The role of large cavity sinus surgery in the management of chronic rhinosinusitis in non-steroidal anti-inflammatory drug exacerbated respiratory disease: a single-centre experience and long-term outcomes.

OBJECTIVE: This study aimed to discuss the role of large cavity functional endoscopic sinus surgery in the management of chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease. METHODS: This was a retrospective review of patients undergoing large cavity functional endoscopic sinus surgery for non-steroidal anti-inflammatory drug exacerbated respiratory disease from January 2016 to March 2022. Population characteristics, pre- and post-operative number of functional endoscopic sinus surgical procedures, endoscopic polyp grade, Lund-Mackay score and nasal symptoms were recorded. RESULTS: Thirteen consecutive patients with a median age of 47 years were included. They all failed maximal medical treatment and/or conservative functional endoscopic sinus surgery and underwent large cavity sinus surgery followed by post-operative maximal medical therapy. All patients showed an improvement in nasal symptoms with improved Lund-Mackay scores post-operatively. The median length of follow up was 1.5 years. CONCLUSION: Large cavity functional endoscopic sinus surgery seems to halt the progression of chronic rhinosinusitis with nasal polyps in non-steroidal anti-inflammatory drug exacerbated respiratory disease. In this case series, large cavity functional endoscopic sinus surgery combined with optimal post-operative medical treatment appeared to switch off chronic rhinosinusitis with nasal polyps in patients with non-steroidal anti-inflammatory drug exacerbated respiratory disease.

Lessons from rhinology and facial plastic surgery clinical negligence claims in England 2013-2018.

OBJECTIVE: This study reviewed all rhinology clinical negligence claims in the National Health Service in England between 2013 and 2018. METHOD: All clinical negligence claims held by National Health Service Resolution relating to rhinology in England between 1 April 2013 and 1 April 2018 were reviewed. RESULTS: There were 171 rhinology related claims with a total estimated potential cost of £13.6 million. There were 119 closed claims (70 per cent) with a total cost of £2.3 million, of which 55 claims resulted in payment of damages. Over three quarters of all rhinology claims were associated with surgery (n = 132). Claims associated with endoscopic sinus surgery had the highest mean cost per claim (£172 978). Unnecessary pain (33.9 per cent) and unnecessary operation (28.1 per cent) were the most commonly cited patient injuries. CONCLUSION: Patient education and consent have been highlighted as key areas for improvement from this review of rhinology related clinical negligence claims. A shift in clinical practice towards shared decision making could reduce litigation in rhinology.

Intranasal sodium citrate in quantitative and qualitative olfactory dysfunction: results from a prospective, controlled trial of prolonged use in 60 patients.

OBJECTIVES: We have previously shown that treatment with intranasal sodium citrate may be beneficial in post-infectious olfactory dysfunction. Sodium citrate reduces free intranasal calcium and is, therefore, thought to prevent calcium-mediated feedback inhibition at the level of the olfactory receptor. We aimed to determine whether treatment with a 2-week course of intranasal sodium citrate improves quantitative olfactory function in patients with post-infectious impairment. We also aimed to determine whether sodium citrate is beneficial in treating qualitative olfactory dysfunction. METHODS: We performed a prospective, controlled study. Patients applied intranasal sodium citrate solution to the right nasal cavity for 2 weeks. The left nasal cavity was untreated and, therefore, acted as an internal control. Monorhinal olfactory function was assessed using the "Sniffin' Sticks" composite 'TDI' score, before and after treatment. The presence of parosmia and phantosmia was also assessed. RESULTS: Overall, there was a significant increase in TDI after treatment (using the best of right and left sides). Treatment with sodium citrate did not significantly improve quantitative olfactory function, compared to control. The proportion of patients reporting parosmia did not change significantly after treatment. However, there was a significant reduction in the proportion of patients reporting phantosmia, at the end of the study period. CONCLUSIONS: Treatment with intranasal sodium citrate for a period of 2 weeks does not appear to improve quantitative olfactory function in patients with post-infectious impairment, compared to control. It may, however, be beneficial in treating phantosmia, which should be further addressed in future work.

Evaluation of historic in vivo data to characterise the emetic properties of liquid cleaning products and provide a framework for the development of an in silico predictive algorithm.

Accidental ingestion of household cleaning products frequently results in emesis but the physicochemical properties responsible are not known. To investigate whether data collected during in vivo animal studies performed >30 years ago could provide novel insights into the components responsible, we re-analysed original studies from a total of 74 liquid cleaning formulations. The incidence of emesis was dose-related with ED50 values between 0.012 and 8.4 ml/kg and 57% of formulations having an ED50 ≤ 1 ml/kg. The median latency for emesis was 10.0 min (95% CI, 8-12 min) and number of vomits in 60 min ranged from 1 to 10 (median 2). From the ED100, latency and number of vomits we derived a "vomiting index" (VI) for a subset of 15 formulations which revealed an association between a high VI, a high percentage of non-ionic surfactants/high ionic strength, and a pH of ~10 which we propose are causally linked with the possible mechanism(s) discussed. The limitations of using historic data are discussed but analysis of such data has provided novel insights into the emetic characteristics of this class of products and has informed the development of an in silico model to predict the emetic liability of novel formulations without additional in vivo studies.

Endovascular clot retrieval for acute ischaemic stroke due to basilar artery occlusion in childhood.

Endovascular clot retrieval (ECR) is an emerging therapy for treatment of acute ischaemic stroke (AIS) in adults, including basilar artery occlusion (BAO). Its role in children is not well established. We report four consecutive children with AIS due to BAO treated with ECR in Sydney, Australia. We reviewed the literature to characterize the 'natural course' of AIS due to BAO in children not treated with thrombolysis or ECR, and compared their outcome with our patients and reported children with BAO treated with ECR. Despite delays in diagnosis, ECR achieved recanalization in our four children. Three children had a good outcome (Paediatric Modified Rankin Score [PedmRS] 0-2). One child with acute leukaemia suffered recurrent basilar occlusion and died of brainstem dysfunction. Literature review identified 111 children exhibiting the natural course of AIS due to BAO, among whom 42% had good outcomes (PedmRS 0-2), 48% had significant residual disability (PedmRS 3-5), and 10% died. Of 34 children treated with ECR, 28 (82%) had good outcomes (PedmRS 0-2), five (15%) had significant residual disability (PedmRS 3-5), and one (3%) died. Complications of ECR were uncommon. These observations suggest ECR may be beneficial for children with AIS due to BAO. WHAT THIS PAPER ADDS: Children with acute ischaemic stroke (AIS) due to basilar artery occlusion (BAO) experience significant morbidity and mortality. Endovascular clot retrieval may be beneficial in children with AIS due to BAO.

Case report of a child bearing a novel deleterious splicing variant in PIGT.

RATIONALE: Trio family-based whole exome sequencing (WES) is a powerful tool in the diagnosis of rare neurodevelopmental diseases, even in patients with the unclear diagnosis. There have been previous reports of variants in the phosphatidylinositol glycan anchor biosynthesis class T (PIGT) gene associated with multiple congenital anomalies, with a total of 14 affected individuals across 8 families. PATIENT CONCERNS: An 18-month-old boy of Greek ancestry presented with global developmental delay, generalized tonic-clonic seizures, hypotonia, renal cysts, esotropia, bilateral undescended testes, bilateral vesicoureteric reflux, marked cardiac dextroposition, bilateral talipes equinovarus, and dysmorphic features. DIAGNOSIS: WES revealed 2 compound heterozygous variants in the PIGT gene, c.[494-2A>G]; [547A>C]/p.[Asp122Glyfs*35]; [Thr183Pro]. The splicing mutation was demonstrated to lead to the skipping of exon 4. INTERVENTIONS: Seizures, infections, and other main symptoms were treated. OUTCOMES: The patient died at 2 years of age before the molecular diagnosis was achieved. Genetic counseling has been offered to the family. LESSONS: Most of the clinical features of the patient are in agreement with the previously described PIGT cases corroborating the usefulness of WES as a diagnostic tool.

Rhinological interventions for obstructive sleep apnoea - a systematic review and descriptive meta-analysis.

OBJECTIVES: Obstructive sleep apnoea is a common chronic sleep disorder characterised by collapse of the upper airway during sleep. The nasal airway forms a significant part of the upper airway and any obstruction is thought to have an impact on obstructive sleep apnoea. A systematic review was performed to determine the role of rhinological surgical interventions in the management of obstructive sleep apnoea. METHODS: A systematic review of current literature was undertaken; studies were included if they involved comparison of a non-surgical and/or non-rhinological surgical intervention with a rhinological surgical intervention for treatment of obstructive sleep apnoea. RESULTS: Sixteen studies met the selection criteria. The pooled data suggest that there are reductions in the apnoea/hypopnea index and respiratory disturbance index following nasal surgery. However, the current body of studies is too heterogeneous for statistically significant meta-analysis to be conducted. CONCLUSION: Nasal surgery may have limited benefit for a subset of patients based on current evidence.

Structural Plasticity of the Primary and Secondary Olfactory cortices: Increased Gray Matter Volume Following Surgical Treatment for Chronic Rhinosinusitis.

Functional plasticity of the adult brain is well established. Recently, the structural counterpart to such plasticity has been suggested by neuroimaging studies showing experience-dependent differences in gray matter (GM) volumes. Within the primary and secondary olfactory cortices, reduced GM volumes have been demonstrated in patients with olfactory loss. However, these cross-sectional studies do not provide causal evidence for GM volume change, and thereby structural plasticity. Disorders of the peripheral olfactory system, such as chronic rhinosinusitis (CRS), provide an ideal model to study GM structural plasticity, given that patients may experience long periods of olfactory impairment, followed by near complete recovery with treatment. We therefore performed a prospective longitudinal study in patients undergoing surgical treatment for CRS. We used voxel-based morphometry (VBM) to investigate GM volume change in 12 patients (M:F = 7:5; 47.2 ±â€¯14.9 years), 3 months post-op. There was a significant improvement in olfactory function according to birhinal psychophysical testing. We performed a voxel-wise region of interest analysis, with significance corrected for number of regions (p < 0.0036corr). We found significantly increased post-operative GM volumes within the primary (left piriform cortex, right amygdala) and secondary (right orbitofrontal cortex, caudate nucleus, hippocampal-parahippocampal complex and bilateral temporal poles) olfactory networks, and decreased GM volumes within the secondary network only (left caudate nucleus and temporal pole, bilateral hippocampal-parahippocampal complex). As a control measure, we assessed GM change within V1, S1 and A1, where there were no suprathreshold voxels. To our knowledge, this is the first study to demonstrate GM structural plasticity within the primary and secondary olfactory cortices, following restoration of olfaction.

The internal nasal valve: a validated grading system and operative guide.

PURPOSE: Nasal obstruction is a highly subjective and commonly reported symptom. The internal nasal valve (INV) is the rate limiting step to nasal airflow. A static INV grading score was devised with regard to visibility of the middle turbinate. METHODS: A prospective study of all patients who underwent primary external functional septorhinoplasty in 2017 for nasal obstruction. All patients' INV score was assessed pre- and postoperatively in a blinded and independent fashion by surgeons of varying seniority. RESULTS: Twenty-eight patients were studied, with mean age 30.9 years and follow-up 18.8 weeks. Inter-rater and test-retest reliability of INV grading were excellent, with Cronbach's alpha 0.936 and 0.920, respectively. There was also statistically significant improvement in both subjective and objective postoperative outcome measures including nasal inspiratory peak flows. CONCLUSIONS: We demonstrate a novel, easy to interpret, clinically valuable grading system of the static internal nasal valve that is reliable and reproducible.

Patient experience of nasal obstruction and its clinical assessment.

BACKGROUND: The correlation between objective and subjective nasal obstruction is poor, and dissatisfaction rates after surgery for nasal obstruction are high. Accordingly, novel assessment techniques may be required. This survey aimed to determine patient experience and preferences for the measurement of nasal obstruction. METHOD: Prospective survey of rhinology patients. RESULTS: Of 72 questionnaires distributed, 60 were completed (response rate of 83 per cent). Obstruction duration (more than one year) (χ2 = 13.5, p = 0.00024), but not obstruction severity, affected willingness to spend more time being assessed. Questionnaires (48 per cent) and nasal inspiratory peak flow measurement (53 per cent) are the most commonly used assessment techniques. Forty-nine per cent of participants found their assessment unhelpful in understanding their obstruction. Eighty-two per cent agreed or strongly agreed that a visual and numerical aid would help them understand their blockage. CONCLUSION: Many patients are dissatisfied with current assessment techniques; a novel device with visual or numerical results may help. Obstruction duration determines willingness to undergo longer assessment.

Acquired Genetic and Epigenetic Variation in Human Pluripotent Stem Cells.

Human pluripotent stem cells (hPSCs) can acquire non-random genomic variation during culture. Some of these changes are common in tumours and confer a selective growth advantage in culture. Additionally, there is evidence that reprogramming of human induced pluripotent stem cells (hiPSCs) introduces mutations. This poses a challenge to both the safety of clinical applications and the reliability of basic research using hPSCs carrying genomic variation. A number of methods are available for monitoring the genomic integrity of hPSCs, and a balance between practicality and sensitivity must be considered in choosing the appropriate methods for each use of hPSCs. Adjusting protocols by which hPSCs are derived and cultured is an evolving process that is important in minimising acquired genomic variation. Assessing genetic variation for its potential impact is becoming increasingly important as techniques to detect genome-wide variation improve.

A UK survey of current ENT practice in the assessment of nasal patency.

BACKGROUND: Nasal obstruction is a common ENT complaint; however, decisions on its management are challenging, with high rates of dissatisfaction following surgery. This study investigated the practice of UK clinicians in the evaluation of nasal patency. METHOD: Seventy-eight UK-based rhinologists were surveyed at the 2015 British Academic Conference in Otolaryngology. RESULTS: Clinical history and examination are almost universally used to evaluate nasal blockage. The most commonly used test was the nasal misting pattern (73 per cent), followed by peak nasal inspiratory flow (19 per cent). The Sino-Nasal Outcome Test 22 or 23 was utilised by 29 per cent of respondents. Sixty-three per cent of respondents reported that a lack of equipment was the principle reason for not using objective measures, followed by time constraints and a lack of correlation with symptom scores. CONCLUSION: British clinicians rely on clinical skills to evaluate nasal blockage. There is a desire for a simple, non-invasive device that objectively measures airflow for nasal breathing during physiological resting and correlates with subjective symptom scores.

ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism.

Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data. We report deletions that generate chimeric ATAD3B/ATAD3A fusion genes in individuals from four unrelated families with fatal congenital pontocerebellar hypoplasia, whereas a case with genomic rearrangements affecting the ATAD3C/ATAD3B genes on one allele and ATAD3B/ATAD3A genes on the other displays later-onset encephalopathy with cerebellar atrophy, ataxia and dystonia. Fibroblasts from affected individuals display mitochondrial DNA abnormalities, associated with multiple indicators of altered cholesterol metabolism. Moreover, drug-induced perturbations of cholesterol homeostasis cause mitochondrial DNA disorganization in control cells, while mitochondrial DNA aggregation in the genetic cholesterol trafficking disorder Niemann-Pick type C disease further corroborates the interdependence of mitochondrial DNA organization and cholesterol. These data demonstrate the integration of mitochondria in cellular cholesterol homeostasis, in which ATAD3 plays a critical role. The dual problem of perturbed cholesterol metabolism and mitochondrial dysfunction could be widespread in neurological and neurodegenerative diseases.

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance.

Centrally located GLP-1 receptors modulate gastric slow waves and cardiovascular function in ferrets consistent with the induction of nausea.

Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients. GLP-1 receptors are distributed widely in the brain, where they contribute to mechanisms of emesis, reduced appetite and aversion, but it is not known if these centrally located receptors also contribute to a modulation of gastric slow wave activity, which is linked causally to nausea. Our aim was to investigate the potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd ventricle to modulate emesis, feeding and gastric slow wave activity. Thermoregulation and cardiovascular parameters were also monitored, as they are disturbed during nausea. Ferrets were used as common laboratory rodents do not have an emetic reflex. A guide cannula was implanted into the 3rd ventricle for delivering a previously established dose of exendin-4 (10nmol), which had been shown to induce emesis and behaviours indicative of 'nausea'. Radiotelemetry recorded gastric myoelectric activity (GMA; slow waves), blood pressure and heart rate variability (HRV), and core temperature; food intake and behaviour were also assessed. Exendin-4 (10nmol, i.c.v.) decreased the dominant frequency of GMA, with an associated increase in the percentage of bradygastric power (lasting ~4h). Food intake was inhibited in all animals, with 63% exhibiting emesis. Exendin-4 also increased blood pressure (lasting ~24h) and heart rate (lasting ~7h), decreased HRV (lasting ~24h), and caused transient hyperthermia. None of the above parameters were emesis-dependent. The present study shows for the first time that gastric slow waves may be modulated by GLP-1 receptors in the brain through mechanisms that appear independent from emesis. Taken together with a reduction in HRV, the findings are consistent with changes associated with the occurrence of nausea in humans.

Peak nasal inspiratory flow correlates with quality of life in functional endoscopic sinus surgery.

OBJECTIVES: Whilst nasal function and airflow improve subjectively following functional endoscopic sinus surgery (FESS), a clinically useful and objective tool for quantifying such improvement is lacking. The peak nasal inspiratory flow (PNIF) metre offers convenient and objective measures of nasal patency. However, it has not yet been established whether changes in PNIF after surgery reflect changes in subjective disease burden. In this study we aimed to determine whether changes in PNIF correlate with commonly used subjective symptom and quality of life outcome measures following FESS for chronic rhinosinusitis (CRS). DESIGN: Prospective cohort. SETTING: Royal National Throat Nose and Ear Hospital. PARTICIPANTS: Thirty-seven patients undergoing FESS for CRS, with or without polyps (21 male, mean age 48.8). MAIN OUTCOME MEASURES: PNIF, "SNOT-22", "NOSE" and "VAS" questionnaires were performed before and after surgery. RESULTS: In all patients, there was a strong negative correlation between change in PNIF and change in "SNOT-22" score following surgery (Pearson r=-.64, P<.0001). Strong negative correlations were also seen during subgroup analysis of patients with and without polyps (r=-.57, P=.006 and r=-.67, P=.005, respectively). Change in PNIF correlated significantly with change in "NOSE" score following surgery in all patients and those without polyps (r=-.54, P=.0005 and r=-.68, P=.003). There were no significant correlations between PNIF and VAS (nasal obstruction). CONCLUSIONS: Changes in PNIF after FESS appear to best reflect improvements in quality of life in CRS as measured using the "SNOT-22" questionnaire.

The effect of intranasal sodium citrate on olfaction in post-infectious loss: results from a prospective, placebo-controlled trial in 49 patients.

OBJECTIVES: Free calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. Several previous studies have supported this hypothesis, particularly in post-infectious olfactory loss. We therefore aimed to determine whether treatment with intranasal sodium citrate improves olfactory function in patients with post-infectious impairment. DESIGN: Prospective, single-blind, placebo-controlled trial. SETTING: Interdisciplinary Smell and Taste Clinic, TU Dresden (tertiary referral centre). PARTICIPANTS: Forty-nine adult participants with post-infectious olfactory impairment (M : F = 11 : 38, mean age 58.71 ± 11.03 years). MAIN OUTCOME MEASURES: Olfactory function (odour threshold and identification) before and after treatment as determined using "Sniffin' Sticks". Patients were treated monorhinally with 1 mL sodium citrate solution. The contralateral nasal cavity was treated with 1 mL physiological sodium chloride solution, which acted as internal control. Clinical improvement was assumed where threshold or identification score increased by ≥2.5 or 3 points, respectively, or ≥5.5 points together. RESULTS: We demonstrated a statistically significant improvement in composite threshold + identification scores following treatment with sodium citrate, compared with placebo. This was true for all patients (mean improvement 0.87 ± 2.68 points, P = 0.04), and on subgroup analysis in those with hyposmia (mean improvement 1.15 ± 2.37 points, P = 0.02). However, the effect size did not reach clinical significance. CONCLUSIONS: Further basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post-infectious olfactory loss.

Body dysmorphic disorder in patients undergoing septorhinoplasty surgery: should we be performing routine screening?

OBJECTIVE: Body dysmorphic disorder (BDD) is defined as having a preoccupation with a perceived flaw in one's appearance, which appears slight to others and significantly interferes with a person's functioning. When undetected in septorhinoplasty patients, it will often lead to poor outcomes. DESIGN: We performed a prospective cohort study to determine the prevalence of BDD in our patients and whether surgical correction could be considered. SETTING AND PARTICIPANTS: We recruited 34 patients being considered for septorhinoplasty in a tertiary referral rhinology clinic and a control group of 50 from the otology clinic giving a total of 84. MAIN OUTCOME MEASURES: Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ), the sino-nasal outcome test-23 (SNOT-23) and underwent nasal inspiratory peak flow (NIPF). Those found to be at high risk for BDD were referred to a clinical psychologist. RESULTS: Of the septorhinoplasty patients, 11 (32%) were high risk for BDD. Following psychological assessment, 7 (63%) patients were felt to be unsuitable for surgery and were offered psychological therapy. SNOT-23 scores were significantly higher in the BDD group indicating a negative impact on quality of life. NIPF readings were not significantly different in the BDD group compared to the control group. CONCLUSIONS: The BDDQ is a valid tool for identifying patients at risk of BDD. A close working relationship with clinical psychology has been advantageous to help the selection process of candidates for surgery when there is a high risk of BDD.

Insights into the central pathways involved in the emetic and behavioural responses to exendin-4 in the ferret.

BACKGROUND: GLP-1 receptor agonists are utilised for the treatment of Type-2 diabetes but can be associated with undesirable effects of nausea and vomiting. OBJECTIVES: To investigate the role of GLP-1 receptors in mechanisms of emesis, behaviours indicative of nausea (BIN) and food intake in the ferret. RESULTS: Exendin-4 (10 and 30nmol, i.c.v.) induced emesis, inhibited food intake, and increased the frequency of BIN. Increases in c-Fos in the brainstem, midbrain and forebrain occurred in animals exhibiting emesis; no activation of the brainstem occurred in animals not vomiting. Exendin-4 (10nmol, i.c.v.) when preceded by i.c.v. saline (15µl), was not emetic but induced BIN and inhibited food intake; exendin (9-39) (100nmol) reduced BIN only. c-Fos showed that consistent with the absence of emesis in saline/exendin-4 treated animals there was no increase in c-Fos in the brainstem, but it increased in midbrain and forebrain nuclei. Excepting the amygdala, exendin (9-39) was without efffect on the increases in c-Fos. Analysis of c-Fos data showed a positive linear relationship between midbrain and forebrain areas irrespective of the occurrence of emesis induced by exendin-4. In contrast, brainstem and midbrain c-Fos levels were positively correlated, but only in animals with emesis. CONCLUSIONS: The brainstem is critical for exendin-4-induced emesis but suppression of food intake and BIN involves more rostral brain sites. Exendin-4-induced BIN and c-Fos activation of the amygdala are sensitive to exendin (9-39), whereas the suppression of food intake is not implicating separate control mechanisms for emesis and BIN.

Outcomes in endoscopic sinus surgery: olfaction, nose scale and quality of life in a prospective cohort study.

OBJECTIVES: To determine the efficacy of endoscopic sinus surgery (ESS) on olfactory function in chronic rhinosinusitis patients with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and to compare the nasal obstruction and symptom evaluation (NOSE) scale before and after surgery. DESIGN: A prospective cohort study SETTING: Royal National Throat and Nose and Ear Hospital, London UK. PARTICIPANTS: One hundred and thirteen patients with CRS; 60 CRSwNP and 53 CRSsNP. OUTCOME MEASUREMENTS: Olfaction was measured using both the University of Pennsylvania Smell Investigation Test (UPSIT) and the 'sense of smell' visual analogue scale (VAS). The NOSE scale, the sinonasal outcome test (SNOT 22) and the Lund-Kennedy (LK) surgeon reported scores were also measured pre- and postoperatively at 6 months. RESULTS: The UPSIT psychophysical measurement significantly improved following ESS in the CRSwNP subgroup as did the patients perceived VAS sense of smell. However, in the CRSsNP subgroup, the improved VAS and UPSIT measurements were not significant. The NOSE, SNOT 22 and LK scores all improved significantly. The olfactory improvement as measured by the UPSIT correlated to the SNOT-22, but a correlation between the NOSE score and UPSIT was not found. CONCLUSIONS: Endoscopic sinus surgery significantly improved the patient's perceived and measured sense of smell in the CRSwNP subgroup which is the most surgically responsive CRS subgroup. Additionally, improved olfaction in the CRSwNP subgroup is most likely to improve the patient's quality of life. Endoscopic sinus surgery significantly improved the NOSE scale in both CRS subgroups at 6 months following surgery.