Acquired genetic changes in human pluripotent stem cells: origins and consequences.

In the 20 years since human embryonic stem cells, and subsequently induced pluripotent stem cells, were first described, it has become apparent that during long-term culture these cells (collectively referred to as 'pluripotent stem cells' (PSCs)) can acquire genetic changes, which commonly include gains or losses of particular chromosomal regions, or mutations in certain cancer-associated genes, especially TP53. Such changes raise concerns for the safety of PSC-derived cellular therapies for regenerative medicine. Although acquired genetic changes may not be present in a cell line at the start of a research programme, the low sensitivity of current detection methods means that mutations may be difficult to detect if they arise but are present in only a small proportion of the cells. In this Review, we discuss the types of mutations acquired by human PSCs and the mechanisms that lead to their accumulation. Recent work suggests that the underlying mutation rate in PSCs is low, although they also seem to be particularly susceptible to genomic damage. This apparent contradiction can be reconciled by the observations that, in contrast to somatic cells, PSCs are programmed to die in response to genomic damage, which may reflect the requirements of early embryogenesis. Thus, the common genetic variants that are observed are probably rare events that give the cells with a selective growth advantage.

Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue.

OBJECTIVE: Hirschsprung disease (HSCR) is a severe congenital disorder affecting 1:5000 live births. HSCR results from the failure of enteric nervous system (ENS) progenitors to fully colonise the gastrointestinal tract during embryonic development. This leads to aganglionosis in the distal bowel, resulting in disrupted motor activity and impaired peristalsis. Currently, the only viable treatment option is surgical resection of the aganglionic bowel. However, patients frequently suffer debilitating, lifelong symptoms, with multiple surgical procedures often necessary. Hence, alternative treatment options are crucial. An attractive strategy involves the transplantation of ENS progenitors generated from human pluripotent stem cells (hPSCs). DESIGN: ENS progenitors were generated from hPSCs using an accelerated protocol and characterised, in detail, through a combination of single-cell RNA sequencing, protein expression analysis and calcium imaging. We tested ENS progenitors' capacity to integrate and affect functional responses in HSCR colon, after ex vivo transplantation to organotypically cultured patient-derived colonic tissue, using organ bath contractility. RESULTS: We found that our protocol consistently gives rise to high yields of a cell population exhibiting transcriptional and functional hallmarks of early ENS progenitors. Following transplantation, hPSC-derived ENS progenitors integrate, migrate and form neurons/glia within explanted human HSCR colon samples. Importantly, the transplanted HSCR tissue displayed significantly increased basal contractile activity and increased responses to electrical stimulation compared with control tissue. CONCLUSION: Our findings demonstrate, for the first time, the potential of hPSC-derived ENS progenitors to repopulate and increase functional responses in human HSCR patient colonic tissue.

Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.

The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFß-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities.

GABRA1-Related Disorders: From Genetic to Functional Pathways.

OBJECTIVE: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features and the functional effects of GABRA1 variants to establish genotype-phenotype correlations. METHODS: Genetic and electroclinical data of 27 individuals (22 unrelated and 2 families) harboring 20 different GABRA1 variants were collected and accompanied by functional analysis of 19 variants. RESULTS: Individuals in this cohort could be assigned into different clinical subgroups based on the functional effect of their variant and its structural position within the GABRA1 subunit. A homogenous phenotype with mild cognitive impairment and infantile onset epilepsy (focal seizures, fever sensitivity, and electroencephalographic posterior epileptiform discharges) was described for variants in the extracellular domain and the small transmembrane loops. These variants displayed loss-of-function (LoF) effects, and the patients generally had a favorable outcome. A more severe phenotype was associated with variants in the pore-forming transmembrane helices. These variants displayed either gain-of-function (GoF) or LoF effects. GoF variants were associated with severe early onset neurodevelopmental disorders, including early infantile developmental and epileptic encephalopathy. INTERPRETATION: Our data expand the genetic and phenotypic spectrum of GABRA1 epilepsies and permit delineation of specific subphenotypes for LoF and GoF variants, through the heterogeneity of phenotypes and variants. Generally, variants in the transmembrane helices cause more severe phenotypes, in particular GoF variants. These findings establish the basis for a better understanding of the pathomechanism and a precision medicine approach in GABRA1-related disorders. Further studies in larger populations are needed to provide a conclusive genotype-phenotype correlation. ANN NEUROL 2023.

