A scoping review to map evidence regarding key domains and questions in the management of non-traumatic wrist disorders.

Introduction: Non-traumatic wrist disorders (NTWD) are commonly encountered yet sparse resources exist to aid management. This study aimed to produce a literature map regarding diagnosis, management, pathways of care and outcome measures for NTWDs in the United Kingdom. Methods: An interdisciplinary team of clinicians and academic researchers used Joanna Briggs Institute guidelines and the PRISMA ScR checklist in this scoping review. A mixed stakeholder group of patients and healthcare professionals identified 16 questions of importance to which the literature was mapped. An a-priori search strategy of both published and non-published material from five electronic databases and grey literature resources identified records. Two reviewers independently screened records for inclusion using explicit eligibility criteria with oversight from a third. Data extraction through narrative synthesis, charting and summary was performed independently by two reviewers. Results: Of 185 studies meeting eligibility criteria, diagnoses of wrist pain, De Quervain's syndrome and ulna-sided pain were encountered most frequently, with uncontrolled non-randomised trial or cohort study being the most frequently used methodology. Diagnostic methods used included subjective questioning, self-reported pain, palpation and special tests. Best practice guidelines were found from three sources for two NTWD conditions. Seventeen types of conservative management, and 20 different patient-reported outcome measures were suggested for NTWD. Conclusion: Substantial gaps in evidence exist in all parts of the patient journey for NTWD when mapped against an analytic framework (AF). Opportunities exist for future rigorous primary studies to address these gaps and the preliminary concerns about the quality of the literature regarding NTWD.

The Use of a Dehydrated Cellularized Collagen Matrix to Replace Fibrotic Vocal Fold Mucosa.

OBJECTIVES: Fibrosis of the vocal fold lamina propria reduces vocal cord vibration resulting in a chronically hoarse voice. We describe a novel approach using umbilical cord-derived mesenchymal stem cells in a dehydrated collagen matrix (cellogen) to reconstruct the delicate balance of extracellular matrix within the vocal fold lamina propria whilst limiting the host inflammatory response to the implant. METHODS: Human umbilical cord-derived mesenchymal stem-cells were embedded in bovine type I collagen hydrogel and dehydrated using the RAFT™ 3D culture system. The extracellular matrix, cellular viability and composition, paracrine profile, and genomic profile were assessed and the scaffold engrafted onto the hind muscle of NUDE mice. RESULTS: The cells retained stem-cell markers following fabrication and secreted collagen III, fibronectin, and glycosaminoglycans within the scaffold. Electron microscopy showed the scaffold consisted of single strands of protein with interspersed bundles of a similar size to native vocal fold lamina propria. The use of the dehydration step improved cell viability and upregulated the expression of genes important in wound healing and matrix organization compared with unmodified collagen hydrogel carriers. The cells were shown to secrete exosomes and cytokines and, following engraftment within an immunocompromised mouse model, appeared to modulate the host inflammatory response compared with controls. CONCLUSION: This article provides a scalable cell-protein scaffold that with further modifications could provide a replacement for lost or damaged vocal fold mucosa. Further investigations are required to assess the mechanical properties of the scaffold and inhibit the differentiation of the umbilical cord-derived stem-cells following implantation. Laryngoscope, 134:882-893, 2024.

The use of basic fibroblast growth factor to improve vocal function: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis examines if intralaryngeal injection of basic fibroblast growth factor 2 (FGF2) can improve voice outcomes in those with vocal disability. DESIGN: A Systematic review of original human studies reporting voice outcomes following intra-laryngeal injection of basic fibroblast growth factor 2 in those with vocal dysfunction. Databases searched were Medline (1946-July 2022), Embase (1947-July 2022), Cochrane database and Google Scholar. SETTING: Secondary or tertiary care centres that undertook the management of voice pathology Hospital. PARTICIPANTS: Inclusion criteria were original human studies reporting voice outcome measurements following intralaryngeal injection of FGF2 to treat vocal fold atrophy, vocal fold scarring, vocal fold sulcus or vocal fold palsy. Articles not written in English, studies that did not include human subjects and studies where voice outcome measures were not recorded before and after FGF2 injection were excluded from the review. MAIN OUTCOME MEASURES: The primary outcome measure was maximum phonation time. Secondary outcome measures included acoustic analysis, glottic closure, mucosal wave formation, voice handicap index and GRBAS scale. RESULTS: Fourteen articles were included out of a search of 1023 and one article was included from scanning reference lists. All studies had a single arm design without control groups. Conditions treated were vocal fold atrophy (n = 186), vocal cord paralysis (n = 74), vocal fold fibrosis (n = 74) and vocal fold sulcus (n = 56). A meta-analysis of six articles reporting on the use of FGF2 in patients with vocal fold atrophy showed a significant increase of mean maximum phonation time of 5.2 s (95% CI: 3.4-7.0) at 3-6 months following injection. A significant improvement in maximum phonation time, voice handicap index and glottic closure was found following injection in most studies assessed. No major adverse events were reported following injection. CONCLUSIONS: To date, intralaryngeal injection of basic FGF2 appears to be safe and it may be able to improve voice outcomes in those with vocal dysfunction, especially vocal fold atrophy. Randomised controlled trials are needed to further evaluate efficacy and support the wider use of this therapy.

The life-cycle and restoration of the human vocal fold.

Objective: To better understand the challenges of designing therapies to treat damaged vocal fold lamina propria, it is essential to understand the biophysical and pathophysiological mechanisms involved in vocal fold development, maintenance, injury, and aging. This review critically analyses these points to try and direct future efforts and new strategies toward science-based solutions. Data Sources & Review Methods: MEDLINE, Ovid Embase, and Wed of Science databases were used to identify relevant literature. A scoping review was performed following the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews checklist. Results: The layered arrangement of the vocal fold, develops during early childhood and is maintained during adulthood unless injury occurs. The stellate cells of the macular flava are likely to be important in this process. The capacity for vocal fold regeneration and growth is lost during adulthood and repair results in the deposition of fibrous tissue from resident fibroblasts. With advancing age, viscoelastic tissue declines, possibly due to cell senescence. Strategies aimed at replacing fibrous tissue within the vocal folds must either stimulate resident cells or implant new cells to secrete healthy extracellular protein. Injection of basic fibroblast growth factor is the most widely reported therapy that aims to achieve this. Conclusions: The pathways involved in vocal fold development, maintenance and aging are incompletely understood. Improved understanding has the potential to identify new treatment targets that could potentially overcome loss of vocal fold vibratory tissue.

Agreement between methods and terminology used to assess the kinematics of the Nordic hamstring exercise.

The Nordic hamstring exercise (NHE) is employed as a component of preventative training programmes to minimise hamstring strain injury risk. Variation in the methods and terminology used to assess the NHE makes comparison between studies difficult. We aimed to compare the utility of kinetic and kinematic metrics by comparing several collected concurrently. 18 male recreational rugby union participants completed 3 bilateral NHE repetitions on a hamstring device equipped with in-line strain gauge load cells, integrated with a 3-dimensional motion tracking system. Mean break-point angle occurred after the angle at first acceleration (121.5 ± 10.4° vs. 119.2 ± 7.1°) whereas break-torque angle (BTA) occurred later in the NHE action (126.0 ± 9.8°) showing highest correlation to the angle at greatest acceleration (123.9 ± 7.9°, r = 0.85). Future research should consider movement quality as the angular velocity of the knee joint at BTA demonstrated large variation (range = 3.6-93.4 deg·s1), with high intrasubject variability of relative trunk-to-thigh angle at peak-torque (range = 0.4-44.7°). This study proposes standardisation of methods and terminology used to define the NHE. Measuring BTA is recommended to represent the point at which hamstring muscle failure occurs, specific to the proposed injury mechanism during high-speed running.

GMP compliant isolation of mucosal epithelial cells and fibroblasts from biopsy samples for clinical tissue engineering.

Engineered epithelial cell sheets for clinical replacement of non-functional upper aerodigestive tract mucosa are regulated as medicinal products and should be manufactured to the standards of good manufacturing practice (GMP). The current gold standard for growth of epithelial cells for research utilises growth arrested murine 3T3 J2 feeder layers, which are not available for use as a GMP compliant raw material. Using porcine mucosal tissue, we demonstrate a new method for obtaining and growing non-keratinised squamous epithelial cells and fibroblast cells from a single biopsy, replacing the 3T3 J2 with a growth arrested primary fibroblast feeder layer and using pooled Human Platelet lysate (HPL) as the media serum supplement to replace foetal bovine serum (FBS). The initial isolation of the cells was semi-automated using an Octodissociator and the resultant cell suspension cryopreservation for future use. When compared to the gold standard of 3T3 J2 and FBS containing medium there was no reduction in growth, viability, stem cell population or ability to differentiate to mature epithelial cells. Furthermore, this method was replicated with Human buccal tissue, providing cells of sufficient quality and number to create a tissue engineered sheet.

Pediatric Rapid Response Nurse Deployment to Pediatric Trauma Activations: A Process Improvement Initiative.

BACKGROUND: Prolonged emergency department length of stay in trauma patients is associated with increased hospital length of stay and inhospital mortality. This problem is compounded in pediatric patients, as injured children have less physiologic reserve and may exhibit only subtle warning signs before decompensation. OBJECTIVE: To determine the impact of deploying pediatric rapid response nurses to full trauma activations for patients transferred to the pediatric intensive care unit on emergency department length of stay. METHODS: This is a before-and-after analysis of a quality improvement initiative deploying pediatric rapid response nurses to full trauma activations. Trauma registry data collected from January 2016 to August 2020 were statistically analyzed. Demographic and outcome variables were assessed by unpaired t test and χ2 analysis. RESULTS: A total of 94 patients met inclusion criteria as full activations admitted to the intensive care unit during the study period. The preimplementation group (n = 60) was 88% (n = 53) male, with a median age of 6.9 years and a median Injury Severity Score of 21. The postimplementation group (n = 34) was 62% (n = 21) male, with a median age of 5.6 years and a median Injury Severity Score of 17. The emergency department length of stay decreased from median (interquartile range) 48.5 (36.0-84.75) min (preimplementation) to 36.5 (27.5-55.5) min (postimplementation; p = .019). CONCLUSION: Deployment of pediatric rapid response nurses to full trauma activations facilitates the assessment and transfer of pediatric trauma to the intensive care unit and decreases emergency department length of stay.

Development of a Novel Nordic Hamstring Exercise Device to Measure and Modify the Knee Flexors' Torque-Length Relationship.

The Nordic hamstring exercise (NHE) has been shown to reduce hamstring injury risk when employed in training programs. This study investigates a novel device to modify the NHE torque-length relationship of the knee flexors, as targeting the hamstrings at a more extended length may have benefits for hamstring strain injury prevention and rehabilitation. Eighteen recreational male participants completed three bilateral NHE repetitions at a conventional 0° flat position, a 10° incline, and a 10° decline slope on a novel device (HALHAM°). Measures of peak torque and break-torque angle explored the effect of inclination on the knee flexors' length-tension relationship. Relative thigh-to-trunk angle and angular velocity of the knee joint were used to assess influence of inclination on technique and exercise quality. Break-torque angle increased when performed at an incline (134.1 ± 8.6°) compared to both the decline (112.1 ± 8.3°, p <0.0001, g = 2.599) and standard flat NHE positions (126.0 ± 9.8°, p = 0.0002, g = 0.885). Despite this, altering inclination did not affect eccentric knee flexor peak torque (decline = 132.0 ± 63.1 Nm, flat = 149.7 ± 70.1 Nm, incline = 148.9 ± 64.9 Nm, F = 0.952, p = 0.389), angular velocity of the knee joint at break-torque angle (decline = 23.8 ± 14.4°, flat = 29.2 ± 22.6°, incline = 24.5 ± 22.6°, F = 0.880, p = 0.418) or relative thigh-to-trunk angle at break-torque angle (decline = 20.4 ± 10.4°, flat = 16.7 ± 10.8°, incline = 20.2 ± 11.2°, F = 1.597, p = 0.207). The report recommends the use of arbitrary metrics such as break-torque angle that can be replicated practically in the field by practitioners to assess proxy muscle length changes i.e., the angular range over which the torque can be produced. Inclination of the Nordic hamstring exercise leads to hamstring muscle failure at longer muscle lengths without reductions in the maximal force exuded by the muscle. Therefore, the NHE performed on an incline may be a more effective training intervention, specific to the proposed mechanism of hamstring strain injury during sprinting that occurs whilst the muscle is rapidly lengthening. Using a graded training intervention through the inclinations could aid gradual return-to-play rehabilitation.

Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.

OBJECTIVES: To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis. METHODS: Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua. RESULTS: Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell (P = .04 and P = .02) and taste recovery (P = .02 and P = .01). Ethnicity (being white) showed to positively influence only taste recovery (P = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs (P = .02 and P = .011, respectively). Working on a COVID-19 ward did not influence prognosis. CONCLUSIONS: The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity. LEVEL OF EVIDENCE: 4.

Appearance and management of COVID-19 laryngo-tracheitis: two case reports.

We present two cases of coronavirus disease 2019 (COVID-19)-related laryngotracheitis in good-prognosis, ventilated patients who had failed extubation. As the pandemic continues to unfold across the globe and better management of those with respiratory failure develops, this may be an increasingly common scenario. Close ENT-intensivist liaison, meticulous team preparation, early consideration of rigid endoscopy and prospective data collection and case sharing are recommended.

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.

Using a Three-Dimensional Collagen Matrix to Deliver Respiratory Progenitor Cells to Decellularized Trachea In Vivo.

IMPACT STATEMENT: This article describes a method for engrafting epithelial progenitor cells to a revascularized scaffold in a protective and supportive collagen-rich environment. This method has the potential to overcome two key limitations of existing grafting techniques as epithelial cells are protected from mechanical shear and the relatively hypoxic phase that occurs while grafts revascularize, offering the opportunity to provide epithelial cells to decellularized allografts at the point of implantation. Advances in this area will improve the safety and efficacy of bioengineered organ transplantation.

Aluminum granuloma in a child secondary to DTaP-IPV vaccination: A case report.

Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum-containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP-IPV vaccine. We present the case of a 6-year-old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum-containing DTaP-IPV (Kinrix) vaccine. The nodule was eventually excised 14 months after its initial appearance, after which her symptoms resolved. Histologic inspection demonstrated a dense, deep dermal and subcutaneous nodular mixed infiltrate of lymphocytes, histiocytes, and eosinophils, with germinal center formation. The bluish, amphophilic granular cytoplasm found in most of the histiocytes is a characteristic feature of "aluminum granulomas." This adverse reaction should be considered in any patient presenting with similar findings in the weeks following a DTaP-IPV vaccination or other aluminum-containing vaccines. Furthermore, the self-limiting tendency of these nodules should not preclude affected patients from any future vaccinations, though vaccines without aluminum should be preferentially selected when possible.

Tissue-Engineered Larynx: Future Applications in Laryngeal Cancer.

PURPOSE OF REVIEW: This article reviews the latest developments in tissue engineering for the larynx with a specific focus on the treatment of laryngeal cancer. RECENT FINDINGS: Challenges in tissue engineering a total larynx can be divided into scaffold design, methods of re-mucosalization, and how to restore laryngeal function. The literature described a range of methods to deliver a laryngeal scaffold including examples of synthetic, biomimetic, and biological scaffolds. Methods to regenerate laryngeal mucosa can be divided into examples that use a biological dressing and those that engineer a new mucosal layer de novo. Studies aiming to restore laryngeal function have been reported, but to date, the optimum method for achieving this as part of a total laryngeal transplant is yet to be determined. SUMMARY: There is great potential for tissue engineering to improve the treatments available for laryngeal cancer within the next 10 years. A number of challenges exist however and advances in restoring function must keep pace with developments in scaffold design.

Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series.

Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations.