The Potential Role of Reactive Oxygen Species Produced by Low-Density Neutrophils in Periodontitis.

OBJECTIVE: Neutrophils own an arsenal of dischargeable chemicals that enable them to handle bacterial challenges, manipulating innate immune response and actual participation in acquired immunity. The reactive oxygen species (ROS) are one of the most important chemicals that neutrophils discharge to eradicate pathogens. Despite their beneficial role, the ROS were strongly correlated to periodontal tissue destruction. Lowdensity neutrophils (LDN) have been recognized for producing enhanced quantities of ROS. However, the potential role of ROS produced by LDN in periodontitis is unknown. The aim of the study was to investigate the impact of ROS produced by LDN in periodontal diseases. MATERIALS AND METHODS: Venous blood and periodontal parameters were obtained from 100 systemically healthy subjects divided into 40 participants with healthy periodontium in the control group and 60 with unstable periodontitis in the study group. Flow cytometry was used to measure the production of ROS by LDN in both groups. STATISTICAL ANALYSIS: The data were analyzed for normal distribution using the Shapiro-Wilk test at p < 0.05, Spearman's correlations, and Mann-Whitney U test. Statistical analysis was performed in SPSS v25. RESULTS: No difference between the groups had been obtained in ROS production by LDN. However, a significant positive correlation existed between ROS and clinical attachment loss in periodontitis. CONCLUSION: LDN exhibits the same ROS generation capacity in the control and periodontitis groups.

Undergraduate perceptions on the educational value of a novel ENT e-Learning platform.

ENT is a consistently under-represented specialty in medical school curricula. With social distancing measures limiting face-to-face (FtF) teaching and clinical opportunities, we created an e-Learning platform to consolidate and improve knowledge on common ENT emergencies. Following invitation to medical students undergoing their rotation in ENT at University Hospital Wales (UHW) Cardiff, five focus groups were shown an e-Learning module and interviewed between June and July 2021. 13 medical students participated in total (9 female, 4 male, median age 22 years). These structured interviews were recorded and transcribed. Transcripts were analysed using the qualitative data analysis software NVivo (QSR International, UK). The modules were found to be concise, clinically relevant and beneficial to student confidence in recognising and managing ENT emergencies. While e-Learning will likely never replace face-to-face learning, it was perceived to be a beneficial resource both academically and practically- especially in the context of limited clinical opportunities.

Simulated laryngoscopy with supraglottic high-pressure source ventilation: an in vitro study of tracheal airflow to determine optimal positioning of laryngoscope and jet ventilation cannula.

PURPOSE: To investigate how variations in positioning of laryngoscope and location of jet cannula on the laryngoscope body influence tracheal airflow during simulated high-pressure source supraglottic (HPSV) jet ventilation laryngoscopy using an anatomical model. METHODS: A Broncho Boy Bronchoscopy model was modified to allow recording of tracheal airflow. A laryngoscope was suspended and positioned to simulate laryngoscopy. HPSV was delivered by a jet cannula attached to the body of the laryngoscope. Different combinations of laryngoscope angulation and cannula attachment were used and air flow recorded for each combination. Statistical analysis assessed the variations in flow. RESULTS: Significant statistical differences in flow effect (P < 0.05) were shown, indicating that laryngoscope position and attachment of jet cannula have a significant effect on tracheal airflow. Highest flows were achieved by anterior positioning of laryngoscope combined with anterolateral attachment of cannula (> 1 L/s) compared to downward or either side (< 0.6 L/s). CONCLUSION: Significant differences in tracheal airflow arise from different positions of both laryngoscope and jet cannula with supraglottic HPSV. Optimal locations for both are apparent and collaborative interaction with anaesthetist emphasised. The experimental setup could be a potential simulation tool.

Sensitivity of human papillomavirus­positive and ­negative oropharyngeal cancer cell lines to ionizing irradiation.

