One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy.

OBJECTIVE: Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. STUDY DESIGN: Retrospective study with approval by our Ethics Committee. METHODS: The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. RESULTS: Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. CONCLUSIONS: Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. LEVEL OF EVIDENCE: level 4.

Changes in serum basic fibroblast growth factor concentration following intracordal injection.

Objective: Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. Methods: This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. Results: The mean pre- and post-injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre- and post-injective was -2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post-injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post-injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. Conclusion: In this study, the dosage of trafermin we injected and post-injective serum bFGF concentrations were dose-dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level of Evidence: Level IV.

Evaluation of Safety After Intracordal Basic Fibroblast Growth Factor Injection.

OBJECTIVES: Although there are many reports of voice improvement with intracordal trafermin (a basic fibroblast growth factor) injections under local anesthesia, few papers have documented the safety of trafermin. Therefore, we aimed to investigate whether trafermin is safer than control drugs (triamcinolone acetonide) early after intracordal injection under local anesthesia. METHODS: We conducted a retrospective review from the medical records of patients who underwent intracordal injection with trafermin and triamcinolone acetonide under local anesthesia at our institution. Early postinjective complications were defined as changes in vital signs and chief complaints early after intracordal injection. RESULTS: A total of 699 and 297 patients underwent intracordal injection under local anesthesia with trafermin and triamcinolone acetonide, respectively. Of these, 227 and 130 patients had early postinjective complications with trafermin and triamcinolone acetonide, retrospectively. The most common complications occurring with trafermin was increased blood pressure in 39 cases (5.58%): 17 cases (2.43%) of blood pressure increase of ≥20 mm Hg. Other complications included pharyngeal discomfort in 37 (5.29%), lightheadedness in 33 (4.72%), and phlegm discharge in 29 (4.15%). Triamcinolone acetonide caused pharyngeal discomfort in 28 patients (9.43%), phlegm discharge in 17 patients (5.72%), lightheadedness in 12 patients (4.04%), sore throat in 11 patients (3.70%), increased blood pressure in 10 patients (3.37%): 7 cases (2.36%) of blood pressure increase of ≥20 mm Hg, and dizziness in seven patients (2.36%). Statistical analysis of the complications between trafermin and triamcinolone acetonide showed no significant differences. CONCLUSIONS: The proportion of early postinjective complications from intracordal injection of trafermin is no significant difference in that of triamcinolone acetonide. The results suggest that the early postinjective complications are not due to the drug action of trafermin, but rather to complications from the intracordal injection procedures. Intracordal trafermin injection may be safe in the short term.

Age-dependent treatment effect of vocal fold steroid injection for benign vocal fold lesions.

Objective: Benign vocal fold lesions (BVFLs) cause voice disorders and impair social life. Recently, office-based vocal fold steroid injection (VFSI) has gained attention as a minimally invasive treatment for BVFLs. This study aimed to analyze the age-dependent treatment effect of VFSI and to clarify the indications for treatment. Methods: In this retrospective cohort study, a total of 83 patients with BVFLs were treated with a similar regimen of VFSI. Three or four months after the injection, age-dependent phonological functions were evaluated. The differences between pre- and post-treatment findings were analyzed using the Wilcoxon matched-pair signed-rank test, and the correlation between patient age and improvement rates were determined by Pearson's correlation coefficient. Results: Improvement in voice handicap index (VHI), which was the primary endpoint, was observed. Subjective and objective voice quality measurements also showed significant improvements. Subgroup analyses revealed that there was no age-related difference in the improvement of voice quality and that there was no improvement in aerodynamic effect in patients over 45 years of age. Conclusion: This study clarified the age-dependent treatment effect of VFSI and provided the important suggestion of establishing indication criteria for BVFLs. The study results provided clarity on the indication criteria of VFSI and served as an important indicator for tailoring treatment to patients' needs. Level of Evidence: 4.

Intracordal injection therapy for vocal fold scarring: Steroid versus basic fibroblast growth factor.

Objectives: Vocal fold scarring is caused by replacement of vocal fold mucosa with fibrous tissue due to repeated inflammation or trauma. It can lead to severe dysphonia. It is currently treated conservatively and with phonosurgery and intracordal injections. Intracordal injection of steroid or basic fibroblast growth factor (bFGF) has been recently found to be useful for treating vocal fold scarring that does not respond to voice therapy. Methods: This retrospective study involved the administration of steroid injection and bFGF injection bilaterally under local anesthesia in 16 patients each. Laboratory measurements of voice parameters were performed before and 3-6 months after injection. Results: In the steroid injection group, the Voice Handicap Index (VHI) score significantly improved from 57.1 to 40.5, total Grade, Roughness, Breathiness, Asthenia, Strain (tGRBAS) score significantly improved from 4.2 to 2.6, and mean speech fundamental frequency (SFF) increased from 192.5 to 211.4 dB, but there was no improvement in maximum phonation time (MPT) and mean airflow rate (MFR). In the bFGF injection group, significant improvements in the VHI score (from 53.3 to 35.7), MPT (from 16.9 to 21.8 s) and MFR (from 314.6 to 210.5 ml/s) were seen; however, the tGRBAS score did not improve. In addition, the SFF significantly decreased from 178.1 to 160.5 Hz. Conclusion: These results suggest that both steroid and bFGF injections are effective for treating vocal fold scarring, with steroids improving voice quality and bFGF improving glottic closure, thereby contributing to improvements in VHI scores. Level of Evidence: 4.

Long-term results and safety of fibroblast growth factor injection for unilateral vocal fold paralysis.

Objectives: Treatments for unilateral vocal fold paralysis (UVFP) include conservative voice rehabilitation, vocal fold injection, and laryngeal framework surgery. We proposed basic fibroblast growth factor (bFGF) injection as a potential novel treatment for UVFP and have reported the short-term results. In this study, we present the long-term results and safety of vocal fold bFGF injection as a treatment for UVFP. Methods: This retrospective study included 42 patients (25 males and 17 females) with UVFP who were administered a local injection of bFGF. The injection regimen involved injecting FGF (0.5 µg/ml in 0.5 ml per side) into the bilateral vocal folds using a 23-gauge injection needle. Phonological outcomes were evaluated 6 months and 12 months after the injection. Results: Overall, 26 patients received a single injection of bFGF, six patients received an additional injection, and 10 patients received the additional framework surgery. Maximum phonation time, mean flow rate, pitch range, jitter and shimmer percentages, the total GRBAS (grade, roughness, breathiness, asthenia, strain) score, and voice handicap index scores improved significantly in the long term. In patients who received the additional injection or framework surgery, the effects of bFGF injection were temporary, but did not interfere with the performance of the framework surgery. Conclusion: In total, 42 patients who underwent vocal fold bFGF injections were reviewed. The bFGF injections were effective and safe in the long-term results for UVFP in the selected cases. Some patients with severe symptoms benefited from the additional framework surgery but not the additional bFGF injection.

Assessment of Dysphonia Using the Japanese Version of the Voice Handicap Index and Determination of Cutoff Points for Screening.

INTRODUCTION: The Voice Handicap Index (VHI) is recognized as a useful subjective assessment method for dysphonia. The original VHI has been translated into numerous other languages, including Japanese (J-VHI). Although the reliability and validity of the J-VHI have already been established, the cutoff point has not been determined. The aims of this study were to investigate the relationship between the J-VHI and other voice laboratory measurements, and determine the cutoff point. METHOD: This study included 167 dysphonic patients and 55 healthy volunteers. All patients and volunteers completed the J-VHI at the initial visit, and the following outcomes were determined: VHI scores of patients with dysphonia and healthy volunteers, VHI scores according to disease, cutoff point, and correlations between VHI scores and other voice laboratory measurements. RESULTS: Both the total VHI (VHI-T) and individual domain (functional domain [VHI-F], emotional domain [VHI-E], physical domain [VHI-P]) scores were significantly higher in the dysphonia group compared to the healthy volunteer group. VHI-T, VHI-F, and VHI-E scores were significantly lower in the benign mucosal lesion subgroup, compared to the other disease subgroups. The G scale and B scale of the grade-roughness-breathiness-asthenia-strain scale showed a significant association with VHI-T, VHI-F, and VHI-P scores. Similarly, the A scale showed a significant association with VHI-T, VHI-F, and VHI-E scores. The cutoff point (12) for VHI-T was chosen from the receiver operating characteristic curve to maximize sensitivity and specificity. Similarly, the cutoff points for VHI-F (5), VHI-P (5), and VHI-E (3) were also obtained. Significant differences in maximum phonation time, pitch range, G scale, and B scale were observed between the VHI-T negative (VHI ≤ 12) and positive (VHI-T > 13) groups. CONCLUSION: These findings suggest that self-evaluation using the VHI could serve as an independent assessment and screening tool for patients with dysphonia.

Effect of intracordal injection under local anesthesia on vital signs in high-risk patients.

OBJECTIVE: Intracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. METHODS: A retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. RESULTS: The average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. CONCLUSION: Intracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.

Comparison of therapeutic effects of steroid injection by benign vocal fold lesion type.

