Setting up a nurse-led 2-week-wait head and neck cancer diagnostic service.

The number of urgent '2-week-wait' referrals to hospital for people with suspected head and neck cancer being sent by primary care is constantly growing and it is becoming increasingly difficult for head and neck cancer services to meet this demand. In order for trusts to meet their Faster Diagnosis Standards, there needs to be an effective and efficient way to ensure there is capacity for patients to receive the appropriate assessments and diagnostic investigations without compromising the quality of care delivered. This article presents the proposal of introducing a nurse-led 2-week-wait clinic to meet the ever-growing demands on the service. There is discussion of the consultant-led training programme used to upskill an advanced nurse practitioner in a single-centre study, as well as explanation of the processes followed to maintain patient safety throughout the pilot project. There will also be consideration of clinical governance and discussion of how patient satisfaction with the novel service will be measured.

Structures and Spectroscopic Properties of Polysulfide Radical Anions: A Theoretical Perspective.

The potential involvement of polysulfide radical anions Sn•- is a recurring theme in discussions of the basic and applied chemistry of elemental sulfur. However, while the spectroscopic features for n = 2 and 3 are well-established, information on the structures and optical characteristics of the larger congeners (n = 4-8) is sparse. To aid identification of these ephemeral species we have performed PCM-corrected DFT calculations to establish the preferred geometries for Sn•- (n = 4-8) in the polar media in which they are typically generated. TD-DFT calculations were then used to determine the number, nature and energies of the electronic excitations possible for these species. Numerical reliability of the approach was tested by comparison of the predicted and experimental excitation energies found for S2•- and S3•-. The low-energy (near-IR) transitions found for the two acyclic isomers of S4•- (C2h and C2v symmetry) and for S5•- (Cs symmetry) can be understood by extension of the simple HMO π-only chain model that serves for S2•- and S3•-. By contrast, the excitations predicted for the quasi-cyclic structures Sn•- (n = 6-8) are better described in terms of σ → σ* processes within a localized 2c-3e manifold.

The impact of 2 weeks wait referral on survival of head and neck cancer patients.

PURPOSE: This study aims to evaluate the association between 2 weeks wait referral and survival in the head and neck cancer. METHODS: Retrospective cohort study of consecutively discussed new head and neck cancer patients at large United Kingdom Cancer Alliance including two tertiary referral hospitals and two district general hospital. RESULTS: A total of 276 cancer patients were included for analysis. Patients referred under the 2 weeks wait had were seen and diagnosed sooner from referral (p < 0.0001 and p < 0.0001 respectively). However, this did not translate into better survival outcomes. No survival differences were seen between those patients that were managed within the proposed cancer targets and those that were not. CONCLUSIONS: The 2 weeks wait head and neck cancer pathway did not offer a survival advantage. Targeting the delay in referral as well as delay in treatment to prevent late-stage cancer presentation is paramount. Fulfilment of cancer time targets do not translate into better outcomes and should not be prioritised to clinical judgement.

Water soluble swallow for leak detection after total laryngectomy post radiotherapy.

AIM: Pharyngeal leak (PL) and pharyngocutaneous fistula (PCF) are serious complications following total laryngectomy and their incidence is higher in the salvage setting. The aim of this study is to describe the accuracy of water soluble swallow (WSS) to rule out salivary postoperative leak after salvage total laryngectomy (STL) to expedite start of oral intake. MATERIAL AND METHODS: Retrospective study including patients undergoing STL between 2008 and 2021 at Guy's Hospital. WSS was routinely performed within 15 days post operation. RESULTS: Sixty-six patients underwent STL. Nine developed clinically diagnosed PCF; one died before having WSS. Fifty-six patients underwent WSS post STL. WSS was performed within 15 days after STL when no postoperative complications occurred (76.8%). Among patients undergoing WSS with no clinical suspicion for fistula (56), PL was identified in 15 cases (26.8%). They were managed conservatively; PCF was avoided in 7(46.7%) cases. Three patients (7.3%) developed PCF after having started oral intake with a negative WSS. These three cases were further analysed, 2 cases where recorded at the beginning of the studied period when less experience was available possibly leading to incorrect results. Sensitivity and negative predictive value (NPV) for fistula prediction were 72.7% and 92.7%, respectively. CONCLUSION: Taking into account the high NPV of WSS, it is safe to start oral intake after negative WSS. Further studies to evaluate its accuracy earlier on after SLT are justified taking into account the results and the impact that delayed feeding has on patient's quality of life.

Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.

Association between delays to patient admission from the emergency department and all-cause 30-day mortality.

BACKGROUND: Delays to timely admission from emergency departments (EDs) are known to harm patients. OBJECTIVE: To assess and quantify the increased risk of death resulting from delays to inpatient admission from EDs, using Hospital Episode Statistics and Office of National Statistics data in England. METHODS: A cross-sectional, retrospective observational study was carried out of patients admitted from every type 1 (major) ED in England between April 2016 and March 2018. The primary outcome was death from all causes within 30 days of admission. Observed mortality was compared with expected mortality, as calculated using a logistic regression model to adjust for sex, age, deprivation, comorbidities, hour of day, month, previous ED attendances/emergency admissions and crowding in the department at the time of the attendance. RESULTS: Between April 2016 and March 2018, 26 738 514 people attended an ED, with 7 472 480 patients admitted relating to 5 249 891 individual patients, who constituted the study's dataset. A total of 433 962 deaths occurred within 30 days. The overall crude 30-day mortality rate was 8.71% (95% CI 8.69% to 8.74%). A statistically significant linear increase in mortality was found from 5 hours after time of arrival at the ED up to 12 hours (when accurate data collection ceased) (p<0.001). The greatest change in the 30-day standardised mortality ratio was an 8% increase, occurring in the patient cohort that waited in the ED for more than 6 to 8 hours from the time of arrival. CONCLUSIONS: Delays to hospital inpatient admission for patients in excess of 5 hours from time of arrival at the ED are associated with an increase in all-cause 30-day mortality. Between 5 and 12 hours, delays cause a predictable dose-response effect. For every 82 admitted patients whose time to inpatient bed transfer is delayed beyond 6 to 8 hours from time of arrival at the ED, there is one extra death.

Commentary: Global Alzheimer's disease and Alzheimer's disease related dementia research funding organizations support and engage the research community throughout the COVID-19 pandemic.

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Role of Thyroidectomy in Recurrent Laryngeal Carcinoma.

OBJECTIVE: Management of recurrent laryngeal cancer presents a major challenge, and salvage laryngectomy is complicated by previous oncologic treatments. Thyroidectomy as part of salvage laryngectomy adds a nonnegligible degree of morbidity. The purpose of this study is to assess the rate of thyroid gland invasion in patients undergoing salvage laryngectomy to determine relevant predictive factors. STUDY DESIGN: Case series with chart review. SETTING: Department of Otorhinolaryngology, Head and Neck Surgery, Guy's Hospital, London, United Kingdom. METHODS: A retrospective review of patients undergoing salvage laryngectomy between 2009 and 2019 was undertaken. Preoperative cross-sectional imaging and histopathological analysis were performed to define evidence and predictors of thyroid gland invasion (TGI). RESULTS: Fifty-one patients had salvage laryngectomy. Histological evidence of TGI was found in 4 patients (7.8%). No significant relationship was found between histological TGI and subsite of primary carcinoma, degree of differentiation, T staging, or radiological TGI. Preoperative computed tomography had a high negative predictive value for TGI. CONCLUSION: Thyroidectomy should be carefully considered in patients undergoing salvage laryngectomy, and its extent should be defined on an individual basis. Total thyroidectomy should not routinely be performed in salvage laryngectomy or pharyngolaryngectomy in patients with no preoperative radiological evidence of TGI on cross-sectional imaging, unless there is intraoperative evidence of TGI.

Low temperature insights into the crystal and magnetic structure of a neutral radical ferromagnet.

The crystal structure of the radical ferromagnet 1a at 2 K reveals a contraction in the unit cell c constant which, at the molecular level, translates into a decrease in slippage of the radical π-stacks and an increase in ferromagnetic exchange interactions along the stacking axis. The results of BS-DFT calculations using long-range corrected functionals are consistent with an overall ferromagnetic topology.

Risk stratified follow up for head and neck cancer patients - An evidence based proposal.

Head and neck squamous cell carcinoma (HNSCC) has a significant impact on patients' quality of life and treatment can be associated with severe morbidity. Following completion of treatment, patients are followed up in order to detect potentially salvageable recurrences and to manage long-term toxicities. In recent years, a growing interest has been given to risk stratified follow-up interventions to prevent and detect recurrences and manage treatment toxicities in other tumour sites as well as to transfer some of that care to community services. We review the literature for HNSCC and propose a risk stratified follow up protocol to address these issues and assist clinicians in decision making. A shift in patterns of care is suggested in order to provide a basis to improve care for HNSCC patients after complete response to primary treatment.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Perioperative management of cranial diabetes insipidus in a patient requiring a tracheostomy.

Cranial diabetes insipidus (DI), which can cause life-threatening dehydration, is treated with desmopressin, often intranasally. This is challenging in patients whose nasal airflow is altered, such as those requiring tracheostomy. We report the case of a patient, taking intranasal desmopressin for cranial DI, who underwent partial glossectomy, free-flap reconstruction and tracheostomy. Postoperatively, she could not administer nasal desmopressin due to reduced nasal airflow. She developed uncontrollable thirst, polyuria and hypernatraemia. Symptoms were relieved by switching to an enteric formulation. A literature review showed no cases of patients with DI encountering difficulties following tracheostomy. The Royal Society of Endocrinology recommends perioperative planning for such patients, but gives no specific guidance on medication delivery in the context of altered airway anatomy. Careful perioperative planning is required for head and neck patients with DI, particularly for those undergoing airway alteration that may necessitate a change in the mode of delivery of critical medications.

Regulatory and Safety Considerations in Deploying a Locally Fabricated, Reusable Face Shield in a Hospital Responding to the COVID-19 Pandemic.

BACKGROUND: Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of products such as protective face shields. No clear path exists, however, for introducing a locally fabricated product into a clinical setting. METHODS: We describe a research protocol under Institutional Review Board supervision that allowed clinicians to participate in an iterative design process followed by real-world testing in an emergency department. All designs, materials used, testing protocols, and survey results are reported in full to facilitate similar efforts in other clinical settings. FINDINGS: Clinical testing allowed the incident command team at a major academic medical center to introduce the locally fabricated face shield into general use in a rapid but well-controlled manner. Unlike standard hospital face shields, the locally fabricated design was intended to be reusable. We discuss the design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of personal protective equipment, such as face shields. CONCLUSIONS: Our work serves as a case study for robust, local responses to pandemic-related disruption of medical supply chains with implications for health care professionals, hospital administrators, regulatory agencies, and concerned citizens in the COVID-19 and future health care emergencies. FUNDING: : This work was supported by the Harvard MIT Center for Regulatory Sciences, NIH/NCI grants U54-CA225088 and T32-GM007753, and the Harvard Ludwig Center. M.-J.A. is a Friends of McGovern Graduate Fellow.

Rapid prototyping and clinical testing of a reusable face shield for health care workers responding to the COVID-19 pandemic.

Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be adopted by the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.

Radical Dimerization in a Plastic Organic Crystal Leads to Structural and Magnetic Bistability with Wide Thermal Hysteresis.

The nitroxyl radical 1-methyl-2-azaadamantane N-oxyl (Me-AZADO) exhibits magnetic bistability arising from a radical/dimer interconversion. The transition from the rotationally disordered paramagnetic plastic crystal, Me-AZADO, to the ordered diamagnetic crystalline phase, (Me-AZADO)2, has been conclusively demonstrated by crystal structure determination from high-resolution powder diffraction data and by solid-state NMR spectroscopy. The phase change is characterized by a wide thermal hysteresis with high sensitivity to even small applied pressures. The molecular dynamics of the phase transition from the plastic crystal to the conventional crystalline phase has been tracked by solid-state (1H and 13C) NMR and EPR spectroscopies.

The Importance of Electronic Dimensionality in Multiorbital Radical Conductors.

The exceptional performance of oxobenzene-bridged bis-1,2,3-dithiazolyls 6 as single-component neutral radical conductors arises from the presence of a low-lying π-lowest unoccupied molecular orbital, which reduces the potential barrier to charge transport and increases the kinetic stabilization energy of the metallic state. As part of ongoing efforts to modify the solid-state structures and transport properties of these so-called multiorbital materials, we report the preparation and characterization of the acetoxy, methoxy, and thiomethyl derivatives 6 (R = OAc, OMe, SMe). The crystal structures are based on ribbonlike arrays of radicals laced together by S···N' and S···O' secondary bonding interactions. The steric and electronic effects of the exocyclic ligands varies, affording one-dimensional (1D) π-stacked radicals for R = OAc, 1D cofacial dimer π-stacks for R = SMe, and a pseudo two-dimensional (2D) brick-wall arrangement for R = OMe. Variable-temperature magnetic and conductivity measurements reveal strong antiferromagnetic interactions and Mott insulating behavior for the two radical-based structures (R = OAc, OMe), with lower room-temperature conductivities (σRT ≈ 1 × 10-4 and ∼1 × 10-3 S cm-1, respectively) and higher thermal activation energies ( Eact = 0.24 and 0.21 eV, respectively) than found for the ideal 2D brick-wall structure of 6 (R = F), where σRT ≈ 1 × 10-2 S cm-1 and Eact = 0.10 eV. The performance of R = OMe, OAc relative to that of R = F, is consistent with the results of density functional theory band electronic structure calculations, which indicate a lower kinetic stabilization energy of the putative metallic state arising from their reduced electronic dimensionality.

Pancakes under Pressure: A Case Study on Isostructural Dithia- and Diselenadiazolyl Radical Dimers.

The isostructural dimers of the 1,4-phenylene-bridged bis-1,2,3,5-dithia- and bis-1,2,3,5-diselenadiazolyl diradicals 1,4-S/Se are small band gap semiconductors. The response of their molecular and solid state electronic structures to pressure has been explored over the range 0-10 GPa. The crystal structures, which consist of cofacially aligned (pancake) π-dimers packed into herringbone arrays, experience a continuous, near-isotropic compression. While the intramolecular covalent E-E (E = S/Se) bonds remain relatively unchanged with pressurization, the intradimer E···E separations are significantly shortened. Molecular and band electronic structure calculations using density functional theory methods indicate that compression of the π-dimers leads to a widening of the gap Δ E between the highest occupied and lowest unoccupied molecular orbitals of the dimer, an effect that offsets the expected decrease in the valence-to-conduction band gap Eg occasioned by pressure-induced spreading of the valence and conduction bands. Consistent with the predicted consequences of this competition between intra- and interdimer interactions, variable temperature high pressure conductivity measurements reveal at best an order-of-magnitude increase in conductivity with pressure for the two compounds over the pressure range 0-10 GPa. While a small reduction in the thermal activation energy Eact with increasing pressure is observed, extrapolation of the rate of decrease suggests a projected onset of metallization ( Eact ≈ 0) in excess of 20 GPa.

Outcomes of salvage surgery for the oropharynx and larynx: a contemporary experience in a UK Cancer Centre.

INTRODUCTION: The purpose of this study was to review our recent experience of salvage surgery, comparing larynx and oropharynx recurrence patterns. METHODS: A single centre, retrospective review of salvage surgery for recurrent head and neck cancer including patients between 2008 and 2016. RESULTS: 61 patients were identified, 36 underwent salvage laryngectomy and 25 received oropharyngeal resections. The median overall survival of oropharyngeal recurrent tumors was 26 months (95% CI 15-118 months) and for laryngeal tumors was 23 months (95% CI 11-38 months), p = 0.1008. There was a significant overall survival benefit in patients with negative resection margin. The median survival in the negative margin group was 38 months (95% CI 25-108 months) compared to the positive margin group, 9 months (95% CI 5-15 months), p < 0.0001. CONCLUSION: Survival results following surgical salvage in the larynx and oropharynx appear to be similarly poor. Those patients with clear margins appear to have a significantly better prognosis.