Human papillomavirus­positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence and has a much better prognosis than HPV­negative (HPV­) OPSCC with radiotherapy alone, but exactly why is unknown. The present study therefore aimed to further examine the sensitivity and possible changes in gene expression of several HPV+ and HPV­ OPSCC, including various novel cell lines, upon ionizing irradiation (IR). Previously established HPV+ UM­SCC­47, UPCI­SCC­90, CU­OP­2, CU­OP­3 and HPV­ UM­SCC­4, UM­SCC­6, UM­SCC­74a, UM­SCC­19 and newly established CU­OP­17 and CU­OP­20, characterised here, were subjected to 0­6 Gy. Surviving fractions of each cell line were tested by clonogenic assays, and irregularities in cell cycle responses were examined by flow cytometry, while changes in gene expression were followed by mRNA sequencing. HPV+ OPSCC cell lines showed greater variation in sensitivity to ionizing irradiation (IR) and tended to be more sensitive than HPV­ OPSCC cell lines. However, their IR sensitivity was not correlated to the proportion of cells in G2 arrest, and HPV­ cell lines generally showed lower increases in G2 after IR. Upon IR with 2 Gy, mRNA sequencing revealed an increase in minor HPV integration sites in HPV+ cell lines, and some changes in gene expression in OPSCC cell lines, but not primarily those associated with DNA repair. To conclude, HPV+ OPSCC cell lines showed greater variation in their sensitivity to IR, with some that were radioresistant, but overall the HPV+ OPSCC group still tended to be more sensitive to IR than the HPV­ OPSCC group. In addition, HPV+ OPSCC lines were more frequently in G2 as compared to HPV­ cell lines, but the increase in G2 arrest upon IR in HPV+ OPSCC was not correlated to sensitivity to IR. Increases in minor HPV integration sites and changes in gene expression were also demonstrated after irradiation with 2 Gy.

Sensitivity to inhibition of DNA repair by Olaparib in novel oropharyngeal cancer cell lines infected with Human Papillomavirus.

The incidence of Human Papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing rapidly in the UK. Patients with HPV-positive OPSCC generally show superior clinical responses relative to HPV-negative patients. We hypothesised that these superior responses could be associated with defective repair of DNA double strand breaks (DSB). The study aimed to determine whether defective DNA repair could be associated with sensitivity to inhibition of DNA repair using the PARP inhibitor Olaparib. Sensitivity to Olaparib, and induction and repair of DNA damage, were assessed in a panel of 8 OPSCC cell-lines, including 2 novel HPV-positive lines. Effects on cell cycle distribution and levels of PARP1 and p53 were quantified. RNA-sequencing was used to assess differences in activity of DNA repair pathways. Two HPV-positive OPSCC lines were sensitive to Olaparib at potentially therapeutic doses (0.1-0.5 µM). Two HPV-negative lines were sensitive at an intermediate dose. Four other lines, derived from HPV-positive and HPV-negative tumours, were resistant to PARP inhibition. Only one cell-line, UPCISCC90, showed results consistent with the original hypothesis i.e. that in HPV-positive cells, treatment with Olaparib would cause accumulation of DSB, resulting in cell cycle arrest. There was no evidence that HPV-positive tumours exhibit defective repair of DSB. However, the data suggest that a subset of OPSCC may be susceptible to PARP-inhibitor based therapy.

A novel ENT iBook: what do junior doctors think?

Exposure to the specialty of Otolaryngology is limited. It may be consolidated by the use of an iBook as a self-study tool. The purpose of this study was to ascertain the perceptions of junior doctors on the clinical relevance of this novel educational resource. Three focus groups were formed each consisting of five junior doctors (eight female: seven male, median age 27 years). The iBook was found to be clinically relevant to the work of junior doctors, have a clear layout, with adequate interactivity and a good range of integrated multimedia elements.

Identifying the Optimal Water-Occluding Earplugs: A Scientific Simulation Study.

OBJECTIVE: Numerous types of water-occluding earplugs are available as a means of preventing infection in patients with external and middle ear disease. However, little is known about the comparative efficacies of these earplugs with prolonged water exposure. In this study, we assessed the water impermeability of various earplug materials to prolonged water exposure. MATERIALS AND METHODS: Nine earplugs were tested: cotton wool mixed with petroleum jelly, cotton wool externally coated with petroleum jelly, Blu-Tack, foam earplugs, silicone putty, silicone earplugs, flanged earplugs, and hard and soft silicone custom-moulds. Precision-engineered cups were filled with 30 mL water and sealed with lids that contained a 10 mm diameter hole to simulate the ear canal. The aperture was occluded with different earplugs, and the cup was inverted. Computer software was used to record the water loss to the nearest 10 milligrams 720 times over a three-hour period. The test was repeated five times for each material. RESULTS: The water permeability onset, rate, and total amount of water loss varied markedly between the materials; cotton wool mixed with petroleum jelly demonstrated the fastest onset of leak and the highest rate of water loss (p < 0.00001), as well as the largest amount of cumulative water loss (p = 0.00213). The soft silicone custom-mould plugs, hard silicone custom-mould plugs, foam plugs, and silicone putty demonstrated no leaks. CONCLUSION: This study demonstrates a wide range of water permeabilities of commonly used ear-occluding materials during prolonged water exposure. We found that the generally suggested regimen of cotton wool mixed with petroleum jelly may be inefficacious for substantial periods of water exposure.

