Clinical outcomes of functional endoscopic sinus surgery in cystic fibrosis patients - a single centre experience.

BACKGROUND: Endoscopic sinus surgery (ESS) is an established surgical option for cystic fibrosis (CF) patients with chronic rhinosinusitis that is refractory to conventional medical management. Objective and subjective evidence of benefit of ESS in this cohort of patients is currently conflicting in the literature. METHODOLOGY: A single center retrospective study was undertaken of all CF patients (transplanted and non-transplanted) over the age of 16 who underwent an ESS over a six-year period from 2015 to 2021. Patients on triple-therapy CFTR modulators were excluded. Data was collected on demographics, clinical management, and outcome measures. The objective outcome measures were lung function (%predicted FEV1), pulmonary exacerbations (total number of days of IV antibiotics- both ambulatory and in hospital). The subjective outcome measure was SNOT-22 scores preand 6 months post-operatively. A minimally clinical important difference (MCID) in SNOT-22 scores of 9 points was used. RESULTS: 55 patients were included in our study, with a median age of 31 and 53% females. Median Lund-Mackay scores for the cohort was 13 (3- 24). There was a significant improvement in lung function at 1-year post-surgery, and a significant MCID reduction in SNOT-22 scores at 6 months post-surgery across the cohort. Sub-group analysis revealed a sustained MCID reduction in SNOT-22 scores in both lung-transplanted and native lung groups, and in patients with primary ESS or previous ESS. However, there was no post-operative pulmonary function improvement in lung transplanted patients and patients with previous ESS. There was no impact on the rate of pulmonary exacerbations across the cohort. 2 patients in the cohort died secondary to pulmonary disease. CONCLUSIONS: There was a demonstrated clinical and symptomatic benefit of ESS in CF patients in this study. Stricter guidelines for indications for ESS need to be established with regards to CF patients who will undergo ESS in the future.

EPOS 4 Patients.

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was first published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all disciplines dealing with these problems together with patients. The guidelines offer evidence-based recommendations and care pathways for acute and chronic rhinosinusitis in both adults and children. Management of these diseases from the patients' perspective is an important part of EPOS2020. Not only is this included in the main document but, for the first time, we have produced a separate supplement dedicated to and in collaboration with patients, EPOS4Patients, which aims to provide information in an accessible format, to answer frequently asked questions about these diseases and their treatment options as well as including useful patient resources and websites. It has never been more important for patients to be actively involved in their care. Being well informed helps you to make the best decisions together with your doctor.

Omalizumab treats chronic rhinosinusitis with nasal polyps and asthma together-a real life study.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy. OBJECTIVE: To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP. METHODS: SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma. SNOT-22 in a surgery only treated CRSwNP with asthma group (n=24) was compared. RESULTS: Rapid improvement was seen at 4 weeks and 16 weeks of treatment in both CRSwNP and asthma control. The improvement in CRSwNP with Omalizumab was similar to that seen in a group of patients who received upper airway surgery. CONCLUSION: Omalizumab treatment for severe allergic asthma also improves co-existent CRSwNP. Further clinical studies of current and emerging biological agents for severe asthma should include upper airway outcomes. These agents may be effective for severe CRSwNP and comparative studies with surgery are warranted.

Sulfide production kinetics and model of stormwater retention ponds.

Stormwater retention ponds can play a critical role in mitigating the detrimental effects of urbanization on receiving waters that result from increases in polluted runoff. However, the benthic oxygen demand of stormwater facilities may cause significant hypoxia and trigger the production of hydrogen sulfide (H2S). This process is not well-documented and further research is needed to characterize benthic processes in stormwater retention ponds in order to improve their design and operation. In this study, sediment oxygen demand (SOD), sediment ammonia release (SAR) and sediment sulfide production (SSP) kinetics were characterized in situ and in the laboratory. In situ SOD and SSP data were utilized to develop a stormwater retention pond water sulfide concentration model which demonstrates strong correlation with sulfide concentrations observed in situ (r = 0.724, N = 91, p < 0.001) and in laboratory experiments (r = 0.691, N = 38, p < 0.001). At 4 °C, in situ rates of SOD, SAR and SSP were higher than those measured in laboratory. Sulfate-reducing bacteria (SRB) represented 4.99% of the bacteria present in the top 30 cm of the pond sediment, with Desulfobulbaceae spp., Desulfobacteraceae spp. and Desulfococcus spp. being the dominant SRB taxa identified.

Low dimensional model of bursting neurons.

A computationally efficient, biophysically-based model of neuronal behavior is presented; it incorporates ion channel dynamics in its two fast ion channels while preserving simplicity by representing only one slow ion current. The model equations are shown to provide a wide array of physiological dynamics in terms of spiking patterns, bursting, subthreshold oscillations, and chaotic firing. Despite its simplicity, the model is capable of simulating an extensive range of spiking patterns. Several common neuronal behaviors observed in vivo are demonstrated by varying model parameters. These behaviors are classified into dynamical classes using phase diagrams whose boundaries in parameter space prove to be accurately delineated by linear stability analysis. This simple model is suitable for use in large scale simulations involving neural field theory or neuronal networks.

Prediction and verification of nonlinear sleep spindle harmonic oscillations.

This paper examines nonlinear effects in a neural field model of the corticothalamic system to predict the EEG power spectrum of sleep spindles. Nonlinearity in the thalamic relay nuclei gives rise to a spindle harmonic visible in the cortical EEG. By deriving an analytic expression for nonlinear spectrum, the power in the spindle harmonic is predicted to scale quadratically with the power in the spindle oscillation. By isolating sleep spindles from background sleep in experimental EEG data, the spindle harmonic is directly observed.

A feasibility study of using a high-definition intra-operative exoscope in teaching septorhinoplasty.

OBJECTIVE: This pilot study aimed to assess the feasibility of using a high-definition intra-operative exoscope in teaching septorhinoplasty. METHODS: The exoscope was used in septorhinoplasty cases with different trainers and trainees. A high-definition screen displayed real-time, magnified images. Post-procedure, a questionnaire was completed by trainer and trainees, assessing the feasibility, safety and content validity of the exoscope as a septorhinoplasty training tool. RESULTS: Trainees and trainers assigned favourable ratings to all aspects of the exoscope as a training tool, particularly with regard to teaching anatomy and improving visualisation. CONCLUSION: The exoscope is a potentially effective training tool in septorhinoplasty, and is especially useful in improving visualisation, without restricting the operator. Annotatable intra-operative photographs and videos allow trainees to study cases outside of the operating theatre environment. The use of an exoscope for septorhinoplasty in the UK may facilitate increased hands-on involvement earlier in training than is currently typical.

The sinuvertebral nerves at the craniovertebral junction: a microdissection study.

Bogduk et al. (1988, Spine 13:2-8) noted that the joints and ligaments at the cervico-occipital region are susceptible to whiplash injury. The upper three cervical sinuvertebral nerves (SVNs) at the craniovertebral junction (CVJ) are thought to be responsible for mediating pain from the ligaments, dura mater, and soft tissues of the posterior cranial fossa and upper cervical column. The purpose of this study was to describe in detail the origin and course of the SVNs at C0-C1, C1-C2, and C2-C3 intervertebral levels and their anterior intraspinal distribution. A sample comprising 10 adult, 12 fetal (crown rump length = 155-250 mm), and three stillborn neonatal (n = 50 sides) embalmed cadaveric cervical spines was microdissected (Carl Zeiss, Jena, Germany, 8-40× magnification). A laminectomy of the cervical spine with an occipital craniectomy (seven adult and all fetal specimens) or a horizontal section of the intervertebral levels was performed (three adult specimens) to expose the craniocervical canal. In both adult and fetal specimens, all three cervical SVNs arose from two roots, a somatic root (from the spinal nerve or ventral ramus or both) and a sympathetic root (from the vertebral artery plexus or superior cervical ganglion). The C1 and C2 SVNs were variable in number. The C2 and C3 SVN innervated most of the structures at the CVJ as well as the basiocciput region. The C1 SVN supplied a very small part of the atlanto-occipital joint area. The intraspinal courses of all three SVNs consisted of ascending and descending branches closely adherent to the arteries of the CVJ. They supplied the dura mater, the ligaments, adjacent joints, and soft tissues by tiny branches from the main branches. The detailed origins and course are described.

The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

Improving the management of suspected tonsillitis and peritonsillar abscess referred to ENT - a coronavirus disease 2019 service improvement.

BACKGROUND: The impact of coronavirus disease 2019 on healthcare has led to rapid changes in otolaryngology service provisions. As such, new standard operating procedures for the management of suspected tonsillitis or quinsy were implemented in our centre. METHODS: A retrospective audit was performed of acute referrals to ENT of patients with suspected tonsillitis, peritonsillar cellulitis or quinsy, during the 10 weeks before (group 1) and 10 weeks after (group 2) implementation of the new standard operating procedures. RESULTS: Group 2 received fewer referrals. Fewer nasendoscopies were performed and corticosteroid use was reduced. The frequency of quinsy drainage performed under local anaesthetic increased, although the difference was not statistically significant. Hospital admission rates decreased from 56.1 to 20.4 per cent, and mean length of stay increased from 1.13 to 1.5 days. Face-to-face follow up decreased from 15.0 to 8.2 per cent, whilst virtual follow up increased from 4.7 to 16.3 per cent. There were no significant differences in re-presentation or re-admission rates. CONCLUSION: Management of suspected tonsillitis or quinsy using the new standard operating procedures appears to be safe and effective. This management should now be applied to an out-patient setting in otherwise systemically well patients.

Coronavirus disease 2019: changing the future of emergency epistaxis management.

BACKGROUND: Acute epistaxis can be a life-threatening airway emergency, requiring in-patient admission. The coronavirus disease 2019 pandemic placed significant strain on hospital resources, and management has shifted towards an out-patient-centred approach. METHODS: A five-month single-centre retrospective study was undertaken of all epistaxis patients managed by the ENT department. A pre-coronavirus disease 2019 pandemic group was managed with pre-existing guidelines, compared to new guidelines for the coronavirus disease 2019 pandemic group. A telephone survey was performed on out-patients with non-dissolvable packs to assess patient comfort and satisfaction. RESULTS: A total of 142 patients were seen. The coronavirus disease 2019 pandemic group had significantly more patients aged over 65 years (p = 0.004), an increased use of absorbable dressings and local haemostatic agents (Nasopore and Surgiflo), and fewer admissions (all p < 0.0005). Rates of re-presentation and morbidity, and length of hospital stay were similar. The telephone survey revealed out-patient management to be efficacious and feasible. CONCLUSION: The coronavirus disease 2019 pandemic has shifted epistaxis management towards local haemostatic agents and out-patient management; this approach is as safe and effective as previously well-established regimens.

Preferences for steaming of vegetables.

BACKGROUND: Steaming retains vitamins and phytochemicals in vegetables better than boiling; thus, it is important to promote this cooking method. The present study aimed to determine what vegetable would be best to use in a campaign to promote steaming. METHODS: Carrots, broccoli and green cabbage were boiled, steamed or microwave steamed. Untrained assessors (n = 50) evaluated the sensory properties of appearance, texture, taste and overall acceptability using a hedonic rating test on a scale from 1-9. Average scores for overall acceptability were calculated for each type of cooking according to the assessors' usual cooking method. RESULTS: For all features, steaming and microwave steaming were rated significantly higher than boiling for broccoli (for acceptability 6.2 and 7.1 versus 5.1; P < 0.001), whereas carrots were similarly considered better for flavour and overall acceptability. Generally, cabbage was rated lower for all features, with no differences amongst the cooking methods (4.9-5.2 for acceptability). Only two of twenty-one subjects who usually boil vegetables preferred the boiled vegetables in the present study. CONCLUSIONS: Generally, steaming and microwave steaming were preferred for certain vegetables, even by those who normally boil them. Barriers to change need to be considered when planning the promotion of steaming as a regular method of cooking vegetables, although it may be more convincing to use vegetables such as broccoli that are perceived as being most acceptable when steamed.

