A Comparison Between W Score and RYAN Score in Diagnosing Laryngopharyngeal Reflux Disease.

OBJECTIVE: To assess the diagnostic value of the W score in differentiating laryngopharyngeal reflux disease (LPRD) patients from the normal population by pharyngeal pH (Dx-pH) monitoring, compared with the RYAN score. METHODS: One hundred and eight patients with suspected LPRD and complete follow-up results after more than 8 weeks of anti-reflux therapy were enrolled from the Department of Otolaryngology-Head and Neck Surgery, Gastroenterology and Respiratory Medicine of seven hospitals. Their Dx-pH monitoring data before treatment were reanalyzed to obtain the W score in addition to the RYAN score and then the diagnostic sensitivity and specificity were compared and evaluated with reference to the result of anti-reflux therapy. RESULTS: In eighty-seven (80.6%) cases, anti-reflux therapy was effective, and in 21 patients (19.4%), therapy was ineffective. Twenty-seven patients (25.0%) had a positive RYAN score. The W score was positive in 79 (73.1%) patients. There were 52 patients who had a negative RYAN score, but a positive W score. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of the RYAN score were 28.7%, 90.5%, 92.6%, and 23.5%, respectively (kappa = 0.092, P = 0.068), whereas those of the W score for LPRD was 83.9%, 71.4%, 92.4%, and 51.7%, respectively (kappa = 0.484, P < 0.001). CONCLUSIONS: W score is much more sensitive for the diagnosis of LPRD. Prospective studies with larger patient populations are necessary to validate and improve diagnostic efficacy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014931.

Office-Based Photodynamic Therapy Using Locally Applied 5-aminolevulinic Acid and 635 nm Laser for Laryngeal Leukoplakia.

OBJECTIVE: Photodynamic therapy (PDT) is a minimally invasive method with strong tissue selectivity and nonthermal effects. We aim to investigate the efficacy of an in-office method utilizing PDT with local application of 5-aminolevulinic acid (ALA) and 635 nm diode laser for treating laryngeal leukoplakia. STUDY DESIGN: Retrospective cohort study. SETTING: Outpatient clinic-tertiary medical center. METHODS: This study reviewed 32 patients with laryngeal leukoplakia, including 11 recurrent cases after surgery. All the procedures were performed in an office setting under topical anesthesia. Fifteen percent ALA solution was locally applied to the lesion through a flexible laryngoscope. Light illumination was performed using a 635 nm diode laser through a 400 µm optic fiber. The power density was 165 mW/cm2 to reach 100 J/cm2 . Results of laryngostroboscopy and voice evaluation during follow-up were collected. RESULTS: The mean follow-up was 7.91 ± 4.83 (3-18) months. Thirty-nine procedures were performed, including 1 session for 27 patients, 2 sessions for 3 patients, and 3 sessions for 2 patients. The total response rate was 96.875% (31/32), including complete responses in 26 (81.25%) patients, partial responses in 5 patients (15.625%), and no response in 1 patient (3.125%). It appeared that PDT selectively eliminated the leukoplakia without affecting lamina propria and the surrounding normal mucosa remained unharmed. Scores of Voice Handicap Index-10, jitter, shimmer, and harmonic-to-noise ratio were significantly improved after PDT. CONCLUSION: Office-based PDT is an effective, repeatable, and practical method for treating laryngeal leukoplakia. Local application of ALA is sufficient to achieve photodynamic reactions. PDT could eliminate laryngeal leukoplakia selectively while protecting the normal laryngeal structure.

5-Aminolevulinic Acid-Mediated Photodynamic Therapy Improves Vocal Fold Wound Healing in Rats.

OBJECTIVE: Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo. STUDY DESIGN: In vivo. METHODS: Vocal fold stripping was performed in Sprague-Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5-Aminolevulinic Acid (5-ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm2 . PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real-time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin-eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III. RESULTS: PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFß1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm2 PDT group. CONCLUSION: PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:1943-1951, 2023.

Successful treatment of laryngeal leukoplakia by photodynamic therapy with local application of 5-aminolevulinic acid and 635 nm laser: A case report.

Laryngeal leukoplakia is a common disorder in otolaryngology. Presently, the most widely accepted treatment is suspension laryngoscopic surgery under general anesthesia. The high recurrence rate and hoarse voice after surgery make it an intractable disease to treat. Here we report a case of a 67-year-old man who was diagnosed of laryngeal leukoplakia 15 years ago and underwent 5 surgeries because of its repeated recurrences. Two sessions of photodynamic therapy were performed with local application of 5-aminolevulinic acid and irradiation of 635 nm diode laser. Complete response was observed and no recurrence was detected during follow-up of 6 months. Photodynamic therapy with local 5-ALA application and 635 nm laser is safe and well-tolerated. It is a promising modality for laryngeal leukoplakia.

Acoustic parameters for the evaluation of voice quality in patients with voice disorders.

BACKGROUND: To investigate the value of the standard deviation of the fundamental frequency (F0 SD), jitter, and shimmer for the evaluation of voice quality and the description of vocal characteristics in patients with voice disorders. METHODS: This prospective cohort study included 4 groups: vocal cord polyps (VCP) group (n=55), early-stage (stage I-II) laryngeal carcinoma (ELC) group (n=35), mutational falsetto (MF) group (n=17), and a normal control group (n=29). The participants were asked to emit a sustained vowel /a/ and raise the pitch gradually. Acoustic parameters, including F0, F0 SD, jitter, and shimmer, were recorded and analyzed. RESULTS: The F0 SD was highest in the MF group. The F0 SD in the MF group and the ELC group was significantly higher than that in the VCP group and the control group (P<0.05), and the F0 SD in the VCP group was significantly higher than that in the control group (P<0.05). However, there was no significant difference in F0 SD between the MF group and the ELC group (P>0.05). The jitter and shimmer in the ELC group were significantly higher compared to the other groups (P<0.05), and the jitter and shimmer in the VCP group were significantly higher than those in the MF group and the control group (P<0.05). There were no significant differences in jitter or shimmer between the MF group and the control group (P>0.05). CONCLUSIONS: F0 SD, jitter, and shimmer are important parameters for the evaluation of pitch variation during sustained phonations, and can discriminate between MF and voice disorders.

An epidemiological survey of laryngopharyngeal reflux disease at the otorhinolaryngology-head and neck surgery clinics in China.

PURPOSE: Using the Reflux Symptom Index (RSI), this nationwide study aimed to investigate the incidence, diagnostic status, risk factors, and common symptoms of adult laryngopharyngeal reflux disease (LPRD) at otorhinolaryngology-head and neck surgery (OHNS) clinics in China. METHODS: This multicenter cross-sectional survey began at the different institutions ranged from July to October 2017, and the duration was 12 months. A total of 90,440 eligible patients were finally enrolled from 72 medical institutions in China. All these patients completed the questionnaire based on RSI. In this study, LPRD was defined as RSI > 13. RESULTS: There were 9182 with LPRD among the 90,440 eligible participants (10.15%). However, only 1294 had a history of LPRD diagnosis among those with LPRD (14.09%). There were regional differences in the frequency of LPRD (P < 0.001). The proportions of patients with LPRD in males (vs. females), middle- and old-aged patients (vs. young), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking) were significantly higher (all P < 0.001). Middle and old age, current smoking, and drinking history were independent predictors of LPRD (all P < 0.001, OR 1.240, 1.261, and 1.481, respectively). "Sensations of something stuck in throat or a lump in throat", "clearing throat", and "excess throat mucus or postnasal drip" were the most frequent clinical symptoms in patients with LPRD. CONCLUSIONS: LPRD has a high incidence at the OHNS clinics in China. However, the diagnostic status of this disease is not optimistic. Older age, smoking, and drinking history were risk factors for LPRD.

Distinct Acoustic Features and Glottal Changes Define Two Modes of Singing in Peking Opera.

OBJECTIVE: We aimed to delineate the acoustic characteristics of the Laodan and Qingyi role in Peking Opera and define glottis closure states and mucosal wave changes during singing in the two roles. METHODS: The range of singing in A4 (440 Hz) pitch in seven female Peking Opera singers was determined using two classic pieces of Peking Opera. Glottal changes during singing were examined by stroboscopic laryngoscope. The fundamental frequency of /i/ in the first 15 seconds of the two pieces and the /i/ pitch range were determined. The relative length of the glottis fissure and the relative maximum mucosal amplitude were calculated. RESULTS: Qingyi had significantly higher mean fundamental frequency than Laodan. The long-term average spectrum showed an obvious formant cluster near 3000 Hz in Laodan versus Qingyi. No formant cluster was observed in singing in the regular mode. Strobe laryngoscopy showed complete glottal closure in Laodan and incomplete glottal closure in Qingyi in the maximal glottis closure phase. The relative length of the glottis fissure of Laodan was significantly lower than that of Qingyi in the singing mode. The relative maximum mucosal amplitude of Qingyi was significantly lower than that of Laodan. CONCLUSION: The Laodan role and the Qingyi role in Peking Opera sing in a fundamental frequency range compatible with the respective use of da sang (big voice) and xiao sang (small voice). The morphological patterns of glottal changes also indicate that the Laodan role and the Qingyi role sing with da sang and xiao sang, respectively.

The Physiological Basis of Chinese Höömii Generation.

OBJECTIVE: The study aimed to investigate the physiological basis of vibration mode of sound source of a variety of Mongolian höömii forms of singing in China. METHODS: The participant is a Mongolian höömii performing artist who was recommended by the Chinese Medical Association of Art. He used three types of höömii, namely vibration höömii, whistle höömii, and overtone höömii, which were compared with general comfortable pronunciation of /i:/ as control. Phonation was observed during /i:/. A laryngostroboscope (Storz) was used to determine vibration source-mucosal wave in the throat. RESULTS: For vibration höömii, bilateral ventricular folds approximated to the midline and made contact at the midline during pronunciation. Ventricular and vocal folds oscillated together as a single unit to form a composite vibration (double oscillator) sound source. For whistle höömii, ventricular folds approximated to the midline to cover part of vocal folds, but did not contact each other. It did not produce mucosal wave. The vocal folds produced mucosal wave to form a single vibration sound source. For overtone höömii, the anterior two-thirds of ventricular folds touched each other during pronunciation. The last one-third produced the mucosal wave. The vocal folds produced mucosal wave at the same time, which was a composite vibration (double oscillator) sound source mode. CONCLUSIONS: The Höömii form of singing, including mixed voices and multivoice, was related to the presence of dual vibration sound sources. Its high overtone form of singing (whistle höömii) was related to stenosis at the resonance chambers' initiation site (ventricular folds level).

Study on association of peroxisome proliferator-activated receptor α with C-reactive protein, and additional gene-gene interaction in Chinese Han.

BACKGROUND: The aim was to examine the association between 6 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors α (PPAR α) poly morphisms and C-reactive protein (CRP) level, as well as  additional gene-gene interaction among the 6 SNPs. METHODS: A total of 1260 subjects (583 men, 677 women), with a mean age of 41.3 ± 14.6 years old, were selected. Six SNPs of PPAR α were selected for genotyping in the study including: rs135539, rs135551, rs135549, rs1800206, rs1800243 and rs4253623. Linear regression analysis was performed to verify the polymorphism association between SNP with CRP levels. Generalized MDR (GMDR) was employed to analysis the interaction among six SNPs. RESULTS: Linear regression results indicated a significant negative correlation between mutation of rs1800206 and CRP level. The carriers of the V allele (LV + VV) of rs1800206 were associated with a significant decreased level of CRP (regression coefficients was -0.533, standard error was 0.148 (P < 0.001)). However, the other 5 SNPs in PPAR α were not significantly associated with CRP level before or after covariate adjustment. GMDR model indicated that there was a significant two-locus model (P = 0.0107) involving rs1800206 and rs135539, indicating a potential gene-gene interaction between rs1800206 and rs135539. Overall, the two- locus models had a cross-validation consistency of 10 of 10, respectively, and had the testing accuracy of 55.9%, respectively. CONCLUSIONS: Our results support an important association between rs1800206 minor allele (V) of PPAR α and lower CRP level. The interaction analysis showed a combined effect between rs1800206 and rs135539 on the lower CRP level.

Effect of phorbol 12-myristate 13-acetate on function and gene expression of P-glycoprotein in adriamycin-resistant K562/ADM cells.

BACKGROUND/AIMS: Multidrug resistance (MDR) is a critical issue during chemotherapy of cancers. Phorbol 12-myristate 13-acetate (PMA), a diester of phorbol, is a typical activator of protein kinase C (PKC). In the present study, we investigated the effect of PMA on MDR and P-glycoprotein (P-gp) gene expression in K562/ADM cells. METHODS: 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay was used to assess adriamycin (Adr)-induced cytotoxicity towards K562/ADM cells in the absence or presence of PMA. The intracellular accumulation of Adr was measured by determining the mean fluorescence intensity. The effect of PMA on P-gp activity was investigated by rhodamine-123 accumulation and efflux experiment. Protein expression and mRNA expression of P-gp in K562/ADM cells were determined by Western blot analysis and real-time qPCR, respectively. RESULTS: Adr-induced cytotoxicity towards K562/ADM cells was significantly decreased by PMA at 5 µmol/l. Furthermore, intracellular Adr-associated mean fluorescence intensity was attenuated by 53.8% 1 h after exposure to PMA at 5 µmol/l compared with the control group (p < 0.05). A dose-dependent decrease of intracellular rhodamine-123 and increase of efflux activity of P-gp were also observed in K562/ADM cells incubation with PMA. In addition, P-gp mRNA and protein expression were significantly induced by PMA. CONCLUSION: Activation of PKC pathway by PMA can significantly induce expression and activity of P-gp, and thus decrease intracellular Adr level and strengthen MDR in K562/ADM cells.

[Basis of art phonetics in biomedical engineering].

Art phonetics' medicine, a new branch of traditional medicine, has not been developed perfectly, especially in the aspects of objective and scientific study. In this paper, the acoustical and anatiomical basis of art phonetics in viewpoint of biomedical engineering is explored, and then our work of quantitative measurement and analysis of art phonetic is introduced. The experiment data show further that quantitative measurement and analysis plays an important role in art phonetic medicine.