Exploring medical undergraduates' perceptions of the educational value of a novel ENT iBook: a qualitative study.

Undergraduate otolaryngology exposure is limited. It may be consolidated by the use of an iBook as a self-study tool. Following invitation to participate by email, five focus groups were formed, each consisting of six medical students (18 female, 12 male, median age 23 years). The focus group transcripts were imported to the qualitative data analysis software NVivo (QSR International, UK). The iBook was found to have a clear and consistent presentation, and a focused and user-friendly style, with reasonable interactivity and a good range of well-integrated media elements. It was, overall, perceived to be a valuable educational resource by the medical students.

What Are the Trends in Tonsillectomy Techniques in Wales? A Prospective Observational Study of 19,195 Tonsillectomies over a 10-Year Period.

There are a multitude of techniques to undertake tonsillectomy, with hot techniques such as diathermy and coblation being associated with a higher risk of secondary haemorrhage. The UK National Prospective Tonsillectomy Audit (2004) advocated cold steel dissection and ties to be the gold standard. This prospective observational study investigates the trends in tonsillectomy techniques across Wales in the last decade to establish if surgeons have adhered to this national guidance. Data relating to tonsillectomy were extracted over a 10-year period from 1 January 2003 to 31 December 2012 from the Wales Surgical Instrument Surveillance Programme database. A total of 19,195 patients were included. Time-series analysis using linear regression showed there was an increase in the number of bipolar diathermy tonsillectomies by 84% (Pearson's r = 0.762, p = 0.010) and coblation tonsillectomies by 120% (r = 0.825, p = 0.003). In contrast, there was a fall in the number of cold steel dissection tonsillectomies with ties by 60% (r = -0.939, p < 0.001). This observational study suggests that the use of bipolar and coblation techniques for tonsillectomy has increased. This deviation from national guidance may be due to these techniques being faster with less intraoperative bleeding. Further study for the underlying reasons for the increase in these techniques is warranted.

IL-34 Suppresses Candida albicans Induced TNFα Production in M1 Macrophages by Downregulating Expression of Dectin-1 and TLR2.

Candida albicans is a fungus that is an opportunistic pathogen of humans. Normally, C. albicans exists as a harmless commensal and does not trigger inflammatory responses by resident macrophages in skin mucosa, which may be caused by a tolerance of skin macrophage to C. albicans. IL-34 is a recently discovered cytokine, constitutively expressed by keratinocytes in the skin. IL-34 binds to the receptor of M-CSF, thereby stimulating tissue macrophage maturation and differentiation. Resident macrophages exhibit phenotypic plasticity and may transform into inflammatory M1 macrophages for immunity or anti-inflammatory M2 macrophages for tissue repair. M1 macrophages produce higher levels of inflammatory cytokines such as TNFα in response to C. albicans stimulation. In this study, it was demonstrated that IL-34 attenuated TNFα production by M1 macrophages challenged with heat killed Candida (HKC). The molecular mechanism of IL-34 mediated suppression of HKC induced TNFα production by M1 macrophages was by the inhibition of M1 macrophage expression of key C. albicans pattern recognition receptors (PPRs), namely, Toll-like receptor (TLR) 2 and Dectin-1. The results of this study indicated that constitutive IL-34 expressed by skin keratinocytes might suppress resident macrophage responses to C. albicans colonisation by maintaining low levels TLR2 and Dectin-1 expression by macrophages.

Comparison of traditional face-to-face teaching with synchronous e-learning in otolaryngology emergencies teaching to medical undergraduates: a randomised controlled trial.

Undergraduate otolaryngology teaching in the UK is generally limited primarily due to curriculum time constraints with traditional face-to-face (FtF) teaching being restrained by the limitations of time and location. Advances in network technology have opened up new doors for the delivery of teaching in the form of online learning. This study compares a traditional instructor-led lecture with synchronous e-learning (SeL) using otolaryngological emergencies teaching as an educational intervention. A randomised controlled trial was designed involving two groups of medical students attending an otolaryngology emergencies management lecture: one present FtF and the other viewing the streamed lecture online. The primary outcome measure was improvement between pre-and post-lecture test scores. Secondary outcomes comprised the students' ratings of the lecture on a Likert-type scale. Students in both groups had improved test scores following the lecture (p < 0.001 for both groups) and there was no difference in magnitude of improvement in test scores between the two groups (p = 0.168). There was no difference in student ratings between the two groups for the usefulness of the lecture (p = 0.484), interactivity (p = 0.834) and meeting educational needs (p = 0.968). The FtF group, however, was more satisfied overall (p = 0.034). This study demonstrates that SeL may be as effective as FtF teaching in improving students' knowledge on the management of otolaryngological emergencies, and that it is generally positively perceived by medical undergraduates. This highlights the potential utility of e-learning technology in undergraduate otolaryngology training.

Day-case septoplasty: a default pathway or is case selection the key?

Septoplasty has been identified as suitable for day surgery, but is not commonly performed as such. Guidelines for day surgery stipulate that the unexpected re-admission rate should be 2-3 %; however previous studies have not attained this target. The purpose of this study was to ascertain the surgical and patient factors associated with re-admission following day-case septoplasty. A retrospective case-notes analysis of day-case septoplasties between 1 January 2010 and 31 December 2012 was undertaken. Data on patient demographics, surgeon grade and operative technique were examined using a univariate analysis model. A total of 256 septoplasties were performed. 23 patients were admitted, overwhelmingly due to bleeding in the immediate post-operative period, giving an overall admission rate of 9.0 % within the first 24 h. Factors associated with re-admission included the use of intranasal splints (relative risk (RR) 5.34, p < 0.001), the performance of additional operative procedures (RR 4.96, p < 0.001) and surgery on patients with co-morbidities (RR 3.37, p = 0.002). There was no correlation between unexpected admission and patient gender, age, surgeon grade, performance of revision surgery and operative factors including nasal preparation with cocaine, local anaesthetic infiltration, type of incision, number of mucoperichondrial flaps raised, extensive bony dissection, performance of a turbinate procedure, quilting, closure of incision and post-operative packing. Day-case septoplasty in patients with co-morbidities and where additional surgical procedures are performed may be associated with unexpected overnight admission. Thus, safe and efficient day-case septoplasty may not be suitable as a universal default pathway but one where case selection is key.

Does temperature effect tympanometric evaluation of ear canal volume? A scientific study using an Ear Canal Model.

Tympanometric evaluation is a routine part of the complete otological examination. Although tympanometry when performed in standard conditions is known to accurately and precisely assess ear canal volume, the effects of variation in temperature have not been reported upon. This study examines the effect of temperature on the capability of the tympanometer to accurately evaluate external auditory canal volume in both simple and partially obstructed Ear Canal Models. An Ear Canal Model was designed using simple laboratory equipment including a 5 ml calibrated clinical syringe. This was attached to the sensing probe of a Kamplex tympanometer. Two basic trials were undertaken: (a) evaluation of the effect of temperature on the tympanometer in simple canal volume measurement and (b) assessing canal volume with partial canal occlusion. These studies were conducted at 0, 10, 20 and 30 °C in a Thermotron climatic chamber. 1,400 individual test scenarios were completed over the two arms of the study. At volumes of 1.4 cm(3) or below, tympanometry had a very high level of correlation (Spearman's ρ = 1) with the actual volume present at all tested temperatures except 0 °C. There was no significant relationship between temperature and degree of error in ear canal volume measurement in both simple and partially occluded models. The ability of the Kamplex tympanometer to accurately and precisely assess ear canal volume in this scientific model in both simple and partially occluded scenarios up to a volume of 1.4 cm(3) is not effected by ambient temperature. These findings suggest the Kamplex tympanometer could be used as an effective objective tool in both laboratory and human models of the external auditory canal.

Head and neck surgical patients; is it time for a bridle era?