Accurate measurement of microsatellite length by disrupting its tandem repeat structure.

Tandem repeats of simple sequence motifs, also known as microsatellites, are abundant in the genome. Because their repeat structure makes replication error-prone, variant microsatellite lengths are often generated during germline and other somatic expansions. As such, microsatellite length variations can serve as markers for cancer. However, accurate error-free measurement of microsatellite lengths is difficult with current methods precisely because of this high error rate during amplification. We have solved this problem by using partial mutagenesis to disrupt enough of the repeat structure of initial templates so that their sequence lengths replicate faithfully. In this work, we use bisulfite mutagenesis to convert a C to a U, later read as T. Compared to untreated templates, we achieve three orders of magnitude reduction in the error rate per round of replication. By requiring agreement from two independent first copies of an initial template, we reach error rates below one in a million. We apply this method to a thousand microsatellite loci from the human genome, revealing microsatellite length distributions not observable without mutagenesis.

Targeted de novo phasing and long-range assembly by template mutagenesis.

Short-read sequencers provide highly accurate reads at very low cost. Unfortunately, short reads are often inadequate for important applications such as assembly in complex regions or phasing across distant heterozygous sites. In this study, we describe novel bench protocols and algorithms to obtain haplotype-phased sequence assemblies with ultra-low error for regions 10 kb and longer using short reads only. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ∼50% of cytosines to uracils. Sequencing libraries are made from both mutated and unmutated templates. Using de Bruijn graphs and paired-end read information, we assemble each mutated template and use the unmutated library to correct the mutated bases. Templates are partitioned into two or more haplotypes, and the final haplotypes are assembled and corrected for residual template mutations and PCR errors. With sufficient template coverage, the final assemblies have per-base error rates below 10-9. We demonstrate this method on a four-member nuclear family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.

Artificial intelligence chatbots as sources of patient education material for obstructive sleep apnoea: ChatGPT versus Google Bard.

PURPOSE: To perform the first head-to-head comparative evaluation of patient education material for obstructive sleep apnoea generated by two artificial intelligence chatbots, ChatGPT and its primary rival Google Bard. METHODS: Fifty frequently asked questions on obstructive sleep apnoea in English were extracted from the patient information webpages of four major sleep organizations and categorized as input prompts. ChatGPT and Google Bard responses were selected and independently rated using the Patient Education Materials Assessment Tool-Printable (PEMAT-P) Auto-Scoring Form by two otolaryngologists, with a Fellowship of the Royal College of Surgeons (FRCS) and a special interest in sleep medicine and surgery. Responses were subjectively screened for any incorrect or dangerous information as a secondary outcome. The Flesch-Kincaid Calculator was used to evaluate the readability of responses for both ChatGPT and Google Bard. RESULTS: A total of 46 questions were curated and categorized into three domains: condition (n = 14), investigation (n = 9) and treatment (n = 23). Understandability scores for ChatGPT versus Google Bard on the various domains were as follows: condition 90.86% vs.76.32% (p < 0.001); investigation 89.94% vs. 71.67% (p < 0.001); treatment 90.78% vs.73.74% (p < 0.001). Actionability scores for ChatGPT versus Google Bard on the various domains were as follows: condition 77.14% vs. 51.43% (p < 0.001); investigation 72.22% vs. 54.44% (p = 0.05); treatment 73.04% vs. 54.78% (p = 0.002). The mean Flesch-Kincaid Grade Level for ChatGPT was 9.0 and Google Bard was 5.9. No incorrect or dangerous information was identified in any of the generated responses from both ChatGPT and Google Bard. CONCLUSION: Evaluation of ChatGPT and Google Bard patient education material for OSA indicates the former to offer superior information across several domains.

Performance of artificial intelligence chatbots in sleep medicine certification board exams: ChatGPT versus Google Bard.

