Prospective Outcomes of Microlaryngoscopy Versus Office Laser Photoangiolysis for Vocal Fold Polyps.

OBJECTIVE(S): The objective of this study is to compare treatment outcomes for vocal fold polyps (VFPs) between operating room microlaryngoscopy and office-based photoangiolysis with the potassium titanyl phosphate (KTP) laser. METHODS: Prospective nonrandomized cohort study of patients with VFPs undergoing microlaryngoscopy ("OR group") or KTP laser photoangiolysis ("KTP group"). Voice outcomes (patient-reported outcome measures [Voice Handicap Index-10 (VHI-10) and Singing VHI-10 (SVHI-10)], auditory-perceptual measures [Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)], videostroboscopic characteristics [Voice-Vibratory Assessment of Laryngeal Imaging (VALI)], and acoustic and aerodynamic measures) were performed at baseline and regular intervals after intervention. RESULTS: Forty-four subjects (17 OR group, 27 KTP group) with VFPs were enrolled. Mean VHI-10 significantly improved from baseline to each follow-up interval in both groups, except for the 1-2-week interval in the OR group. Mean SVHI-10 improved for both groups at some intervals. Growth curve models and time-to-event analyses for patient-reported outcomes did not differ between groups. There were significant improvements in all categories of auditory-perceptual voice quality and some categories of videostroboscopic characteristics in both groups. No significant trends were identified in acoustic and aerodynamic measures. Improvements in most outcomes did not significantly differ between groups or based on polyp size. There were no major complications. CONCLUSIONS: Significant improvements in patient-reported voice outcomes measures, auditory-perceptual voice evaluation, and videostroboscopic characteristics occur following surgical treatment of vocal fold polyps with either microlaryngoscopy or office-based KTP laser. Long-term voice outcomes do not significantly differ between treatment modalities. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Outcomes of Gender-Affirming Voice and Communication Modification Training for Non-binary Individuals: A Case Series.

OBJECTIVES: There is currently no research reporting solely on outcomes of voice and communication modification training (VCMT) in individuals who identify as non-binary and genderqueer (NBGQ) in the English literature. This study aimed to describe the objective and subjective impact of VCMT on the voice of NBGQ individuals undergoing a 12-week gender-affirming VCMT program. METHODS: A retrospective consecutive case series of NBGQ individuals enrolled in a VCMT program was performed. Demographics, Transgender Self-Evaluation Questionnaire (TSEQ), fundamental frequency (F0), and frequency range were collected before and after the program. RESULTS: Four NBGQ individuals enrolled between January 2019 and June 2021; the mean age was 27.0 years. While all four participants represented in this case series showed improvement in at least one of their initial goals, only one improved both their F0 and TSEQ scores; the other three participants had mixed results. CONCLUSION: NBGQ individuals experienced improvements in self-reported outcomes and changes in acoustic measures after completing VCMT in our case series. Individuals experienced significant improvement in subjective outcomes despite small changes in acoustic measures, and vice versa. More research is needed to better understand the voice and communication needs of NBGQ individuals, along with their outcomes with VCMT. LEVEL OF EVIDENCE: Level 4.

Performers' Perceptions of Vocal Function During Oral Steroid Treatment of Vocal Fold Edema.

OBJECTIVES: Acute vocal fold edema (VFE) is often a consequence of illness, allergy, or voice overuse, causing dysphonia. Although VFE typically resolves with voice rest and treatment of predisposing causes, oral glucocorticoids are often considered for performers with imminent performance demands. There are limited data about performers' perceptions of vocal change during treatment and how this relates to their ability to perform. This study aims to examine performers' self-perceptions of vocal function with steroid treatment. METHODS: Fifty-five performers (34 F; 21 M) diagnosed with VFE who chose treatment with a 6-day methylprednisolone taper were prospectively assessed. They completed the Evaluation of the Ability to Sing Easily (EASE) and reported on their voice use, regimen, performance obligations, and ability to perform. Findings were compared between Day 1 and Day 6 using paired t-tests and nonparametric Wilcoxon signed-rank tests. RESULTS: Nearly all subjects completed scheduled performances without interruption. Following treatment, all subscales of the EASE were decreased at Day 6 (Vocal Function 29.78-20.59; Pathologic Risk Indicator 26.60-17.33; Vocal Concerns 6.10-4.20). These differences were statistically significant (p < 0.0001) and greater in subjects with performances scheduled and subjects who consistently completed vocal warmups. These findings demonstrate significant improvement in several facets of performers' self-perception of function. CONCLUSION: Subjects reported significant improvement in vocal function with oral steroid treatment and were able to meet performance obligations. It remains important that steroids are not prescribed without laryngeal examination. Examination should be repeated when dysphonia persists, recurs swiftly, or when patients seek repeated treatment, as there may be increased risk of adverse outcomes, and continued steroid use may mask underlying chronic pathology that is best treated by other means. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2434-2441, 2022.

Outcomes of Gender-Affirming Voice and Communication Modification for Transgender Individuals.

OBJECTIVES: Transgender individuals' voices are closely related to gender identity. A primary goal of gender-affirming voice modification is to help individuals alter their voices to improve gender congruence; however, there is a paucity of research to support this approach. This study aimed to evaluate the outcomes of a 12-week gender-affirming voice and communication modification program. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective consecutive case series of transgender women enrolled in a voice and communication modification program was performed. Demographics, Trans Woman Voice Questionnaire (TWVQ), fundamental frequency (F0 ), and frequency range were collected before and after the program. A Wilcoxon signed-rank test assessed changes in outcomes. Spearman's rank-order correlation coefficients quantified associations between self-reported outcomes and acoustic measures. RESULTS: A total of 16 trans women individuals were enrolled. The mean age was 31.5 years. After program completion, TWVQ improved 20.4 points, F0 increased 26.5 Hz (spontaneous speech) and 25.7 Hz (reading), and the range increased 24.7 Hz (spontaneous speech) and 0.1 Hz (reading). None of the changes in acoustic measures significantly correlated with improvement in TWVQ scores in the cohort. CONCLUSION: Trans women experience improvements in self-reported outcomes and changes in acoustic measures after completing a gender-affirming voice and communication modification program. Individuals may experience significant improvement in subjective outcomes despite small changes in acoustic measures and vice versa. LEVEL OF EVIDENCE: 4 (case series) Laryngoscope, 132:1615-1621, 2022.

Prospective Evaluation of Safety of Singing on Steroids: Testing the Truth of Received Wisdom.

OBJECTIVES/HYPOTHESIS: Performing while on steroids is widely considered to increase risk of vocal injury. This study aims to determine incidence and type of injury, and changes in performers' voices after treatment of vocal fold edema (VFE) with glucocorticoids. STUDY DESIGN: Prospective Cohort. METHODS: Fifty-five performers (34 female; 21 male) treated for acute VFE with short-course oral glucocorticoids were prospectively evaluated pre- and post-treatment. Subjects underwent videostroboscopy, acoustic/aerodynamic assessment, and functional assessment with the Singing Voice Handicap Index-10 (SVHI-10) and Evaluation of the Ability to Sing Easily (EASE). Blinded reviewers rated videostroboscopic examinations and performed audio-perceptual assessment. Chi-square tests and Wilcoxon signed rank tests were applied for analyses of treatment changes. RESULTS: Following glucocorticoid treatment, two instances of vocal fold hemorrhage (3.6%) and three instances of glottic thrush (5.5%) were observed. These resolved without consequence. Mucosal wave dynamics and edema improved. Nearly all subjects completed scheduled performances, and significant improvement was noted on the EASE, reflecting improved function after treatment. These were further supported by statistically significant improvements in CAPE-V and some acoustic and aerodynamic outcomes (semitone pitch range for females, airflow measures for males). CONCLUSIONS: Oral glucocorticoids appear to be generally safe for performers presenting with acute VFE. The incidence of adverse effects, specifically hemorrhage and thrush, was low and the effects transient. Vocal fold examination should be considered obligatory before prescribing glucorticoids to working performers. A treatment strategy for acute VF edema incorporating glucocorticoids when appropriate appears to result in significant improvements in measures of glottal function including videostroboscopic appearance, subject perception, and auditory perception. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2298-2304, 2021.

Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series.

OBJECTIVES: To describe voice changes as a result of the off-label use of androgen supplementation in women. METHODS: A multi-institutional retrospective consecutive case series identified women taking androgen supplementation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014 and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency, semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected. RESULTS: Nine women presented with voice change after initiation of androgen hormone supplementation. The mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who desired additional muscle gain. Time of symptom onset after hormone therapy initiation was highly variable, ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean fundamental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones. Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and noted some subjective benefit. CONCLUSIONS: Female patients treated with androgen supplementation may experience unintended voice changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised when prescribing these medications to women.

Long-term Follow-up After Radiation Therapy for Laryngeal Amyloidosis.

OBJECTIVES: Laryngeal amyloidosis (LA) is a rare disease characterized by extracellular protein deposition within the larynx. Treatment is difficult due to the frequently submucosal and multifocal nature of disease. The mainstay of treatment is surgical resection; however, recurrence rates are high. Recently, use of radiotherapy (RT), either alone or postoperatively, for LA has been adapted from the management of extramedullary plasmacytoma and has been shown to provide local disease control. Here, we describe the experience with adjuvant RT for LA at our center. STUDY DESIGN: Retrospective case series. METHODS: Retrospective study of patients with amyloidosis of the larynx, with or without other disease sites, seen at a tertiary academic center between 2011 and 2019. Outcomes included disease characteristics, recurrence rates, treatment modalities, and pre- and posttreatment voice handicap index (VHI)-10. RESULTS: Ten patients met eligibility criteria. Mean follow-up time for all patients was 62.0 ± 41.0 months; mean follow-up time after last treatment was 51 ± 55 months. All but one patient underwent surgical resection of disease. Seven patients underwent subsequent RT. Of these seven, six underwent RT at our institution; five received a dose of 45 Gray (Gy); and one received a dose of 20 Gy. All seven completed RT without toxicity-related interruption. Patients undergoing RT underwent 2.1 ± 1.3 surgical procedures prior to RT; no patients required surgery after RT. Mean pretreatment VHI-10 was 22.9 ± 8.1; mean posttreatment VHI-10 was 12.9 ± 13.3. CONCLUSION: RT after surgery for LA can provide good local control without unacceptable toxicity and may decrease the need for further surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1810-1815, 2021.

The discovery and investigation of a crystalline solid solution of an active pharmaceutical ingredient.

Understanding the phase behavior of crystal forms is essential in drug formulation development, as physical stability of the active pharmaceutical ingredient (API) is critical to achieving the desired bioavailability. Solvents greatly impact the physical stability of crystalline solids, resulting in a variety of well-known phase transitions, such as hydrate/solvate formation. However, solvent incorporation may also result in the formation of a less-known crystalline solid solutions (CSSs). The identification and characterization of CSSs and their effect on API physicochemical properties have not been investigated. This is the first reported instance of a CSS for an API. An exhaustive study of the phase behavior of the enantiotropically related polymorphs, I and II, of Benzocaine in water and ethanol revealed that Form I formed a CSS with water below 294.5K. Construction of the phase diagrams of Forms I and II in water and ethanol revealed that CSS formation significantly decreased the phase transition temperature between Forms I and II in water. This change resulted from the increased disorder in the lattice of Form I due to the presence of water. This work demonstrates the importance of understanding the formation of CSSs on the thermodynamic behavior of crystalline pharmaceutical solids.

The effect of ionotropic gelation residence time on alginate cross-linking and properties.

The ability to engineer biocompatible polymers with controllable properties is highly desirable. One such approach is to cross-link carbohydrate polymers using ionotropic gelation (IG). Previous studies have investigated the effect of curing time on alginate cross-linking. Herein, we discuss a novel study detailing the effect of IG residence time (IGRT) on the cross-linking of alginate with calcium ions (Ca2+) along with water migration (syneresis) and their subsequent impact on the pharmaceutical properties of alginate particles. IGRT was shown to have a significant effect on particle size, porosity, density, mechanical strength and swelling of calcium alginate particles as well as drug release mechanism. Furthermore, we describe a novel application of electron dispersive spectroscopy (EDS), in conjunction with Fourier Transform- infra red (FT-IR) spectroscopy, to analyze and monitor the changes in Ca2+ concentration during cross-linking. A simple procedure to determine the concentration and distribution of the surface and internal Ca2+ involved in alginate cross-linking was successfully developed.

Crystal structure of ethyl 4-[(E)-(4-hy-droxy-3-meth-oxy-benzyl-idene)amino]-benzoate: a p-hy-droxy Schiff base.

The title p-hy-droxy Schiff base, C17H17NO4, was synthesized via the condensation reaction of benzocaine with vanillin. The benzyl-idine and benzoate rings are inclined to one another by 24.58 (8)°, and the conformation about the C=N bond is E. In the crystal, mol-ecules are linked by O-H⋯N hydrogen bonds, forming zigzag chains propagating along [010]. Adjacent chains are linked by C-H⋯π and weak offset π-π inter-actions [inter-centroid distance = 3.819 (1) Å], forming sheets parallel to (10-2).

Attainment of surgical competence in otolaryngology training.

OBJECTIVES/HYPOTHESIS: Our aim was to determine the postgraduate year (PGY) of residency at which residents achieve competence in key otolaryngologic procedures as perceived by residents and program directors (PDs), determine resident or programmatic factors affecting PGY at which residents perceive attainment of competence, and evaluate the relationship between resident and PD perceptions for attainment of competence in these procedures. STUDY DESIGN: Cross-sectional survey. METHODS: We surveyed residents and PDs in US otolaryngology residencies in 2011 using SurveyMonkey.com and assessed subjective attainment of competence by residents for 32 otolaryngologic procedures. PGY at which subjective competence achieved per resident perception was determined using a logistic regression model; PD perception was determined by mean calculation. RESULTS: Two hundred seventy-seven residents (19.45%) and 39 PDs (37.86%) completed surveys. Residents achieved subjective competence later than expected by PDs for 25 of 32 procedures, although differences were generally small. The largest disparities were observed for nonsurgical office-based procedures, for which <90% of residents reported competence by PGY-5, whereas PDs expected competence before PGY-3. The greatest number of disparities was present in the subspecialty area of facial plastic and reconstructive surgery. Male gender predicted earlier self-reported attainment of competence in 10 of 32 procedures (P < .05). Degrees held, fellowship plans, and the size of the program were not significant predictors of PGY at which residents reported competence for most procedures. CONCLUSIONS: We provide baseline data on PGY at which residents and PDs feel competence is achieved in key otolaryngologic procedures. These results may guide milestone development for resident training and assessment. LEVEL OF EVIDENCE: NA.

Management of patients with cochlear implants and ventriculoperitoneal shunts.

OBJECTIVES: The aim of this study is to provide an overview of each device, discuss conditions that may predispose to the requirement of both devices, and consider pre- and post-operative issues arising from the co-existence of advanced technologies. In addition, relevant surgical anatomy and technique in the placement of both cochlear implant (CI) after ventriculoperitoneal shunt (VPS) and VPS after CI are reviewed. METHODS: Review of literature. RESULTS: Issues relevant to CI and VPS include predisposing conditions, magnetic resonance imaging compatibility, infectious risk, surgical technique, complication management, and a host of other issues. DISCUSSION: Patients with hydrocephalus and severe-to-profound hearing loss are a unique patient population with unique pre-, intra-, and post-operative issues. Thorough understanding of the indications, radiology, anatomy, technology, and potential complications can allow for these patients to achieve the full benefit of these lifechanging surgeries.

Templated nucleation of acetaminophen on spherical excipient agglomerates.

We investigated the effect of spherical agglomeration of heterogeneous crystalline substrates on the nucleation of acetaminophen (AAP). Optical and electron microscopy showed that the surface morphologies of single crystal triclinic lactose and D-mannitol differed significantly from their counterparts formed via spherical agglomeration. Spherical agglomerates of lactose were shown to enhance the nucleation rate of acetaminophen (AAP) by a factor of 11 compared to single crystal lactose; however, no such enhancement was observed for D-mannitol. X-ray powder diffraction identified the presence of new crystal faces of lactose present only in the spherical agglomerates However, D-mannitol did not show any significant change in crystal morphology. The new crystal faces of triclinic lactose were analyzed using geometric lattice matching software and molecular dynamics simulations to establish any new and significant epitaxial matches between lactose and AAP. A coincident lattice match and a large favorable energy interaction from hydrogen bonding were observed between the (141¯) and (001) crystal faces of lactose and AAP, respectively. The enhanced nucleation kinetics, X-ray data, and computational studies indicated that the spherical crystallization of lactose exposed the (141¯) face on the surface of the agglomerates, which subsequently enhanced the nucleation rate of AAP through geometric lattice matching and molecular functionality. This study highlights the importance of exploring different heterogeneous substrate morphologies for enhancing nucleation kinetics.

Solubility, metastable zone width measurement and crystal growth of the 1:1 benzoic acid/isonicotinamide cocrystal in solutions of variable stoichiometry.

The solubility and crystal growth of the 1:1 cocrystal between benzoic acid and isonicotinamide from 95% ethanol was studied through the creation of a ternary phase diagram at differing temperatures and turbidity measurements. From the solubility measurements thermodynamic properties of the system were evaluated, which indicate little solution binding of the two components supported by in situ FT-IR spectra. Cooling crystallisation from solutions of differing composition suggests differing crystal growth characteristics. An excess of benzoic acid appears to increase the metastable zone width and reduce the crystal size through interactions along the fastest growth axis, while an excess of isonicotinamide decreases the metastable zone width with increased crystal size.