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.

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, 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.

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.

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.

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.

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.

Eagle syndrome and carotid artery dissection: a rare skull base cause of stroke.

Eagle's syndrome is a rare collection of symptoms that occur secondary to an elongated styloid process or calcified stylohyoid ligament irritating its surrounding structures. Classically, this presents as unilateral throat pain or rarely, as acute neurological symptoms secondary to compression of the internal carotid artery: so called 'stylocarotid syndrome'. Significant neurological events in teenagers, secondary to Eagle syndrome have not been reported. We discuss the rare case of a teenage boy, diagnosed with right internal carotid artery dissection and middle cerebral artery infarction, with no cause initially identified. Following further admission with a transient neurological episode, he was noted to have elongated styloid processes with the right abutting the site of carotid dissection. He underwent styloidectomy and has since remained symptom free. This case highlights the importance of considering anatomical variants when assessing young patients with neurological symptoms, and the potential morbidity and mortality benefit that early surgical intervention may have.

Chd1 protects genome integrity at promoters to sustain hypertranscription in embryonic stem cells.

Stem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 mediates hypertranscription in pluripotent cells but its mechanism of action remains poorly understood. Here we report a novel role for Chd1 in protecting genome integrity at promoter regions by preventing DNA double-stranded break (DSB) accumulation in ES cells. Chd1 interacts with several DNA repair factors including Atm, Parp1, Kap1 and Topoisomerase 2ß and its absence leads to an accumulation of DSBs at Chd1-bound Pol II-transcribed genes and rDNA. Genes prone to DNA breaks in Chd1 KO ES cells are longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin regulation, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to accumulation of endogenous DNA breaks, with important implications for developmental and cancer biology.

Feasibility of Free Flap Reconstruction Following Salvage Robotic-Assisted Resection of Recurrent and Residual Oropharyngeal Cancer in 3 Patients.

INTRODUCTION: Human papilloma virus (HPV)-positive oropharyngeal cancer carries a good prognosis when managed with primary chemoradiotherapy. However, the dramatically increasing rate of this disease means more patients are now developing recurrence, with surgery remaining the mainstay of treatment. Despite this, there is no agreed technique for excision of recurrent oropharyngeal cancer. OBJECTIVE: We describe the transoral robotic technique employed by our head and neck multidisciplinary team (MDT) in the management of patients with recurrent HPV positive oropharyngeal cancer and assess their symptom severity using quality of life and swallowing questionnaires. METHOD: Three (2 males:1 female, mean age 60.7 years) patients with recurrent or residual p16 positive oropharyngeal cancer following radical chemoradiotherapy were identified. All patients underwent selective neck dissection, tracheostomy, and transoral robotic surgery (TORS)-assisted partial oropharyngeal resection with the resultant defect closed with a robotic assisted radial forearm free flap (RFFF). Patient quality of life, symptom severity, and swallowing were assessed pre- and postoperatively using the University of Washington Quality of Life score and MD Anderson Dysphagia Index (MDADI). RESULTS: Histopathological examination revealed complete clearance of the primary lesion in all cases. Two patients made uneventful recoveries, while one patient developed a chest infection and tracheocutaneous fistula managed conservatively. Mean inpatient stay was 15 days (range 8-27). University of Washington Quality of Life and MDADI scores showed a mild improvement in symptoms following surgery. CONCLUSION: Surgical management of recurrent oropharyngeal cancer remains a technical challenge; however, MDT discussion and judicious use of TORS oropharyngeal resection and RFFF can result in good oncological and quality of life outcomes with acceptable postoperative complications and symptoms.