An observational pragmatic quality-of-life study on paediatric tonsillectomy and waiting for surgery.

PURPOSE: To investigate parental perceptions of the effects of tonsillectomy on their child's quality of life while awaiting and following surgery in an Australian public health system. METHODS: An observational pragmatic study was undertaken at a tertiary Australian hospital. Parents of paediatric patients (2-16 years of age) listed for tonsillectomy completed a validated quality-of-life questionnaire (T-14 Paediatric Throat Disorders Outcome Test) at the initial consultation, on day of surgery, 6 weeks post-operatively and 6 months post-operatively. T-14 scores were compared using the Related-Samples Wilcoxon Signed Rank Test. RESULTS: Parents of 167 children participated in this study. There was a median wait time of 174 days (IQR 108-347) from the initial consultation until the day of surgery, with no significant change in median T-14 scores (35 [IQR 22-42] vs 36 [IQR 22-42]; n = 63; p > 0.05). There was a significant decrease from pre-operative T-14 scores to 6 weeks post-operatively (33.5 [IQR 22-42] vs 2 [IQR 0-5]; n = 160; p < 0.001), and this was sustained with a minor improvement at 6 months post-operatively (6 weeks 2 [IQR 0-5] vs 6 months 0 [IQR 0-2]; n = 148; p < 0.001). CONCLUSIONS: Paediatric tonsillectomy improves quality of life with a sustained benefit in the long term. There is no improvement to the patient's quality of life while awaiting tonsillectomy, thus patient welfare can be improved through reducing waiting times for surgery.

BiZact™ tonsillectomy: Predictive factors for post-tonsillectomy haemorrhage from a 1717 case series.

OBJECTIVE: To determine primary and secondary post-tonsillectomy haemorrhage (PTH) rates and identify predictive factors in a cohort of consecutive adult and paediatric BiZact™ tonsillectomy cases. SETTING: Retrospective cohort study. Patients from Flinders Medical Centre, Noarlunga Hospital and private otolaryngology practices who underwent BiZact™ tonsillectomy from 2017 to 2020. DATA COLLECTED: patient age, indication for tonsillectomy, surgeon experience, time and severity of PTH, including return to theatre. Each secondary PTH was graded using the Stammberger classification. Logistic regression was utilised to identify predictors of secondary PTH. RESULTS: One thousand seven hundred and seventeen patient medical records were assessed (658 adults and 1059 children). The primary PTH rate was 0.1%, and secondary PTH rate was 5.9%. The majority of secondary PTH cases were Stammberger grade A (80/102, 78.4%) requiring observation only. Few secondary PTH required medical intervention (grade B; 9/102, 8.8%), return to theatre (grade C; 12/102, 11.8%), or blood transfusion (grade D; 1/102, 1.0%), with no death reported (grade E; 0/102, 0.0%). Recurrent secondary PTH occurred in 8 patients (0.5%). Predictive factors of secondary PTH in children were surgeon experience with trainees having greater chance of PTH (OR 2.502, 95% CI 1.345-4.654; p = .004) and age of child (OR 1.095, 95% CI 1.025-1.170; p = .007). Surgeon experience was a predictive factor for adults (OR 3.804, 95% CI 2.139-6.674; p < .001). CONCLUSIONS: BiZact™ tonsillectomy has a low primary PTH rate, with a secondary PTH rate comparable to other 'hot tonsillectomy' techniques. The majority of PTH events were minor and self-reported. There appears to be a learning curve for trainee surgeons.

Health Related Quality of Life T-14 Outcomes for Pediatric Bizact Tonsillectomy.

Objectives: The objective of this study was to assess the T-14 outcomes of the BizactTM device for tonsillectomy in a pediatric population. Methods: A case series chart review was undertaken at a public tertiary teaching hospital and private otolaryngology practice, with data collected from pediatric patients who underwent a BizactTM tonsillectomy between July 2016 and October 2019 for any indication, whose parents consented to completing the T-14 questionnaire providing a parental perspective of the child's quality of life. Primary outcomes were T-14 scores recorded preoperatively and 6 weeks post-operatively. Secondary outcome measures were postoperative complications, including hemorrhage and readmission. Results: 146 patients were identified. There was a significant improvement in T-14 scores from a median of 24 (Interquartile range (IQR) 18-33) prior to surgery to 2 (IQR 0-4) at 6 weeks postoperatively (p < 0.001). The post-tonsillectomy hemorrhage rate was 6.1% (9/146 participants). Conclusions: Pediatric BizactTM tonsillectomy is effective in treating common indications for pediatric tonsillectomy, reflected by improved parent-reported health-related quality of life T-14 scores postoperatively.

Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.

Importance: Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. Objective: To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed. Design, Setting, and Participants: Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018. Interventions: Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51). Main Outcomes and Measures: Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS. Results: Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood). Conclusions and Relevance: In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.

The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.

This scoping review identifies the mechanistic pathways of metformin when used to treat head and neck cancer cells, in the pre-clinical setting. Understanding the underlying mechanisms will inform future experimental designs exploring metformin as a potential adjuvant for head and neck cancer. This scoping review was conducted according to the Joanna-Briggs Institute framework. A structured search identified 1288 studies, of which 52 studies fulfilled the eligibility screen. The studies are presented in themes addressing hallmarks of cancer. Most of the studies demonstrated encouraging anti-proliferative effects in vitro and reduced tumor weight and volume in animal models. However, a few studies have cautioned the use of metformin which supported cancer cell growth under certain conditions.

Sleep apnea multi-level surgery trial: long-term observational outcomes.

STUDY OBJECTIVES: The sleep apnea multi-level surgery (SAMS) randomized clinical trial showed surgery improved outcomes at 6 months compared to ongoing medical management in patients with moderate or severe obstructive sleep apnea (OSA) who failed continuous positive airway pressure therapy. This study reports the long-term outcomes of the multi-level surgery as a case series. METHODS: Surgical participants were reassessed >2 years postoperatively with the same outcomes reported in the main SAMS trial. Primary outcomes were apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS), with secondary outcomes including other polysomnography measures, symptoms, quality of life, and adverse events. Long-term effectiveness (baseline to long-term follow-up [LTFU]) and interval changes (6 month to LTFU) were assessed using mixed effects regression models. Control participants were also reassessed for rate of subsequent surgery and outcomes. RESULTS: 36/48 (75%) of surgical participants were reevaluated (mean (standard deviation)) 3.5 (1.0) years following surgery, with 29 undergoing polysomnography. AHI was 41/h (23) at preoperative baseline and 21/h (18) at follow-up, representing persistent improvement of -24/h (95% CI -32, -17; p < 0.001). ESS was 12.3 (3.5) at baseline and 5.5 (3.9) at follow-up, representing persistent improvement of -6.8 (95% CI -8.3, -5.4; p < 0.001). Secondary outcomes were improved long term, and adverse events were minor. Interval change analysis suggests stability of outcomes. 36/43 (84%) of the control participants were reevaluated, with 25 (69%) reporting subsequent surgery, with symptom and quality of life improvements. CONCLUSION: Multi-level upper airway surgery improves OSA burden with long-term maintenance of treatment effect in adults with moderate or severe OSA in whom conventional therapy failed. CLINICAL TRIAL: Multi-level airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true; ACTRN12614000338662.

Prognostic Value of 18 F-Fluoro-Deoxyglucose-Positron Emission Tomography Volumetric Parameters in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: This study evaluates and compares the prognostic significance of 18 F-fluoro-deoxyglucose-positron emission tomography (18 F-FDG PET) volumetric parameters in human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A retrospective review of all patients treated for OPSCC with curative intent between 2012 and 2018 was performed. Volumetric parameters analyzed included the maximum standardized uptake value (SUVmax ), SUVpeak , metabolic tumor volume (MTV), and total lesion glycolysis (TLG) in both the primary tumor and nodal metastases. Prognostic significance was determined using Cox proportional hazards models for disease-free survival (DFS) and overall survival (OS). RESULTS: Primary tumor MTV and TLG significantly correlated with both DFS and OS however the commonly reported SUVmax was not found to be predictive. Nodal measures of SUVmax , MTV, and TLG were not significant predictors of survival outcomes. CONCLUSION: A higher burden of metabolically active primary tumor as measured on volumetric 18 F-FDG PET parameters is associated with poorer DFS and OS. This improved prognostication may be used to counsel patients and select those appropriate for treatment de-escalation in the future. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1667-1672, 2023.