Early enteral feeding is vital for successful outcomes in patients who have undergone open pharyngeal surgery, with nasogastric tube (NGT) feeding being a safe and accepted method of providing enteral nutrition in the short-term. Securing the NGT is key to ensure adequate caloric consumption and avoid the potential complications of re-siting the tube. The aim of this study was to compare the efficacy of utilising an anterior septal suture to a bridle system for NGT fixation. A sheep's head model was used to represent the nasal cavity of post-operative patients and a fine-bore NGT was passed. The NGT was secured with either an anterior septal suture or bridle system. A pulley system of weights was applied until the NGT slipped or snapped. Each weight and condition was investigated five times. The anterior and posterior septum were examined for evidence of damage for each condition. At 5 kg the anterior septal suture allowed the NGT to slip and the tube began to become distorted. At 5.5 kg the anterior septal suture snapped the NGT. In comparison, the bridle system was able to sustain a weight up to 15.5 kg (Fisher's exact test, p = 0.0079). There was no evidence of damage to the anterior or posterior septum for each condition. The bridle system was able to fix the NGT without slippage or damage at higher weights than the anterior septal suture. This suggests there may be potential benefits of stronger NGT fixation with reduced tube damage using bridle systems in patients, but further research is required in this domain.

Health costs and consequences: have UK national guidelines had any effect on tonsillectomy rates and hospital admissions for tonsillitis?

Tonsillectomy is a common therapeutic option in the management of recurrent tonsillitis. In 1999, the Scottish Intercollegiate Guidelines Network (SIGN) introduced SIGN 34 outlining appropriate indications for tonsillectomy. Following concerns of increasing hospital admissions for tonsillitis, in 2009 ENT UK suggested that too few tonsillectomies were being undertaken. This study analyses the effect the SIGN guidelines have had on trends in population rates of tonsillectomy and hospital admissions for tonsillitis and peritonsillar abscess in England, Scotland and Wales. A retrospective study was undertaken using the health databases of England, Scotland and Wales between 1999 and 2010. Tonsillectomy, acute tonsillitis and peritonsillar abscess were identified using national classification codes. Changes in rate of tonsillectomy and hospital admissions for tonsillitis and peritonsillar abscess were assessed using a linear regression model. 699,898 tonsillectomies were undertaken in the three national cohorts over the study period. Linear regression analysis suggested that implementation of SIGN 34 significantly reduced the population rate of tonsillectomy in England (p = 0.005) and Wales (p = 0.003) but not in Scotland (p = 0.24), and indicated there had been an increase in hospital admissions for acute tonsillitis in all cohorts (England p = 0.000008, Scotland p = 0.03, Wales p = 0.000005) and peritonsillar abscess in England (p < 0.05) and Wales (p = 0.03). SIGN 34 has reduced tonsillectomy rates in England and Wales but not in Scotland. This finding is associated with increasing hospital admissions for acute tonsillitis in all national cohorts, which may suggest that the current stipulated guidelines miss patients who would benefit from surgical intervention.

Have two UK national guidelines had any effect on grommets day-case utilisation and rate over the last 10 years?

UNLABELLED: Grommets insertion is a common otolaryngological procedure for the treatment of persistent otitis media with effusion. In 2002, the Department of Health (DoH) Day Surgery guidelines stipulated that at least 75% of grommets insertions should be undertaken as day-cases. In 2008, after governmental perception of a higher than necessary grommet insertion rate, the National Institute for Health and Clinical Excellence (NICE) guidelines aimed at reducing inappropriate grommet insertions. This study analyses the effect these national interventions have had on grommets insertion in England and Wales. A retrospective study was undertaken. Data were extracted from the patient episode databases of England (Health Episode Statistics) and Wales (Patient Episode Database of Wales) from 2000 until 2010 using OPCS-4 code D151. Statistical change in practice following the introduction of the interventions was assessed using linear regression. RESULTS: 341,526 and 16,400 grommets insertions were performed in England and Wales, respectively. Linear regression analysis demonstrated that implementation of the Day Surgery guidelines significantly improved day-case rates in both national cohorts (England P < 0.0001, Wales P < 0.0001) and reduced mean waiting times for grommets insertion in both cohorts (England P < 0.05, Wales P < 0.01). Regression analysis also showed that implementation of the NICE guidelines had no effect on the number of grommet insertions in England (P > 0.5) and Wales (P > 0.5). In conclusion, the DoH guidelines have increased grommets day-case provision and reduced waiting times in both England and Wales, whereas the NICE guidelines have not affected overall levels of grommet insertion in either national cohort.

The acute effects of changes to AV delay on BP and stroke volume: potential implications for design of pacemaker optimization protocols.

BACKGROUND: The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. METHODS AND RESULTS: To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (P<0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, -0.65 mm Hg/beat; r=0.95 [95% CI, 0.86-0.98]); in contrast, stroke volume did not decline (P=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, P<0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8±3.5 versus 2.3±1.4; P<0.001). CONCLUSIONS: Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode.