Multidisciplinary guidance for safe tracheostomy care during the COVID-19 pandemic: the NHS National Patient Safety Improvement Programme (NatPatSIP).

The COVID-19 pandemic is causing a significant increase in the number of patients requiring relatively prolonged invasive mechanical ventilation and an associated surge in patients who need a tracheostomy to facilitate weaning from respiratory support. In parallel, there has been a global increase in guidance from professional bodies representing staff who care for patients with tracheostomies at different points in their acute hospital journey, rehabilitation and recovery. Of concern are the risks to healthcare staff of infection arising from tracheostomy insertion and caring for patients with a tracheostomy. Hospitals are also facing extraordinary demands on critical care services such that many patients who require a tracheostomy will be managed outside established intensive care or head and neck units and cared for by staff with little tracheostomy experience. These concerns led NHS England and NHS Improvement to expedite the National Patient Safety Improvement Programme's 'Safe Tracheostomy Care' workstream as part of the NHS COVID-19 response. Supporting this workstream, UK stakeholder organisations involved in tracheostomy care were invited to develop consensus guidance based on: expert opinion; the best available published literature; and existing multidisciplinary guidelines. Topics with direct relevance for frontline staff were identified. This consensus guidance includes: infectivity of patients with respect to tracheostomy indications and timing; aerosol-generating procedures and risks to staff; insertion procedures; and management following tracheostomy.

Developing control algorithms of a voluntary cough for an artificial bioengineered larynx using surface electromyography of chest muscles: A prospective cohort study.

OBJECTIVE: This prospective cohort study investigates the prediction of a voluntary cough using surface electromyography (EMG) of intercostal and diaphragm muscles, to develop control algorithms for an EMG-controlled artificial larynx. SETTING: The Ear Institute, London. MAIN OUTCOME MEASURES: Electromyography onset compared to voluntary cough exhalation onset and to 100 ms (to give the artificial larynx the time to close the bioengineered vocal cords) before voluntary cough exhalation onset, in twelve healthy participants. RESULTS: In the 189 EMG of intercostal muscle-detected voluntary coughs, 172 coughs (91% CI 70-112) were detected before onset of cough exhalation and 128 coughs (67.6% CI 33.7-101.7) 100 ms before onset of cough exhalation. In the 158 EMG of diaphragm muscle-detected voluntary coughs, 149 coughs (94.3% CI 76.3-112.3) were detected before onset of cough exhalation and 102 coughs (64.6% CI 26.6-102.6) 100 ms before onset of cough exhalation. More coughs were detected before onset of cough exhalation when combining EMG activity of intercostal and diaphragm muscles and comparing this to intercostal muscle activity alone (183 coughs [96.8% CI 83.8-109.8] vs 172 coughs, P = .0294). When comparing the mentioned combination to diaphragm muscle activity alone, the higher percentage of detected coughs before cough exhalation onset was not found to be significant (183 coughs vs 149 coughs, P = .295). In addition, more coughs were detected 100 ms before onset of cough exhalation with the mentioned combination of EMG activity and comparing this to intercostal muscles alone (149 coughs [78.8% CI 48.8-108.8] vs 128 coughs, P = .0198) and to diaphragm muscles alone (149 coughs vs 102 coughs, P = .0038). CONCLUSIONS: Most voluntary coughs can be predicted based on combined EMG signals of intercostal and diaphragm muscles, and therefore, these two muscle groups will be useful in controlling the bioengineered vocal cords within the artificial larynx during a voluntary cough.

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study.

In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

Development of resorbable nanocomposite tracheal and bronchial scaffolds for paediatric applications.

BACKGROUND: Congenital tracheal defects and prolonged intubation following premature birth have resulted in an unmet clinical need for tracheal replacement. Advances in stem cell technology, tissue engineering and material sciences have inspired the development of a resorbable, nanocomposite tracheal and bronchial scaffold. METHODS: A bifurcated scaffold was designed and constructed using a novel, resorbable nanocomposite polymer, polyhedral oligomeric silsesquioxane poly(ϵ-caprolactone) urea urethane (POSS-PCL). Material characterization studies included tensile strength, suture retention and surface characteristics. Bone marrow-derived mesenchymal stem cells (bmMSCs) and human tracheobronchial epithelial cells (HBECs) were cultured on POSS-PCL for up to 14 days, and metabolic activity and cell morphology were assessed. Quantum dots conjugated to RGD (l-arginine, glycine and l-aspartic acid) tripeptides and anticollagen type I antibody were then employed to observe cell migration throughout the scaffold. RESULTS: POSS-PCL exhibited good mechanical properties, and the relationship between the solid elastomer and foam elastomer of POSS-PCL was comparable to that between the cartilaginous U-shaped rings and interconnective cartilage of the native human trachea. Good suture retention was also achieved. Cell attachment and a significant, steady increase in proliferation were observed for both cell types (bmMSCs, P = 0·001; HBECs, P = 0·003). Quantum dot imaging illustrated adequate cell penetration throughout the scaffold, which was confirmed by scanning electron microscopy. CONCLUSION: This mechanically viable scaffold successfully supports bmMSC and HBEC attachment and proliferation, demonstrating its potential as a tissue-engineered solution to tracheal replacement.

Reliability of OperaVOX against Multidimensional Voice Program (MDVP).

OBJECTIVE: To evaluate the agreement between OperaVOX and MDVP. DESIGN: Cross sectional reliability study. SETTING: University teaching hospital. METHODS: Fifty healthy volunteers and 50 voice disorder patients had supervised recordings in a quiet room using OperaVOX by the iPod's internal microphone with sampling rate of 45 kHz. A five-seconds recording of vowel/a/was used to measure fundamental frequency (F0), jitter, shimmer and noise-to-harmonic ratio (NHR). All healthy volunteers and 21 patients had a second recording. The recorded voices were also analysed using the MDVP. The inter- and intrasoftware reliability was analysed using intraclass correlation (ICC) test and Bland-Altman (BA) method. Mann-Whitney test was used to compare the acoustic parameters between healthy volunteers and patients. RESULTS: Nine of 50 patients had severe aperiodic voice. The ICC was high with a confidence interval of >0.75 for the inter- and intrasoftware reliability except for the NHR. For the intersoftware BA analysis, excluding the severe aperiodic voice data sets, the bias (95% LOA) of F0, jitter, shimmer and NHR was 0.81 (11.32, -9.71); -0.13 (1.26, -1.52); -0.52 (1.68, -2.72); and 0.08 (0.27, -0.10). For the intrasoftware reliability, it was -1.48 (18.43, -21.39); 0.05 (1.31, -1.21); -0.01 (2.87, -2.89); and 0.005 (0.20, -0.18), respectively. Normative data from the healthy volunteers were obtained. There was a significant difference in all acoustic parameters between volunteers and patients measured by the Opera-VOX (P < 0.001) except for F0 in females (P = 0.87). CONCLUSION: OperaVOX is comparable to MDVP and has high internal consistency for measuring the F0, jitter and shimmer of voice except for the NHR.

The recruitment of patients to trials in head and neck cancer: a qualitative study of the EaStER trial of treatments for early laryngeal cancer.

