Injection laryngoplasty with autologous fascia for treatment of unilateral vocal fold paralysis

The purpose of this dissertation was to study the applicability of minced autologous fascia graft for injection laryngoplasty of unilateral vocal fold paralysis (UVFP). Permanence of augmentation and host versus graft tissue reactions were of special interest. The topic deals with phonosurgery, which is a subdivision of the Ear, Nose and Throat-speciality of medicine. UVFP results from an injury to the recurrent or the vagal nerve. The main symptom is a hoarse and weak voice. Surgery is warranted for patients in whom spontaneous reinnervation and a course of voice therapy fails to improve the voice. Injection laryngoplasty is a widespread surgical technique which aims to restore glottic closure by augmenting the atrophied vocal muscle, and also by turning the paralyzed vocal fold towards midline. Currently, there exists a great diversity of synthetic, xenologous, homologous, and autologous substances available for injection. An autologous graft is perfect in terms of biocompatibility. Free fascia grafts have been successfully used in the head and neck surgery for decades, but fascia had not been previously applied into the vocal fold. The fascia is harvested from the lateral thigh under local anesthesia and minced into paste by scissors. Injection of the vocal fold is performed in laryngomicroscopy under general anesthesia. Three series of clinical trials of injection laryngoplasty with autologous fascia (ILAF) for patients with UVFP were conducted at the Department of Otorhinolaryngology of the Helsinki University Central Hospital. The follow-up ranged from a few months to ten years. The aim was to document the vocal results and possible morbidity related to graft harvesting and vocal fold injection. To address the tissue reactions and the degree of reabsoprtion of the graft, an animal study with a follow-up ranging from 3 days to 12 months was performed at the National Laboratory Animal Center, University of Kuopio. Harvesting of the graft and injection was met with minor morbidity. Histological analysis of the vocal fold tissue showed that fascia was well tolerated. Although some resorption or compaction of the graft during the first months is evident, graft volume is maintained well. When injected deep and laterally into the vocalis muscle, the fascia graft allows normal vibration of the vocal fold mucosa to occur during phonation. Improvement of voice quality was seen in all series by multiple objective parameters of voice evaluation. However, the vocal results were poor in cases where the nerve trauma was severe, such as UVFP after chest surgery. ILAF is most suitable for correction of mild to moderate glottic gaps related to less severe nerve damage. Our results indicate that autologous fascia is a feasible and safe new injection material with good and stable vocal results. It offers a practical solution for surgeons who treat this complex issue.HYKS Korvaklinikalla toteutetussa väitöstutkimuksessa selvitettiin autologisen faskian eli omaa kudosta olevan vapaan lihaskalvosiirteen soveltuvuutta äänihuulihalvauksen kirurgisessa hoidossa. Väitösaihe käsittelee äänihuulikirurgiaa, joka kuuluu korva-, nenä- ja kurkkutautien erikoisalaan. Äänihuulihalvaus on yleisimmin seurausta kasvaimen tai leikkauskomplikaation aiheuttamasta hermovammasta. Pääoire on käheä ja heikko ääni, josta aiheutuu potilaille merkittävä kommunikaatiohaitta. Käheyden voimakkuus ja paranemisennuste riippuu vamman vaikeusasteesta. Lievemmät tapaukset kuntoutuvat puheterapeutin toimesta ääniterapialla. Kirurgiaa tarvitaan vaurioissa, joissa hermon toiminta ei spontaanisti palaudu riittävästi. Injektiolaryngoplastiassa halvaantuneeseen äänihuuleen ruiskutetaan ainetta, joka korvaa surkastuneen lihasmassan ja kääntää äänihuulen keskiviivaan. Toimiva äänihuuli saa siihen näin kontaktin ja ääni palautuu. Täyteaineita on tarjolla laaja valikoima. Potilaan omaa kudosta l. autologista siirrettä käyttämällä vältetään monia ongelmia, joita on liittynyt aiemmin paljon käytettyihin synteettisiin materiaaleihin, kuten Tefloniin ja silikoniin. Kun kokeilut 1990-luvun alussa rasvakudoksella eivät antaneet pysyvää tulosta äänihuulessa, päätettiin Korvaklinikalla kokeilla faskiaa l. lihaskalvoa. Faskiasta on pitkä kokemus mm. tärykalvon paikkausleikkauksista, mutta äänihuulessa sitä ei ollut aiemmin käytetty. Faskiasiirre otetaan paikallispuudutuksessa potilaan reisilihaksesta. Se pilkotaan saksilla pastaksi, potilas nukutetaan ja faskia injisoidaan äänihuuleen leikkausmikroskoopin ja erikoisruiskun avulla. Väitöstutkimus aloitettiin Korvaklinikalla v.1998. Se koostuu eläinkokeesta ja kolmesta potilastutkimuksesta. Eläintyön tavoite oli selvittää faskian aiheuttamat kudosreaktiot ja siirteen pysyvyys äänihuulessa. Potilastutkimusten seuranta-aika vaihteli muutamasta kuukaudesta 10 vuoteen. Niissä tavoitteena oli mitata objektiivisin menetelmin leikkaustulos eli äänen laatu sekä arvioida leikkaustekniikan turvallisuutta ja mahdollisia myöhäisongelmia. Tutkimuksessa osoitettiin, että faskia on hyvin siedetty ja stabiili siirre äänihuulessa. Se ei aiheuta vierasesinereaktiota. Alkuvaiheessa todettiin lievä tulehdus, joka ei vaadi antibioottihoitoa. Leikkaustekniikka on kirurgille verrattain helppo omaksua ja potilaalle turvallinen. Merkittäviä leikkauskomplikaatioita ei esiintynyt, myös leikkauksen jälkeinen haitta siirteen ottokohdalla on vähäinen. Äänitulokset olivat hyvät kaikissa tutkimuksissa, joskin pitkän seuranta-ajan (3-10 v.) tuloksissa oli enemmän vaihtelevuutta. Johtopäätös tästä oli että injektiotekniikka faskialla ei ole käyttökelpoinen vaikeimmissa hermovammoissa. Tulostemme perusteella faskiainjektio on käyttökelpoinen ja turvallinen äänihuulihalvauksen kirurginen hoito, joka soveltuu parhaiten lievien ja keskivaikeiden hermovammojen aiheuttaman käheyden korjaamiseen. Se tarjoaa äänikirurgille uuden käytännöllisen tekniikan tämän monimuotoisen ja usein vaikeahoitoisen vamman korjaamiseksi

Autologous fat injection to face and neck: from soft tissue augmentation to regenerative medicine

Minimally-invasive autologous fat injection of the head and neck region can be considered a valid alternative to major invasive surgical procedures both for aesthetic and functional purposes. The favourable outcomes of autologous fat injection in otolaryngological practice are due to the filling of soft tissue and, mainly, to the potential regenerative effect of adipose-derived mesenchymal stem cells. Herewith, some important biological preliminary remarks are described underlying the potential of autologous fat injection in regenerative medicine, and personal experience in using it for both consolidated clinical applications, such as fat grafting to the face and vocal fold augmentation in the treatment of glottic incompetence, and more recent applications including the treatment of post-parotidectomy Frey syndrome and velopharyngeal insufficiency

Numerical Modeling of Vocal Control and Patient-specific Surgical Planning of Type 1 Thyroplasty

This study aims to develop knowledge about the roles of intrinsic laryngeal muscles on voice control in both healthy and disordered conditions through comprehensive computational models. The phonation simulator was built by combining a three-dimensional high-fidelity MRI-based model of the larynx, active muscle mechanics, and fluid-structure-acoustic interaction model, which enabled the exploration of the underlayer mechanisms of the link between individual and/or group muscles contractions under both symmetric and asymmetric activations, vocal fold posture, vocal fold vibration, and voice outcomes during voice production. The first part of this research extensively investigated the effects of cricothyroid and thyroarytenoid muscle activations on voice characteristics through a parametric study. The role of these intrinsic muscles in the adjustment of geometrical and mechanical properties of vocal fold pre-phonatory posture, glottic flow aerodynamics, and acoustic and how all these components interact were explored. Results were comprehensively validated, and the link between elements of phonation was described in detail. In the next step, due to the model\u27s ability in the individual muscle activations, unilateral vocal fold paralysis was simulated, and the characteristics of disordered voice were analyzed. The voice simulator was then combined with the implant insertion model and genetic algorithm method to build a computational framework for patient-specific surgical planning of type 1 thyroplasty. This surgery is a standard procedure for treating unilateral vocal fold paralysis; however, it is subject to challenges mainly due to the small size of the implant and the high sensitivity of the voice outcome to the implant shape and position. Therefore, although the patient\u27s voice could be improved, the results might not be as satisfying as expected. Despite actual surgery, with very little room for try and error, the ideal implant could be achieved by optimizing the implant based on the patient\u27s desired voice using the presented computational framework. Both healthy and diseased cases and the corrected case using the optimized implant were simulated. Results revealed that the optimized implant could restore the aerodynamic and acoustic features of the disordered voice in producing a sustained vowel utterance. Furthermore, the performance of the implant in the pitch gliding test, which was simulated using temporal activation of the cricothyroid and thyroarytenoid muscles based on the first part of the study, was evaluated. In the final step, a physics-informed neural network-based algorithm was presented to reconstruct the three-dimensional cyclic vibration of vocal fold using two-dimensional sparse experimental data and laws of physics. Key acoustic parameters and vibratory dynamics of vocal folds and other parameters, such as flow rate, pressure distribution, and contact force, which are difficult to measure experimentally, were successfully predicted

Vocal Fold Fibroblast Response to Mechanical Stress

The role of exercise in vocal fold wound healing has been overlooked. Data from numerous other systems suggest a positive role of tissue mobilization to facilitate optimal wound healing and biomechanically superior tissue. The current study sought to investigate the potential role of mechanical signaling to attenuate the inflammatory and alter the synthetic properties of fibroblasts cultured from the vocal folds. Vocal fold fibroblasts were subjected to one of four conditions: no treatment, IL-1â alone, mechanical stress alone, or mechanical stress plus IL-1â. Results suggest that mechanical stress may limit the inflammatory phenotype of vocal fold fibroblasts in the short-term (4 hours), but not in the long-term (24 hours). In fact, 24 hours of mechanical stress may actually increase the inflammatory response. In addition, neither IL-1â nor mechanical stress had an effect on vocal fold fibroblast synthesis of extracellular matrix proteins. As a potential explanation for the current findings, it is hypothesized that the vocal folds may be more resilient to mechanical stress given the inherently stressful environment associated with phonation

Vocal cord palsy as a sequela of paediatric cardiac surgery – a review

Background: Vocal cord palsy is one of the recognised complications of complex cardiac surgery in the paediatric population. While there is an abundance of literature highlighting the presence of this complication, there is a scarcity of research focusing on the pathophysiology, presentation, diagnosis, and treatment options available for children affected by vocal cord palsy. Materials and methods: Electronic searches were conducted using the search terms: “Vocal Cord Palsy,” “VCP,” “Vocal Cord Injury,” “Paediatric Heart Surgery,” “Congenital Heart Surgery,” “Pediatric Heart Surgery,” “Vocal Fold Movement Impairment,” “VFMI,” “Vocal Fold Palsy,” “PDA Ligation.” The inclusion criteria were any articles discussing the outcomes of vocal cord palsy following paediatric cardiac surgery. Results: The two main populations affected by vocal cord palsy are children undergoing aortic arch surgery or those undergoing PDA ligation. There is paucity of prospective follow-up studies; it is therefore difficult to reliably assess the current approaches and the long-term implications of management options. Conclusion: Vocal cord palsy can be a devastating complication following cardiac surgery, which if left untreated, could potentially result in debilitation of quality of life and in severe circumstances could even lead to death. Currently, there is not enough high-quality evidence in the literature to aid recognition, diagnosis, and management leaving clinicians to extrapolate evidence from adult studies to make clinical judgements. Future research with a focus on the paediatric perspective is necessary in providing evidence for good standards of care

C-9 and Other Microgravity Simulations

This document represents a summary of medical and scientific evaluations conducted aboard the C-9 or other NASA-sponsored aircraft from June 30, 2006, to June 30, 2007. Included is a general overview of investigations manifested and coordinated by the Human Adaptation and Countermeasures Office. A collection of brief reports that describe tests conducted aboard the NASA-sponsored aircraft follows the overview. Principal investigators and test engineers contributed significantly to the content of the report, describing their particular experiment or hardware evaluation. Although this document follows general guidelines, each report format may vary to accommodate differences in experiment design and procedures. This document concludes with an appendix that provides background information about the Reduced Gravity Program

NanoClusters Enhance Drug Delivery in Mechanical Ventilation

The overall goal of this thesis was to develop a dry powder delivery system for patients on mechanical ventilation. The studies were divided into two parts: the formulation development and the device design. The pulmonary system is an attractive route for drug delivery since the lungs have a large accessible surface area for treatment or drug absorption. For ventilated patients, inhaled drugs have to successfully navigate ventilator tubing and an endotracheal tube. Agglomerates of drug nanoparticles (also known as `NanoClusters') are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. This Thesis systematically investigated formulations of NanoClusters and their aerosol performance in a conventional inhaler and a device designed for use during mechanical ventilation. These engineered powders of budesonide (NC-Bud) were delivered via a Monodose® inhaler or a novel device through commercial endotracheal tubes, and analyzed by cascade impaction. NC-Bud had a higher efficiency of aerosol delivery compared to micronized stock budesonide. The delivery efficiency was independent of ventilator parameters such as inspiration patterns, inspiration volumes, and inspiration flow rates. A novel device designed to fit directly to the ventilator and endotracheal tubing connections and the Monodose® inhaler showed the same efficiency of drug delivery. The new device combined with NanoCluster formulation technology, therefore, allowed convenient and efficient drug delivery through endotracheal tubes. Furthermore, itraconazole (ITZ), a triazole antifungal agent, was formulated as a NanoCluster powder via milling (top-down process) or precipitation (bottom-up process) without using any excipients. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized stock ITZ and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state while milled ITZ NanoClusters maintained the crystalline character. Overall, NanoClusters prepared by various processes represent a potential engineered drug particle approach for inhalation therapy since they provide effective aerosol properties and stability due to the crystalline state of the drug powders. Future work will continue to explore formulation and delivery performance in vitro and in vivo