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Author(s): Margalit, Danielle N; Sacco, Assuntina G; Cooper, Jay S; Ridge, John A; Bakst, Richard L; Beadle, Beth M; Beitler, Jonathan J; Chang, Steven S; Chen, Allen M; Galloway, Tom J; Koyfman, Shlomo A; Mita, Carol; Robbins, Jared R; Tsai, C Jillian; Truong, Minh T; Yom, Sue S; Siddiqui, Farzan | Abstract: BackgroundThe aims of this systematic review are to (a) evaluate the current literature on the impact of postoperative therapy for resected squamous cell carcinoma of the head and neck (SCCHN) on oncologic and non-oncologic outcomes and (b) identify the optimal evidence-based postoperative therapy recommendations for commonly encountered clinical scenarios.MethodsAn analysis of the medical literature from peer-reviewed journals was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Prospective studies and methodology-based systematic reviews and meta-analyses of postoperative therapy for SCCHN were identified by searching Medline (OVID) and EMBASE (Elsevier) using controlled vocabulary terms (ie, National Library of Medicine Medical Subject Headings [MeSH], EMTREE). Study screening and selection was performed with Covidence software and full-text review. The RAND/UCLA appropriateness method was used by the expert panel to rate the appropriate use of postoperative therapy, and the modified Delphi method was used to come to consensus.ResultsA total of 5660 studies were identified and screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 101 studies from 1977 to 2020 were identified, including 77 with oncologic endpoints and 24 with function and quality of life endpoints. All studies reported staging prior to the implementation of American Joint Committee on Cancer (AJCC-8).ConclusionsProspective clinical studies and systematic reviews identified through the PRISMA systematic review provided good evidence for consensus statements regarding the appropriate use of postoperative therapy for resected SCCHN. Further research is needed in domains where consensus by the expert panel could not be achieved for the appropriateness of specific postoperative therapeutic interventions.

Objective Eating disorders (EDs) compromise the health and functioning of affected individuals, but it can often take them several years to acknowledge their illness and seek treatment. Early identification of individuals with EDs is a public health priority, and innovative approaches are needed for such identification and ultimate linkage with evidence-based interventions. This study examined whether Internet activity data can predict ED risk/diagnostic status, potentially informing timely interventions. Method Participants were 936 women who completed a clinically validated online survey for EDs, and 231 of them (24.7%) contributed their Internet browsing history. A machine learning algorithm used key attributes from participants' Internet activity histories to predict their ED status: clinical/subclinical ED, high risk for an ED, or no ED. Results The algorithm reached an accuracy of 52.6% in predicting ED risk/diagnostic status, compared to random decision accuracy of 38.1%, a relative improvement of 38%. The most predictive Internet search history variables were the following: use of keywords related to ED symptoms and websites promoting ED content, participant age, median browsing events per day, and fraction of daily activity at noon. Discussion ED risk or clinical status can be predicted via machine learning with moderate accuracy using Internet activity variables. This model, if replicated in larger samples where it demonstrates stronger predictive value, could identify populations where further assessment is merited. Future iterations could also inform tailored digital interventions, timed to be provided when target online behaviors occur, thereby potentially improving the well-being of many individuals who may otherwise remain undetected.

Background Xerostomia is one of the most common long-term adverse effects of radiotherapy for head and neck cancer patients. Contralateral submandibular gland transfer (SMG-T) before radiotherapy was shown to reduce xerostomia compared to pilocarpine. We sought to evaluate a modification of this surgery preserving the ipsilateral facial artery and vein to simplify the SMG-T. Methods Eighteen patients planned for head and neck intensity modulated radiotherapy to both necks were reviewed. Surgical complications were recorded. The grade of xerostomia was assessed after treatment completion. Results There were no minor or major complications resulting from the modified SMG-T. At 24.5-months follow up, the incidence of post-treatment moderate to severe xerostomia was 16.7%. No locoregional recurrence occurred. Only one patient had distant solitary lung metastasis. Conclusion The modified SMG-T technique is a practical and effective method to reduce the dose of radiation to the contralateral SMG and limit post-treatment xerostomia.

Background Radiotherapy (RT), the main treatment for patients with head and neck cancer, can lead to dental complications. Methods We identified 244 patients with squamous cell carcinoma of the tonsil treated with RT from 2004 to 2013. For each patient, we contoured the 10 tooth-bearing regions and calculated the radiation dose (gray, Gy) to each region. From this data set, we built two predictive models to determine the expected maximum radiation dose, one for the non-molar regions and another for the molar regions. Results For the non-molars, the final model included location, T-classification, and overall stage, with a median absolute prediction error of 7.0 Gy. For the molars, the final model included location, T-classification, overall stage, and treatment year, with a median absolute error of 6.0 Gy. Conclusions Our current model offers a good estimation of the maximum radiation dose delivered to different regions of the jaw; future work will independently validate these models.

BACKGROUND Head and neck squamous cell carcinoma of unknown primary site (HNSCCUP) is a diagnostic challenge. Identification of an ultraviolet (UV) light-related DNA damage signature using next-generation sequencing (NGS) can classify the primary site of origin as cutaneous. METHODS A 62-year-old male was seen with 2 months of left neck swelling. He was a lifetime nonsmoker but had a history of cutaneous squamous cell carcinoma (SCC) of the left helix. He was also found to have left hilar adenopathy. He had a p16-negative HNSCCUP on fine needle aspiration (FNA) biopsy of the left neck. RESULTS NGS of the FNA specimen revealed a high number of somatic mutations that were mostly C to T transitions, indicating a UV mutation signature and confirming the diagnosis of cutaneous SCC. CONCLUSIONS Identification of a UV DNA damage signature with NGS distinguishes HNSCCUP of cutaneous vs mucosal or other squamous cell carcinoma origin.

This is the peer reviewed version of the following article: Leon, Yom-Tov, Johnson, Petticrew, Williamson, Lampos, Cox. What on-line searches tell us about public interest and potential impact on behaviour in response to minimum unit pricing of alcohol in Scotland. Addiction. 2021;116(8):2008-2015, which has been published in final form at https://doi.org/10.1111/add.15388. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Aims - To investigate whether the introduction of minimum unit pricing (MUP) in Scotland on 1 May 2018 was reflected in changes in the likelihood of alcohol-related queries submitted to an internet search engine, and in particular whether there was any evidence of increased interest in purchasing of alcohol from outside Scotland. Design - Observational study in which individual queries to the internet Bing search engine for 2018 in Scotland and England were captured and analysed. Fluctuations over time in the likelihood of specific topic searches were examined. The patterns seen in Scotland were contrasted with those in England. Setting - Scotland and England. Participants - People who used the Bing search engine during 2018. Measurements - Numbers of daily queries submitted to Bing in 2018 on eight alcohol-related topics expressed as a proportion of queries on that day on any topic. These daily likelihoods were smoothed using a 14-day moving average for Scotland and England separately. Findings - There were substantial peaks in queries about MUP itself, cheap sources of alcohol and online alcohol outlets at the time of introduction of MUP in May 2018 in Scotland, but not England. These were relatively short-lived. Queries related to intoxication and alcohol problems did not show a MUP peak, but were appreciably higher in Scotland than in England throughout 2018. Conclusions - Analysis of internet search engine queries appears to show that a fraction of people in Scotland may have considered circumventing minimum unit pricing in 2018 by looking for on-line alcohol retailers. The overall higher levels of queries related to alcohol problems in Scotland compared with England mirrors the corresponding differences in alcohol consumption and harms between the countries.

OBJECTIVES/HYPOTHESIS Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P

Pseudomonas aeruginosa uses its type III secretion system to inject the effector proteins ExoS and ExoU into eukaryotic cells, which subverts these cells to the bacterium's advantage and contributes to severe infections. We studied the environmental reservoirs of exoS+ and exoU+ strains of P. aeruginosa by collecting water, soil, moist substrates and plant samples from environments in the Chicago region and neighbouring states. Whole-genome sequencing was used to determine the phylogeny and type III secretion system genotypes of 120 environmental isolates. No correlation existed between geographic separation of isolates and their genetic relatedness, which confirmed previous findings of both high genetic diversity within a single site and the widespread distribution of P. aeruginosa clonal complexes. After excluding clonal isolates cultured from the same samples, 74 exoS+ isolates and 16 exoU+ isolates remained. Of the exoS+ isolates, 41 (55%) were from natural environmental sites and 33 (45%) were from man-made sites. Of the exoU+ isolates, only 3 (19%) were from natural environmental sites and 13 (81%) were from man-made sites (p < 0.05). These findings suggest that man-made water systems may be a reservoir from which patients acquire exoU+ P. aeruginosa strains.