We aimed to investigate the factors contributing to poor recruitment to the EaStER trial "Early Stage glottic cancer: Endoscopic excision or Radiotherapy" feasibility study. We performed a prospective qualitative assessment of the EaStER trial at three centres to investigate barriers to recruitment and implement changes. Methods used included semi-structured interviews, focus groups and audio-recordings of recruitment encounters. First, surgeons and recruiters did not all accept the primary outcome as the rationale for the trial. Surgeons did not always adhere to the trial eligibility criteria leading to variations between centres in the numbers of "eligible" patients. Second, as both treatments were considered equally successful, recruiters and patients focused on the pragmatics of the different trial arms, favouring surgery over radiotherapy. The lack of equipoise was reflected in the way recruiters presented trial information. Third, patient views, beliefs and preferences were not fully elicited or addressed by recruiters. Fourth, in some centres, logistical issues made trial participation difficult. This qualitative research identified several major issues that explained recruitment difficulties. While there was insufficient time to address these in the EaStER trial, several factors would need to be addressed to launch further RCTs in head and neck cancer. These include the need for clear ongoing agreement among recruiting clinicians regarding details in the study protocol; an understanding of the logistical issues hindering recruitment at individual centres; and training recruiters to enable them to explain the need for randomisation and the rationale for the RCT to patients.

A national analysis of the outcome of major head and neck cancer surgery: implications for surgeon-level data publication.

OBJECTIVES: To undertake a national outcomes analysis following major head and neck cancer surgery in order to identify risk factors for complications and in-hospital mortality, as well as areas whose closer examination and formal benchmarking in the context of local and national quality assurance audits may lead to improved results for this condition. DESIGN: An analysis using Hospital Episode Statistics data. SETTINGS: All units undertaking major head and neck cancer surgery in England. MAIN OUTCOME MEASURES: Cancer sites, co-morbidities, social deprivation, surgical and non-surgical treatments, complications, and in-hospital mortality were recorded. Regression analysis was used for casemix adjustment and for identifying independent predictors of complications and mortality. Funnel plots were used for data visualisation. RESULTS: We identified 10,589 major head and neck cancer operations performed in England between 2006 and 2011. There were 7312 males, and mean age at surgery was 63 ± 13 years. Oral cavity (42%) and the larynx (28%) were the commonest cancer sites. At least one complication occurred in 33.1% of patients, and there were 322 (3.05%) in-hospital deaths. Variables associated with in-hospital mortality were trust volume, age, co-morbidities, performing emergency major surgery and performing a tracheostomy or reconstructive surgery. Occurrence of major medical complications including pulmonary infections (7%), major acute cardiovascular events (4.7%) and acute renal failure (0.6%) also increased mortality risk. The analysis identified units that were outside of crude and risk-adjusted 99.8% limits of confidence for complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows significant national variation and is associated with fixed risk factors like age and co-morbidities, but also with modifiable risk factors like performing major surgery during an emergency admission, tracheostomy, reconstructive surgery and medical complications. We propose that the quality of tracheostomy care, reconstructive surgery, emergency major surgery rate, and occurrence and treatment of major medical complications should be closely examined and formally benchmarked as part of loco-regional and national quality improvement audits.

Laryngeal transplantation in minipigs: early immunological outcomes.

Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vß spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vß repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.

Laryngological presentations and patient-reported outcome measures in Ehlers-Danlos syndrome.

OBJECTIVE: This study aimed to characterise the laryngological presentations of Ehlers-Danlos syndrome and conduct a preliminary exploration of patient-reported outcome measures. METHODS: This paper describes a retrospective case series of patients with Ehlers-Danlos syndrome seen by the senior author between 2005 and 2019. A literature review was conducted to summarise the existing findings. RESULTS: Twenty-one patients met the inclusion criteria. All reported symptoms were grouped; this showed that swallowing, voice and hyolaryngeal skeletal complex problems were commonest. Patient-reported outcome measures were available for eight patients, which showed large variations in: the Reflux Severity Index (median = 25.5; range = 0-33), Eating Assessment Tool score (median = 21.5; range = 0-35) and Voice Handicap Index (median = 21.5; range = 0-104). Twelve studies met our literature review inclusion criteria, involving at least 91 patients with laryngological presentations of Ehlers-Danlos syndrome. CONCLUSION: Ehlers-Danlos syndrome patients experience musculoskeletal issues, which in the throat manifest as hyolaryngeal skeletal complex problems. Future studies with larger patient numbers are required to validate laryngological patient-reported outcome measure tools in Ehlers-Danlos syndrome.

Laryngeal transplantation in minipigs: vascular, myologic and functional outcomes.

There is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. Regenerative medicine offers promise, but cannot presently deliver implants with functioning neuromuscular units. A single well-documented laryngeal transplant in man was a qualified success, but more information is required before clinical trials may be proposed. We studied the early response of the larynx to laryngeal transplantation between 17 pairs of NIH minipigs full matched at the MHC2 locus. Following iterative technical improvements, pigs had good swallowing and a patent airway at 1 week. No significant changes in mucosal blood flux were observed compared with pre-operative measurements. Changes in muscle morphology and fibre phenotype were observed in transplant muscles retrieved after 7 days: the levels of fast and slow myosin heavy chain (MyHC) protein were reduced and embryonic MyHC was up regulated consistent with denervation induced atrophy. At 1 week laryngeal transplantation can result in good swallowing, and is not associated with clinical evidence of ischemia-reperfusion injury in MHC-matched pigs.

Development of perioperative care for pigs undergoing laryngeal transplantation: a case series.

Pigs are ideal animal models for airway surgical research, facilitating the successful translation of science into clinical practice. Despite their ubiquitous use, there is a paucity of information on the perioperative care of pigs, especially for major procedures. In a series of experiments to investigate laryngeal transplantation, we combined veterinary and medical experience to develop protocols for perioperative management of pigs, including high dependency care. Novel airway management methods were developed. A pain scoring system was used to direct analgesia use. Fluid balance and electrolytes were monitored closely. Recent animals received a central venous line via the femoral vein two days prior to transplantation to facilitate blood sampling and drug delivery. Intensive monitoring and airway management were required to ensure a successful outcome. Methods for optimal perioperative care are proposed. These results will help future groups wishing to use pigs in airway research, will reduce numbers of animals used and improve animal welfare.

Complications following gastrostomy tube insertion in patients with head and neck cancer: a prospective multi-institution study, systematic review and meta-analysis.

OBJECTIVES: To measure morbidity and mortality rates following insertion of gastrostomy tubes in head and neck cancer patients. To determine evidence for any relationship between gastrostomy insertion technique and complication rates. DESIGN: A prospective cohort study and qualitative systematic review. SETTING: Multi-cancer networks in the South West of England, Hampshire and the Isle of White. PARTICIPANTS: One hundred and seventy-two patients with head and neck cancer undergoing gastrostomy tube insertion between 2004 and 2005. Percutaneous endoscopic gastrostomy (PEG) was performed in 121 patients. Fifty-one patients had radiologically inserted gastrostomy (RIG). Twenty-seven studies reporting outcomes following 2353 gastrostomy procedures for head and neck cancer. MAIN OUTCOME MEASURES: Post-procedure mortality, major and minor complications. RESULTS: In the present series, mortality rates were 1.0% (1/121) for PEG and 3.9% (2/51) for RIG. Overall major complication rates following PEG and RIG were 3.3% (4/121) and 15.6% (9/51) respectively. In our systematic review and meta-analysis of 2379 head and neck cancer patients, we observed fatality rates of 2.2% (95% CI 0.014-0.034) following PEG and 1.8% (95% CI 0.010-0.032) following RIG. Furthermore, major complication rates following PEG were 7.4% (95% CI 5.9-9.3%) and 8.9% (95% CI 7.0-11.2%) after RIG. CONCLUSIONS: Procedure related mortality rates following gastrostomy in head and neck cancer patients are higher than those in mixed patient populations. Major complication rates following RIG in head and neck cancer patients are greater than those following PEG. Major complications following PEG in patients with head and neck cancer appear no worse than in mixed pathology groups. We have identified that RIG is associated with increased morbidity and mortality in patients who are ineligible for PEG. The serious nature of the complications associated with gastrostomy particularly in patients with head and neck cancer requires careful consideration by the referring physician.

Improving cellular migration in tissue-engineered laryngeal scaffolds.

OBJECTIVE: To modify the non-porous surface membrane of a tissue-engineered laryngeal scaffold to allow effective cell entry. METHODS: The mechanical properties, surface topography and chemistry of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane were characterised. A laser technique introduced surface perforations. Micro computed tomography generated porosity data. Scaffolds were seeded with cells, investigated histologically and proliferation studied. Incubation and time effects were assessed. RESULTS: Laser cutting perforated the polymer, connecting the substructure with the ex-scaffold environment and increasing porosity (porous, non-perforated = 87.9 per cent; porous, laser-perforated at intensities 3 = 96.4 per cent and 6 = 89.5 per cent). Cellular studies confirmed improved cell viability. Histology showed cells adherent to the scaffold surface and cells within perforations, and indicated that cells migrated into the scaffolds. After 15 days of incubation, scanning electron microscopy revealed an 11 per cent reduction in pore diameter, correlating with a decrease in Young's modulus. CONCLUSION: Introducing surface perforations presents a viable method of improving polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane as a tissue-engineered scaffold.

In vivo implantation of a tissue engineered stem cell seeded hemi-laryngeal replacement maintains airway, phonation, and swallowing in pigs.

Laryngeal functional impairment relating to swallowing, vocalisation, and respiration can be life changing and devastating for patients. A tissue engineering approach to regenerating vocal folds would represent a significant advantage over current clinical practice. Porcine hemi-larynx were de-cellularised under negative pressure. The resultant acellular scaffold was seeded with human bone marrow derived mesenchymal stem cells and primary human epithelial cells. Seeded scaffolds were implanted orthotopically into a defect created in the thyroid cartilage in 8 pigs and monitored in vivo for 2 months. In vivo assessments consisted of mucosal brushing and bronchoscopy at 1, 2, 4, and 8 weeks post implantation followed by histological evaluation post termination. The implanted graft had no adverse effect on respiratory function in 6 of the 8 pigs; none of the pigs had problems with swallowing or vocalisation. Six out of the 8 animals survived to the planned termination date; 2 animals were terminated due to mild stenosis and deep tissue abscess formation, respectively. Human epithelial cells from mucosal brushings could only be identified at Weeks 1 and 4. The explanted tissue showed complete epithelialisation of the mucosal surface and the development of rudimentary vocal folds. However, there was no evidence of cartilage remodelling at the relatively early censor point. Single stage partial laryngeal replacement is a safe surgical procedure. Replacement with a tissue engineered laryngeal graft as a single procedure is surgically feasible and results in appropriate mucosal coverage and rudimentary vocal fold development.

Immediate selective laryngeal reinnervation in vagal paraganglioma patients.

OBJECTIVE: This prospective case series aimed to present the outcomes of immediate selective laryngeal reinnervation. METHODS: Two middle-aged women with vagal paraganglioma undergoing an excision operation underwent immediate selective laryngeal reinnervation using the phrenic nerve and ansa cervicalis as the donor nerve. Multidimensional outcome measures were employed pre-operatively, and at 1, 6 and 12 months post-operatively. RESULTS: The voice handicap index-10 score improved from 23 (patient 1) and 18 (patient 2) at 1 month post-operation, to 5 (patient 1) and 1 (patient 2) at 12 months. The Eating Assessment Tool 10 score improved from 20 (patient 1) and 24 (patient 2) at 1 month post-operation, to 3 (patient 1) and 1 (patient 2) at 12 months. There was slight vocal fold abduction observed in patient one and no obvious abduction in patient two. CONCLUSION: Selective reinnervation is safe to perform following vagal paraganglioma excision conducted on the same side. Voice and swallowing improvements were demonstrated, but no significant vocal fold abduction was achieved.