Impact of tongue base mucosectomy on quality-of-life outcomes: systematic review and single-centre experience.

PURPOSE: Tongue base mucosectomy (TBM) is a well-established procedure in investigating cervical squamous cell carcinoma of occult primary. However, its risks have not been balanced against its benefits with validated tools. METHODS: A systematic literature review was conducted for reported complications and quality-of-life outcomes following TBM. The complications and quality-of-life outcomes following TBM at our institution are then reported using objective metrics and validated assessment tools, including Performance Status Scale for Head and Neck Cancer Patients (PSS-HNS), University of Washington Quality-of-life Questionnaire (UW-QOL) and M. D. Anderson Dysphagia Inventory (MDADI). RESULTS: Eighteen studies met the criteria for inclusion in the systematic review. Of these, 9 addressed swallowing outcomes described in text, without using validated assessment tools. No studies reported taste, speech and pain outcomes after TBM. Post-operative bleeding was not consistently reported. 20 patients underwent robotic TBM at our institution between 2017 and 2023. The primary tumour was identified in 50% (10/20) of cases. The median time to commencing soft diet and median time of NG feeding was 0 days. The median return to normalcy of diet score was 95. Median post-treatment UW-QOL pain and swallowing scores were 100 and 70 respectively. The median speech score was 100, saliva 70, and taste 70. The median normalised MDADI scores were: global 80; emotional 67; functional 80 and physical 65. CONCLUSIONS: Validated assessment tools better inform patients about treatment options and can help compare post-TBM results across institutions. Our data demonstrates that TBM patients have a functional post-operative swallow, are pain and gastrostomy free, even after adjuvant treatment. Routine post-operative insertion of NG tube is not necessary.

Phosphoproteomics predict response to midostaurin plus chemotherapy in independent cohorts of FLT3-mutated acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is a bone marrow malignancy with poor prognosis. One of several treatments for AML is midostaurin combined with intensive chemotherapy (MIC), currently approved for FLT3 mutation-positive (FLT3-MP) AML. However, many patients carrying FLT3 mutations are refractory or experience an early relapse following MIC treatment, and might benefit more from receiving a different treatment. Development of a stratification method that outperforms FLT3 mutational status in predicting MIC response would thus benefit a large number of patients. METHODS: We employed mass spectrometry phosphoproteomics to analyse 71 diagnosis samples of 47 patients with FLT3-MP AML who subsequently received MIC. We then used machine learning to identify biomarkers of response to MIC, and validated the resulting predictive model in two independent validation cohorts (n = 20). FINDINGS: We identified three distinct phosphoproteomic AML subtypes amongst long-term survivors. The subtypes showed similar duration of MIC response, but different modulation of AML-implicated pathways, and exhibited distinct, highly-predictive biomarkers of MIC response. Using these biomarkers, we built a phosphoproteomics-based predictive model of MIC response, which we called MPhos. When applied to two retrospective real-world patient test cohorts (n = 20), MPhos predicted MIC response with 83% sensitivity and 100% specificity (log-rank p < 7∗10-5, HR = 0.005 [95% CI: 0-0.31]). INTERPRETATION: In validation, MPhos outperformed the currently-used FLT3-based stratification method. Our findings have the potential to transform clinical decision-making, and highlight the important role that phosphoproteomics is destined to play in precision oncology. FUNDING: This work was funded by Innovate UK grants (application numbers: 22217 and 10054602) and by Kinomica Ltd.

Survival outcomes in head and neck squamous cell carcinoma of unknown primary: A national cohort study.