BACKGROUND: Benign vocal fold lesions (BVFLs) can cause voice changes, including reduced loudness and pitch range. In recent times, with progression in endoscopic technology, office-based vocal fold steroid injection (VFSI) has been used as an alternative therapy for BVFLs. AIMS/OBJECTIVES: In this study, we analyzed the efficacy and safety of VFSI to investigate the mechanism underlying its therapeutic effects and determine the conditions in which VFSI will be most effective. MATERIALS AND METHODS: In this retrospective cohort study, we included 40 condition-matched patients (8 patients per lesion) with chorditis, vocal nodules, vocal polyps, Reinke's edema (RE), or vocal scars who received similar regimens of steroid injection using a commercial preparation of triamcinolone acetonide. Their phonological outcomes were evaluated 2 or 3 months after the injection. RESULTS: Significant improvements were observed in Voice Handicap Index scores, results of laboratory voice evaluation, and voice quality measured using the Grade, Roughness, Breathiness, Asthenia, Strain scale in all participants. In subgroup analysis, VFSI was highly effective against chorditis and vocal nodules, but less effective against RE and vocal scars. CONCLUSIONS: Single-dose VFSI is valuable as an alternative to voice rehabilitation and laryngo-microsurgery, but higher concentrations or repeated injections are required for intractable lesions.

Validation of the Japanese Version of the Singing Voice Handicap Index.

PURPOSE: The aim of the present study was to translate the Singing Voice Handicap Index (SVHI) into Japanese and validate the Japanese version of the SVHI. METHODS: The SVHI was translated into Japanese from the validated original version, and the questionnaire was administered to 102 singers with voice problems and 88 healthy singers. Internal consistency and test-retest methods were implemented to evaluate the reliability of this index. The internal consistency method assessed validity via Cronbach's α, and test-retest reliability was analyzed by the intraclass correlation coefficient (ICC) and limits of agreement (LoA) according to the Bland Altman method. Construct validity was verified by confirming correlations between SVHI scores and visual analog scale (VAS) scores for disability in singing using Spearman correlation. Discriminant validity was evaluated by comparing SVHI scores between singers with voice problems and healthy singers using t tests. Using the Tukey's honestly significant difference (HSD) test, we also compared the Voice Handicap Index (VHI) and SVHI scores among three groups: healthy singers, singers with voice problems solely during singing, and singers with voice problems during both speaking and singing. RESULTS: The Japanese version of the SVHI showed excellent internal consistency (Cronbach's α = 0.981) and test-retest reliability (ICC: 0.93). The 95 percent LoA was calculated to be between -20.8 and 33.9. Construct validity was verified through correlated SVHI and VAS scores (r = 0.736, P < 0.001). Discriminant validity was verified as the SVHI scores of singers with voice problems were higher than those of healthy singers (77.8±37.5 vs. 30.0±26.5, P < 0.001). There were no statistically significant differences in VHI scores between singers with voice problems solely during singing and healthy singers; however, the SVHI scores of singers with voice problems solely during singing were significantly higher than those of healthy singers (63.4±36.8 vs. 30.0±26.5, P < 0.001). CONCLUSION: We confirmed that the Japanese version of the SVHI is a valid and reliable self-rated questionnaire for measuring the patient-perceived impact of singing voice problems among Japanese singers.

Predominant Vertical Location of Benign Vocal Fold Lesions by Sex and Music Genre: Implication for Pathogenesis.

OBJECTIVES/HYPOTHESIS: Vertical locations of vocal fold mucosal lesions (VFMLs) vary along the free edge. As the vertical contact area of vocal folds (VFs) depends on the vocal register, lesions may occur in the contact area of more frequently used vocal registers. This study investigated the cause of location variations by comparing the vertical sites of VFMLs in singers of both sexes with different music genres. STUDY DESIGN: Retrospective review. METHODS: Sixty professional classical and rock singers (11 male classical [M-classical], 22 male rock [M-rock], 13 female classical [F-classical], and 14 female rock [F-rock] singers) who underwent microlaryngeal surgery for VF polyps and nodules and their 108 lesions were enrolled. The VF free edge was vertically divided into three equal parts and classified into the following four lesion sites: upper, middle, lower, and multiple sites. RESULTS: Upper lesions were most common among F-classical singers (73.9%), whereas lower lesions were most common among M-classical (90.0%) and M-rock (60.6%) singers. Among lesions localized to a single site, lower lesions were most common among F-rock singers (37.0%). F-classical singers had significantly more upper lesions than the other groups (P < .001). M-classical singers had significantly more lower lesions than female singers of any genre (P < .001). CONCLUSION: Upper lesions were most common among F-classical singers who mostly used the head voice. Lower lesions were most common among singers who mainly used the modal voice. This study suggests that sex, the dominant vocal register used for singing, and mechanical stress on VFs influence the vertical site of VFMLs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2284-E2291, 2021.