ENT training amongst general practitioners: results from a questionnaire.

OBJECTIVES: To evaluate the level of undergraduate and post-graduate ENT exposure amongst general practitioners and their perceived quality of this training. A secondary aim was to examine whether general practitioners believe ENT department based rotations should remain in the undergraduate curriculum. METHOD: An online questionnaire-based survey was sent to general practices in England. RESULTS: A total of 417 general practitioners completed the questionnaire. Sixty-seven per cent had completed an ENT rotation at medical school whereas 27 per cent had undertaken a postgraduate placement in ENT. Fifty-one per cent had received post-graduate teaching in ENT, mainly in the form of lectures. The majority of general practitioners were not satisfied with their training in ENT at undergraduate and post-graduate levels. Eighty-five per cent of general practitioners believed formal hospital-based ENT training should remain in the undergraduate curriculum. CONCLUSION: General practitioners reported insufficient exposure to ENT during both post-graduate and undergraduate training. Proposals to outsource undergraduate ENT teaching to affiliated departments such as general practice are of concern.

An objective test of stochastic behavior in riverine water quality models.

Predictions of river water quality models are subject to substantial uncertainties, which depend not only on parameterization and calibration strategies but also on the structure of the conceptual model itself. To evaluate the importance of this effect and associated implications for stochastic models, investigations were conducted based on a segment of the Potomac River in the eastern USA. Two commonly used conceptual representations of real-world processes were used, and their simulation of DO, BOD and NH(4) components scrutinized. A GLUE approach to the inverse problem was then used to examine how uncertainty changed along the river network for each conceptual model. Differences were observed not only between deterministic instances of each conceptual model, but also between their response surfaces as a whole. Uncertainties within the river network are substantially influenced by the selection of calibration data used, as well as the primary source of the constituent examined. The suggested methodology can be used to test conceptual model validity for specific applications. The results of this study will help users select and assess models for varied problems, and refine appropriate data collection and monitoring schemes.

Endoscopic transnasal image-guided approach to diagnosis in orbital apex and optic canal lesions.

OBJECTIVE: Prompted by a recurring skull base multidisciplinary team debate on the necessity of securing a definitive tissue diagnosis before initiating treatment for lesions of the orbital apex, a review of anterior skull base procedures over an 11-year period was undertaken. METHODS: Data collected prospectively on cases from 2006 to 2017 were analysed. Presenting symptoms, imaging and histology findings, outcomes, complications, and impact on treatment were evaluated. All surgery was carried out endoscopically with the aid of image guidance. RESULTS: Twenty-one patients undergoing endoscopic orbital apex and/or optic canal biopsy were included. The mean patient age was 49 years. Five malignant tumours were identified, five benign tumours, seven infective cases (two tuberculosis and five fungal) and two cases of immunoglobulin G4 related disease. Two patients had non-diagnostic biopsies (one lesional) and were treated successfully as Tolosa-Hunt syndrome cases. CONCLUSION: A successful diagnosis was achieved in nearly all cases without adverse impact, other than one cerebrospinal fluid leakage case. Management was directly influenced by the outcome in all cases.

Automated characterization of multiple alpha peaks in multi-site electroencephalograms.

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.

Mean field model of acetylcholine mediated dynamics in the thalamocortical system.

A recent continuum model of the large scale electrical activity of the thalamocortical system is generalized to include cholinergic modulation. The model is examined analytically and numerically to determine the effect of acetylcholine (ACh) on its steady states, linear stability, spectrum, and temporal responses. Changing the ACh concentration moves the system between zones of one, three, and five steady states, showing that neuromodulation of synaptic strength is a possible mechanism by which multiple steady states emerge in the brain. The lowest firing rate steady state is always stable, and subsequent fixed points alternate between stable and unstable. Increasing ACh concentration changes the form of the spectrum. Increasing the tonic level of ACh concentration increases the magnitudes of the N100 and P200 in the evoked response potential (ERP), without changing the timing of these peaks. Driving the system with a pulse of cholinergic activity results in a transient increase in the firing rate of cortical neurons that lasts over 10s. Step-like increases in cortical ACh concentration cause increases in the firing rate of cortical neurons, with rapid responses due to fast acting nicotinic receptors and slower responses due to muscarinic receptor suppression of intracortical connections.

A systematic, data-driven approach to the combined analysis of microarray and QTL data.

High-throughputtechnologies inevitably produce vast quantities of data. This presents challenges in terms of developing effective analysis methods, particularly where the analysis involves combining data derived from different experimental technologies. In this investigation, a systematic approach was applied to combine microarray gene expression data, quantitative trait loci (QTL) data and pathway analysis resources in order to identify functional candidate genes underlying tolerance to Trypanosoma congolense infection in cattle. We automated much of the analysis using Taverna workflows previously developed for the study of trypanotolerance in the mouse model. Pathways represented by genes within the QTL regions were identified, and this list was subsequently ranked according to which pathways were over-represented in the set of genes that were differentially expressed (over time or between tolerant N'dama and susceptible Boran breeds) at various timepoints after T. congolense infection. The genes within the QTLthat played a role in the highest ranked pathways were flagged as good targets for further investigation and experimental confirmation.

Genomics approaches to study the biology underlying resistance to trypanosomiasis--some unexpected lessons.

An international multidisciplinary consortium is conducting a programme of research on the host response to trypanosome infection. This builds upon quantitative trait loci (QTL) mapping which identified genome regions influencing susceptibility to pathology following T. congolense infection in both cattle and mice. The approach uses expression analysis to examine the response of both susceptible and resistant strains and a series of novel informatics tools to identify pathways which are activated as a result of challenge, and those which are differentially used by resistant and susceptible strains. Of particular interest are those pathways which simultaneously satisfy both criteria, i.e. are significantly differentially activated and contain genes within QTL regions. However, it is important to stress that it is not required that the genes within the QTL region are differentially expressed themselves.

Neural mechanisms of ERP change: combining insights from electrophysiology and mathematical modeling.

Using a standardized database of EEG data, recorded during the habituation and oddball paradigms, changes in the auditory event-related potential (ERP) are demonstrated on the time scale of seconds and minutes. Based on previous research and a mathematical model of neural activity, neural mechanisms that could account for these changes are proposed. When the stimulus tones are not relevant to a task, N100 magnitude decreases substantially for the first repetition of a stimulus pattern and increases in response to a variant tone. It is argued these short-term changes are consistent with the hypothesis that there is a refractory period in the neural elements underlying the ERP. In the oddball paradigm, when the stimulus tones are task-relevant, the magnitudes of both N100 and P200 for backgrounds decrease over the entire six-minute recording session. It is argued that these changes are mediated by a decreasing arousal level, and consistent with this, a subject's electrodermal activity (EDA) is shown to reduce over the recording session. By fitting ERPs generated by a biophysical model of neural activity, it is shown that the changes in the background ERPs over the recording session can be reproduced by changing the strength of connections between populations of cortical neurons. For ERPs elicited by infrequent stimuli, there is no corresponding trend in the magnitudes of N100 or P300 components. The effects of stimuli serial order on ERPs are also assessed, showing that the N100 for background ERPs and the N100 and P300 for target ERPs increases as the probability, and expectancy, of receiving a task relevant stimulus increases. Cortical neuromodulation by acetylcholine (ACh) is proposed as a candidate mechanism to mediate the ERP changes associated with attention and arousal.