Endoscopic-assisted transorbital extended orbital exenteration: A multi-institutional preclinical study.

BACKGROUND: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE). METHODS: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized. RESULTS: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. CONCLUSIONS: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes.

Characterisation of novel influenza-derived HLA-B*18:01-restricted epitopes.

Objectives: Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8+ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8+ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8+ T cell responses across broad populations. Consequently, the rational design of a CD8+ T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules. Methods: Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*18:01 molecule. Results: Using CD8+ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01+ individuals and confirmed their HLA-B*18:01 restriction. We subsequently compared CD8+ T cell responses towards the previously identified highly immunogenic HLA-B*18:01-restricted NP219 peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*18:01 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*18:01 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides. Conclusion: Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*18:01-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.

Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design: This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting: The trial was set in 17 NHS secondary care hospitals in the UK. Participants: A total of 378 eligible participants aged > 18 years were recruited. Interventions: Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures: The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes - Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements - peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results: At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were -20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval -23.6 to -16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations: COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions: Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration: This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants' nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS.

Fighting flu: novel CD8+ T-cell targets are required for future influenza vaccines.

Seasonal influenza viruses continue to cause severe medical and financial complications annually. Although there are many licenced influenza vaccines, there are billions of cases of influenza infection every year, resulting in the death of over half a million individuals. Furthermore, these figures can rise in the event of a pandemic, as seen throughout history, like the 1918 Spanish influenza pandemic (50 million deaths) and the 1968 Hong Kong influenza pandemic (~4 million deaths). In this review, we have summarised many of the currently licenced influenza vaccines available across the world and current vaccines in clinical trials. We then briefly discuss the important role of CD8+ T cells during influenza infection and why future influenza vaccines should consider targeting CD8+ T cells. Finally, we assess the current landscape of known immunogenic CD8+ T-cell epitopes and highlight the knowledge gaps required to be filled for the design of rational future influenza vaccines that incorporate CD8+ T cells.

Pediatric Inferior Turbinate Hypertrophy: Diagnosis and Management. A YO-IFOS Consensus Statement.

OBJECTIVE: Pediatric inferior turbinate hypertrophy (PedTH) is a frequent and often overlooked cause or associated cause of nasal breathing difficulties. This clinical consensus statement (CCS) aims to provide a diagnosis and management framework covering the lack of specific guidelines for this condition and addressing the existing controversies. METHODS: A clinical consensus statement (CCS) was developed by a panel of 20 contributors from 7 different European and North American countries using the modified Delphi method. The aim of the CCS was to offer a multidisciplinary reference framework for the management of PedTH on the basis of shared clinical experience and analysis of the strongest evidence currently available. RESULTS: A systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria was performed. From the initial 96 items identified, 7 articles were selected based on higher-evidence items such as randomized-controlled trials, guidelines, and systematic reviews. A 34-statement survey was developed, and after three rounds of voting, 2 items reached strong consensus, 17 reached consensus or near consensus, and 15 had no consensus. CONCLUSIONS: Until further prospective data are available, our CCS should provide a useful reference for PedTH management. PedTH should be considered a nasal obstructive disease not necessarily related to an adult condition but frequently associated with other nasal or craniofacial disorders. Diagnosis requires clinical examination and endoscopy, whereas rhinomanometry, nasal cytology, and questionnaires have little clinical role. Treatment choice should consider the specific indications and features of the available options, with a preference for less invasive procedures. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1437-1444, 2024.

Does offering small financial incentives to smokers at the time of being wait-listed for surgery increase smoking cessation by the day of surgery? A randomised feasibility trial.

OBJECTIVE: This study aims to assess whether offering small financial incentives to smokers on elective surgery wait-lists is feasible and increases quitting before surgery. DESIGN: Randomised controlled trial, prospective, double-blinded. SETTING: Single-centre, Australian metropolitan public hospital. PARTICIPANTS: 620 adult smokers (≥10 cigarettes per day) were randomised on being wait-listed for elective surgery and 404 underwent operations (28 January 2021-31 July 2022) at the hospital (65.2%) by trial's end. INTERVENTION: Intervention participants were offered at wait-listing an $A70 supermarket voucher for verified abstinence on the day of surgery, provided they registered an intention to quit before surgery. Registrants intending to quit were also referred to Quitline. Neither intervention was offered to control participants (usual care). Smokers wait-listed from 17 May 2021 were offered an increased incentive of $A140. MAIN OUTCOME MEASURES: Primary outcome, quitting at least 24 hours before surgery, verified by exhaled carbon monoxide testing. Feasibility outcomes were the proportion taking up offers, ease of patient contact and disputes about quit status. RESULTS: Of 620 randomised participants (control 312, intervention 308), 404 had surgery at the hospital during the trial (control 214, intervention 190), which was lower than expected (for COVID-19 reasons). Offering $A70 resulted in 21.9% registering to quit, increasing to 32.6% with $A140. Telephone calls were the most effective means to gain registrations. The proportion of intervention group patients verified quit at least 24 hours before surgery was similar to controls (9.5% vs 8.9%, OR 1.1, 95% CI 0.5 to 2.2). Quitline contact was higher in the intervention group (13.2% vs 2.3%, OR 6.3, 95% CI 2.3 to 21.6). Disputes over test results did not occur, but 17.4% of intervention participants claiming quit failed verification. CONCLUSION: A single offer of financial rewards for perioperative cessation was feasible, without achieving clinically important quit differences. TRIAL REGISTRATION NUMBER: ACTRN12620000130965.

Clinical effectiveness of septoplasty versus medical management for nasal airways obstruction: multicentre, open label, randomised controlled trial.

OBJECTIVE: To assess the clinical effectiveness of septoplasty. DESIGN: Multicentre, randomised controlled trial. SETTING: 17 otolaryngology clinics in the UK's National Health Service. PARTICIPANTS: 378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score >30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale). INTERVENTIONS: Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex. MAIN OUTCOME MEASURES: The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures. RESULTS: Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P<0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections. CONCLUSIONS: Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16168569.

Offering mailed nicotine replacement therapy and Quitline support before elective surgery: a randomised controlled trial.

OBJECTIVE: To assess whether offering free mailed nicotine replacement therapy (NRT) and telephone counselling to smokers on elective surgery waiting lists increases quitting before surgery. DESIGN, SETTING: Randomised, controlled trial at Frankston Hospital, a public tertiary referral hospital in Melbourne. PARTICIPANTS: Adult smokers added to elective surgery waiting lists for operations at least ten days in the future, 1 April 2019 - 3 April 2020. INTERVENTION: In addition to normal care, intervention participants received a brochure on the risks of low frequency smoking, an offer of Quitline call-back registration, and an offer of mailed NRT according to reported daily smoking: 1-9 cigarettes/day, 2 mg lozenges; 10-15/day, 7-14 mg patches [three weeks] and 2 mg lozenges; > 15/day, 7-21 mg patches [five weeks] and 2 mg lozenges. MAIN OUTCOME MEASURES: Primary outcome: quitting at least 24 hours before surgery, verified by exhaled carbon monoxide testing. SECONDARY OUTCOMES: quitting at least four weeks before surgery, adverse events, and (for those who had quit before surgery) abstinence three months after surgery. RESULTS: Of 748 eligible participants (control, 363; intervention, 385), 516 (69%) had undergone elective surgery when the trial was terminated early (for COVID-19-related reasons) (intervention group, 274; control group, 242). 122 of the 385 intervention participants (32%) had accepted the offer of cessation support. The proportions of intervention participants who quit at least 24 hours before surgery (18% v 9%; odds ratio [OR], 1.97; 95% CI, 1.22-3.15) or at least four weeks before surgery (9% v 4%; OR, 2.20; 95% CI, 1.08-4.50) were larger than for the control group. Three months after surgery, 27 of 58 intervention (47%) and 12 of 25 control participants (48%) who quit before surgery reported not smoking in the preceding seven days. No major adverse events were reported. CONCLUSION: Uptake of free mailed NRT and Quitline support by smokers on elective surgery waiting lists was good, and offering additional support was associated with higher proportions of smokers quitting before surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619000032156 (prospective).

One year into the COVID-19 pandemic: What do we know so far from studies assessing risk and mitigation of droplet aerosolisation during endonasal surgery? A systematic review.

OBJECTIVES: As we pass the anniversary of the declaration of a global pandemic by the World Health Organisation, it invites us to reflect upon the inescapable changes that coronavirus has wrought upon ENT and, in particular, rhinological practice. As it remains unclear when we will emerge from the shadow of COVID-19, a critical analysis of the evidence base on both the assessment and mitigation of risk is vital for ENT departments worldwide. This article presents a systematic review of the literature examining articles which consider either the quantification of risk or strategies to mitigate risk specifically in the setting of rhinological surgery. DESIGN: Systematic literature review. RESULTS: The literature search yielded a total of 3406 returns with 24 articles meeting eligibility criteria. A narrative synthesis stratified results into two broad themes: (1) those which made an assessment as to the aerosolisation of droplets during sinus surgery, further sub-divided into work which considered macroscopically visible droplets and that which considered smaller particles; (2) and those studies which examined the mitigation of this risk. CONCLUSION: Studies considering the aerosolisation of both droplets and smaller particles suggest endonasal surgery carries significant risk. While results both highlight a range of innovative adjunctive strategies and support suction as an important intervention to reduce aerosolisation, appropriate use of personal protective equipment (PPE) should be considered mandatory for all healthcare professionals involved in rhinological surgery. Studies have demonstrated that close adherence to PPE use is effective in preventing COVID-19 infection.

