Characterising the allergic fungal rhinosinusitis microenvironment using full-length 16S rRNA gene amplicon sequencing and fungal ITS sequencing.

INTRODUCTION: Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2-mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS. METHODOLOGY: We undertook a cross-sectional study of AFRS patients and non-fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short-read next-generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full-length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT). RESULTS: Thirty-two AFRS and 29 non-fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p = .07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p = .03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p = .005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p = .008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi. CONCLUSION: A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross-kingdom pathophysiological mechanisms.

Differential proteomic expression in non-functional pituitary neuroendocrine tumours and pituitary glands.

INTRODUCTION: Pituitary neuroendocrine tumours (PitNETs) are common accounting for 10 to 25 % of all intracranial tumours. This project describes the feasibility of developing a novel membrane-based biomarker that could be used for fluorescent guided surgery. The aim was to catalogue the differential expression of membrane proteins between non-functional PitNETs and pituitary glands. METHODOLOGY: Ten pituitary gland tissue specimens were obtained from the National Institute of Health (NIH) NeuroBio-Bank and twenty non-functional PitNETs were obtained from the Northwestern University Nervous System Tumour Bank. Mass spectrometry analysis using an Orbitrap Fusion Lumos Tribrid Mass Spectrometer linked to a Dionex Ultimate 3000 UPLC system was undertaken. Data Dependent Acquisition Mass Spectrometry and Data Independent Acquisition Mass Spectrometry was then completed. Pathway enrichment analysis was performed using clusterProfiler v4.6.0. Functional enrichment analysis was conducted using Gene Ontology terms and Reactome pathways. RESULTS: Differential expression analysis between the two groups revealed a total of 2110 significant differently expressed proteins (DEPs), with 1387 of these also having a Log2 fold change either greater than 1, or less than -1. Of the 2110 DEPs, 925 were upregulated in tumours compared to control, while 1185 were downregulated. CONCLUSION: We have demonstrated a proteomic comparison between non-functional PitNETs and normal pituitary glands. These results demonstrate differences consistent with contemporary literature but shows that NOTCH3 and PTPRJ are up-regulated in non-functional PitNETs compared to pituitary glands.

Enhanced phylogenetic insights into the microbiome of chronic rhinosinusitis through the novel application of long read 16S rRNA gene amplicon sequencing.

INTRODUCTION: 16S rRNA next generation sequencing (NGS) has been the de facto standard of microbiome profiling. A limitation of this technology is the inability to accurately assign taxonomy to a species order. Long read 16S sequencing platforms, including Oxford Nanopore Technologies (ONT), have the potential to overcome this limitation. The paranasal sinuses are an ideal niche to apply this technology, being a low biomass environment where bacteria are implicated in disease propagation. Characterising the microbiome to a species order may offer new pathophysiological insights. METHODOLOGY: Cohort series comparing ONT and NGS biological conclusions. Swabs obtained endoscopically from the middle meatus of 61 CRSwNP patients underwent DNA extraction, amplification and dual sequencing (Illumina Miseq (NGS) and ONT GridION). Agreement, relative abundance, prevalence, and culture correlations were compared. RESULTS: Mean microbiome agreement between sequencers was 61.4%. Mean abundance correlations were strongest at a familial/genus order and declined at a species order where NGS lacked resolution. The most significant discrepancies applied to Corynebacterium and Cutibacterium, which were estimated in lower abundance by ONT. ONT accurately identified 84.2% of cultured species, which was significantly higher than NGS. CONCLUSIONS: ONT demonstrated superior resolution and culture correlations to NGS, but underestimated core sinonasal taxa. Future application and optimisation of this technology can advance our understanding of the sinonasal microenvironment.

Study of the

The ^{22}Mg(α,p)^{25}Al reaction rate has been identified as a major source of uncertainty for understanding the nucleosynthesis flow in Type-I x-ray bursts. We report a direct measurement of the energy- and angle-integrated cross sections of this reaction in a 3.3-6.9 MeV center-of-mass energy range using the MUlti-Sampling Ionization Chamber (MUSIC). The new ^{22}Mg(α,p)^{25}Al reaction rate is a factor of ∼4 higher than the previous direct measurement of this reaction within temperatures relevant for x-ray bursts, resulting in the ^{22}Mg waiting point of x-ray burst nucleosynthesis flow to be significantly bypassed via the (α,p) reaction.

Direct Measurement of Resonances in

We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to ∼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.

Constraining the

The ^{30}P(p,γ)^{31}S reaction plays an important role in understanding the nucleosynthesis of A≥30 nuclides in oxygen-neon novae. The Gaseous Detector with Germanium Tagging was used to measure ^{31}Cl ß-delayed proton decay through the key J^{π}=3/2^{+}, 260-keV resonance. The intensity I_{ßp}^{260}=8.3_{-0.9}^{+1.2}×10^{-6} represents the weakest ß-delayed, charged-particle emission ever measured below 400 keV, resulting in a proton branching ratio of Γ_{p}/Γ=2.5_{-0.3}^{+0.4}×10^{-4}. By combining this measurement with shell-model calculations for Γ_{γ} and past work on other resonances, the total ^{30}P(p,γ)^{31}S rate has been determined with reduced uncertainty. The new rate has been used in hydrodynamic simulations to model the composition of nova ejecta, leading to a concrete prediction of ^{30}Si:^{28}Si excesses in presolar nova grains and the calibration of nuclear thermometers.

Low pH nasal rinse solution enhances mupirocin antimicrobial efficacy.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common condition negatively impacting a patient's quality of life. It has been hypothesized that bacterial biofilms are involved in the pathogenesis of CRS due to their persistence and difficulty to eradicate with conventional antibiotic therapy. Hence, the topical delivery of antibiotics via nasal rinse solution has gained a lot of attention due to the ability to deliver higher local concentrations, with less systemic absorption and side effects. This study investigates the efficacy of mupirocin dissolved in the 3 most commonly used sinus rinses in Australia Neilmed (isotonic saline), Flo Sinus Care (sodium chloride, sodium bicarbonate, potassium chloride, glucose anhydrous and calcium lactate and Pentahydrate) and FloCRS (sodium chloride, potassium chloride and xylitol). METHODS: Planktonic and biofilm cultures of S. aureus (ATCC25923, 2 methicillin-resistant S. aureus (MRSA) (C222 and C263), and 2 methicillin-susceptible S. aureus (MSSS) (C311 and C349) clinical isolates) were treated with mupirocin dissolved in three sinus rinses (Neilmed, Flo Sinus Care and FloCRS with different pH). To establish whether pH was a significant factor in determining antibiotic activity, experiments with Flo CRS were performed both at pH 5.64 and elevated pH 7.7. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for planktonic cells. The biofilm biomass and metabolic activity were assessed by using crystal violet assay and alamarBlue assay respectively. RESULTS: The combination of mupirocin in low pH (pH 5.64) sinus rinse (FloCRS) had the highest efficacy in reducing the growth of S. aureus in both the planktonic and biofilm forms. Mupirocin diluted in FloCRS (pH 5.64) showed a significantly higher reduction in both biomass and metabolic activity than that was observed when mupirocin was diluted in Neilmed, Flo Sinus Care or FloCRS (pH 7.7). CONCLUSION: The choice of irrigant solution for topical mupirocin delivery appears to be important for antimicrobial activity. The delivery of mupirocin via low pH FloCRS could be useful in eliminating S. aureus biofilms present on the sinus mucosa of patients with CRS.

