Throat and voice problems in Ehlers-Danlos syndromes and hypermobility spectrum disorders.

A small number of case reports and observational studies describe chronic nasal congestion, upper airway obstruction, dysphonia, vocal cord abnormalities, and swallowing abnormalities in the Ehlers-Danlos syndromes. Little is known of the causes and therefore treatments of these, yet they are not uncommon findings in persons with hypermobility-related conditions presenting in the healthcare setting. We have a specialist multidisciplinary ear, nose, and throat and speech therapy practice with accumulating observational and empirical experience of managing these conditions, which include altered voice, choking, high dysphagia and anterior and deep neck pains. Here, we present our experience, some illustrative cases, and suggestions for future work in this evolving field.

Bioengineered airway epithelial grafts with mucociliary function based on collagen IV- and laminin-containing extracellular matrix scaffolds.

Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease.Here, we investigated the influence of the extracellular matrix (ECM) on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts. In vitro, primary human bronchial epithelial cells (HBECs) adhered most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their ECM protein content and airway epithelial cell adherence.Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air-liquid interface (ALI), bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory epithelium with mucociliary function. Using in vivo chick chorioallantoic membrane (CAM), rabbit airway and immunocompromised mouse models, we showed short-term preservation of the cell layer following transplantation.Our results demonstrate the feasibility of generating HBEC grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.

Vocal nodules management.

Vocal fold nodules present the voice clinic team with a number of clinical dilemmas which are not as simple as previously thought. The definition, aetiology, prevalence and diagnosis are all poorly understood. Furthermore, treatment evidence for both behavioural and surgical approaches is weak. This paper reviews the published evidence pertaining to all of these aspects. Specific areas of uncertainty that remain include poorly defined nomenclature, the natural history of paediatric vocal nodules, the establishment of criteria to measure successful treatment, optimal configuration of speech therapy regimens and the rationale for surgical intervention. The authors suggest the development of evidence-based guidelines for UK practice.

Feasibility of vocal fold abduction and adduction assessment using cine-MRI.

OBJECTIVE: Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) METHODS: Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). RESULTS: VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). CONCLUSION: Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. KEY POINTS: • Cine-MRI is used to assess vocal folds (VFs) mobility: abduction and adduction. • New quantitative metrics are derived from VF position and abduction potential. • Cine-MRI able to depict the difference between normal and abnormal VF mobility. • Cine-MRI derived quantitative metrics have good repeatability.

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering.

RATIONALE: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts. OBJECTIVES: To define a scalable cell culture system to deliver airway epithelium to clinical grafts. METHODS: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures. MEASUREMENTS AND MAIN RESULTS: 3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model. CONCLUSIONS: Our method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.

Tissue Engineered Airways: A Prospects Article.

An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs, and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularized organs. To date, a number of different decellularization techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however, there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilize in accomplishing the aim of developing an ideal tracheal prosthesis. J. Cell. Biochem. 117: 1497-1505, 2016. © 2016 Wiley Periodicals, Inc.

Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model.

Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissue-engineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cell-mediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.

A potential platform for developing 3D tubular scaffolds for paediatric organ development.

Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content. Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS-PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS-PCL and a new lamination method was explored. Porogen (40, 60 or 105 µm) were introduced to POSS-PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS-PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 µm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS-PCL. These bilayered-tubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored.

Tracheal bioengineering: the next steps. Proceeds of an International Society of Cell Therapy Pulmonary Cellular Therapy Signature Series Workshop, Paris, France, April 22, 2014.

There has been significant and exciting recent progress in the development of bioengineering approaches for generating tracheal tissue that can be used for congenital and acquired tracheal diseases. This includes a growing clinical experience in both pediatric and adult patients with life-threatening tracheal diseases. However, not all of these attempts have been successful, and there is ongoing discussion and debate about the optimal approaches to be used. These include considerations of optimal materials, particularly use of synthetic versus biologic scaffolds, appropriate cellularization of the scaffolds, optimal surgical approaches and optimal measure of both clinical and biologic outcomes. To address these issues, the International Society of Cell Therapy convened a first-ever meeting of the leading clinicians and tracheal biologists, along with experts in regulatory and ethical affairs, to discuss and debate the issues. A series of recommendations are presented for how to best move the field ahead.

Design and development of nanocomposite scaffolds for auricular reconstruction.

Auricular reconstruction using sculpted autologous costal cartilage is effective, but complex and time consuming and may incur donor site sequelae and morbidity. Conventional synthetic alternatives are associated with infection and extrusion in up to about 15% of cases. We present a novel POSS-PCU nanocomposite auricular scaffold, which aims to reduce extrusion rates by mimicking the elastic modulus of human ears and by encouraging desirable cellular interactions. The fabrication, physicochemical properties (including nanoscale topography) and cellular interactions of these scaffolds were compared to Medpor®, the current synthetic standard. Our scaffold had a more similar elastic modulus (5.73 ± 0.17MPa) to ear cartilage (5.02 ± 0.17MPa) compared with Medpor®, which was much stiffer (140.9 ± 0.04MPa). POSS-PCU supported fibroblast ingrowth and proliferation; significantly higher collagen production was also produced by cells on the POSS-PCU than those on Medpor®. This porous POSS-PCU nanocomposite scaffold is therefore a promising alternative biomaterial for auricular surgical reconstruction. FROM THE CLINICAL EDITOR: In this paper, a novel POSS-PCU nanocomposite auricular scaffold is described to reduce extrusion rates by having a much closer elastic modulus of human ears than the currently available synthetic standard. Enabling desirable cellular interactions may lead to the successful clinical application of these novel scaffolds.

Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted natural killer T cells in the joints of RA patients.

OBJECTIVES: While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA. METHODS: NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay. RESULTS: We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion. CONCLUSIONS: While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.

Management Options for Bilateral Vocal Fold Impairment: Scoping Review to Assess the Potential of Soft Robotics Solutions.

OBJECTIVES: This scoping review aims to comprehensively assess current surgical interventions for bilateral vocal fold paralysis (BVFP), addressing the heterogeneity in treatment outcomes. Additionally, it explores the potential role of soft robotics as an innovative approach to improve outcomes in BVFP management. METHODS: This scoping review systematically examines literature from MEDLINE, Embase, and Scopus databases. Inclusion criteria encompass studies related to BVFP management with measurable subjective or objective outcomes. Studies with populations solely under the age of 18 were excluded. Four reviewers independently screened 2263 studies, resulting in the selection of 125 papers for data extraction. Information included study characteristics, interventions, and outcomes. Data synthesis involved both quantitative and qualitative analyses. RESULTS: The review identified 145 surgical interventions grouped into seven types: tracheostomy, cordectomy, arytenoidectomy, lateralization, combined procedures and others. Outcome measures fit into the following categories: "objective voice," "subjective voice," "aerodynamics," "dyspnea," "decannulation," "swallow," and "quality of life." Positive outcomes were predominant across all interventions, with arytenoidectomy and cordectomy showing relatively lower rates of successful objective and subjective voice outcomes. This could be the result of prioritizing improved airway status. Soft robotics is hypothesized as a potential solution to the limitation of current interventions sacrificing voice for breathing. CONCLUSIONS: The main aim of current surgical interventions for BVFP is expanding glottic aperture. Yet achieving optimal outcomes remains elusive due to complex airflow dynamics and potential impacts on phonatory function and swallowing. The current review underscores the need for a more nuanced, personalized approach, considering individual anatomical and physiological variations. Soft robotics emerges as a promising avenue to address this variability. However, challenges such as implantation procedures, long-term care, and patient education require careful consideration. Collaboration between medical professionals, engineers, and robotics specialists is essential for translating these principles into practical solutions.

Tunable Light-Responsive Polyurethane-urea Elastomer Driven by Photochemical and Photothermal Coupling Mechanism.

Light-driven soft actuators based on photoresponsive materials can be used to mimic biological motion, such as hand movements, without involving rigid or bulky electromechanical actuations. However, to our knowledge, no robust photoresponsive material with desireable mechanical and biological properties and relatively simple manufacture exists for robotics and biomedical applications. Herein, we report a new visible-light-responsive thermoplastic elastomer synthesized by introducing photoswitchable moieties (i.e., azobenzene derivatives) into the main chain of poly(ε-caprolactone) based polyurethane urea (PAzo). A PAzo elastomer exhibits controllable light-driven stiffness softening due to its unique nanophase structure in response to light, while possessing excellent hyperelasticity (stretchability of 575.2%, elastic modulus of 17.6 MPa, and strength of 44.0 MPa). A bilayer actuator consisting of PAzo and polyimide films is developed, demonstrating tunable bending modes by varying incident light intensities. Actuation mechanism via photothermal and photochemical coupling effects of a soft-hard nanophase is demonstrated through both experimental and theoretical analyses. We demonstrate an exemplar application of visible-light-controlled soft "fingers" playing a piano on a smartphone. The robustness of the PAzo elastomer and its scalability, in addition to its excellent biocompatibility, opens the door to the development of reproducible light-driven wearable/implantable actuators and lightweight soft robots for clinical applications.

The Global Experience of Laryngeal Transplantation: Series of Eleven Patients in Three Continents.

BACKGROUND: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. OBJECTIVE: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. METHODOLOGY: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. RESULTS: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. CONCLUSIONS: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Interventional and intrinsic airway homeostasis and repair.

Human airways are a paragon of intrinsic engineering. They experience 7,000-10,000 liters of airflow/day, have a 70-m(2) surface area, and undergo complete renewal every 100-400 days. Despite this, airways are susceptible to aging, injury, and diseases that are major causes of mortality. Current airway regeneration research is focused both on understanding the cells and strategies responsible for maintaining intrinsic tissue homeostasis as well as on establishing clinical interventions for improving repair.

Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study.

BACKGROUND: Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. METHODS: A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor ß to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. FINDINGS: The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. INTERPRETATION: Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. FUNDING: Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.

The body as a living bioreactor: a feasibility study of pedicle flaps for tracheal transplantation.

Reconstruction of long-segment tracheal stenosis remains problematic. Ex vivo transplantation of stem cell-derived tracheas has been established in humans using external tissue bioreactors. These bioreactors, however, are not widely accessible. Thus, we are developing a rotational flap-based "internal bioreactor" to allow in vivo stem cell engraftment in a pre-vascularized recipient bed. This muscle will also then serve as a carrier for the transplanted trachea during rotation into position for airway reconstruction. Herein, we present a study investigating the feasibility of two pedicle muscle flaps for implantation and subsequent tracheal transplantation. Trapezius and latissimus flaps were raised using established surgical techniques. The length and width of each flap, along with the distance from the pedicle takeoff to the trachea, were measured. The overall ability of the flaps to reach the trachea was assessed. Twelve flaps were raised in 5 fresh adult human cadavers. For the trapezius flap, averages were: flap length of 16.4 cm, flap width of 5.95 cm at the tip, and distance from the pedicle takeoff to the trachea of 11.1 cm. For the latissimus dorsi flap, averages were: flap length of 35.4 cm, flap width of 7.25 cm at the tip, and distance from the pedicle takeoff to the trachea of 27.3 cm. All flaps showed sufficient durability and rotational ability. Our results show that both trapezius and latissimus dorsi flaps can be transposed into the neck to allow tension-free closure of tracheal defects. For cervical tracheal transplantation, both flaps are equally adequate. We believe that trapezius and latissimus dorsi muscle flaps are potential tracheal implantation beds in terms of vascular supply, durability, and rotational ability.

Functional Outcomes Following Delayed Laryngeal Reinnervation Of Patients with Vagal Paralysis After Paraganglioma and Schwannoma Surgery.

PURPOSE: We present a prospective case series that aimed to report the functional (voice and swallowing) outcomes of delayed laryngeal reinnervation following vagal interruption by resection of vagal paraganglioma and schwannoma. MATERIALS AND METHODS: A dedicated, anonymized database was established in 2012 with a minimum eighteen-month follow up set for this report. Internationally validated self- and observer-reported measures were recorded preoperatively and at six, 12 and, 18 months together with demographics, diagnoses, and operative details. RESULTS: A total of eight patients with a median age of 46 (37-54) underwent excision of vagal paraganglioma (five) and schwannoma (three) with few mild complications. Three underwent selective and five non selective reinnervation. Seven out of eight patients underwent synchronous injection medialization. The voice handicap index (VHI-30) improved from a baseline median 83 (range 52-102) to 7.5 (5-58) at 18 months; maximum phonation time improved from median 8 (range 5-15) to 10.5 (8.5-11); voice grade ("G" in grade, roughness, breathiness, asthenia, and strain [GRBAS] scoring) improved from median three (severe impairment, range 0-3) to one (mild impairment, 0-2); Eating Assessment Tool (EAT-10) score improved from median 12 (range 3.5-27) preoperatively to one (0-16); and reflux symptom index (RSI) improved from median 25 (range 17-36) to 7 (0-36). One patient exhibited no discernible reinnervation, while the remainder exhibited good cord bulk and tone, though without purposive abduction. CONCLUSION: Delayed laryngeal reinnervation for high vagal paralysis is a safe technique associated with good voice and swallowing outcomes by 12-18 months. Potential confounders in this small series and the absence of a control arm both limit conclusions, but this study suggests that further prospective, controlled studies, and/or case registration are merited.

Barriers to research progress for perioperative care practitioners working in cardiothoracic surgery.

Policy and research literature worldwide support the need to build research capacity and capability among non-medical practitioners within healthcare systems. However, there exists a paucity of evidence on whether practitioners in cardiothoracic surgery are attuned to this and on what barriers or enablers exist. A survey was carried out with non-medical practitioners working in cardiothoracic surgery in the United Kingdom to explore attitudes towards health research and audit, and to identify current challenges and barriers to surgical research and audit as perceived by cardiothoracic nurses and allied health professionals. A total of 160 completed questionnaires were returned. 99% of respondents supported the need for research and believed that evidence-based surgical care improves outcomes for patients. Seventy-two percent reported that their employer motivates them to take part in national research or audit but, only 22% were allocated time to do so within their role; 96% reported their interest in being involved in research and audit, yet only 30% believed they had the skills to undertake research, and 96% reported needing additional training. More work is needed to increase awareness, capacity and capability among cardiothoracic surgery care practitioners, and indeed other specialities to achieve research progress.