Identification and analysis of Nonlinear behaviors of vocal fold biomechanics during phonation to assess efficacy of surgery for benign laryngeal Diseases.

BACKGROUND: Current voice assessments focus on perceptive evaluation and acoustic analysis. The interaction of vocal tract pressure (PVT) and vocal fold (VF) vibrations are important for volume and pitch control. However, there are currently little non-invasive ways to measure PVT. Limited information has been provided by previous human trials, and interactions between PVT and VF vibrations and the potential clinical application remain unclear. Here, we propose a non-invasive method for monitoring the nonlinear characteristics of PVT and VF vibrations, analyze voices from pathological and healthy individuals, and evaluate treatment efficacy. METHOD: Healthy volunteers and patients with benign laryngeal lesions were recruited for this study. PVT was estimated using an airflow interruption method, VF vibrational frequency was calculated from accelerometer signals, and nonlinear relationships between PVT and VF vibrations were analyzed. Results from healthy volunteers and patients, as well as pre- and post-operation for the patients, were compared. RESULTS: For healthy volunteers, nonlinearity was exhibited as an initial increase and then prompt decrease in vibrational frequency at the end of phonation, coinciding with PVT equilibrating with the subglottal pressure upon airflow interruption. For patients, nonlinearity was present throughout the phonation period pre-operatively, but showed a similar trend to healthy volunteers post-operatively. CONCLUSION: This novel method simultaneously monitors PVT and VF vibration and helps clarify the role of PVT. The results demonstrate differences in nonlinear characteristics between healthy volunteers and patients, and pre-/post-operation in patients. The method may serve as an analysis tool for clinicians to assess pathological phonation and treatment efficacy.

Improvement in swallowing safety after injection laryngoplasty in patients with unilateral vocal paralysis complicated with aspiration.

BACKGROUND: The benefit of injection laryngoplasty (IL) on voice for unilateral vocal fold paralysis (UVFP) is supported increasingly in literatures, yet less is known for swallowing. Also, prevalence of patient-reported dysphagia is substantially higher than instrumental studies. This prospective study focused on swallowing outcomes, with predetermined flexible endoscopic evaluation of swallowing (FEES) protocol that simulates daily life situation. METHODS: Adult patients with UVFP and aspiration receiving IL were recruited. Voice outcome measurements, as well as swallowing outcomes including Eating Assessment Tool (EAT-10) and FEES, which challenged patients with different fluid volumes: 10 mL, 20 mL, and 90 mL cup sipping were evaluated. RESULTS: Significant improvements were demonstrated in all voice outcomes. Significant changes were also presented inEAT-10 (P < 0.01). Pre-operatively, penetration-aspiration scale (PAS) was 1.5 ± 1.3, 1.9 ± 1.7 and 2.3 ± 1.8 for 10 mL, 20 mL and 90 mL serial sipping, and improved to 1.1 ± 0.3, 1.1 ± 0.4 and 1.4 ± 0.7 post-operatively (P < 0.01). Safe swallowing (PAS ≤ 2) was achieved in all, except for one patient, who presented with a post-injection PAS of 4 (material enters the airway, contacts the vocal folds, and is ejected from the airway) on 90 mL cup sipping, whose pre-injection PAS was 7 (residue in trachea). CONCLUSION: Maintaining swallowing function suitable for social environment is important. Our results demonstrated the feasibility of the predetermined FEES protocol, and positive effects of IL on both voice and swallowing outcomes.

Effects of surgery on the relationship between subglottic pressure and fundamental frequency in vocal fold dynamics in patients with benign laryngeal diseases.

PURPOSE: Subglottic pressure (Ps) and fundamental frequency (F0) play important roles in governing vocal fold (VF) dynamics. Theoretical description, model simulation, excised larynx and animal models have been used in previous studies, yet clinically applicable measurements are still lacking. This study aimed to evaluate the effects of surgery for benign laryngeal lesions by investigating the relationship between F0 and Ps. METHODS: Patients with benign laryngeal lesions who underwent phonosurgery were prospectively recruited. Participants were instructed to sustain voicing the vowel /o/ at three incremental frequencies four semitones apart in the modal register (F01, F02, F03). F0 was estimated by VF vibration on the accelerometer. Ps change was achieved and measured using the airflow interruption method. RESULTS: Thirteen patients with a mean age (SD) of 43.5 (12.4) years were included. The change in F0 per unit change of Ps, which is the slope (Hz/kPa) of the regression line of the frequency-pressure data pairs, decreased as the tension of the VF increased. The slopes significantly increased after the operation for F01 and F02 (36.43 ± 14.68 preoperatively, 53.91 ± 30.71 postoperatively, p = 0.011 and 26.02 ± 10.71; 34.85 ± 17.92, p = 0.046, respectively). In addition, there was a significant decrease in phonation threshold pressure and improvements in the grade, roughness, breathiness, asthenia, strain scale, and the voice handicap inventory-10. CONCLUSIONS: The relationship between F0 and Ps may serve as an objective assessment of the outcomes in the treatment of benign laryngeal diseases with clinical relevance.

Proactive Swallowing Rehabilitation in Patients with Recurrent Oral Cancer Receiving Salvage Treatment: Long-Term Swallowing-Related Outcomes.

The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life in patients with recurrent oral cancer in the first 2 years after salvage treatment. Consecutive adult patients with recurrent oral cancer who received salvage surgery and free flap reconstruction were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, 18 and 24 months were evaluated. A total of 50 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in BW and FOIS from one month, and in MDADI from three months. All patients were free of tube feeding at 18-24 months and tolerated diet with special preparations or compensation. Safe swallowing could be achieved in approximately 80% participants after 12 months of diet modification or compensatory maneuvers. Proactive swallowing therapy was feasible in patients with recurrent oral cancer receiving salvage treatment. Although this patient population might have pre-existing dysphagia from previous treatments, rehabilitation could facilitate safe per oral intake and maintain adequate nutrition with adaptive maneuvers or compensatory strategies. Patients who underwent proactive swallowing rehabilitation had better recovery in the functional oral intake level.

An alternative surgical technique for advanced tongue/tongue base cancer without free flap reconstruction.

BACKGROUND/PURPOSE: Locally advanced tongue or tongue base cancer is recommended to be treated by radical resection that is usually detrimental to physiological functions. This study reports the efficacy and treatment outcome of the patients who had received total glossectomy and laryngeal suspension without lip-split mandibulotomy and free flap reconstruction to preserve laryngopharyngeal function. METHODS: From 2010 to 2018, 37 consecutive patients who had received the surgery were retrospectively recruited. RESULTS: The overall five-year survival is 72%. The postoperative dependent rate of feeding tube and tracheostomy largely decreases within 1-year follow-up. Treated by this surgical method, these patients are free from facial disfiguration, donor site morbidity, and destructive mastication and occlusion. It is also feasible to perform this surgical technique in the recurrent cases previously treated by chemoradiation. CONCLUSION: Total glossectomy with laryngeal suspension can be successfully applied to locally advanced tongue or tongue base cancer, and benefits the patients with improved survival and preserved physiological function. Especially surgeons for free flap reconstruction are understaffed at some regional or district hospitals.

Radiation-induced swallowing dysfunction in patients with head and neck cancer: A literature review.

Swallowing dysfunction is a prevailing state following radiotherapy in patients with head and neck cancer. Following the advancement of cancer treatment in recent years, the survival rate of head and neck cancer has gradually increased. Simultaneously, patients with head and neck cancer suffer due to the long-duration and more prominent swallowing dysfunction states. Based on an extensive literature review, we aimed to explore the mechanisms, risk factors, and clinical evaluations of swallowing dysfunction and their related symptoms following radiotherapy. These include functional changes of the muscles, trismus, xerostomia, neuropathy, and lymphedema. When swallowing dysfunction occurs, patients usually seek medical help and are referred for rehabilitation therapy, such as muscle strengthening and tongue resistance exercise. Furthermore, clinicians should discuss with patients how and when to place the feeding tube. Only through detailed evaluation and management can swallowing dysfunction resolve and improve the quality of life of patients with head and neck cancer following radiotherapy.

Long-term swallowing-related outcomes in oral cancer patients receiving proactive swallowing therapy.

OBJECTIVES: The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life (QoL) in oral cancer patients in the first two years after definitive treatment. MATERIALS AND METHODS: Consecutive adult patients with locally advanced oral cancer who received radical surgery, free flap reconstruction, and adjuvant radiotherapy were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, and 24 months were evaluated. RESULTS: A total of 104 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in FOIS from one month, and in BW and MDADI from three months. A total of 94% patients were free of tube feeding at 12 months but with a diet requiring special preparations or compensation. Safe swallowing could be achieved in approximately 90% of the participants after six months with diet modification or compensatory maneuvers. BW at 18 and 24 months did not differ significantly from baseline. CONCLUSION: Proactive swallowing therapy is feasible for patients with locally advanced oral cancer receiving definitive treatments. It facilitates safe oral intake and adequate nutrition. Patients who performed swallowing exercises had a faster and better recovery in swallowing function and swallowing-related QoL.

Objective evaluation of biomaterial effects after injection laryngoplasty - Introduction of artificial intelligence-based ultrasonic image analysis.

OBJECTIVE: Hyaluronic acid (HA) can be degraded over time. However, persistence of the effects after injection laryngoplasty (IL) for unilateral vocal fold paralysis (UVFP), longer than expected from HA longevity, has been observed. The purpose of the study was to develop a methodology with clinical utility for objective evaluation of the temporal change in HA volume after IL using artificial intelligence (AI)-based ultrasonic assessment. DESIGN, SETTING AND PARTICIPANTS: Imaging phantoms simulating injected HA were built in different volumes for designing the algorithm for machine learning. Subsequently, five adult patients who had undergone IL with HA for UVFP were recruited for clinical evaluation. MAIN OUTCOME MEASURES: Estimated volumes were evaluated for injected HA by the automatic algorithm as well as voice outcomes at 2 weeks, and 2 and 6 months after IL. RESULTS: On imaging phantoms, contours on each frame were described well by the algorithm and the volume could be estimated accordingly. The error rates were 0%-9.2%. Moreover, the resultant contours of the HA area were captured in detail for all participants. The estimated volume decreased to an average of 65.76% remaining at 2 months and to a minimal amount at 6 months while glottal closure remained improved. CONCLUSION: The volume change of the injected HA over time for an individual was estimated non-invasively by AI-based ultrasonic image analysis. The prolonged effect after treatment, longer than HA longevity, was demonstrated objectively for the first time. The information is beneficial to achieve optimal cost-effectiveness of IL and improve the life quality of the patients.

Estimating vocal fold stiffness: Using the relationship between subglottic pressure and fundamental frequency of phonation as an analog.

OBJECTIVE: The stiffness of the vocal folds is an important factor in voice production, yet clinically applicable measurements are still lacking. It has been demonstrated in an in vivo canine model that fundamental frequency (F0 ) increased linearly as subglottic pressure (Ps ) increased, but with a lesser slope for higher levels of vocal fold tension. In this study, the relationship between F0 and Ps was investigated using the airflow interruption method in awake patients non-invasively. DESIGN: Healthy volunteers enrolled for evaluation. SETTING: Single-centre. PARTICIPANTS: Thirty-three healthy volunteers aged 20 and older were recruited, with one excluded for a recent asthma attack. MAIN OUTCOME MEASURES: The relationships between F0 and Ps , described as the slope (Hz/kPa), were investigated when the participants sustained voicing the vowel/o/at 3 incremental frequencies 4 semitones apart in the modal register (F1, F2 and F3). RESULTS: Thirty-two healthy volunteers (20 females, 12 males) aged 20-47 years were enrolled for final analyses. There was a statistically significant difference in the slopes of the linear regression lines of F0 -Ps , depending on the frequency with which the vowel/o/ was produced (P < .001). The slope differed significantly between F2 and F1 (P < .001; P = .015), F3 and F1 (P < .001; P = .002) and F3 and F2 (P < .001; P = .005) for both women and men, respectively. CONCLUSIONS: It was demonstrated that the higher the vocal fold tension, the smaller the slope between F0 and Ps . Using the relationship between F0 and Ps as an analog of vocal fold stiffness is potentially practical for clinical application.

Nonintubated laryngomicrosurgery with Transnasal Humidified Rapid-Insufflation Ventilatory Exchange: A case series.

BACKGROUND: Nonintubation anaesthesia for laryngomicrosurgery (LMS) provides both excellent visualization of the surgical field and complete examination on vocal cord. However, adequate oxygenation remains challenging during nonintubated LMS. Recently, transnasal humidified rapid-insufflation ventilator exchange (THRIVE) has been reported effectively maintaining apneic oxygenation in patient with difficult airways. The feasibility and safety of nonintubated LMS with THRIVE was evaluated in this case series. METHODS: From September 2016 to February 2017, a total of 23 patients receiving nonintubated LMS were included. Anaesthesia was induced and maintained through target-controlled propofol infusion and muscle relaxation with THRIVE oxygen support. Perioperative data were collected from medical records and analysed. RESULTS: The mean (±SD) duration of the operation was 12.4 (±4.4) min. The mean (±SD) total anaesthesia time (from induction to emergence) was 24.1 (±6.4) min. 22 patients received nonintubated LMS with surgical satisfaction without intraoperative desaturation. One patient who underwent laryngeal tumour biopsy experienced a single episode of desaturation. A 5.5-mm tracheal tube was needed for short-term mechanical ventilation to regain SpO2 to 100%. No significant complication was noted in all patients. All patients discharged as per schedule on the next day after surgery as intubated LMS patients in our hospital. CONCLUSION: Nonintubated LMS with THRIVE is a feasible and safe alternative to intubated LMS with a small size tracheal tube to provide a better surgical field. However, for patients with easy-bleeding tumor, intubated LMS remains suggestive for better airway protection.

Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation.

Small-molecule compounds targeting trinucleotide repeats in DNA have considerable potential as therapeutic or diagnostic agents against many neurological diseases. NiII (Chro)2 (Chro=chromomycin A3) binds specifically to the minor groove of (CCG)n repeats in duplex DNA, with unique fluorescence features that may serve as a probe for disease detection. Crystallographic studies revealed that the specificity originates from the large-scale spatial rearrangement of the DNA structure, including extrusion of consecutive bases and backbone distortions, with a sharp bending of the duplex accompanied by conformational changes in the NiII chelate itself. The DNA deformation of CCG repeats upon binding forms a GGCC tetranucleotide tract, which is recognized by NiII (Chro)2 . The extruded cytosine and last guanine nucleotides form water-mediated hydrogen bonds, which aid in ligand recognition. The recognition can be accounted for by the classic induced-fit paradigm.

Migrated Implant Causing Refractory Headache in Rhinoplasty.

Alloplastic materials are popular and readily available for use in nasal augmentations. Among them, silicone implant is one of the most widely used, especially in certain areas in Asia for its reasonable cost and relatively simple operative technique. A major disadvantage of silicone is its notorious mobility after implantation and rate of extrusion if traumatized or exposed. Here, an unusual complication of a silicone implant for rhinoplasty was presented. We report a case of a 58-year-old woman who had augmentation rhinoplasty 20 years ago suffered from headache for over a year. Brain lesion and neurologic causes were ruled out by neurologists and physician in family medicine. Local finding showed upwardly deviated nasion and vague shape of silicone implant underneath the skin on nasal dorsum.

The structural basis of actinomycin D-binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats.

The potent anticancer drug actinomycin D (ActD) functions by intercalating into DNA at GpC sites, thereby interrupting essential biological processes including replication and transcription. Certain neurological diseases are correlated with the expansion of (CGG)n trinucleotide sequences, which contain many contiguous GpC sites separated by a single G:G mispair. To characterize the binding of ActD to CGG triplet repeat sequences, the structural basis for the strong binding of ActD to neighbouring GpC sites flanking a G:G mismatch has been determined based on the crystal structure of ActD bound to ATGCGGCAT, which contains a CGG triplet sequence. The binding of ActD molecules to GCGGC causes many unexpected conformational changes including nucleotide flipping out, a sharp bend and a left-handed twist in the DNA helix via a two site-binding model. Heat denaturation, circular dichroism and surface plasmon resonance analyses showed that adjacent GpC sequences flanking a G:G mismatch are preferred ActD-binding sites. In addition, ActD was shown to bind the hairpin conformation of (CGG)16 in a pairwise combination and with greater stability than that of other DNA intercalators. Our results provide evidence of a possible biological consequence of ActD binding to CGG triplet repeat sequences.