INTRODUCTION: To investigate factors influencing survival in head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: A retrospective observational cohort study was conducted, over 5 years from January 2015, in UK Head and Neck centres, of consecutive adults undergoing 18F-Fluorodeoxyglucose-PET-CT within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients treated as HNSCCUP underwent survival analysis, stratified by neck dissection and/or radiotherapy to the ipsilateral neck, and by HPV status. RESULTS: Data were received from 57 centres for 965 patients, of whom 482 started treatment for HNSCCUP (65.7% HPV-positive, n = 282/429). Five-year overall survival (OS) for HPV-positive patients was 85.0% (95% CI 78.4-92.3) and 43.5% (95% CI 32.9-57.5) for HPV-negative. HPV-negative status was associated with worse OS, disease-free (DFS), and disease-specific (DSS) survival (all p < .0001 on log-rank test) but not local control (LC) (p = .16). Unilateral HPV-positive disease treated with surgery alone was associated with significantly worse DFS (p < .0001) and LC (p < .0001) compared to radiotherapy alone or combined modalities (5-year DFS: 24.9%, 82.3% and 94.3%; 5-year LC: 41.8%, 98.8% and 98.6%). OS was not significantly different (p = .16). Unilateral HPV-negative disease treated with surgery alone was associated with significantly worse LC (p = .017) (5-year LC: estimate unavailable, 93.3% and 96.6%, respectively). Small numbers with bilateral disease precluded meaningful sub-group analysis. CONCLUSIONS: HPV status is associated with variable management and outcomes in HNSCCUP. Unilateral neck disease is treated variably and associated with poorer outcomes when managed with surgery alone. The impact of diagnostic oropharyngeal surgery on primary site emergence, survival and functional outcomes is unestablished.

The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. Design, Setting, and Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Main Outcomes and Measures: Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). Results: A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions and Relevance: In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Serum Proteomic Signatures of Common Health Outcomes among Older Adults.

INTRODUCTION: In aging populations, the coexistence of multiple health comorbidities represents a significant challenge for clinicians and researchers. Leveraging advances in omics techniques to characterize these health conditions may provide insight into disease pathogenesis as well as reveal biomarkers for monitoring, prognostication, and diagnosis. Researchers have previously established the utility of big data approaches with respect to comprehensive health outcome measurements in younger populations, identifying protein markers that may provide significant health information with a single blood sample. METHODS: Here, we employed a similar approach in two cohorts of older adults, the Baltimore Longitudinal Study of Aging (mean age = 76.12 years) and InCHIANTI Study (mean age = 66.05 years), examining the relationship between levels of serum proteins and 5 key health outcomes: kidney function, fasting glucose, physical activity, lean body mass, and percent body fat. RESULTS: Correlations between proteins and health outcomes were primarily shared across both older adult cohorts. We further identified that most proteins associated with health outcomes in the older adult cohorts were not associated with the same outcomes in a prior study of a younger population. A subset of proteins, adiponectin, MIC-1, and NCAM-120, were associated with at least three health outcomes in both older adult cohorts but not in the previously published younger cohort, suggesting that they may represent plausible markers of general health in older adult populations. CONCLUSION: Taken together, these findings suggest that comprehensive protein health markers have utility in aging populations and are distinct from those identified in younger adults, indicating unique mechanisms of disease with aging.

Vascularized Tissue to Reduce Fistula After Salvage Total Laryngectomy: A Network Meta-analysis.

OBJECTIVE: Salvage laryngectomy is more predisposed to complications than primary operations, with pharyngocutaneous fistula (PCF) being among the most challenging to manage. Vascularized flaps are increasingly employed during salvage laryngectomy, with a previous review finding a PCF incidence of 31.2% and 22.2% after primary and flap-assisted closure respectively. We aim to better define the role of vascularized flaps after salvage laryngectomy by performing an updated review comparing the rate of PCF in those undergoing primary or vascularized flap-assisted closure. DATA SOURCES: Pubmed/Medline, CINAHL, and CENTRAL. REVIEW METHODS: An updated literature review was conducted of English language literature from 2003 to 2023. A random effects and network meta-analysis of odds ratios (OR) and pooled proportions were conducted. RESULTS: Literature search found 31 studies, including seven from the previous review. Overall random effects pooled PCF rate was 25% (95% CI 0.21; 0.30, I2 = 72%, p = <0.01), whereas incidence in primary closure was 37% (95% CI 0.32; 0.43, I2 = 60%, p = <0.01) and 19% (95% CI 0.12; 0.20, I2 = 47%, p = <0.01) after flap closure. Pooled OR was 0.39 (95% CI 0.28; 0.55, I2 = 36%, p = 0.04) in favor of vascularized tissues. The number needed to treat was 6.5. The rate of PCF was lower after free and pedicled flaps, and on-lay and patch closure compared to primary closure techniques. Network meta-analysis found all combinations of closure techniques and vascularized tissue were superior to primary closure. CONCLUSION: The updated analysis has demonstrated a widening in the rates of PCF between primary and vascularized flap-assisted closure. Surgeons should strongly consider the use of free or pedicled flaps in any salvage laryngectomy procedure. Laryngoscope, 134:2991-3002, 2024.

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.

Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers. Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity. Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs. Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

Transoral robotic surgery without adjuvant therapy: A systematic review and meta-analysis of the association between surgical margins and local recurrence.

BACKGROUND: Transoral robotic surgery (TORS) is increasingly employed in the management of oropharyngeal cancer without adjuvant treatment. Attaining safe surgical margins is paramount to preventing local recurrence (LR), but the necessary surgical margin dimension remains contentious. METHODS: Systematic review and meta-analysis of studies reporting margin status and LR following TORS without adjuvant therapy for primary OPSCC. RESULTS: The search identified 269 articles and 11 were selected for inclusion, with 406 patients included in the meta-analysis. Heterogeneity was noted in the definition of "close" margins. Random-effects pooled rate of positive margins was 7 % (95 % CI 0.04-0.12, I2 = 54 %, p = 0.02) and close margins was 7 % (95 % CI 0.02-0.27, I2 = 86 %, p=<0.01). The random-effects overall rate of LR was 6 % (95 % CI 0.04-0.10, I2 = 11 %, p = 0.35), 13 % (95 % CI 0.02-0.620, I2 = 0 %, p = 1.0) after a positive margin, and 3 % (95 % CI 0.03-0.24, I2 = 23 %, p = 0.26) after a close margin. Odds ratio (OR) for LR indicated higher risk of LR for positive compared to close margins (7.5; 95 % CI 1.31-42.91, I2 = 0 %, p = 0.51), and a slightly lower risk of LR between close and negative margins (2.22; 95 % CI 0.67-7.38, I2 = 0 %, p = 0.8). A lack of frozen-section analysis (OR 2.91, p = 0.36) and HPV-negative disease (OR 1.68, p = 0.03) were associated with an elevated risk of LR. CONCLUSIONS: TORS as a standalone treatment is associated with low rates of LR; however, the literature is hampered by considerable heterogeneity in margin definitions. Larger multicentre studies are required to determine the precise margin cut-off required for oropharyngeal tumours managed with TORS alone.

The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab.

BACKGROUND: The combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in melanoma tissue from patients with type 2 diabetes. METHOD: To evaluate the impact of diabetes on oncological outcomes of patients with advanced melanoma treated with nivolumab plus the LAG3 inhibitor relatlimab we performed a retrospective multicenter study. RESULTS: Overall, 129 patients were included: 88 without diabetes before the treatment, 37 who were diagnosed with type 2 diabetes before the start of treatment, and 4 without diabetes before treatment who developed immune checkpoint inhibitor-induced diabetes (ICI-DM). PFS was 21.71 months (95% CI: 15.61-27.81) in patients without diabetes, 10.23 months (95% CI: 5.81-14.66) in patients with type 2 diabetes, and 50.85 months (95% CI: 23.04-78.65) in patients who developed ICI-DM. OS was 37.94 months (95% CI: 31.02-44.85) in patients without diabetes, 22.12 months (95% CI: 14.41-29.85) in those with type 2 diabetes and 57.64 months (95% CI: 42.29-72.99) in those who developed ICI-DM. Multivariate analysis showed that the presence of diabetes and LDH was correlated with OS and PFS. The mean OS was 64.63 months in subjects with low levels of glucose (< 137 mg/dl) and 36.27 months in those with high levels (hazard ratio 0.16, 95% CI: 0.04-0.58; p = 0.005). The patients whose glucose blood level increased after 3 months of treatment with nivolumab + relatinib compared to baseline (ratio of blood level at baseline/after 3 months > 1.5) had a worse prognosis than those whose glucose level had not increased. This result was observed also in subgroups treated either in first line or further lines. Patients who developed ICI-DM during the study period had better outcomes than the overall population and patients without diabetes. CONCLUSIONS: LAG3 inhibition for treating metastatic or unresectable melanoma has a reduced efficacy in patients with type 2 diabetes, possibly due to a low expression of LAG3 in tumor tissue. Higher level evidence should be obtained.

Functional and quality-of-life outcomes following salvage surgery for recurrent squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.

BACKGROUND: Recurrent head and neck squamous cell carcinomas (HNSCC) are frequently managed with salvage surgery, but the impact these operations have on function and quality-of-life (QoL) is understudied. This review aimed to provide a quantitative and qualitative assessment of the functional and QoL effects of salvage surgical procedures. METHODS: Systematic review and meta-analysis were conducted of studies reporting QoL and function following salvage HNSCC resections. RESULTS: The search identified 415 articles and 34 were selected for inclusion. Pooled random effects analysis revealed long-term feeding and tracheostomy tube rates of 18% and 7%. Pooled long-term feeding tube rates in open oral and oropharyngeal, transoral robotic, total and partial laryngectomy surgeries were 41%, 25%, 11% and 4%. Eight studies used validated QoL questionnaires. CONCLUSIONS: Functional and QoL outcomes from salvage surgery are acceptable, but appear to be worse following open procedures. Prospective studies measuring changes over time are needed to assess these procedures impact on patient well-being.

Smell-related quality of life changes after total laryngectomy: a multi-centre study.

PURPOSE: A total laryngectomy creates an alternate airway for gas exchange that bypasses the upper aerodigestive tract. The subsequent reduction in nasal airflow, and therefore, reduction in deposition of particles to the olfactory neuroepithelium leads to hyposmia or anosmia. The aim of this study was to assess the quality of life impairment conferred by anosmia following laryngectomy and identify any specific patient-related risk factors that are associated with poorer outcomes. METHODS: Consecutive patients with a total laryngectomy presenting for review at three tertiary head and neck services (in Australia, the United Kingdom and India) over a 12-month period were recruited. Patient demographic and clinical data were collected, and each subject completed the validated assessment of self-reported olfactory functioning and olfaction-related quality of life questionnaire (ASOF). Dichotomous comparisons were performed using the student's unpaired t-test for continuous variables (SRP), a chi-squared test for categorical variables, and a Kendall's tau-b for ordinal variables (SOC) to assess for a correlation with poorer questionnaire scores. RESULTS: A total of 66 laryngectomees (13.4% female; age 65.7 ± 8.6 years) were included in the study. The mean SRP score of the cohort was found to be 15.6 ± 7.4, while the mean ORQ score was noted to be 16.4 ± 8.1. No other specific risk factors associated with poorer quality of life were identified. CONCLUSION: A significant quality of life detriment from hyposmia is conferred following laryngectomy. Further research to assess treatment options and the patient population that would best benefit from these interventions is required.

The experience of patients with lung cancer during the COVID-19 pandemic and its importance for post-pandemic outpatient cancer care planning: A cross sectional study exploring the roles of age and frailty.

INTRODUCTION: The COVID-19 pandemic impacted the care and experiences of people with cancer, but it presented an opportunity to improve the delivery of outpatient care post-pandemic. MATERIALS AND METHODS: We performed an observational cross-sectional study with people with lung cancer throughout the COVID-19 pandemic. A survey investigated patients' experiences and preferences regarding the delivery of cancer care to plan for post-pandemic care, as well as the pandemic's impact on their functional status (physical and psycho-social), exploring the role of age and frailty. RESULTS: Amongst 282 eligible participants, 88%, 86%, and 59% of patients reported feeling appropriately supported during the pandemic by their cancer centre, friends/family, and primary care services, respectively. Remote oncology consultations were delivered to 90% of patients during the pandemic, of which 3% did not meet patients' expectations. Regarding post-pandemic outpatient care preferences, face-to-face appointments were preferred by 93% for the first appointment, by 64% when discussing imaging results, and by 60% for reviews during anti-cancer treatments. Older patients aged 70 years and above were more likely to favour face-to-face appointments (p = 0.007), regardless of their frailty status. Patient preferences changed over time, with the more recent participants preferring remote appointments during anti-cancer treatments (p = 0.0278). Regarding the pandemic's impact, abnormal levels of anxiety and depression were found in 16% and 17% of patients, respectively. Younger patients experienced higher abnormal levels of anxiety and depression (p = 0.036, p = 0.021). Amongst the older sub-group, those with frailty had higher levels of anxiety and depression (p < 0.001). Amongst all participants, 54% reported a considerable negative impact from the pandemic on different aspects of their daily life, particularly emotional and psychological health and sleep patterns, which were more marked in younger patients and the older sub-group with frailty. Older patients without frailty reported the least impact on their functional status. DISCUSSION: There is a need for more personalised outpatient consultation options during cancer care. Whilst there is a preference for face-to-face consultations for older patients, following the pandemic there is a growing acceptance of remote consultations particularly during anti-cancer treatment. Older patients with lung cancer without frailty were less affected by the pandemic than those with frailty and younger patients, requiring less support from healthcare services.

Validating Confined Flame Noise Simulation Using External Sensor.

Advancements in lean premixed combustion have increased the efficiency and reduced the amount of greenhouse gas emissions, but they have led to increased noise emissions due to higher turbulence and mixing fluctuations. This study used an external sensor (microphone) to validate the simulation of the combustion noise of a confined space. An experimental facility with a laboratory-scale furnace was used to carry out the measurement, and the simulation of the confined flame noise was conducted in OpenFOAM. The simulation utilized the Partially Stirred Reactor (PaSR) and a hybrid computational aeroacoustics (CAA) approach using the large eddy simulation (LES)/the Ffwocs Williams-Hawkings (FWH) method. Additionally, unsteady Reynolds-averaged Navier-Stokes (URANS)/the FWH method was tested for a comparison with the LES prediction. A sensor which was placed outside the enclosure for ease of access was then used to validate the results of the numerical model. The sensor data agreed with the LES/FWH results including the amplitude and frequency of the primary combustion peak and the overall sound pressure level (OASPL). This suggested that a sensor which was placed outside the enclosure could serve as a validation tool for the simulation of the confined flames despite the sound reflections from the walls.

HMG20B stabilizes association of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block.

Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we applied mass spectrometry technologies. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is co-located on chromatin with GFI1 and LSD1 genome-wide; the strongest HMG20B binding co-locates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing LSD1 on chromatin at GFI1 binding sites. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukemia cell differentiation block.

Paediatric tracheobronchomalacia: Incidence, patient characteristics, and predictors of surgical intervention.

OBJECTIVES: Tracheobronchomalacia (TBM), a condition where an abnormality of the tracheal walls causes collapse during the respiratory cycle, is a common cause of airway obstruction in childhood. TBM can present with a large spectrum of disease severity and underlying pathologies that may be managed medically and surgically, and it is not always clear which patients would most benefit from surgical intervention. We aim to describe the incidence, patient characteristics, and predictors of surgical intervention in a large cohort of paediatric patients. METHODS: We performed a retrospective review of all children diagnosed with TBM to a paediatric Otolaryngology unit in the west of Scotland between 2010 and 2020. Odds ratios for clinical predictors of surgery were calculated using logistic regression with uni- and multivariate analysis. RESULTS: 249 patients were identified of which 219 proceeded to data collection. Primary malacia was noted in 161 (73.5%) and secondary in 58 (26.5%). Causes of secondary malacia included compression by the innominate artery (11%) and vascular rings (7.8%). Surgical interventions were performed in 28 patients (12.8%) including division of vascular ring, aortopexy, and surgical tracheostomy. Multivariate analysis showed secondary TBM, acute life-threatening events, and difficulty weaning from mechanical ventilation were independent risk factors for surgical intervention. CONCLUSIONS: TBM can present with a myriad of airway symptoms and is frequently associated with other airway and mediastinal pathologies necessitating multiple interventions. Children aged <1 year present with a more severe form of the disease and the presence of particular independent risk factors may indicate a need for surgical intervention.