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Abstract Background Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. CompARE is designed to test alternative approaches to intensified treatment for these patients to improve survival. Methods CompARE is a pragmatic phase III, open-label, multicenter randomised controlled trial with an adaptive multi-arm, multi-stage design and an integrated QuinteT Recruitment Intervention. Eligible OPC patients include those with human papillomavirus (HPV) negative, T1–T4, N1–N3 or T3–4, N0, or HPV positive N3, T4, or current smokers (or ≥ 10 pack years previous smoking history) with T1–T4, N2b–N3. CompARE was originally designed with four arms (one control [arm 1] and three experimental: arm 2—induction chemotherapy followed by arm 1; arm 3—dose-escalated radiotherapy plus concomitant cisplatin; and arm 4—resection of primary followed by arm 1). The three original experimental arms have been closed to recruitment and a further experimental arm opened (arm 5—induction durvalumab followed by arm 1 and then adjuvant durvalumab). Currently recruiting are arm 1 (control): standard treatment of 3-weekly cisplatin 100 mg/m2 or weekly 40 mg/m2 with intensity-modulated radiotherapy using 70 Gy in 35 fractions ± neck dissection determined by clinical and radiological assessment 3 months post-treatment, and arm 5 (intervention): one cycle of induction durvalumab 1500 mg followed by standard treatment then durvalumab 1500 mg every 4 weeks for a total of 6 months. The definitive and interim primary outcome measures are overall survival time and event-free survival (EFS) time, respectively. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complication rates, and cost-effectiveness. The design anticipates that after approximately 7 years, 84 required events will have occurred to enable analysis of the definitive primary outcome measure for this comparison. Planned interim futility analyses using EFS will also be performed. Discussion CompARE is designed to be efficient and cost-effective in response to new data, emerging new treatments or difficulties, with the aim of bringing new treatment options for these patients. Trial registration ISRCTN ISRCTN41478539 . Registered on 29 April 2015

IntroductionEvolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient.MethodThe review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms.ResultsThere were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings.DiscussionSymptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.

Objectives This study aims to assess the feasibility to perform transoral robotic surgery (TORS) with a new robotic platform, the Versius Surgical System (CMR Surgical, UK) in a preclinical cadaveric setting in accordance to stage 0 of the IDEAL-D framework.Design IDEAL stage 0 preclinical assessment of the Versius Robotic System in TORS in human cadavers.Setting All procedures were performed in a simulated operating theatre environment at a UK surgical training centre.Participants 11 consultant head and neck surgeons from the UK, mainland Europe and the USA took part in TORS procedures on six human cadavers.Interventions 3 key index procedures were assessed that represent the core surgical workload of TORS: lateral oropharyngectomy, tongue base resection and partial supraglottic laryngectomy.Main outcome measures The primary outcome was the successful completion of each surgical procedure. Secondary outcomes included the optimisation of system setup, instrumentation and surgeon-reported outcomes for feasibility of each component procedural step.Results 33 cadaveric procedures were performed and 32 were successfully completed. One supraglottic laryngectomy was not fully completed due to issues dividing the epiglottic cartilage with available instrumentation. Surgeon-reported outcomes met the minimal level of feasibility in all procedures and a consensus that it is feasible to perform TORS with Versius was reached. Available instrumentation was not representative of other robotic platforms used in TORS and further instrument optimisation is recommended before wider dissemination.Conclusions It is feasible to perform TORS with the Versius Surgical System (CMR Surgical) within a pre-clinical cadaveric setting. Clinical evaluation is needed and appropriate with the system. Further instrument development and optimisation is desirable.

Introduction Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials.Methods and analysis WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches.Ethics and dissemination The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities.

Objective Coronary CT angiography (CCTA) permits both qualitative and quantitative analysis of atherosclerotic plaque and may be a suitable risk modifier in assessing patients at intermediate risk of atherosclerotic cardiovascular disease. We sought to determine the association of plaque components with long-term major adverse cardiovascular events (MACEs) in asymptomatic intermediate-risk patients, compared with conventional coronary artery calcium (CAC) score.Methods 100 intermediate-risk patients underwent double-blinded CCTA. Follow-up was conducted at 10 years and data were cross-referenced with the National Death Index. The primary outcome was MACE, which was a composite of death, acute coronary syndrome (ACS), revascularisation and stroke.Results The median time from CCTA to follow-up was 9.5 years. 83 patients completed follow-up interview and mortality data were available on all 100 patients. MACE occurred in 17 (20.5%) patients, which included 2 (2%) deaths, 8 (10%) ACS, 3 (4%) strokes and 5 (6%) revascularisation procedures. 47 (57%) patients had mixed plaque, which was predictive of MACE (OR 4.68 (95% CI 1.19 to 18.5) p=0.028). The burden of non-calcified and mixed plaque, defined by non-calcified plaque segment stenosis score, was also a predictor of long-term MACE (OR 1.59 (95% CI 1.18 to 2.13) p=0.002). Neither calcified plaque (OR 3.92 (95% CI 0.80 to 19.3)) nor CAC score (OR 1.01 (95% CI 0.999 to 1.02)) was associated with long-term MACE.Conclusion The presence and burden of mixed plaque on CCTA is associated with an increased risk of long-term MACE among asymptomatic intermediate-risk patients and is a superior predictor to CAC score.

Single point eddy covariance measurements of the Earth’s surface energy budget frequently identify an imbalance between available energy and turbulent heat fluxes. While this imbalance lacks a definitive explanation, it is nevertheless a persistent finding from single-site measurements; one with implications for atmospheric and ecosystem models. This has led to a push for intensive field campaigns with temporally and spatially distributed sensors to help identify the causes of energy balance non-closure. Here we present results from the Chequamegon Heterogeneous Ecosystem Energy-balance Study Enabled by a High-density Extensive Array of Detectors 2019 (CHEESEHEAD19)—an observational experiment designed to investigate how the Earth’s surface energy budget responds to scales of surface spatial heterogeneity over a forest ecosystem in northern Wisconsin. The campaign was conducted from June–October 2019, measuring eddy covariance (EC) surface energy fluxes using an array of 20 towers and a low-flying aircraft. Across the domain, energy balance residuals were found to be highest during the afternoon, coinciding with the period of surface heterogeneity-driven mesoscale motions. The magnitude of the residual varied across different sites in relation to the vegetation characteristics of each site. Both vegetation height and height variability showed positive relationships with the residual magnitude. During the seasonal transition from latent heat-dominated summer to sensible heat-dominated fall the magnitude of the energy balance residual steadily decreased, but the energy balance ratio remained constant at 0.8. This was due to the different components of the energy balance equation shifting proportionally, suggesting a common cause of non-closure across the two seasons. Additionally, we tested the effectiveness of measuring energy balance using spatial EC. Spatial EC, whereby the covariance is calculated based on deviations from spatial means, has been proposed as a potential way to reduce energy balance residuals by incorporating contributions from mesoscale motions better than single-site, temporal EC. Here we tested several variations of spatial EC with the CHEESEHEAD19 dataset but found little to no improvement to energy balance closure, which we attribute in part to the challenging measurement requirements of spatial EC.

Abstract Background Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Methods Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Results Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. Conclusion For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

Abstract Background Methods for developing national recommendations vary widely. The successful adoption of new guidance into routine practice is dependent on buy-in from the clinicians delivering day-to-day patient care and must be considerate of existing resource constraints, as well as being aspirational in its scope. This initiative aimed to produce guidelines for the management of head and neck squamous cell carcinoma of unknown primary (HNSCCUP) using a novel methodology to maximise the likelihood of national adoption. Methods A voluntary steering committee oversaw 3 phases of development: 1) clarification of topic areas, data collection and assimilation, including systematic reviews and a National Audit of Practice; 2) a National Consensus Day, presenting data from the above to generate candidate consensus statements for indicative voting by attendees; and 3) a National Delphi Exercise seeking agreement on the candidate consensus statements, including representatives from all 58 UK Head and Neck Multidisciplinary Teams (MDT). Methodology was published online in advance of the Consensus Day and Delphi exercise. Results Four topic areas were identified to frame guideline development. The National Consensus Day was attended by 227 participants (54 in-person and 173 virtual). Results from 7 new systematic reviews were presented, alongside 7 expert stakeholder presentations and interim data from the National Audit and from relevant ongoing Clinical Trials. This resulted in the generation of 35 statements for indicative voting by attendees which, following steering committee ratification, led to 30 statements entering the National Delphi exercise. After 3 rounds (with a further statement added after round 1), 27 statements had reached ‘strong agreement’ (n = 25, 2, 0 for each round, respectively), a single statement achieved ‘agreement’ only (round 3), and ‘no agreement’ could be reached for 3 statements (response rate 98% for each round). Subsequently, 28 statements were adopted into the National MDT Guidelines for HNSCCUP. Conclusions The described methodology demonstrated an effective multi-phase strategy for the development of national practice recommendations. It may serve as a cost-effective model for future guideline development for controversial or rare conditions where there is a paucity of available evidence or where there is significant variability in management practices across a healthcare service.

This article discusses the challenges in managing head neck squamous cell cancer from an unknown primary (HSCCUP) due to a lack of contemporary evidence and evolving understanding of the role of human papillomavirus (HPV) in head and neck cancer. Despite these limitations, various organizations have produced guidelines for managing HSCCUP using different methodologies. The article presents the results of a consensus process involving multiple stakeholders and centers, which led to the publication of consensus statements in the United Kingdom National Multidisciplinary Guidelines. The authors of the document, Vinidh Paleri, John Hardman, Tom Roques, and Ben O'Leary, made significant contributions to the work and have no conflicts of interest to report. The peer review history of the article is available for further reference. [Extracted from the article]

The observing system design of multidisciplinary field measurements involves a variety of considerations on logistics, safety, and science objectives. Typically, this is done based on investigator intuition and designs of prior field measurements. However, there is potential for considerable increases in efficiency, safety, and scientific success by integrating numerical simulations in the design process. Here, we present a novel numerical simulation–environmental response function (NS–ERF) approach to observing system simulation experiments that aids surface–atmosphere synthesis at the interface of mesoscale and microscale meteorology. In a case study we demonstrate application of the NS–ERF approach to optimize the Chequamegon Heterogeneous Ecosystem Energy-balance Study Enabled by a High-density Extensive Array of Detectors 2019 (CHEESEHEAD19). During CHEESEHEAD19 pre-field simulation experiments, we considered the placement of 20 eddy covariance flux towers, operations for 72 h of low-altitude flux aircraft measurements, and integration of various remote sensing data products. A 2 h high-resolution large eddy simulation created a cloud-free virtual atmosphere for surface and meteorological conditions characteristic of the field campaign domain and period. To explore two specific design hypotheses we super-sampled this virtual atmosphere as observed by 13 different yet simultaneous observing system designs consisting of virtual ground, airborne, and satellite observations. We then analyzed these virtual observations through ERFs to yield an optimal aircraft flight strategy for augmenting a stratified random flux tower network in combination with satellite retrievals. We demonstrate how the novel NS–ERF approach doubled CHEESEHEAD19's potential to explore energy balance closure and spatial patterning science objectives while substantially simplifying logistics. Owing to its modular extensibility, NS–ERF lends itself to optimizing observing system designs also for natural climate solutions, emission inventory validation, urban air quality, industry leak detection, and multi-species applications, among other use cases.

The paper examines how Hindu nationalist social service organizations, specifically the Deseeya Seva Bharathi (DSB), reconfigured the religious conception of ‘Seva’ to advance the project of constructing a Hindu social identity during the COVID-19 pandemic in the state of Kerala. The southern Indian state of Kerala has remained an exception in the story of the rise of the Hindu nationalist movement in contemporary India, which has repeatedly failed to make any considerable political inroads in the state. However, the disastrous economic consequences and livelihood challenges during the COVID-19 pandemic in the state, which was heavily dependent on foreign remittance and service industries, have opened up new spaces of engagement for Hindu nationalists. Drawing on the fieldwork conducted in central Kerala during the pandemic, this paper will elaborate on how the DSB used the crisis moment of the pandemic to reach out to economically and socially disadvantaged communities using the language of ‘Seva’ to build a Hindu social identity, which imbues the influence of majoritarian Hindu nationalist politics. The paper argues that the DSB’s articulation of ‘Seva’ as a distinct and superior form of social service that is ‘self-less’, ‘non-instrumental’ and ‘non-reciprocal’ is significant in understanding the growing appeal of Hindu nationalist social service in the contested political sphere of Kerala, which is marked by competing social provisions by the state as well as other secular and religious groups. The paper notes that the reconfiguration of ‘Seva’ as a continuous religious concept enables Hindu nationalists to attain greater acceptance and legitimacy that even the secular state welfare could not achieve, while also concealing the inherent instrumental nature of its social service towards the construction of a Hindu social identity in the region.

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Introduction: Evolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient. Method: The review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms. Results: There were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings. Discussion: Symptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of different carbonaceous fillers, carbon black (CB) biocarbon (BC), and a hybrid filler of both (BC-CB), in a natural rubber matrix. It was found that the addition of hybrid filler based on a sustainable biocarbon (BC) and carbon black (CB) revealed a significant effect on reducing the rolling resistance properties. Dried distillers’ grain with solubles (DDGS), a co-product from corn ethanol industry pyrolyzed at 900 °C, was used to produce the biocarbon. As compared to the carbon black, the particle size of the biocarbon was larger which was reflected in the tensile strength of the biocarbon composites. This observation was correlated using swelling studies and found to be proportional to their crosslink density. The thermal characterizations showed similar transitions and degradation mechanisms in all the composites, which confirmed a comparatively similar behavior of BC with CB. Moreover, these findings justify further tuning of biocarbon into nanosize and this could expand the scope in the utilization of this sustainable filler for the fabrication of various rubber products such as tires and hoses, etc.

Land surface utilization in the Indian subcontinent has undergone dramatic transformations over the years, altering the region’s surface energy flux partitioning. The resulting changes in moisture availability and atmospheric stability can be critical in determining the season’s monsoon rainfall. This study uses fully coupled global climate model simulations with idealized land cover to elucidate the consequences of land surface alterations. We find that an increase in forest cover, in general, increases precipitation in India. However, precipitation is not a linear function of forest-covered-area due to the spatially heterogeneous nature of the impact. A fully forest-covered India receives less precipitation than when the forest covers only the eastern side of India, occupying just about half the area. This signifies the importance of the east-west gradient in vegetation cover observed over India. Using an energy balance model, we diagnose that the diverse nature of this precipitation response results from three different pathways: evaporation from the surface, the net energy input into the atmosphere, and moist stability. Evaporation exhibits a linear relationship with forest-covered-area and reveals minimal spatial heterogeneity. On the contrary, the influence through the other two pathways is found to be region specific. Rainfall modulation via changes in net energy input is dominant in the head Bay of Bengal region, which is susceptible to convective systems. Whereas impact through stability changes is particularly significant south of 20 ^∘ N. In addition, we find that moisture advection modulates the significance of these pathways over northwest India. Thus, the impact of land cover changes act via three effective mechanisms and are region dependent. The findings in this study have broader ramifications since the dominant region-specific mechanisms identified are expected to be valid for other forcings and are not just limited to the scenarios considered here.