Analysis of Droplet Splatter Patterns During Coblation Tonsil Surgery in the Covid-19 Pandemic.

OBJECTIVES: To assess droplet splatter around the surgical field and surgeon during simulated Coblation tonsil surgery to better inform on mitigation strategies and evaluate choice of personal protective equipment. METHODS: This was an observational study performed using a life-size head model to simulate tonsil surgery and fluorescein-soaked strawberries to mimic tonsils. The Coblation wand was activated over the strawberries for 5 minutes. This was repeated 5 times with 2 surgeons (totalling 10 data sets). The presence of droplet around the surgical field and anatomical subsites on the surgeon was assessed in binary fashion: present or not present. The results were collated as frequency of droplet detection and illustrated as a heatmap; 0 = white, 1-2 = yellow, 3-4 = orange, and 5 = red. RESULTS: Fluorescein droplets were detected in all 4 quadrants of the surgical field. The frequency of splatter was greatest in the upper (nearest to surgeon) and lower quadrants. There were detectable splatter droplets on the surgeon; most frequently occurring on the hands followed by the forearm. Droplets were also detected on the visor, neck, and chest albeit less frequently. However, none were detected on the upper arms. CONCLUSION: Droplet splatter can be detected in the immediate surgical field as well as on the surgeon. Although wearing a face visor does not prevent splatter on the surgical mask or around the eyes, it should be considered when undertaking tonsil surgery as well as a properly fitted goggle. LEVEL OF EVIDENCE: 5.

Endoscopic balloon dilatation of the olfactory cleft - a feasibility study of a novel technique in cadavers.

OBJECTIVE: Smell dysfunctions are common with almost 20% percent of the population affected. There are no interventional solutions for these patients. The aim of this study is to investigate the feasibility and security of the balloon dilatation technique. METHODS: This paper describes interventional steps and determines the feasibility and safety of endoscopic olfactory cleft dilatation via balloon device. We included 10 nasal cavities in the study and dilated olfactory cleft areas via balloon device. RESULTS: We could smoothly perform the procedure and did not observe any fractures on the skull base or olfactory cleft of the cadavers after dilatation. CONCLUSIONS: A combination of this intervention with medical treatments can be promising for smell dysfunctions.

Droplet and bone dust contamination from high-speed drilling during mastoidectomy.

OBJECTIVES: The aim of this study was to examine contamination from otolaryngologic procedures involving high-speed drilling, specifically mastoid surgery, and to assess the adequacy of PPE in such procedures. DESIGN AND SETTING: Mastoid surgery was simulated in a dry laboratory using a plastic temporal bone, microscope and handheld drill with irrigation and suction. Comparisons of distance of droplet and bone dust contamination and surgeon contamination were made under differing conditions. Irrigation speed, use of microscope and drill burr size and type were compared. MAIN OUTCOME MEASURES: Measurement of the distance of field contamination while performing simulated mastoidectomy and location of surgeon contamination. RESULTS: There was a greater distance field contamination and surgeon contamination without the use of the microscope. Contamination was reduced by using a smaller drill burr and by using a diamond burr when compared to a cutting burr. The use of goggles and a face mask provided good protection for the surgeon. However, the microscope alone may provide sufficient protection to negate the need for goggles. CONCLUSIONS: While the risks of performing mastoid surgery during the coronavirus pandemic cannot be completely removed, they can be mitigated. Such factors include using the microscope for all drilling, using smaller size drill burrs and creating a safe zone around the operating table.

Reducing the risks of endoscopic sinonasal surgery in the Covid-19 era.

OBJECTIVES: Many routine sinonasal procedures utilising powered instruments are regarded as aerosol-generating. This study aimed to assess how different instrument settings affect detectable droplet spread and patterns of aerosolised droplet spread during simulated sinonasal surgery in order to identify mitigation strategies. DESIGN: Simulation series using three-dimensional (3-D) printed sinonasal model. Fluorescein droplet spread was assessed following microdebriding and drilling of fluorescein-soaked grapes and bones, respectively. SETTING: University dry lab. PARTICIPANTS: 3-D printed sinonasal model. MAIN OUTCOME MEASURES: Patterns of aerosolised droplet spread. RESULTS AND CONCLUSION: There were no observed fluorescein droplets or splatter in the measured surgical field after microdebridement of nasal polyps at aspecific irrigation rate and suction pressure. Activation of the microdebrider in the presence of excess fluid in the nasal cavity (reduced or blocked suction pressure, excessive irrigation fluid or bleeding) resulted in detectable droplet spread. Drilling with either coarse diamond or cutting burs resulted in detectable droplets and greater spread was observed when drilling within the anterior nasal cavity. High-speed drilling is a high-risk AGP but the addition of suction using a third hand technique reduces detectable droplet spread outside the nasal cavity. Using the instrument outside the nasal cavity inadvertently, or when unblocking, produces greater droplet spread and requires more caution.

A Comparison between Mygind and Kaiteki positions in administration of drops to the olfactory cleft.

OBJECTIVES: Topical nasal steroids are a common treatment intervention for olfactory dysfunction. Penetration of topical treatment to the olfactory cleft (OC), such as nasal drops, is greatly dependent on the position of the head when the treatment is administered. We aimed to examine the penetrance of nasal drops to the OC in two different head positions: the Mygind (lying head back) position and the Kaiteki position. DESIGN AND SETTING: The specimens were firstly positioned in Mygind, and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostrils in each of the head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). PARTICIPANTS: Twelve fresh-frozen cadaver specimens. MAIN OUTCOME MEASURES: Penetration of the dye into the OC. RESULTS: The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34 (standard deviation, SD = 0.92), as compared to 1.76 (SD = 0.65) in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (P > .05). CONCLUSION: Both Mygind and Kaiteki head positions are reasonable options for patients considering topical nasal drops for olfaction impairment. The preference of one position over the other should be determined by patient's preference and comfort.

Quality-of-life changes following three-dimensional printing of prosthesis for large nasal septal perforations-Our experience of 13 patients.

Nasal septal perforations can be caused by a number of aetiology including intra-nasal drug abuse, trauma and iatrogenic causes.

Hospital entrance smoking is reduced by broadcasting recorded antitobacco messages from Australian primary school children over entrance public address system.

ISSUE ADDRESSED: Smoking near hospital entrances occurs frequently despite smoke-free policies, resulting in multiple issues including second-hand smoke exposure (SHS) to vulnerable populations. Primary school children were engaged through their health curriculum to produce antismoking audio recordings for broadcast over a hospital entrance loudspeaker system to determine if this reduced smoking. METHOD: Students produced original recordings against hospital grounds smoking during class workshops, from which a collection (n = 16) was selected. Episodes of entrance smoking and total entrance traffic were recorded using security camera infrastructure over a 5-week period. A computer-controlled entrance loudspeaker played a message which was followed by silence until a new (different) message was played. Intensity of messaging was moderate in week 3 (every 5 minutes), increasing to high in week 4 (3 minutely) and compared to no messages (weeks 1-2 preintervention) and week 5 (postintervention). RESULTS: Smokers presented 316 times, smoking 523 cigarettes over 155 hours of observation (patients 70.6%, visitors 29.4%). SHS exposure was high given 172 others used the entrance/hour. Smoking was highest in the preintervention period (weeks 1-2), median five cigarettes/hr [IQR,3-7 (min = 0, max = 12)], falling to four cigarettes/hr during 5-minutely broadcasts [IQR,2-5 (min = 1, max = 14)] (P = .06), but zero cigarettes/hr during 3-minutely broadcasts [IQR,0-1(min = 0, max = 7)] (P < .0001). Postintervention (no broadcasts), smoking increased from zero to 1 cigarette/hr [IQR,0-3 (min = 0, max = 5)]; (P = .052). Nonsmoker movements did not change significantly between each period. CONCLUSION: Intensive (3 minutely) broadcasting of short antismoking messages significantly reduced hospital entrance smoking. SO WHAT?: Health services can positively interact with the health curriculum of primary schools against tobacco use while developing low-cost strategies to effectively deter entrance smoking.

Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

PURPOSE: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features. EXPERIMENTAL DESIGN: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting. RESULTS: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations. CONCLUSIONS: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.

Draf III frontal sinus surgery for the treatment of Pott's puffy tumour in adults: our case series and a review of frontal sinus anatomy risk factors.

PURPOSE: We present our case series of four adult patients with Pott's puffy tumour (PPT), successfully treated with Draf III over a mean period of 11 months. A critical review of the literature is also provided. METHODS: A retrospective review of patients undergoing Draf III for PPT from January 2018 to January 2019 was performed. RESULTS: Four consecutive male patients ranging from 26 to 62 years, with a mean age of 49.5 ± 16.3 years, undergoing Draf III for Pott's puffy tumour were included. Two patients had a Kuhn type IV frontal cell narrowing the frontonasal pathway and presented without previous sinus surgery, whereas the other two had previous sinus surgery. The success rate of the operation was 100% with an average length of follow-up of 11 months (range 5-18). CONCLUSION: In our experience, the Draf III procedure is a highly effective treatment of PPT. In particular, we have demonstrated it to be very effective in accessing highly positioned Kuhn type IV cells.