PURPOSE: To conduct a comparative performance evaluation of GPT-3.5, GPT-4 and Google Bard in self-assessment questions at the level of the American Sleep Medicine Certification Board Exam. METHODS: A total of 301 text-based single-best-answer multiple choice questions with four answer options each, across 10 categories, were included in the study and transcribed as inputs for GPT-3.5, GPT-4 and Google Bard. The first output responses generated were selected and matched for answer accuracy against the gold-standard answer provided by the American Academy of Sleep Medicine for each question. A global score of 80% and above is required by human sleep medicine specialists to pass each exam category. RESULTS: GPT-4 successfully achieved the pass mark of 80% or above in five of the 10 exam categories, including the Normal Sleep and Variants Self-Assessment Exam (2021), Circadian Rhythm Sleep-Wake Disorders Self-Assessment Exam (2021), Insomnia Self-Assessment Exam (2022), Parasomnias Self-Assessment Exam (2022) and the Sleep-Related Movements Self-Assessment Exam (2023). GPT-4 demonstrated superior performance in all exam categories and achieved a higher overall score of 68.1% when compared against both GPT-3.5 (46.8%) and Google Bard (45.5%), which was statistically significant (p value < 0.001). There was no significant difference in the overall score performance between GPT-3.5 and Google Bard. CONCLUSIONS: Otolaryngologists and sleep medicine physicians have a crucial role through agile and robust research to ensure the next generation AI chatbots are built safely and responsibly.

Enhancing paranasal sinus disease detection with AutoML: efficient AI development and evaluation via magnetic resonance imaging.

PURPOSE: Artificial intelligence (AI) in the form of automated machine learning (AutoML) offers a new potential breakthrough to overcome the barrier of entry for non-technically trained physicians. A Clinical Decision Support System (CDSS) for screening purposes using AutoML could be beneficial to ease the clinical burden in the radiological workflow for paranasal sinus diseases. METHODS: The main target of this work was the usage of automated evaluation of model performance and the feasibility of the Vertex AI image classification model on the Google Cloud AutoML platform to be trained to automatically classify the presence or absence of sinonasal disease. The dataset is a consensus labelled Open Access Series of Imaging Studies (OASIS-3) MRI head dataset by three specialised head and neck consultant radiologists. A total of 1313 unique non-TSE T2w MRI head sessions were used from the OASIS-3 repository. RESULTS: The best-performing image classification model achieved a precision of 0.928. Demonstrating the feasibility and high performance of the Vertex AI image classification model to automatically detect the presence or absence of sinonasal disease on MRI. CONCLUSION: AutoML allows for potential deployment to optimise diagnostic radiology workflows and lay the foundation for further AI research in radiology and otolaryngology. The usage of AutoML could serve as a formal requirement for a feasibility study.

Patient Experience and Preferences for the Assessment of Olfaction: The Patient International Clinical Assessment of Smell Survey.

INTRODUCTION: Olfactory dysfunction (OD) is common and carries significant personal and societal burden of disease. Accurate assessment of olfaction is required for good clinical care and affords patients insight into their condition. However, the accuracy of assessment varies with technique used, and there is presently little standardisation of clinical practice. We therefore aimed to determine experience of and preferences for olfactory assessment in healthcare-seeking adults. METHODS: An anonymous patient co-produced survey was developed in collaboration with a UK-based OD charity. Distribution was via their social media patient forum. "Healthcare seeking" adults (i.e., who had undergone olfactory assessment by a healthcare professional [any care level/speciality] or may do so in the future) were included. RESULTS: 576 people (88.5% female, mean 46 years) responded. Hyposmia, parosmia, and retronasal OD were most frequently reported. 55.2% had been assessed by a healthcare professional - GP most commonly, followed by ENT. Importantly, only 15.6% and 16.9% of respondents had undergone systematic assessment with smell tests or symptom questionnaires, respectively. Most respondents had not undergone imaging. Mean satisfaction was higher in those seen by ENT. Interestingly, respondents prioritise orthonasal odour identification over other forms of smell test. Unfortunately, many felt that healthcare professionals (across specialities) were dismissive towards OD and lacked appropriate knowledge of both its pathophysiology and effects. We propose simple steps that can be taken to improve olfactory assessment, including education and establishment of robust referral networks. CONCLUSION: We hope these results and supporting practical recommendations will inform future service planning, funding allocation and research, as well as better aligning patient and clinician priorities.

Introduction.

It gives us great pleasure to guest edit this special edition on The Disfigured Face. We present a range of manuscripts covering the surgical and non-surgical aspects of managing facial paralysis. We are privileged to include articles from internationally renowned surgeons. We hope our readers enjoy reading these articles and should there be any questions, or errors, please do not hesitate to contact us Best wishes Eamon Shamil and Peter Andrews Facial Reanimation Multidisciplinary Team The Royal National ENT Hospital, University College London Hospitals NHS Foundation Trust, England.

Evaluation of the Patient with Facial Palsy: A Multidisciplinary Approach.

This article aims to provide an overview of the management of facial palsy within a multidisciplinary team setting and discusses considerations used to develop patient-specific management plans. The national landscape of facial function services is also discussed including suggestions on what may enable a more equitable and sustainable service for the future.

Psychological Aspects of Facial Palsy.

This article discusses the psychological effects of facial palsy (FP) in adults. FP is the abnormal functioning of facial muscles resulting from temporary or permanent damage of the facial nerves. Following facial paralysis, patients can develop motor and psychosocial functioning issues impacting quality of life. In addition, real or perceived judgment in social settings of those with FP increases the risk of low self-esteem, anxiety, and depression. Currently, most available research focuses on surgical patients and suggests a lack of psychological support throughout the affliction. A multidisciplinary approach when treating patients with FP can help improve the patient's quality of life.

International clinical assessment of smell: An international, cross-sectional survey of current practice in the assessment of olfaction.

OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.

Litigation in Septorhinoplasty Surgery: A Pan-Specialty Review of National Health Service (the United Kingdom) Data.

Success in septorhinoplasty surgery can be difficult to assess due to a lack of objective and measurable outcomes. If patients' expectations are not met, it places surgeons performing septorhinoplasty at risk of litigation which can be stressful and costly. The National Institute of health (NHS) Resolution is a government-funded organization in the United Kingdom that provides expertise to the NHS on resolving patient concerns. Data were requested from NHS Resolution for claims involving septorhinoplasty surgery over a period of 5 years between April 2015 and April 2020. Rhinoplasty claims performed by all specialties were included. Data included the claim status, incident details, alleged injury, damages claimed, and damages paid. A total of 31 claims were identified by the study, equating to a total cost of £1,347,336.10. Of the 31 claims for rhinoplasty or septorhinoplasty, 9 cases were open (29%, £962,361.00) and 22 cases were closed (71%, £384,975.10). The common causes for claims were "intraoperative problems (32%)," "failure to warn-informed consent (19%)," and "foreign body left in situ (13%)." The most common injuries were "cosmetic disfigurement (39%)," "unnecessary pain (29%)," and "additional/ unnecessary operation (29%)." This study highlights the need for improved awareness of clinical negligence claims among surgeons who perform septorhinoplasty. Results are applicable to all specialties who perform the procedure. The study highlights the importance of assessing patients' motives and expectations prior to surgery and emphasizes the need for a well-documented rigorous consent process.

Safety of day-case endoscopic sinus surgery in England: An observational study using an administrative dataset.

INTRODUCTION: As elective surgical services recover from the COVID-19 pandemic a movement towards day-case surgery may reduce waiting lists. However, evidence is needed to show that day-case surgery is safe for endoscopic sinus surgery (ESS). The aim of this study was to investigate the safety of day-case ESS in England. DESIGN: Secondary analysis of administrative data. METHODS: We extracted data from the Hospital Episodes Statistics database for the 5 years from 1 April 2014 to 31 March 2019. Patients undergoing elective ESS procedures aged ≥17 years were included. Exclusion criteria included malignant neoplasm, complex systemic disease and trans-sphenoidal pituitary surgery. The primary outcome was readmission within 30 days post-discharge. Multilevel, multivariable logistic regression modelling was used to compare outcomes for those operated on as day-cases and those with an overnight stay after adjusting for demographic, frailty, comorbidity and procedural covariates. RESULTS: Data were available for 49 223 patients operated on across 129 NHS hospital trusts. In trusts operating on more than 50 patients in the study period, rates of day-case surgery varied from 20.6% to 100%. Nationally, rates of day-case surgery increased from 64.0% in the financial year 2014/2015 to 78.7% in 2018/2019. Day-case patients had lower rates of 30-day emergency readmission (odds ratio 0.71, 95% confidence interval 0.62 to 0.81). Outcomes for patients operated on in trusts with ≥80% day-case rates compared with patients operated on in trusts with <50% rates of day-case surgery were similar. CONCLUSIONS: Our data support the view that ESS can safely be performed as day-case surgery in most cases, although it will not be suitable for all patients. There appears to be scope to increase rates of day-case ESS in some hospital trusts in England.

The synapse in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and is a risk factor for dementia later in life. Research into the pathophysiology of TBI has focused on the impact of injury on the neuron. However, recent advances have shown that TBI has a major impact on synapse structure and function through a combination of the immediate mechanical insult and the ensuing secondary injury processes, leading to synapse loss. In this review, we highlight the role of the synapse in TBI pathophysiology with a focus on the confluence of multiple secondary injury processes including excitotoxicity, inflammation and oxidative stress. The primary insult triggers a cascade of events in each of these secondary processes and we discuss the complex interplay that occurs at the synapse. We also examine how the synapse is impacted by traumatic axonal injury and the role it may play in the spread of tau after TBI. We propose that astrocytes play a crucial role by mediating both synapse loss and recovery. Finally, we highlight recent developments in the field including synapse molecular imaging, fluid biomarkers and therapeutics. In particular, we discuss advances in our understanding of synapse diversity and suggest that the new technology of synaptome mapping may prove useful in identifying synapses that are vulnerable or resistant to TBI.

Multiplex accurate sensitive quantitation (MASQ) with application to minimal residual disease in acute myeloid leukemia.

Measuring minimal residual disease in cancer has applications for prognosis, monitoring treatment and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10-3) that limit sensitive detection. We developed and characterized the performance of MASQ (multiplex accurate sensitive quantitation), a method with an error rate below 10-6. MASQ counts variant templates accurately in the presence of millions of host genomes by using tags to identify each template and demanding consensus over multiple reads. Since the MASQ protocol multiplexes 50 target loci, we can both integrate signal from multiple variants and capture subclonal response to treatment. Compared to existing methods for variant detection, MASQ achieves an excellent combination of sensitivity, specificity and yield. We tested MASQ in a pilot study in acute myeloid leukemia (AML) patients who entered complete remission. We detect leukemic variants in the blood and bone marrow samples of all five patients, after induction therapy, at levels ranging from 10-2 to nearly 10-6. We observe evidence of sub-clonal structure and find higher target variant frequencies in patients who go on to relapse, demonstrating the potential for MASQ to quantify residual disease in AML.

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease.

PURPOSE: Aspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated. METHODS: A retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up. RESULTS: Higher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response. CONCLUSION: Our study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit.

Awake Rhinology Surgery in Response to the COVID-19 Pandemic in Europe.

BACKGROUND: European health-care systems are faced with a backlog of surgical procedures following the suspension of routine surgery during the COVID-19 crisis. Routine rhinology surgery under general anaesthetic (GA) is now faced with significant challenges which include limited theatre capacity, the negative ramifications of surgical prioritization, reduced patient throughput in secondary care, and additional personal protective equipment requirements. Delayed surgery in rhinology, particularly with regards to chronic rhinosinusitis, has previously been shown to have poorer surgical outcomes, a detrimental effect on quality of life and long-term negative health socio-economic effects. Awake rhinology surgery under local anaesthetic (LA) provides an ideal alternative to GA. It provides a means of operating on patients in a setting alternative to currently oversubscribed main theatres, by utilizing satellite facilities, while ensuring identical surgical outcomes for patients who may otherwise have been forced to wait a long time for their procedure. It also confers additional benefits in terms of shorter recovery time and hospital stay for patients. OBJECTIVES: We have developed a set of recommendations that are intended to help support clinicians and managers to better adopt LA rhinology protocols and minimize the risk to the patient and health-care professionals involved. METHODOLOGY: International roundtable forums were conducted and supplemented by individual interviews. The international board consisted of 12 rhinologists experienced in awake rhinology surgery. Feedback was analysed and shared to develop a consensus of best practice. RECOMMENDATIONS: Local and national guidelines need to be adhered to with specific focus on patient and clinician safety. When performing awake rhinology procedures in the COVID-19 recovery process, consider implementing specific safety measures and workflow practices to safeguard patients and staff and minimize the risk of infection. CONCLUSION: Awake surgery potentially provides quicker access to routine rhinology surgery in the post-COVID-19 recovery phase, ensuring patients are treated in a timely matter, thereby avoiding higher downstream costs, and improving outcomes.