Swallowing biomechanics in tracheostomised critically ill patients compared to age- and gender-matched healthy controls.

Objective: The mechanistic effects of a tracheostomy on swallowing are unclear. Pharyngeal high-resolution manometry with impedance (P-HRM-I) is a novel swallow assessment tool providing quantifiable metrics. This study aimed to characterise swallowing biomechanics in tracheostomised critically ill (non-neurological) patients. Design: Cohort study. Setting: Australian tertiary hospital intensive care unit. Participants: Tracheostomised adults, planned for decannulation. Main outcome measures: Swallowing assessment using P-HRM-I, compared to healthy age- and gender-matched controls. Results: In this tracheostomised cohort (n = 10), the Swallow Risk Index, a global measure of swallow function, was significantly elevated (p < 0.001). At the upper oesophageal sphincter (UOS), hypopharyngeal intrabolus pressure and UOS integrated relaxation pressure were significantly elevated (control 0.65 mmHg [-1.02, 2.33] v tracheostomy 13.7 mmHg [10.4, 16.9], P < 0.001; control -4.28 mmHg [-5.87, 2.69] v tracheostomy 12.2 mmHg [8.83, 15.6], P < 0.001, respectively). Furthermore, UOS opening extent and relaxation time were reduced (control 4.83 mS [4.60, 5.07] v tracheostomy 4.33 mS [3.97, 4.69], P = 0.002; control 0.52 s [0.49, 0.55] v tracheostomy 0.41 s [0.37, 0.45], P < 0.001, respectively). Total pharyngeal contractility (PhCI) measuring pharyngeal pressure generation was significantly elevated (control 199.5 mmHg cm.s [177.4, 221.6] v tracheostomy 326.5 mmHg cm.s [253.3, 399.7]; P = 0.001). Conclusion: In a critically ill tracheostomised cohort, UOS dysfunction was the prevalent biomechanical feature, with elevated pharyngeal pressures. Pharyngeal weakness is not contributing to dysphagia in this cohort. Instead, elevated pharyngeal pressures may represent a compensatory mechanism to overcome the UOS dysfunction. Further studies to extend these findings may inform the development of timely and targeted rehabilitation.

The Nasal Innate Immune Proteome After Saline Irrigation: A Pilot Study in Healthy Individuals.

BACKGROUND: Previous research has shown diminished nasal immune function following nasal saline irrigation (NSI), returning to baseline at 6 hours. The aim of this study was to examine the immune nasal proteome before and after 14 days of nasal irrigation. METHODS: Seventeen healthy volunteers received either isotonic (IsoSal) or low salt (LowNa) NSI. Nasal secretions were collected before and 30 min after NSI at baseline and again after 14 days. Specimens were analyzed using mass spectrometry to detect proteins of relevance to nasal immune function. RESULTS: One thousand eight hundred and sixty-five proteins were identified with significant changes in 71 proteins, of which 23 were identified as part of the innate immune system. Baseline analysis demonstrated an increase of 9 innate proteins after NSI, most after IsoSal. After 14 days, a greater increase in innate peptides was present, with most now in the LowNa group. When NSI solutions were compared, a significant increase in 4 innate proteins, including a 211% in lysozyme, was detected in the LowNa group. CONCLUSION: LowNa NSI demonstrates evidence of improving the innate immune secretions, especially lysozyme, in healthy volunteers.

Anterior Pedicled Nasal Flap in Frontal Sinus Drill-Out Patients: A Randomised Controlled Pilot Study.

Background: The endoscopic modified Lothrop procedure (EMLP) is a common procedure performed in patients with frontal sinus pathology. While performing this procedure, large segments of bone are exposed, which may lead to the promotion of frontal sinus neo-ostium stenosis. Here we examine the peri-operative differences in time to achieve healing in patients where a mucosal flap is used to cover the exposed bone on one side of the neo-ostium. Design: A randomised pilot study with 12 patients undergoing EMLP surgery participated in this study. Methods: Patients were randomised to undergo a mucosal flap on either the left or right side of the neo-ostium. Prior to surgery, patients completed a SNOT-22 and smell identification test. Patients were reviewed until the neo-ostium had healed on both sides. Once healing had occurred, a post-operative SNOT-22 score and smell identification test were recorded. Results: Average time to healing for the frontal sinus neo-ostium was 4.7 vs. 4.2 (p = 0.3) on the flap vs. non-flap side, respectively. There was an average 24.4 point (range: -75 to +9) decrease in SNOT-22 scores post-surgery. The post-operative USPIT score demonstrated an average increase of 6.6 points (range -13 to +27). Conclusion: We did not detect significant differences in peri-operative time toward healing in neo-ostiums where a single flap is utilised. Further studies are needed to determine whether the usage of a single neo-ostium flap affords any benefit over no flap on either ostium. SNOT-22 and UPSIT scores improved post-surgery.

Pharyngeal tongue base augmentation for dysphagia therapy: A prospective case series in patients post head and neck cancer treatment.

BACKGROUND: Dysphagia post head and neck cancer (HNC) multimodality treatment is attributed to reduced pharyngeal strength. We hypothesized that pharyngeal tongue base augmentation for dysphagia (PAD therapy) would increase pharyngeal pressures during swallowing thereby improving swallow symptoms. METHODS: Adults with moderate-severe dysphagia post-HNC treatment had PAD therapy using a temporary filler (hyaluronic acid [HA]), with follow-up long-lasting lipofilling. Swallowing preprocedure and postprocedure was assessed with the Sydney Swallow Questionnaire (SSQ), High-Resolution Pharyngeal Manometry (HRPM), and Videofluoroscopic Swallowing Study (VFSS). Statistical comparison utilized paired tests. RESULTS: Six participants (all male; median age 64 years [IQR 56, 71]) underwent PAD therapy at a median of 47 [IQR 8, 95] months post-treatment. SSQ scores reduced from baseline (mean 1069 [95%CI 703, 1434]) to post-HA (mean 579 [76, 1081], p > 0.05), and post-lipofilling (491 [95%CI 913, 789], p = 0.003, n = 4). Individual participants demonstrated reduced Swallow Risk Index, Bolus Presence Time, and increased Upper Esophageal Sphincter opening, but mesopharyngeal contractile pressures were unchanged. VFSS measures of aspiration, residue, and severity were unchanged. CONCLUSIONS: Novel PAD therapy is safe and improves dysphagia symptoms. Biomechanical swallowing changes are suggestive of more efficacious bolus propulsion with conservative filler volume, but this was unable to resolve residue or aspiration measures.

Swallowing biomechanics before and following multi-level upper airway surgery for obstructive sleep apnea.

STUDY OBJECTIVES: The effect of contemporary multi-level upper airway surgery for obstructive sleep apnea on swallowing is unclear. This study assessed the biomechanical swallowing function in participants with obstructive sleep apnea pre- and post-modified uvulopalatopharyngoplasty and coblation channeling of the tongue. METHODS: In this prospective, longitudinal study, adults diagnosed with moderate-severe obstructive sleep apnea who underwent modified uvulopalatopharyngoplasty and coblation channeling of the tongue surgery had swallowing biomechanics assessed using high-resolution pharyngeal manometry and analyzed with swallowgateway.com. Symptomatic swallowing difficulty was evaluated using the Sydney Swallow Questionnaire (≥ 234). General linear mixed-model analysis was conducted to evaluate the difference pre- and post-modified uvulopalatopharyngoplasty and coblation channeling of the tongue. Data are presented as mean [95% confidence intervals]. RESULTS: High-resolution pharyngeal manometry assessments were conducted in 10 participants (7 men; median age 50 [interquartile range 36-65]) preoperatively and repeated postoperatively at 9 months [interquartile range 6-13]. Self-reported dysphagia was unchanged following surgery (Sydney Swallow Questionnaire =149 [53, 447] to 168 [54, 247]; P = .093). High-resolution pharyngeal manometry outcomes indicated reduced mesopharyngeal pressures (148 [135, 161] to 124 [112, 137] mm Hg s cm; P = .011), reduced hypopharyngeal pressures (113 [101, 125] to 93 [84, 102] mm Hg s cm; P = 0.011), and reduced upper esophageal sphincter relaxation pressure (5 [4, 6] to 2 [1,3] mm Hg; P = 0.001) but no change to velopharyngeal pressures (135 [123, 147] to 137 [117, 157] mm Hg s cm; P = .850) postsurgery. CONCLUSIONS: Modified uvulopalatopharyngoplasty may have less implications on the swallow mechanism than previously suspected. In contrast, the reduction in mesopharyngeal contractile pressures associated with coblation channeling of the tongue, although within normal limits, may affect bolus propulsion. Biomechanical alterations were insufficient to worsen self-reported swallowing function. CITATION: Schar MS, Omari TI, Woods CW, et al. Swallowing biomechanics before and following multi-level upper airway surgery for obstructive sleep apnea. J Clin Sleep Med. 2022;18(4):1167-1176.

Altered swallowing biomechanics in people with moderate-severe obstructive sleep apnea.

STUDY OBJECTIVES: Dysphagia is a common but under-recognized complication of obstructive sleep apnea (OSA). However, the mechanisms remain poorly described. Accordingly, the aim of this study was to assess swallowing symptoms and use high-resolution pharyngeal manometry to quantify swallowing biomechanics in patients with moderate-severe OSA. METHODS: Nineteen adults (4 female; mean (range) age, 46 ± 26-68 years) with moderate-severe OSA underwent high-resolution pharyngeal manometry testing with 5-, 10-, and 20-mL volumes of thin and extremely thick liquids. Data were compared with 19 age- and sex-matched healthy controls (mean (range) age, 46 ± 27-68 years). Symptomatic dysphagia was assessed using the Sydney Swallow Questionnaire. Swallow metrics were analyzed using the online application swallowgateway.com. General linear mixed model analysis was performed to investigate potential differences between people with moderate-severe OSA and controls. Data presented are means [95% confidence intervals]. RESULTS: Twenty-six percent (5 of 19) of the OSA group but none of the controls reported symptomatic dysphagia (Sydney Swallow Questionnaire > 234). Compared with healthy controls, the OSA group had increased upper esophageal sphincter relaxation pressure (-2 [-1] vs 2 [1] mm Hg, F = 32.1, P < .0001), reduced upper esophageal sphincter opening (6 vs 5 mS, F = 23.6, P < .0001), and increased hypopharyngeal intrabolus pressure (2 [1] vs 7 [1] mm Hg, F = 19.0, P < .05). Additionally, upper pharyngeal pressures were higher, particularly at the velopharynx (88 [12] vs 144 [12] mm Hg⋅cm⋅s, F = 69.6, P < .0001). CONCLUSIONS: High-resolution pharyngeal manometry identified altered swallowing biomechanics in people with moderate-severe OSA, which is consistent with a subclinical presentation. Potential contributing mechanisms include upper esophageal sphincter dysfunction with associated upstream changes of increased hypopharyngeal distension pressure and velopharyngeal contractility. CITATION: Schar MS, Omari TI, Woods CM, et al. Altered swallowing biomechanics in people with moderate-severe obstructive sleep apnea. J Clin Sleep Med. 2021;17(9):1793-1803.

Volumetric magnetic resonance imaging analysis of multilevel upper airway surgery effects on pharyngeal structure.

STUDY OBJECTIVES: The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat). METHODS: This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed. RESULTS: The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04-0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement. CONCLUSIONS: This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required. CLINICAL TRIAL: This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014.

Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin.

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10(-12) M to 10(-7) M), carbachol (10(-6) M), or caerulein (10(-10) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) alone or combined with galanin (10(-12) M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10(-6) M and 10(-10) M, respectively. Galanin (10(-12) M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.

Examining the Evidence for an Adult Healthy Middle Ear Microbiome.

Otitis media (OM) is a cluster of diseases of the middle ear that commonly result from bacterial infection. OM subtypes in which the tympanic membrane is intact (acute otitis media and otitis media with effusion) are presumed to result from pathogen translocation through the eustachian tube. Recent molecular-based studies have suggested that a diverse middle ear microbiome exists in the absence of disease. These have been largely unsupported by culture and feature species that commonly contaminate low-biomass sequencing data. Combining culture-based and molecular techniques, we undertook a detailed investigation of the evidence for bacterial colonization of the healthy middle ear. Middle ear (ME), nasopharynx (NP), and external ear canal (EC) swabs were collected from a total of 25 adult patients undergoing cochlear implant, stapedotomy, or translabyrinthine vestibular schwannoma resection. Diagnostic culture, microscopy, quantitative PCR, and 16S rRNA gene amplicon sequencing were used to assess sample bacterial content. EC and NP microbiota were consistent with previous reports. In contrast, bacterial levels in ME samples were not significantly above those in unused control swabs. Commonly detected taxa were among recognized sequencing contaminants (Methylobacterium, Pseudomonas, and Acinetobacter). Linear regression of dominant ME taxa confirmed a negative relationship between relative abundance and bacterial load, consistent with contamination. No bacteria were detected by microscopy or diagnostic culture in any middle ear sample. Our findings cast substantial doubt on previous reports identifying a healthy middle ear microbiome using 16S amplicon sequencing.IMPORTANCE Recent molecular-based studies have suggested that a diverse middle ear microbiome in adults and children can exist in the absence of disease. These studies have been largely unsupported by culture and feature species that commonly contaminate low-biomass sequencing data. While 16S rRNA gene amplicon sequencing has proven to be a highly informative technique in many clinical contexts, it is susceptible to spurious signal arising from sequencing reagent contaminants where sample biomass is low. Combining culture-based and molecular techniques, we undertook a detailed investigation of the evidence for bacterial colonization of the healthy middle ear. In finding no evidence of viable bacterial cells in middle ear samples, our study further underlines the importance of careful consideration of amplicon sequence data derived from very-low-biomass contexts and the value of analytical approaches that combine culture and molecular techniques.

Sleep Apnea Multilevel Surgery (SAMS) trial protocol: a multicenter randomized clinical trial of upper airway surgery for patients with obstructive sleep apnea who have failed continuous positive airway pressure.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a serious and costly public health problem. The main medical treatment, continuous positive airway pressure, is efficacious when used, but poorly tolerated in up to 50% of patients. Upper airway reconstructive surgery is available when medical treatments fail but randomized trial evidence supporting its use is limited. This protocol details a randomized controlled trial designed to assess the clinical effectiveness, safety, and cost-effectiveness of a multilevel upper airway surgical procedure for OSA. METHODS: A prospective, parallel-group, open label, randomized, controlled, multicenter clinical trial in adults with moderate or severe OSA who have failed or refused medical therapies. Six clinical sites in Australia randomly allocated participants in a 1:1 ratio to receive either an upper airway surgical procedure consisting of a modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction, or to continue with ongoing medical management, and followed them for 6 months. RESULTS: Primary outcomes: difference between groups in baseline-adjusted 6 month OSA severity (apnea-hypopnea index) and subjective sleepiness (Epworth Sleepiness Scale). Secondary outcomes: other OSA symptoms (e.g. snoring and objective sleepiness), other polysomnography parameters (e.g. arousal index and 4% oxygen desaturation index), quality of life, 24 hr ambulatory blood pressure, adverse events, and adherence to ongoing medical therapies (medical group). CONCLUSIONS: The Sleep Apnea Multilevel Surgery (SAMS) trial is of global public health importance for testing the effectiveness and safety of a multilevel surgical procedure for patients with OSA who have failed medical treatment. CLINICAL TRIAL REGISTRATION: Multilevel airway surgery in patients with moderate-severe Obstructive Sleep Apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true Australian New Zealand Clinical Trials Registry ACTRN12614000338662, prospectively registered on 31 March 2014.

Comparing surgical experience with performance on a sinus surgery simulator.

BACKGROUND: This study evaluates whether surgical experience influences technical competence using the Flinders sinus surgery simulator, a virtual environment designed to teach nasal endoscopic surgical skills. METHODS: Ten experienced sinus surgeons (five consultants and five registrars) and 14 novices (seven resident medical officers and seven interns/medical students) completed three simulation tasks using haptic controllers. Task 1 required navigation of the sinuses and identification of six anatomical landmarks, Task 2 required removal of unhealthy tissue while preserving healthy tissue and Task 3 entailed backbiting within pre-set lines on the uncinate process and microdebriding tissue between the cuts. RESULTS: Novices were compared with experts on a range of measures, using Mann-Whitney U -tests. Novices took longer on all tasks (Task 1: 278%, P < 0.005; Task 2: 112%, P < 0.005; Task 3: 72%, P < 0.005). In Task 1, novices' instruments travelled further than experts' (379%, P < 0.005), and provided greater maximum force (12%, P < 0.05). In Tasks 2 and 3 novices performed more cutting movements to remove the tissue (Task 2: 1500%, P < 0.005; Task 3: 72%, P < 0.005). Experts also completed more of Task 3 (66%, P < 0.05). CONCLUSIONS: The study demonstrated the Flinders sinus simulator's construct validity, differentiating between experts and novices with respect to procedure time, instrument distance travelled and number of cutting motions to complete the task.

The effect of nasal irrigation formulation on the antimicrobial activity of nasal secretions.

BACKGROUND: Saline-based irrigation solutions are evidence-based rhinological treatments; however, the formulation of these solutions could theoretically alter the function of innate antimicrobial peptides. The aim of this study was to determine if the antimicrobial activity of normal human nasal secretions in vivo is altered by commercially available large volume irrigation solutions. METHODS: Minimally manipulated sinonasal secretions were collected from patients with chronic rhinosinusitis (CRS; n = 10) and normal healthy volunteers (n = 20). In a subset of control patients (n = 10) secretions were collected prior to, and at 1 hour, 6 hours, and 24 hours after nasal irrigation with 4 commercial irrigation solutions. Lysozyme and lactoferrin levels were analyzed and the antimicrobial activity of secretions determined using a radial diffusion assay. RESULTS: The antimicrobial activity of nasal secretions was reduced in CRS patients compared to healthy volunteers (p < 0.01), but there was no significant difference in antimicrobial peptide concentrations. Isotonic nasal irrigation reduced lysozyme and lactoferrin levels, which returned to baseline levels by 6 hours; in addition to a sustained decrease in antimicrobial activity before returning to baseline at 24 hours. Low-salt solution stimulated peptide secretion by approximately 40% at 6 hours and 24 hours, but produced a transient decrease in antimicrobial activity, returning to baseline levels by 6 hours. Hypertonic solution initially decreased lysozyme and lactoferrin levels but maintained baseline levels of antimicrobial activity and increased peptide secretion by approximately 30% at 24 hours. CONCLUSION: The formulation of nasal irrigation solutions significantly affects the measured levels and functionality of sinonasal antimicrobial peptides.

A double-blind randomized controlled trial of normal saline, lactated Ringer's, and hypertonic saline nasal irrigation solution after endoscopic sinus surgery.

BACKGROUND: Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS. METHODS: Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. RESULTS: Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. CONCLUSION: Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.