Background The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. Methods In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. Results The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. Conclusion In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

OBJECTIVE To quantify the rate of late intracranial recurrences among esthesioneuroblastoma patients treated with surgical resection and postoperative radiation. STUDY DESIGN Retrospective review. METHODS All patients receiving definitive-intent therapy for esthesioneuroblastoma between March 1995 and September 2015 were reviewed. Presenting disease extent was categorized based on radiologic, operative, and pathologic findings. Between-group survival differences were assessed using Kaplan-Meier method and log-rank test. Multivariate analyses were performed using Cox proportional hazards model. RESULTS Of 38 patients initially treated at our institution, 53% (20 of 38) presented with intracranial extension. At a median follow-up of 90 months (range, 6-199), 37% (14 of 38) recurred; 5- and 8-year disease-free survival rates were 69% and 54%; and overall survival rates were 81% and 72%, respectively. Among these patients, the dura was the most commonly involved site of relapse (8), followed by local (6), regional (5), and distant extracranial (3) sites; and five patients had ≥ two categories of failure. Eight-year dural disease-free survival was 57% versus 90% (P = 0.017) and 0% versus 87% (P

We studied the eff ect of the two environmental indices, the sub-polar gyre (SPG), and winter and summer North Atlantic Oscillation (NAO), together with mean annual winter and summer temperatures and geographic location on mandible size and body mass of Arctic foxes in Iceland (6345 and 2732 specimens, respectively) during the year of their death. We predicted that when favorable conditions prevailed, large specimens would be selected for, and vice versa. Body size and body mass were signifi cantly aff ected by the environmental parameters (i.e. SPG, NAO, ambient temperature and cloud cover) prevailing during the year of death. Th e eff ect of environmental conditions on body size was much stronger in the less productive region of eastern Iceland, apparently because in areas where food availability is meager, even a small diff erence in climate may tilt the balance from food suffi ciency to food shortage. Western Iceland comprises only a quarter of the total surface area of the country, but its productive seashores are twice as long as those of all the rest of the country combined. It is interesting to note that the eff ect of the SPG, a marine phenomenon in the oceans surrounding Iceland, is refl ected in the condition of the foxes more than the other climatic variables we used in this study, which are largely land-related. Because Arctic foxes in Iceland feed largely on marine birds and invertebrates, the SPG seems to encompass more accurate information regarding the direct ocean forces that aff ect food availability to the foxes.

Background Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN). This is the largest multi-institutional study to date investigating the effect of immune status on disease outcomes in patients with cSCC-HN who underwent surgery and received postoperative radiation therapy (RT). Methods Patients from 3 institutions who underwent surgery and also received postoperative RT for primary or recurrent, stage I through IV cSCC-HN between 1995 and 2015 were included in this institutional review board-approved study. Patients categorized as immunosuppressed had chronic hematologic malignancy, human immunodeficiency/acquired immunodeficiency syndrome, or had received immunosuppressive therapy for organ transplantation ≥6 months before diagnosis. Overall survival, locoregional recurrence-free survival, and progression-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazards regression. Results Of 205 patients, 138 (67.3%) were immunocompetent, and 67 (32.7%) were immunosuppressed. Locoregional recurrence-free survival (47.3% vs 86.1%; P Conclusions Immunosuppressed patients with cSCC-HN had dramatically lower outcomes compared with immunocompetent patients, despite receiving bimodality therapy. Immune status is a strong prognostic factor that should be accounted for in prognostic systems, treatment algorithms, and clinical trial design. Cancer 2017;123:2054-2060. © 2017 American Cancer Society.

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017.

Background There are no level I studies to guide treatment for resectable oropharyngeal squamous cell carcinoma (SCC). Treatment toxicities influence management recommendations. Ongoing investigations are examining deintensified treatments for human papillomavirus (HPV)-associated oropharyngeal SCC. Methods The Appropriateness Criteria panel, using modified Delphi methodology, produced a literature summary, an assessment of treatment recommendations, and cases to illustrate their use. Results A multidisciplinary team produces optimum results. Based on HPV status, smoking history, and staging, patients are divided into groups at low, intermediate, and high-risk of death. In the future, treatment recommendations may be influenced by HPV status, which has changed the epidemiology of oropharyngeal SCC. Conclusion T1 to T2N0M0 resectable oropharyngeal SCC can be treated with surgery or radiation without chemotherapy. Patients with T1-2N1-2aM0 disease can receive radiation, chemoradiation, or transoral surgery with neck dissection and appropriate adjuvant therapy. Patients with T1-2N2b-3M0 disease should receive chemoradiation or transoral surgery with neck dissection and appropriate adjuvant therapy. Concurrent chemoradiation is preferred for T3 to T4 disease. © 2016 American College of Radiology. Head Neck, 2016

Aims To examine the individual determinants that influence satisfaction with medical services at the emergency department and to compare the factors that influence satisfaction for the patients, compared with their companions. Methods Using data from the 2009 Korea Health Panel Survey, Andersen's behavioral model was used to examine the factors that affect satisfaction with service. A logistic regression analysis was conducted with the data. Results Patients who were older, female, and employed were more satisfied with the service, as were patients who visited more frequently and those who had non-surgical treatment. Companions who had less education, were accompanying non-Medicaid-holders, and spent a longer time in the emergency department were less likely to be satisfied. This was in contrast to those who spent a shorter amount of time in the emergency department and who visited due to illness, rather than injury; these companions were more satisfied with the service. When all the factors were analyzed simultaneously, they differed significantly between the two groups of patients and companions. Conclusions Different factors contributed to the satisfaction with the services for the patients and their companions. In order to increase the satisfaction levels and improve the quality of care in emergency departments, it is necessary to consider more specific approaches that reflect the different perspectives of the visitors to the emergency department.

Background Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios. Methods The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma. Conclusion Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. © 2015 American College of Radiology Head Neck, 2015

Introduction Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC. Method We performed a retrospective review of WDTC patients treated with IMRT from 1998–2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded. Results Thirty patients had a median follow-up of 56 months (range = 1–139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0–116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region. Conclusions Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.

Background Aggressive nonmelanomatous skin cancer (NMSC) of the head and neck presents an increasingly common therapeutic challenge for which prospective clinical trials are lacking. Methods The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results The American College of Radiology Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for guiding management of aggressive NMSC. Conclusion Multidisciplinary assessment is vital to guiding the ideal use of surgery, radiation, and systemic therapy in this disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: 175–182, 2016

BACKGROUND HealthCorps provides school wellness programming using curricula to promote changes in nutrition, mental health, and physical activity behaviors. The research objective was to evaluate effects of implementing its curricula on nutrition, mental health, and physical activity knowledge and behavior. METHODS Pre- and postsurvey data were collected (N = 2255) during the 2012–2013 academic year from 14 New York City public high schools. An 18-item knowledge questionnaire addressed 3 domains; 26 behavioral items were analyzed by factor analysis to identify 6 behavior domains, breakfast being a seventh 1-item domain. We examined the effects stratified by sex, applying mixed-effects models to take into account clustering effects of schools and participants adjusted for age. RESULTS The HealthCorps program significantly increased all 3 knowledge domains (p < .05), and significantly changed several key behavioral domains. Boys significantly increased fruits/vegetables intake (p = .03). Girls increased acceptance of new fruits/vegetables (p = .03) and breakfast consumption (p = .04), and decreased sugar-sweetened beverages and energy dense food intake (p = .03). The associations between knowledge and behavior were stronger in boys than girls. CONCLUSION The HealthCorps program significantly increased participants' knowledge on nutrition, mental health, and physical activity. It also improved several key behavioral domains, which are targets of the 2010 Dietary Guidelines to address obesity in youth.