Clinical evaluation of a machine learning-based dysphagia risk prediction tool.

PURPOSE: The rise of digitization promotes the development of screening and decision support tools. We sought to validate the results from a machine learning based dysphagia risk prediction tool with clinical evaluation. METHODS: 149 inpatients in the ENT department were evaluated in real time by the risk prediction tool, as well as clinically over a 3-week period. Patients were classified by both as patients at risk/no risk. RESULTS: The AUROC, reflecting the discrimination capability of the algorithm, was 0.97. The accuracy achieved 92.6% given an excellent specificity as well as sensitivity of 98% and 82.4% resp. Higher age, as well as male sex and the diagnosis of oropharyngeal malignancies were found more often in patients at risk of dysphagia. CONCLUSION: The proposed dysphagia risk prediction tool proved to have an outstanding performance in discriminating risk from no risk patients in a prospective clinical setting. It is likely to be particularly useful in settings where there is a lower incidence of patients with dysphagia and less awareness among staff.

Vocal fold fibroblasts and exposure to vibration in vitro: Does sex matter?

Studies have shown that certain vocal fold pathologies are more common in one sex than the other. This is often explained by differences in the composition of the lamina propria and anatomical differences between female and male vocal folds, resulting in e.g. different fundamental frequencies. Here, we investigated a potential sex-specific voice frequency effect in an in vitro setting using vocal fold fibroblasts from one male and one female donor with and without cigarette smoke extract (CSE) addition. After exposure to either male or female vibration frequency with or without CSE, cells and supernatants were harvested. Gene and protein analysis were performed by means of qPCR, western blot, ELISA and Luminex. We found that exposure of cells to both male and female vibration pattern did not elicit significant changes in the expression of extracellular matrix-, inflammation-, and fibrosis-related genes, compared to control cells. The addition of CSE to vibration downregulated the gene expression of COL1A1 in cells exposed to the female vibration pattern, as well as induced MMP1 and PTGS2 in cells exposed to both female and male vibration pattern. The protein expression of MMP1 and COX2 was found to be significantly upregulated only in cells exposed to CSE and female vibration pattern. To conclude, different vibration patterns alone did not cause different responses of the cells. However, the female vibration pattern in combination with CSE had a tendency to elicit/maintain more pro-inflammatory responses in cells than the male vibration pattern.

Exploring the anti-inflammatory potential of topical hyaluronic acid for vocal fold injury in a rat model.

PURPOSE: Vocal fold injuries are associated with fibrosis and dysphonia, which is a major obstacle to surgical treatment. The aim of this study is to evaluate the effect of topical hyaluronic acid with or without diclofenac on the inflammatory phase of vocal fold wound healing. METHODS: Forty-one male Sprague-Dawley rats were randomly assigned to four groups: an uninjured control group, an injured control group without any treatment, and two intervention groups in which hyaluronic acid with or without diclofenac was applied to the injured vocal fold. Gene expression of inflammatory markers and ECM-related molecules were examined. RESULTS: Vocal fold injury resulted in a significant upregulation of inflammatory parameters [Ptgs2, Il1b and Il10] and Has1. Tgfb1, Has3 and Eln gene expression were significantly downregulated by the topical application of hyaluronic acid. The combination of hyaluronic acid and diclofenac did not result in any significant changes. CONCLUSIONS: Vocal fold wound healing was significantly improved by a single post-operative topical application of hyaluronic acid. The addition of diclofenac may provide no additional benefit.

Prevalence of Benign Vocal Fold Lesions: Long-Term Results From a Single European Institution.

OBJECTIVES/HYPOTHESIS: Hoarseness and limited voice capacity are often associated with benign vocal fold (VF) lesions. Despite their high clinical prevalence, epidemiological investigations focusing on these structural alterations are rare. The aim of the study was to present current European data on five typical lesion types (VF nodules, polyp, cyst, contact granuloma, Reinke´s edema). STUDY DESIGN: Retrospective investigation. METHODS: Video recordings of laryngoscopies from all patients with one of the above-mentioned VF pathologies were subjected to a review process. Data collected arose from a single institution over a period of 13 years. They were evaluated statistically with respect to lesion type, sex, age at first diagnosis, and affected side. RESULTS: In a total of 535 patients, VF polyps occurred most frequently, followed by Reinke's edema and nodules. Each of the lesion types studied was significantly associated with sex and, except VF cysts, all diagnoses were also significantly related to age. Female sex was a risk factor for VF nodules, cysts, and Reinke's edema, whereas male sex was associated with polyps and contact granulomas. VF nodules occurred predominantly in young patients, VF polyps in middle-aged, Reinke's edema, and contact granulomas in later adulthood. The predominantly affected side (bilateral, right, or left VF) depended on sex. CONCLUSIONS: Different prevalences from previous studies resulted from inconsistencies in terms of classification framework, terminology, and definition. In addition to endoscopic findings, socio-cultural backgrounds must also be considered when studying benign VF lesions. Prophylactic voice care education for all populations and concomitant efficacy studies are required. Further research is needed to verify possible correlations between sex and the affected side. A non-binary view could broaden the spectrum of phoniatric research issues.

Comparing Effects of Short- and Long-Term Exposure of Cigarette Smoke Extract on Human Vocal Fold Fibroblasts.

OBJECTIVES: To explore the effects of short- and long-term cigarette smoke extract (CSE) stimulation on the expression of extracellular matrix (ECM) components and inflammatory cytokines in an in vitro model for studying Reinke's edema using human vocal fold fibroblasts (hVFF). STUDY DESIGN: Experimental pilot study using intervention with CSE in vitro. METHODS: Immortalized hVFF were pretreated with 5% CSE or control medium over a period of 2 or 8 weeks, followed by a final 3-day incubation time. We evaluated cell proliferation and examined gene and protein expression of control- and CSE-treated cells using quantitative polymerase chain reaction, Western Blot and enzyme linked immunosorbent assay. RESULTS: Cell numbers of CSE-treated hVFF strongly decreased after 8 weeks and limited the overall duration of the experiment. We observed significant upregulations in gene expression and protein levels of inflammatory markers (cyclooxygenase COX1, COX2) and ECM components (decorin, matrix metalloproteinase 1, transglutaminase 2, gremlin 2) induced by CSE after 2 and 8 weeks. Interleukin 1 receptor 1, prostaglandin I2 synthase, collagen- and hyaluronan-related gene expression showed minor upregulations. The majority of the observed genes were similarly regulated at both time points. However, the CSE-induced mRNA level of COX1 was ablated after 8 weeks. CONCLUSION: Long-term treatment did not yield results significantly different from the short-term protocol. Therefore, we propose that prolonged CSE exposure is not superior to short-term settings, which save both time and materials.

Vocal Fold Fibroblasts in Reinke's Edema Show Alterations Involved in Extracellular Matrix Production, Cytokine Response and Cell Cycle Control.

The voice disorder Reinke's edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke's space, accompanied by pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.

Investigation of Changes in Saliva in Radiotherapy-Induced Head Neck Cancer Patients.

The intact function of the salivary glands is of utmost importance for oral health. During radiotherapy in patients with head and neck tumors, the salivary glands can be damaged, causing the composition of saliva to change. This leads to xerostomia, which is a primary contributor to oral mucositis. Medications used for protective or palliative treatment often show poor efficacy as radiation-induced changes in the physico-chemical properties of saliva are not well understood. To improve treatment options, this study aimed to carefully examine unstimulated whole saliva of patients receiving radiation therapy and compare it with healthy unstimulated whole saliva. To this end, the pH, osmolality, electrical conductivity, buffer capacity, the whole protein and mucin concentrations, and the viscoelastic and adhesive properties were investigated. Moreover, hyaluronic acid was examined as a potential candidate for a saliva replacement fluid. The results showed that the pH of radiation-induced saliva shifted from neutral to acidic, the osmolality increased and the viscoelastic properties changed due to a disruption of the mucin network and a change in water secretion from the salivary glands. By adopting an aqueous 0.25% hyaluronic acid formulation regarding the lost properties, similar adhesion characteristics as in healthy, unstimulated saliva could be achieved.

Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration.

OBJECTIVES: To explore the isolated or combined effects of cigarette smoke extract (CSE) and vibration on human vocal fold fibroblasts (hVFF) in an in vitro setting in order to elucidate their influence in the pathophysiology of Reinke's edema (RE). STUDY DESIGN: Immortalized hVFF were exposed to CSE or control medium under static or vibrational conditions. A phonomimetic bioreactor was used to deliver vibrational patterns to hVFF over a period of 5 days. METHODS: Cytotoxicity was quantified using a lactate dehydrogenase assay. We employed reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Magnetic Luminex(R) assays (R&D Systems, Minneapolis, MN) to assess the influence on extracellular matrix production, fibrogenesis, inflammation, and angiogenesis. RESULTS: We observed significant changes induced by CSE alone (hyaluronic acid, matrix metalloproteinase 1, Interleukin-8, cyclooxygenase [COX]1, COX2, vascular endothelial growth factor [VEGF]D), as well as settings in which only the combination of CSE and vibration led to significant changes (transforming growth factor beta 1, VEGFA, VEGFC). Also, CSE-induced levels of COX2 were only significantly reduced when vibration was applied. CONCLUSION: We were able to explore the cellular effects of CSE and vibration on hVFF by employing a phonomimetic bioreactor. Whereas cigarette smoke is generally accepted as a risk factor for RE, the role of vibration remained unclear as it is difficult to study in humans. Our data showed that some genes and proteins in the pathophysiological context of RE were only affected when CSE in combination with vibration was applied. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E547-E554, 2021.

Proteomic Analysis of Vocal Fold Fibroblasts Exposed to Cigarette Smoke Extract: Exploring the Pathophysiology of Reinke's Edema.

Reinke's edema is a smoking-associated, benign, mostly bilateral lesion of the vocal folds leading to difficulties in breathing and voice problems. Pronounced histological changes such as damaged microvessels or immune cell infiltration have been described in the vocal fold connective tissue, the lamina propria Thus, vocal fold fibroblasts, the main cell type of the lamina propria, have been postulated to play a critical role in disease mediation. Yet information about the pathophysiology is still scarce and treatment is only surgical, i.e. symptomatic. To explore the pathophysiology of Reinke's edema, we exposed near-primary human vocal fold fibroblasts to medium conditioned with cigarette smoke extract for 24 h as well as 4 days followed by quantitative mass spectrometry.Proteomic analyses after 24 h revealed that cigarette smoke increased proteins previously described to be involved in oxidative stress responses in other contexts. Correspondingly, gene sets linked to metabolism of xenobiotics and reactive oxygen species were significantly enriched among cigarette smoke-induced proteins. Among the proteins most downregulated by cigarette smoke, we identified fibrillar collagens COL1A1 and COL1A2; this reduction was validated by complementary methods. Further, we found a significant increase of UDP-glucose 6-dehydrogenase, generating a building block for biosynthesis of hyaluronan, another crucial component of the vocal fold lamina propria In line with this result, hyaluronan levels were significantly increased because of cigarette smoke exposure. Long term treatment of 4 days did not lead to significant changes.The current findings corroborate previous studies but also reveal new insights in possible disease mechanisms of Reinke's edema. We postulate that changes in the composition of the vocal folds' extracellular matrix -reduction of collagen fibrils, increase of hyaluronan- may lead to the clinical findings. This might ease the identification of better, disease-specific treatment options.

Therapy of bilateral vocal fold paralysis: Real world data of an international multi-center registry.

PURPOSE: To collect data on diagnosis, treatment, patient's management, and quality of life in patient with bilateral vocal fold paralysis (BVFP). METHODS: A retrospective, observational, multicenter registry study was performed. Medical records of 326 adults with permanent BVFP (median age: 61 years; 70% female, 60% after thyroid surgery) generated between 2010 and 2017. RESULTS: Median time between BVFP onset and inclusion was 1.2 years. Median post-treatment follow-up was 2 months (range: 0-42). Surgery was treatment of choice in 61.7% of the cases, with a 2-year revision rate of 32.4%. Prior to inclusion, 40.2% of the patients underwent at least one surgery. For tracheotomized patients, decannulation rate was 33.8%. Non-surgical treatments included voice therapy and botulinum toxin injection. Corticosteroid application was the most frequent treatment for post-treatment complications (18%; 1-month after surgery). Older age was an independent predictor for dyspnea (Hazard ratio [HR] = 1.041; CI = 1.005 to 1.079; p = 0.026) and the need for oxygen treatment (HR = 1.098; CI = 1.009 to 1.196; p = 0.031). Current alcohol consumption (HR = 2.565; CI = 1.232 to 5.342; p = 0.012) and a cancer-related etiology (HR = 4.767; CI = 1.615 to 14.067; p = 0.005) were independent factors of higher revision risk. CONCLUSIONS: Surgery for BVFP is currently not standardized but highly variable. Postoperative and BVFP-related complications and revision surgery are frequent. Complications are linked to patients' alcohol drinking habits and BVFP etiology. These results shall be confirmed by the upcoming evaluation of the prospective data of this registry.

Vocal fold paresis: Medical specialists' opinions on standard diagnostics and laryngeal findings.

PURPOSE: There is still no clear consensus on the diagnostic value of specific laryngeal findings in patients with suspected vocal fold paresis (VFP). The aim of the study was to establish expert opinion on criteria for the diagnosis of VFP in Europe. METHODS: A cross-sectional survey using the questionnaire introduced by Wu and Sulica for US American experts was addressed to laryngeal experts in Germany, Austria, and Switzerland and in a second survey wave to members of the European Laryngological Society. RESULTS: 100 respondents returned survey 1 (response rate 47.2%). 26% worked at a university department. 28% regularly used laryngeal electromyography (LEMG). A pathologic test results in LEMG was considered to have the strongest positive predictive value for VFP (79 ± 23%), followed by a decreased vocal fold abduction (70 ± 29%), decreased vocal fold adduction (61 ± 34%), and atrophy of the hemilarynx (61 ± 31%). The multivariate analysis showed the predictive value of LEMG was estimated lower by respondents from non-university hospital (ß = - 16.33; confidence interval (CI) = - 25.63 to - 7.02; p = 0.001) and higher in hospitals with higher frequency of VFP patients per months (ß = 1.57; CI = - 0.98 to 2.16; p < 0.0001). 30 ELS members returned survey 2 (response rate, 8.4%). Their answers were not significantly different to survey 1. CONCLUSIONS: The laryngology experts in Europe rely on LEMG for diagnosis of VFP like the US American experts, but paradoxically only a minority uses LEMG frequently. Next to LEMG, motion abnormities were considered to have the best predictive value for the diagnosis of VFP.

Carotid endarterectomy significantly improves postoperative laryngeal sensitivity.

OBJECTIVE: Iatrogenic injury of the vagus nerve or its branches during carotid endarterectomy (CEA) can result in globus sensation, dysphagia, and even vocal fold immobility. Knowledge of morphologic and functional laryngopharyngeal outcomes after CEA is poor. The present study was performed to determine potential iatrogenic damage to the laryngeal innervation after CEA. An area of particular interest was the supraglottic sensory threshold, which was examined by Fiberoptic Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST; Pentax Medical Company, Montvale, NJ), a validated and safe method for the determination of the motor and sensory components of swallowing. METHODS: FEESST was used preoperatively in 32 patients scheduled to undergo CEA and twice postoperatively to examine the motor and sensory components of swallowing. In this endolaryngeal examination, laryngopharyngeal sensory thresholds (in mm Hg) were defined as normal at <4.0 mm Hg air pulse pressure (APP), moderate deficit at 4.0 to 6.0 mm Hg APP, or severe deficit at >6.0 mm Hg APP, with a value >10.0 mm Hg APP indicating abolished laryngeal adductor reflex. Acoustic voice parameters were also analyzed for further functional changes of the larynx. RESULTS: The mean ± standard deviation preoperative FEESST measures showed no significant differences (P = .065) between the operated-on side (6.73 ± 1.73 mm Hg) and the opposite side (5.83 ± 1.68 mm Hg). At 2 days postoperatively, the threshold increased (P = .001) to 7.62 ± 1.98 mm Hg on the operated-on side. A laryngopharyngeal mucosal hematoma on the operated side was endoscopically detectable in eight patients (30.8%); in these patients, we found a markedly elevated (P = .021) measure of 9.50 ± 0.93 mm Hg. On the opposite (nonoperated-on) side of the laryngopharynx, the thresholds remained at the same level as preoperatively over all assessments (P >.05), whereas the differences between the operated and nonoperated-on sides and the hematoma and nonhematoma groups were highly significant (P = .004 and P = .001, respectively). Surprisingly, the sensory threshold on the operated-on side (6.08 ± 2.02 mm Hg) decreased significantly at the 6-week follow-up, even in relation to the preoperative measure (P = .022). With the exception of one patient with permanent unilateral vocal fold immobility, no signs of nerve injury were detected. CONCLUSIONS: In accordance with previous reports, injuries to the recurrent laryngeal nerve during CEA seem to be rare. In most patients, postoperative symptoms (globus, dysphagia, dysphonia) and signs fade within a few weeks without any specific therapeutic intervention. This study shows an improved long-term postoperative superior laryngeal nerve function with regard to laryngopharyngeal sensitivity.

Stem cell approaches for vocal fold regeneration.

OBJECTIVES/HYPOTHESIS: Current interventions in the management of vocal fold (VF) dysfunction focus on conservative and surgical approaches. However, the complex structure and precise biomechanical properties of the human VF mean that these strategies have their limitations in clinical practice and in some cases offer inadequate levels of success. Regenerative medicine is an exciting development in this field and has the potential to further enhance VF recovery beyond conventional treatments. Our aim in this review is to discuss advances in the field of regenerative medicine; that is, advances in the process of replacing, engineering, or regenerating the VF through utilization of stem cells, with the intention of restoring normal VF structure and function. DATA SOURCES: English literature (1946-2015) review. METHODS: We conducted a systematic review of MEDLINE for cases and studies of VF tissue engineering utilizing stem cells. RESULTS: The three main approaches by which regenerative medicine is currently applied to VF regeneration include cell therapy, scaffold development, and utilization of growth factors. CONCLUSION: Exciting advances have been made in stem cell biology in recent years, including use of induced pluripotent stem cells. We expect such advances to be translated into the field in the forthcoming years. Laryngoscope, 126:1865-1870, 2016.

Voice and respiratory outcomes after permanent transoral surgery of bilateral vocal fold paralysis.

OBJECTIVES/HYPOTHESIS: Bilateral vocal fold paralysis (BVFP) is a rare but life-threatening condition mostly caused by iatrogenic damage to the peripheral recurrent laryngeal nerve. Endoscopic enlargement techniques have been the standard treatment for decades. However, prospective studies using internationally accepted phoniatric and respiratory evaluation guidelines are rare. STUDY DESIGN: Prospective observational multicenter study. METHODS: Twelve clinical centers screened 61 patients, of whom 36 were eligible according to the study protocol. Subjects were assessed with specific phoniatric and respiratory tests preoperatively and at 1 and 6 months postoperatively. RESULTS: Important respiratory parameters improved significantly 6 months postoperatively (peak expiratory and expiratory flow), confirming that a glottal enlargement effectively reduced the obstruction. Objective parameters dealing with voice quality worsened significantly (maximum phonation time, voice range profile, hoarseness), whereas subjective voice assessment (VHI-12) did not change significantly. CONCLUSION: Endoscopic glottal enlargement is an effective method for relieving symptoms of dyspnea due to BVFP. Postoperatively, voice quality objectively worsened; however, this was not perceived by the patients themselves. Laryngostroboscopic findings did not correlate strongly with voice and respiratory outcomes. LEVEL OF EVIDENCE: 2b.

Permanent transoral surgery of bilateral vocal fold paralysis: a prospective multi-center trial.

OBJECTIVES/HYPOTHESIS: To describe postoperative adverse events (AEs) and outcomes after transoral surgery for bilateral vocal fold paralysis (BVFP). STUDY DESIGN: Prospective observational multicenter study. METHODS: Thirty-six patients with BVFP underwent transoral surgery using standard surgical procedures to unilaterally widen the glottic area. Postoperative adverse events (AEs) including severe adverse events (SAEs) were registered continuously. Pre- and 6-month postoperative evaluations included the 6-Minute Walk Test, the 36-Item Short Form Health Survey (SF-36), the Glasgow Benefit Inventory, the 12-Item Voice Handicap Index (VHI-12), and a Fiberoptic Endoscopic Evaluation of Swallowing graded according to the Penetration-Aspiration-Scale. RESULTS: The patients underwent posterior cordotomy, partial arytenoidectomy, or permanent laterofixation as single procedures or in combination. Forty-seven percent of the patients had postoperative AEs. Dyspnea was the most frequent AE (45%). In 40% of AEs, the events were severe (SAEs), and 72.5% were related to the study intervention. Revision surgery leading to prolonged hospitalization or rehospitalization was necessary in nine cases (25%). Laterofixation was correlated to a decreased risk of AEs (P = 0.042). Six months after surgery, a significant improvement was seen in the SF-domains: Physical component score (P = 0.008), physical functioning (P = 0.001), physical role (P = 0.031), and vitality (P = 0.032). Concerning the voice handicap, only the VHI-12 physical subscore showed a decrease (P = 0.005). The total score and other VHI-12 subscores did not change significantly (all P > 0.05). CONCLUSION: BCVP patients profit from modern transoral surgery for unilateral glottic widening; quality of life is improved; and the voice is preserved. Nevertheless, postoperative complications are frequent. LEVEL OF EVIDENCE: 2b.

Age effects on extracellular matrix production of vocal fold scar fibroblasts in rats.

Vocal fold (VF) fibroblasts are the central subject of interest in fibrogenesis and wound healing after VF injury. Scar fibroblasts (SF) exhibit an aberrant production of several extracellular matrix (ECM) components which lead either to VF fibrosis or scarless wound healing. This study aimed to investigate the role of age at the time of injury on ECM production of SF. This is designed as an animal study. VF injury was established unilaterally in eight male Sprague-Dawley rats [3 months of age (n = 4), 11 months of age (n = 4)], while the other side was left intact. Three months after injury the larynges were excised and fibroblasts were extracted from VF [normal fibroblasts (NF)­scar fibroblasts (SF)] and cultured in vitro. After first passage, VF fibroblasts were plated in 24-well plates and levels of hyaluronic acid (HA) and collagen type I were determined enzymatically from supernatant after 24 and 72 h. Cultured SF from younger animals produced significantly higher levels of HA compared to NF fibroblasts from the same animals. HA concentrations of the older animals did not differ significantly between the NF and SF cultures, but the range in SF cultures was large. In contrast to previous studies, we found that even 3 months after VF injury cultured SF from young animals expressed higher levels of HA in comparison to SF from older animals. No difference in collagen levels were observed between the younger and older animals. Age of animals is an essential factor during VF healing and has to be considered for study design.

Subjective and objective vocal parameters in women with polycystic ovary syndrome.

INTRODUCTION: Despite the relatively high prevalence of the polycystic ovary syndrome (PCOS) affecting up to 15% of all women of reproductive age, only little is known about vocal changes related to this endocrinologic disorder that is characterized by biochemical or clinical hyperandrogenism, impaired cycles, and/or polycystic ovaries. The aim of our study was to describe objective and subjective vocal changes in women with a diagnosed PCOS compared with a control group. MATERIALS AND METHODS: Our study group comprised 34 women-24 cases with confirmed PCOS and 10 controls in whom PCOS was excluded. A complete endocrinologic laboratory status was obtained by all participants; study procedures included a videolaryngostroboscopy, voice recording, and completion of the German version of the Voice Handicap Index. RESULTS: A trend toward lower mean fundamental frequency was detectable, but this failed statistical significance. No differences were found in the objective and subjective voice parameters. CONCLUSION: Elevated serum levels of androgens, as found in women with PCOS, were shown not to have an impact on the subjective and objective voice parameters.

Regenerative medicine of the larynx. Where are we today? A review.

Tissue engineering is a multidimensional process combining cells, scaffold matrices, and chemical signals to produce a structure similar to a target tissue. These techniques have opened a completely new field in diagnosis and therapy in numerous fields, including that of laryngology. Laryngeal tissue engineering has emerged in the last decade, although clinical applications are rare. The reasons therefore are numerous including ethical reasons, as well as the extremely complex anatomical structure of the vocal fold. The search for new treatment options has also enlarged our knowledge about the microphysiology and micropathophysiology of the vocal fold. To date, only specific growth factors are in clinical use for treatment of vocal fold atrophy. Big advances have been made in creating state-of-the-art scaffolds with various techniques including biomaterials as well as fully synthetic polymers. These scaffolds are supposed to provide an optimal environment for residual or implanted cells. Several in vitro settings showed practicability of these scaffolds, also in studying effects of growth factors. Cell therapy is a powerful tool in regenerative medicine but bears the uncertainty of possible malignant transformation. The aim of this review was to give a comprehensive overview about current knowledge in the field of laryngeal tissue engineering and regenerative medicine, including restoration of both vocal folds and laryngeal cartilage, and furthermore to elucidate further trends in this fascinating field.