was analyzed via Quant-iT Picogreen assay and hematoxylin and eosin staining. Bone marrow-derived MSCs were then seeded onto the decellularized VF matrices. Morphology, metabolic activity, DNA content, and gene expression were assessed using LIVE/DEAD Cell Viability, alamarBlue Cell Viability Assay, Quant-iT Picogreen assay, and quantitative polymerase chain reaction, respectively.Results: The most successful decellularization protocol removed 95% DNA content within 1 day, compared to several days required for previously described protocols. Histology confirmed the retention of extracellular matrix (ECM) and its components, including glycosaminoglycans, collagen, and fibrin, while void of nuclear/cellular content. Decellularized scaffolds were then seeded with BM-MSCs. Similar DNA quantities were observed after 24 hours of seeding within the VF-ECM scaffold when compared to cells on tissue culture plastic (TCP). LIVE/DEAD staining of the seeded VF-ECM confirmed excellent cell viability, and the metabolic activity of BM-MSCs increased significantly on VF-ECM compared to TCP. Endoglin gene expression decreased, suggestive of differentiation.Conclusion: Porcine VFs can be efficiently decellularized within 5 hours using a combination of sodium deoxycholate and peracetic acid. Decellularized VF-ECM supported attachment and growth of human BM-MSCs, with evidence of differentiation.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Given that the vocal folds are active organs of respiration, reports of dyspnea in the context of glottic insufficiency are not uncommon. We hypothesize that improved glottal closure via framework surgery or vocal fold augmentation improves dyspnea symptoms.Study Design: Retrospective review.Methods: Charts of patients undergoing procedures to correct glottal insufficiency, either via vocal fold augmentation (VFA) or medialization laryngoplasty (ML) between December 2012 and September 2015 were reviewed (n = 189). Modified Borg Dyspnea Scale (MBDS) and Modified Medical Research Council Dyspnea Scale (MMRCDS) data were collected before and after intervention. Age, body mass index (BMI), and sex, as well as pulmonary and cardiac comorbidities were considered. Subgroup analysis was performed on individuals with subjective dyspnea prior to intervention.Results: For the entire cohort, differences in the MMRCDS and MBDS were not statistically different pre- and postintervention (P = .20 and P = .12, respectively). Patients with BMI <30 experienced more improvement on the MBDS (P = .03). Both the MMRCDS and MMBDS improved post-procedure (P = .001 and P = .001, respectively) in patients reporting dyspnea prior to intervention.Conclusions: Patients with glottic insufficiency and dyspnea prior to intervention to improve glottic closure had a significant reduction in dyspnea following treatment. Conversely, subjects without complaints of dyspnea prior to intervention had variable outcomes with regard to dyspnea symptoms. Additionally, based on data from the entire cohort, VFA or ML did not worsen dyspnea symptoms. These data may assist in counseling and/or selection of patients considered for procedures to improve glottic closure.Level Of Evidence: 4. Laryngoscope, 128:427-429, 2018. [ABSTRACT FROM AUTHOR]

In this review of neurocontrol of movement after spinal cord injury, we discuss neurophysiological evidences of conducting and processing mechanisms of the spinal cord. We illustrate that external afferent inputs to the spinal cord below the level of the lesion can modify, initiate, and maintain execution of movement in absence or partial presence of brain motor control after chronic spinal cord injury. We review significant differences between spinal reflex activity elicited by single and repetitive stimulation. The spinal cord can respond with sensitization, habituation, and dis-habituation to regular repetitive stimulation. Therefore, repetitive spinal cord reflex activity can contribute to the functional configuration of the spinal network. Moreover, testing spinal reflex activity in individuals with motor complete spinal cord injury provided evidences for subclinical residual brain influence, suggesting the existence of axons traversing the injury site and influencing the activities below the level of lesion. Thus, there are two motor control models of chronic spinal cord injury in humans: 'discomplete' and 'reduced and altered volitional motor control.' We outline accomplishments in modification and initiation of altered neurocontrol in chronic spinal cord injury people with epidural and functional electrical stimulation. By nonpatterned electrical stimulation of lumbar posterior roots, it is possible to evoke bilateral extension as well as rhythmic motor outputs. Epidural stimulation during treadmill stepping shows increased and/or modified motor activity. Finally, volitional efforts can alter epidurally induced rhythmic activities in incomplete spinal cord injury. Overall, we highlight that upper motor neuron paralysis does not entail complete absence of connectivity between cortex, brain stem, and spinal motor cells, but there can be altered anatomy and corresponding neurophysiological characteristics. With specific input to the spinal cord below the level of the lesion, the clinical status of upper motor neuron paralysis without structural modification can be modified, and movements can be initiated. Thus, external afferent input can partially replace brain control. [ABSTRACT FROM AUTHOR]

Flexible laryngoscopes are common outpatient surveillance tools. Cleansing of these scopes between patients must be quick, effective, and safe. One sterilant that largely meets these criteria is ortho-phthalaldehyde (OPA); however, infrequently, patients may develop allergic reactions to it. We present three cases of patients who developed significant allergic reactions following repeated laryngoscopic examinations. Subsequent intradermal allergy testing confirmed sensitivity to OPA. In addition, we reviewed the current literature, which includes 17 similar reactions reported in nine patients across disciplines. Allergic reaction to OPA is uncommon, but a potentially under-reported severe complication of repeated endoscopy. [ABSTRACT FROM AUTHOR]

Therapeutic monocolonal antibodies (MAbs) are a new, rapidly growing class of medications that frequently have poorly characterized side-effect profiles. We present a patient who developed inflammatory lesions of the vocal folds in temporal relation to the initiation of alirocumab. Lesions of the vocal folds represent a previously unreported adverse effect of alirocumab therapy, making it the second MAb documented with such a side effect. The potential laryngeal effects of alirocumab specifically, and of MAbs more broadly, warrant investigation. Laryngoscope, 127:1652-1654, 2017. [ABSTRACT FROM AUTHOR]

This study employs validated cough assessment tools to prospectively determine the impact of tramadol on cough severity and quality of life in subjects with neurogenic cough. The study was a prospective case series with planned data collection at a tertiary care academic medical center laryngology practice. Sixteen consecutive collected subjects with neurogenic cough prospectively completed pre- and posttreatment validated cough assessment tools, the cough severity index (CSI) and Leicester Cough Questionnaire (LCQ). All subjects in the study reported at least some improvement in their cough symptoms. In a Wilcoxon signed rank test that compared paired results, CSI scores improved from 23 to 14 and LCQ scores improved from 74 to 103 ( P = .003 and P = .005, respectively). This small preliminary assessment suggests that tramadol warrants additional evaluation as a treatment for neurogenic cough. [ABSTRACT FROM AUTHOR]