Precision in Thermal Therapy: Clinical Requirements and Solutions from Nanotechnology

The heating of diseased tissue as a therapeutic measure has gained increased clinical attention, mostly due to its target‐specificity that minimizes side effects. However, to ensure a successful therapy, heating has to be homogeneous and highly localized, as well as, within a certain temperature range. Therefore, precise control over thermal treatments is a clinical prerequisite to minimize treatment and safety margins. Although this requirement is mentioned frequently, past research has focused predominantly on improving thermometry resolution and heating efficiency through tedious material optimization. Here, current clinical applications of thermal therapy with their challenges are first highlighted, especially with respect to treatment control and margins. Thereafter, it is quantitatively shown that clinically available thermometry fulfills the requirements and future research should focus on achieving better temperature control instead. With nanotechnology, novel strategies based on self‐limiting nanoparticle systems and particle‐based thermometers with active feed‐back control have also become available and are discussed. All of these approaches are systematically compared and analyzed with respect to their clinical applicability. The extent to which control over thermal therapy is necessary is also discussed alongside a presentation of the existing methods which fulfill the set requirements for clinical success and what issues remain to be tackled by research in the near future.ISSN:2366-398

Differences in patient satisfaction with virtual telephone clinics in a tertiary referral centre for otolaryngology during and after lockdown measures during the SARS-Cov2 pandemic

Introduction: The SARS-Cov2 pandemic has caused considerable disruption to provision of routine outpatient care. This pandemic has necessitated a more modern and innovative approach to clinics, which could potentially change outpatient organisation and improve efficiency in the long term. Telephone clinics are the most practical way to deliver healthcare at a distance. Aim: The purpose of the present study was to assess patient satisfaction with a virtual telephone clinic in a tertiary referral centre for otolaryngology first during the height of the SARS-Cov2 pandemic, and subsequently at a physical follow-up appointment after easing of "lockdown" measures. Methods: Patients were enrolled prospectively via a telephone interview over a 1-week period during the height of the "lockdown" measures, and subsequently at a physical appointment when measures eased. Results: Overall, patients responded very positively in the anonymised questionnaire at the time of their virtual appointment. However, at a subsequent physical appointment, there was a reduction in overall favourable responses from patients. While patients still thought virtual clinics were a good idea and convenient in the context of SARS-Cov2, we noted a reduction in satisfaction in other key aspects of their care. Notably, patients were less likely to think that virtual clinics were able to properly address their condition. Conclusion: While virtual clinics remain a useful tool during the height of lockdown measures during the SARS-Cov2 pandemic, we did note a significant reduction in favourable responses to virtual appointments over physical ones upon easing of lockdown measures. Patients remained cautious in suggesting that outpatient appointments may be replaced by virtual clinics.</p

Mortality risk in post-operative head and neck cancer patients during the SARS-Cov2 pandemic: early experiences

Purpose: The objective of this report is to outline our early experience with head and neck cancer patients in a tertiary referral center, during the SARS-Cov2 pandemic, and to describe the poor outcomes of patients who acquired the infection. Methods: In this case series from a single-center, national tertiary referral center for head and neck cancer we describe three consecutive head and neck cancer patients who contracted SARS-Cov2 during their inpatient stay. Results: Of the three patients described in our case series that contracted SARS-Cov2, two patients died from SARS-Cov2 related illness. Conclusion: We have demonstrated the significant implications that SARS-Cov2 has on head and neck cancer patients, with 3 patients acquiring SARS-Cov2 in hospital, and 2 deaths in our that cohort. We propose a complete separation in the location of where these patients are being managed, and also dedicated non-SARS-Cov2 staff for their peri-operative management. Level of evidence: IV.</p

A Tri-Layered Hydrogel Scaffold for Vocal Fold Tissue Engineering

The lamina propria within the vocal fold (VF) is a complex multi-layered tissue that increases in stiffness from the superficial to deep layer, where this characteristic is crucial for VF sound production. Tissue engineered scaffolds designed for VF repair must mimic the biophysical nature of the native vocal fold and promote cell viability, cell spreading, and vibration with air flow. In this study, we present a unique tri-layered, partially-degradable hydrogel scaffold that mimics the multi-layered structure of the VF lamina propria. Using thiol-norbornene photochemistry, tri-layered hydrogel scaffolds were fabricated via layer-by-layer stacking with increasing polymer concentration from the top to middle to deep layer. Mechanical analysis confirmed hydrogel modulus increased with increasing polymer concentration. Partially-degradable hydrogels promoted high cell viability and cell spreading in 3D as assessed via live/dead and cytoskeleton staining, respectively. Importantly, partially-degradable hydrogels maintained some degree of the 3D polymer network following protease exposure, while still enabling encapsulated cells to remodel their local environment via protease secretion. Finally, the tri-layered hydrogel scaffold successfully vibrated and produced sound in proof-of-concept air flow studies. This work represents a critical first step towards the design of a multi-layered, hydrogel scaffold for vocal fold tissue engineering

Rate of occult neck nodal metastasis in primary and salvage laryngectomy

The role of neck dissection (ND) in advanced laryngeal cancer remains controversial. Cervical nodal metastases confer a worse prognosis with higher rates of local recurrence and reduced overall survival observed in this population. Elective ND for clinically node negative (N0) patients during laryngectomy has been associated with reduced rates of regional recurrence; however, the addition of this surgical intervention introduces risk of complications including accessory nerve injury, wound healing issues and infection. Select European society guidelines, such as the German guidelines for treatment of laryngeal cancer, recommend ipsilateral ND for lateralised laryngeal malignancy and bilateral ND for midline lesions, while guidelines in the United Kingdom and the National Comprehensive Cancer Network (NCCN) in the United States offer more broad recommendations encompassing numerous surgical options. In salvage laryngectomy, the role of N0 elective ND remains equally ambiguous. The overall rate of occult metastasis following salvage laryngectomy with ND has been reported as 3%–19%. Many studies pre-date the development of advanced radiological investigations and therapeutic techniques. Recent attempts at meta-analysis found only three papers suitable for inclusion in pooled analysis.</p

Pattern of nodal metastasis of cutaneous squamous cell carcinoma involving the temporal bone

Objective: The objective of this study was to explore the pattern of lymph-node spread of SCCs involving the temporal bone. Methods: We retrospectively reviewed all cutaneous SCCs involving the temporal bone over a 20-year time-period. Forty-one patients were eligible. Results: Mean age was 72.8 years. The diagnosis was cutaneous SCC in all cases. All patients underwent a temporal bone resection, 70.7% had a neck-dissection and 78.0% a parotidectomy. Level 2 was the most common area of neck metastasis, and occurred in 12.2%. The parotid had disease in 34.1%. 51.2% of patients underwent free-flap reconstruction. Mean overall survival of the cohort was 4.2 years. Conclusions: Overall, the rate of cervical nodal metastasis was 22.0% and 13.5% in the occult setting. The parotid was involved in 34.1% and 10.0% in the occult setting. Results from the present study support consideration for performing a parotidectomy at the time of temporal bone resection, while a neck dissection can be performed for adequate staging of the nodal basin. Level of Evidence: 3</p

The role of surgery for anaplastic thyroid carcinoma in the era of targeted therapeutics: a scoping review

Background Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant-targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) ( Conclusions There is no clear agreement in the literature regarding the limits of surgical resection in locoregionally advanced ATC. A definition of surgically resectable disease will be required to guide surgical decision making in ATC, particularly with the potential to reduce tumor burden using neoadjuvant targeted treatment in suitable patients.</p

The Relationship Between Different Measures of Oral Reading Fluency and Reading Comprehension in Second-Grade Students Who Evidence Different Oral Reading Fluency Difficulties

Purpose: The purpose of this study was to examine whether different measures of oral reading fluency relate differentially to reading comprehension performance in two samples of second-grade students: (a) students who evidenced difficulties with nonsense-word oral reading fluency, real-word oral reading fluency, and oral reading fluency of connected text (ORFD), and (b) students who evidenced difficulties only with oral reading fluency of connected text (CTD). Method: Participants (ORFD, n = 146 and CTD, n = 949) were second-grade students who were recruited for participation in different reading intervention studies. Data analyzed were from measures of nonsense-word oral reading fluency, real-word oral reading fluency, oral reading fluency of connected text, and reading comprehension that were collected at the pre-intervention time point. Results: Correlational and path analyses indicated that real-word oral reading fluency was the strongest predictor of reading comprehension performance in both samples and across average and poor reading comprehension abilities. Conclusion: Results of this study indicate that real-word oral reading fluency was the strongest predictor of reading comprehension and suggest that real-word oral reading fluency may be an efficient method for identifying potential reading comprehension difficulties. © American Speech-Language-Hearing Association

Theorizing the Westphalian system of states: international relations from absolutism to capitalism

This article provides a new approach, revolving around contested property relations, for theorizing the constitution, operation and transformation of geopolitical systems, exemplified with reference to early modern international relations. Against the cross-paradigmatic IR consensus that equates the Westphalian Settlement with the codification of modern international relations, the article shows to which degree 17th and 18th century European geopolitics remained tied to rather unique pre-modern practices. These cannot be understood on the basis of realist or constructivist premises. In contrast, the theoretical argument is that the proprietary and personalized character of dynastic sovereignty was predicated on pre-capitalist property relations. Dynasticism, in turn, translated into historically specific patterns of conflict and cooperation that were fundamentally governed by the competitive logic of geopolitical accumulation. The decisive break to international modernity comes with the rise of the first modern state — England. After the establishment of a capitalist agrarian property regime and the transformation of the English state in the 17th century, post-1688 Britain starts to restructure international relations in a long-term process of geopolitically combined and socially uneven development

Global variations in heart failure etiology, management, and outcomes

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper–middle-income, lower–middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper–middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower–middle-income countries (39.5%) (P &lt; .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper–middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower–middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper–middle-income countries (ratio = 2.4), similar in lower–middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper–middle-income countries (9.7%), then lower–middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower–middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally