Quantifying Health Utility of Age-related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) negatively impacts voice and quality of life (QOL). This study aims to determine utility-based QOL in ARVA patients, correlate findings with traditional patient-reported outcome measures (PROMs), and generate utility-based inferences. METHODS: Forty ARVA patients were prospectively recruited from a tertiary care center. Health utility was measured using standard gamble, time trade-off, and visual analog scale, assessing participants' current health states relative to defined comparison states (blindness/death). Traditional PROMs (Voice Handicap Index-10 [VHI-10] and Voice-Related Quality of Life Scale [V-RQOL]) were also collected. Descriptive and paired statistics were performed to determine health utility, and Pearson correlation assessed the association between PROMs and health utilities. RESULTS: Mean health utility in ARVA was 0.84 ± 0.22, 0.88 ± 0.17, and 0.62 ± 0.25 using standard gamble, time trade-off, and visual analog scale, respectively. There were positive correlations between V-RQOL and time trade-off (r = 0.66; p < 0.0001) as well as with standard gamble (r = 0.47; p = 0.002). Participants with ARVA reported no difference in health utility impact between their voice impairment and monocular blindness (Mean dif 10.9; 95% CI -1.6, 23.5; p = 0.101). Patients with ARVA were willing to part with an average 4.6 ± 6.1 years of life to restore normal voice. CONCLUSIONS: ARVA patients view their voice impairment as a significant health decrement, comparable to monocular blindness. These findings underscore the substantial impact of ARVA on QOL and highlight the need for continued research and new therapies. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Sensitivity of Videolaryngostroboscopic Rating Tools to Differences in Dysphonia Severity.

OBJECTIVES: This study evaluated the validity of two videolaryngostroboscopic (VLS) rating tools to detect differences in VLS ratings between normophonic speakers, mild, and moderate-severely dysphonic speakers. METHODS: Sixteen rigid VLS exams were obtained from four normophonic controls and 12 speakers with dysphonia (8 =mild, 4 =moderate-severe) secondary to laryngeal pathology. Eight clinicians rated nine vibratory VLS parameters for each exam using both the Voice-vibratory Assessment of Laryngeal Imaging (VALI) tool and a 100 mm visual analog scales (VAS). Ratings obtained for both right and left vocal folds (eg, mucosal wave, amplitude of vibration, nonvibrating portion) were averaged. One rating of overall severity of laryngeal function using a 100 mm VAS also was obtained. ANOVAs were used to evaluate differences in VLS parameters between three speaker groups (normophonic, mildly dysphonic, moderate-severely dysphonic) using these two rating tools. RESULTS: There were statistically significant differences between controls and moderate-severely dysphonic speakers and for all VLS parameters except phase symmetry (P < 0.05) for both VALI and VAS ratings. Differences between mildly dysphonic and moderate-severely dysphonic and speakers were observed for 4/6 VALI ratings (mucosal wave, nonvibratory portions, phase closure, and regularity) and 5/6 parameters (mucosal wave, amplitude of vibration, nonvibratory portions, phase closure, and regularity) for VAS ratings. Significant differences between controls and mildly dysphonic speakers were not observed for VLS parameter rated using the VALI. There were significant differences between controls and mildly dysphonic speakers for 3/6 parameters (mucosal wave, amplitude of vibration, nonvibratory portion) using a VAS. Ratings of overall severity of laryngeal function differed between all levels of dysphonia severity. CONCLUSIONS: Significant differences in VLS ratings were observed for comparisons of normophonic and moderate-severely dysphonic speakers and mild to moderately dysphonic speakers using the VALI and the VAS. However, the VAS scale appeared to better differentiate differences in VLS measures between normophonic speakers and those with mild dysphonia. Future studies should consider rating scale sensitivity when VLS rating tools are selected for clinical and research purposes.

Quantitative Evaluation of Vocal Bowing Following Bilateral Thyroplasty in Age-Related Vocal Atrophy.

OBJECTIVE: Age-related vocal atrophy (ARVA) is associated with vocal fold bowing, persistent glottal gap during phonation, and dysphonia. Bilateral medialization thyroplasty is sometimes performed in patients with ARVA to improve vocal fold closure and voice. We set out to quantify stroboscopic changes in vocal fold bowing, glottal closure, and abduction angle following bilateral thyroplasty and determine how these changes affect voice quality among patients with ARVA. METHODS: Fifteen individuals with ARVA who underwent bilateral medialization thyroplasty were included in this study. Two independent investigators calculated bowing index (BI), normalized glottal gap area (NGGA), and maximum abduction angle from laryngostroboscopic exams using ImageJ™. Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) and patient-reported measures were collected before and after thyroplasty. RESULTS: Thyroplasty resulted in a 10-point improvement in overall CAPE-V (Mean dif -10; 95% CI -17, -3.3, p < 0.01) and VHI-10 (mean dif -3.8; 95% CI -9.8, 2.3, p = 0.19, n = 8). NGGA and BI significantly decreased following surgery (mean dif -78; 95% CI -155, -1.5, p = 0.05; and mean dif -2.1; 95% CI -2.4, -0.84, p < 0.01, respectively). BI correlated with CAPE-V scores (r = 0.66, 95% CI 0.22, 0.87, p < 0.01). When considering the normalized combined contributions of both NGGA and BI, there was a stronger correlation in CAPE-V scores (r = 0.87, 95% CI 0.50, 0.97, p < 0.01) compared with either measure alone. CONCLUSIONS: Thyroplasty resulted in a decrease in vocal fold bowing, glottal gap area, and CAPE-V scores in patients with ARVA. Correction of vocal bowing and glottal gap, following bilateral thyroplasty, improved voice measures following surgery. Quantitative evaluation of vocal fold morphology may be valuable when assessing the severity and treatment-response in patients with ARVA following bilateral thyroplasty. Laryngoscope, 134:835-841, 2024.

Treatments for Age-related Vocal Atrophy: A Systematic Review.

OBJECTIVE: Age-related vocal atrophy (ARVA) can dramatically affect voice, communication, and quality of life. The objectives of this systematic review were to (1) determine whether treatments for ARVA were superior to controls (2) compare the relative efficacy of procedural and behavioral treatments (3) review the various types of outcome measures, and (4) evaluate the quality of studies. REVIEW METHODS: The literature was searched using strategies designed by a medical librarian (2/18/21, updated 3/9/22). Studies investigating treatments for bilateral vocal atrophy were included. Studies involving unilateral atrophy, presbyphonia (without endoscopic findings), or an absent comparator group were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was used to guide this study. RESULTS: After applying the inclusion/exclusion criteria, 8 articles remained, including 4 randomized trials and 4 cohort studies, and a narrative synthesis was performed. Surgical and behavioral treatments for ARVA appeared to be superior to control groups, based on specific outcome measures. However, the superiority of these treatments over controls was not uniformly observed across multiple outcome measures. When comparing different treatments, superiority could not be established based on the quality and completeness of the studies included in the systematic review. Outcome measures also varied between individual studies. Finally, the risk of bias was analyzed and scored. Consistent point deductions among reviewed studies were noted. CONCLUSIONS: When comparing treatments for ARVA. Surgery and voice therapy were both superior to control groups based on specific outcome measures from different domains. Superiority of one treatment could not be established. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2846-2855, 2023.

Advantages of bilayered vascular grafts for surgical applicability and tissue regeneration.

Nanofibrous scaffolds are part of an intense research effort to design the next generation of vascular grafts. With electrospinning, the production of micro- and nano-fiber-based prostheses is simple and cost effective. An important parameter for tissue regeneration in such scaffolds is pore size. Too small pores will impede cell infiltration, but too large pores can lead to problems such as blood leakage. In this study, bilayered grafts were made by electrospinning a high-porosity graft with a low-porosity layer on either the luminal or the adventitial side. Grafts were characterized in vitro for fiber size, pore size, total porosity, water and blood leakage, mechanical strength, burst pressure and suture retention strength, and were evaluated in vivo in the rat abdominal aorta replacement model for 3 and 12 weeks. In vitro blood leakage through these bilayered grafts was significantly reduced compared with a high-porosity graft. All grafts had an excellent in vivo outcome, with perfect patency and no thrombosis. Cell invasion and neovascularization were significantly reduced in the grafts with a low-porosity layer on the adventitial side, and there was no significant difference between the grafts in endothelialization rate or intimal hyperplasia. By tailoring the microarchitecture of biodegradable vascular prostheses, it is therefore possible to optimize the scaffold for tissue regeneration while preventing blood leakage, and thus facilitating applicability in the clinic.

Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration.

An intraperitoneal (IP) monotherapy in nu/nu mice with subcutaneous xenografts of a human prostate epithelial cancer cell line:DU145 was undertaken with an aldehyde dehydrogenase 3 inhibitor MATE, that is a potent apoptogen on (DU145) in culture but not on their human prostate epithelial normal counterparts [13] . Tumour growth was slowed down but treatment had to be done 5days/week. To try to potentiate the action of MATE in vivo, a bitherapy was undertaken based on the synergetic apoptotic effect that had been observed previously in culture on DU145 treated with a methional mimic METLICO and DIMATE, an inhibitor of ALDH1 and ALDH3 [19]. The bitherapy with METLICO/MATE administered IP was as effective as the monotherapy with MATE alone by IP, but at a 2-fold lower dose of MATE and at a dose of METLICO that had no growth-inhibitory effect as a monotherapy . Hence there was definite synergism with bitherapy. To try to increase the efficacy of bitherapy, it was administered by the intra-tumoral (IT) route using the recently developed 20-bars-pressurized microinjection system from CERMA [16, 17]. IT administration of the bitherapy was indeed more effective than that by IP as regards tumour volumes are concerned. Histopathological analysis of IT-treated tumours confirmed that there were many necrotized zones but intact cells were still present. Approaches for treating a wider zone of tumour tissue by IT-bitherapy are discussed.