Low pH nasal rinse solution enhances mupirocin antimicrobial efficacy.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common condition negatively impacting a patient's quality of life. It has been hypothesized that bacterial biofilms are involved in the pathogenesis of CRS due to their persistence and difficulty to eradicate with conventional antibiotic therapy. Hence, the topical delivery of antibiotics via nasal rinse solution has gained a lot of attention due to the ability to deliver higher local concentrations, with less systemic absorption and side effects. This study investigates the efficacy of mupirocin dissolved in the 3 most commonly used sinus rinses in Australia Neilmed (isotonic saline), Flo Sinus Care (sodium chloride, sodium bicarbonate, potassium chloride, glucose anhydrous and calcium lactate and Pentahydrate) and FloCRS (sodium chloride, potassium chloride and xylitol). METHODS: Planktonic and biofilm cultures of S. aureus (ATCC25923, 2 methicillin-resistant S. aureus (MRSA) (C222 and C263), and 2 methicillin-susceptible S. aureus (MSSS) (C311 and C349) clinical isolates) were treated with mupirocin dissolved in three sinus rinses (Neilmed, Flo Sinus Care and FloCRS with different pH). To establish whether pH was a significant factor in determining antibiotic activity, experiments with Flo CRS were performed both at pH 5.64 and elevated pH 7.7. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for planktonic cells. The biofilm biomass and metabolic activity were assessed by using crystal violet assay and alamarBlue assay respectively. RESULTS: The combination of mupirocin in low pH (pH 5.64) sinus rinse (FloCRS) had the highest efficacy in reducing the growth of S. aureus in both the planktonic and biofilm forms. Mupirocin diluted in FloCRS (pH 5.64) showed a significantly higher reduction in both biomass and metabolic activity than that was observed when mupirocin was diluted in Neilmed, Flo Sinus Care or FloCRS (pH 7.7). CONCLUSION: The choice of irrigant solution for topical mupirocin delivery appears to be important for antimicrobial activity. The delivery of mupirocin via low pH FloCRS could be useful in eliminating S. aureus biofilms present on the sinus mucosa of patients with CRS.

Outcomes of intubation and endoscopic DCR in functional nasolacrimal duct obstruction.

BACKGROUND: To ascertain the success of lacrimal intubation and DCR in alleviating epiphora due to functional nasolacrimal duct obstruction (FNLDO). METHODS: Consecutive adult patients with epiphora attending a tertiary lacrimal clinic from May 2010 to February 2021 were reviewed to identify cases with FNLDO. FNLDO was defined as epiphora with the exclusion of alternate causes of watering on clinical examination, patent lacrimal syringing, normal DCG, and post-sac delay on DSG. Epiphora resolution and improvement rates in FNLDO were compared between lacrimal intubation and endo-DCR. RESULTS: 23 endo-DCRs (20 patients, 65% females, mean age 68.9±12.2) and 41 intubations (29 patients, 61.2% females, mean age 65.0±14.1) performed in FNLDO were included. Resolution of epiphora was achieved in 15 of the DCR procedures (median follow-up 9 months) compared to 14 of intubations (median follow-up 10 months). Significant epiphora improvement (i.e., either improvement or resolution) was noted in 21 DCRs and 24 intubations. Seven patients undergoing intubation as the primary procedure had endo-DCR performed following the intubation. Among respondents to a phone questionnaire, 53.8% who had endo-DCR (median 69 months) and 50% that had intubation (median 28 months) reported significant improvement in epiphora. CONCLUSIONS: Improvement in epiphora due to FNLDO was approximately 59% in intubations, while the success of endo-DCR was higher (91%). The long-term results of these interventions warrant further investigation.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

First Direct Measurement of an Astrophysical p-Process Reaction Cross Section Using a Radioactive Ion Beam.

We have performed the first direct measurement of the ^{83}Rb(p,γ) radiative capture reaction cross section in inverse kinematics using a radioactive beam of ^{83}Rb at incident energies of 2.4 and 2.7A MeV. The measured cross section at an effective relative kinetic energy of E_{cm}=2.393 MeV, which lies within the relevant energy window for core collapse supernovae, is smaller than the prediction of statistical model calculations. This leads to the abundance of ^{84}Sr produced in the astrophysical p process being higher than previously calculated. Moreover, the discrepancy of the present data with theoretical predictions indicates that further experimental investigation of p-process reactions involving unstable projectiles is clearly warranted.

The clinical outcomes of medical therapies in chronic rhinosinusitis are independent of microbiomic outcomes: a double-blinded, randomised placebo-controlled trial.

BACKGROUND: Oral and topical corticosteroids, and antibiotics form the mainstay medical treatment of chronic rhinosinusitis (CRS). Clinical outcomes vary depending on the chosen therapy, resident microbiome and disease phenotype. We conducted a double- blinded, placebo-controlled Randomised Controlled Trial (RCT) to investigate effects of medical therapy on clinical outcomes and associated microbiome shifts. METHODOLOGY: Fifty eligible patients (CRS with and without polyps) were treated for 3 weeks after randomisation into 3 arms: na- mely oral prednisolone, topical budesonide irrigations and oral doxycycline; each with appropriate placebo. Clinical scoring and microbiome swabs were performed on enrolment, at treatment completion and 3-weeks post treatment completion. Microbiome analysis was performed using the llumina-MiSeq next generation sequencing platform and QIME-2 pipeline. RESULTS: Significant improvement in clinical scores was observed in prednisolone and budesonide arms at treatment completion but not with antibiotic. Sub-group analysis showed more pronounced effects in patients with polyposis. Corynebacterium and Staphylococcus species predominated, with variable bacterial relative abundance among different treatments at all time-points. The only significant microbiome finding was an increase in bacterial diversity in topical budesonide group immediately after treatment, which returned to baseline 3-weeks post treatment. CONCLUSION: Clinical improvement was significant with oral and topical steroid but not empirical antibiotic. Although there were some associated microbiome changes with the various treatments, we could not ascertain the consistency of these and whether they do have a clinical significance at all.

The global transcriptomic signature in sinonasal tissues reveals roles for tissue type and chronic rhinosinusitis disease phenotype.

BACKGROUND: RNA sequencing (RNA-Seq) allows the characterization of a global transcriptomic signature in a least-biased fashion, but few studies have applied this method to investigate the pathophysiology of CRS. METHODS: We collected mucosal tissue samples from 6 CRS without nasal polyps (CRSsNP), 6 CRS with nasal polyps (CRSwNP), and 6 control patients. Additional matched polyp samples were collected from the 6 CRSwNP patients. RNA was extracted and sequenced on the Illumina HiSeq-2500. Differential gene expression and pathway analyses were performed. RESULTS: CRSsNP showed evidence of upregulated interferon-mediated immunity, MHC-class-I mediated antigen presentation, CXCR3 binding, neutrophil chemotaxis and degranulation, and potential downregulation of genes related to cilia movement and production. CRSwNP polyp tissue showed upregulation of B-cell mediated immune responses, but reduced expression of genes related to epithelial morphogenesis and haemostasis. Polyps also showed a generalized reduction of positive gene regulation. The sinonasal transcriptomic signature was largely determined by tissue type (polyp versus mucosa) and disease phenotype, with minimal signal originating from the individual patient. CONCLUSION: RNA-Seq is a useful tool to explore the complex pathophysiology of CRS. Our findings stress the importance of tissue selection in molecular research utilizing sinonasal tissue, and demonstrate the limitation of the sNP/wNP paradigm (and the importance of endotyping). On the other hand, classical CRSsNP/wNP disease phenotypes played some role in determining the global transcriptomic signature, and should not be hastily discarded. The value of RNA-Seq-described transcriptomic signatures in exploring endotypes is yet to be explored in future studies.

Scoping review of chronic rhinosinusitis proteomics.

BACKGROUND: Progressive advances in proteomic technology has improved our understanding of the chronic rhinosinusitis (CRS) pathogenesis and endotypes. This scoping review aims to present a comprehensive and descriptive analysis of nasal mucosa and mucus proteome of CRS patients. METHODOLOGY: Studies investigating the proteome of nasal mucosa and mucus from healthy and CRS patients via mass spectrometry were included. Critical appraisal of methodological quality was conducted with extraction of protein lists. Gene set enrichment analysis (GSEA) was performed on studies including CRS patients. RESULTS: 2962 proteins were identified in the 21 studies included in this review. Eleven studies investigated the nasal mucus proteome and ten studies investigated the nasal mucosa proteome. Studies demonstrated heterogeneity in patients, sampling and mass spectrometry methodology. Samples from CRS patients suggested a trend in enrichment of immune system and programmed cell death pathways. Increased expression of proteins involved in cellular components including the cytoskeleton and adherens junctions was also present in CRS. CONCLUSIONS: Alterations in the healthy sinonasal proteome may lead to the increased immunological, metabolic and tissue remodeling processes observed in CRS. However, it is difficult to draw significant conclusions from the GSEA due to the heterogeneity present in the limited literature available. These findings allow us to direct further research to better understand CRS pathogenesis and its endotypes.

Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis.

BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro. METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts. RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion. CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.

European position paper on diagnostic tools in rhinology.

The accurate diagnosis of rhinologic disease depends on the clinical history, examination findings and, in many cases, further investigations. There are a wide variety of diagnostic tests available, the choice of which depends upon the condition being assessed. This position paper is intended to provide an up-to-date comprehensive description of the diagnostic tools available to rhinologists, allergists, general otolaryngologists and other physicians with an interest in sinonasal disease. The literature has been reviewed and evidence-based recommendations are included. The relevant history and examination techniques are described, including endoscopic assessment of the nose. General and disease-specific quality of life instruments are an important tool in assessing the impact of rhinologic disease and the response to treatment. Relevant blood tests are discussed, as well as the various methods of allergy testing. Techniques for collecting microbiological and tissue samples are described, as well as the use of more specialised tests such as nasal nitric oxide and those evaluating ciliary structure and function. Imaging techniques and their indications are included. Chemosensory (smell and taste) testing is explained, and the available techniques for objective measurement of nasal airflow and patency are reviewed. Prompt and accurate diagnosis allows appropriate management to be initiated; an understanding of the currently available diagnostic tools is a vital part of the assessment of rhinologic disease.

The persistence of intracellular Staphylococcus aureus in the sinuses: a longitudinal study.

BACKGROUND: Staphylococcus aureus (S. aureus) can reside within the sinonasal mucosa in chronic rhinosinusitis patients and causes recurrent infections. Within the host cell, S. aureus can evade host immune detection enabling its own survival. We hypothesise that S. aureus can persist within the sinonasal epithelium for a prolonged period without immune activation. METHODOLOGY: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing two sinus surgeries were included. Immunohistochemistry and Haematoxylin and Eosin stains were used to determine intracellular S. aureus (ICSA) status and inflammatory cell count, respectively. One-way ANOVA and paired t-tests were performed for comparison between ICSA subgroups and within each subgroup, respectively. RESULTS: Histopathological specimens from 34 patients (68 procedures) were included. ICSA positivity (ICSA+) was seen in 43 specimens (63.2%) from 26 (76%) patients. 18 (52.9%) of those were ICSA+ in both operations while 8 (23.5%) patients were ICSA+ in only one of the operations. 8 (23.5%) patients were ICSA negative in both operations. There was no difference in the number of eosinophils, lymphocyte and neutrophils between ICSA subgroups. CONCLUSIONS: This study demonstrated that S. aureus is found intracellularly within CRSwNP tissue at multiple time points without an increase in the number of eosinophils, lymphocytes and neutrophils. This finding supports our hypothesis that ICSA is able to escape from host detection and resides within the sinonasal mucosa despite intense treatment.

Can high-fidelity 3D models be a good alternative for cadaveric materials in skill assessment for endoscopic sinus surgery? A comparison study in assessment for surgical performance in 3D models and cadavers.

Introduction: Traditionally formal assessment of surgical skills has not been part of a surgeon's accreditation process. The widely adopted apprentice model of "on-the-job training" does create additional risk for the patients. In the past surgical training has used cadavers, but these are expensive, require dedicated wet-lab facilities and are in increasingly short supply. In many countries religious and cultural practices also preclude cadaveric use. Recent 3D-printed technology allows mass reproduction of high-fidelity 3D models. In this study, we examined the utility of 3D sinus models compared to cadaver dissection for surgical skill assessment for endoscopic sinus surgery (ESS). Materials and methods: A total of 17 otolaryngologists performed Endoscopic Sinus Surgery (ESS) on 3D printed sinus models and then repeated these procedures on cadavers. Their surgical performance was assessed with the Objective Structured Assessment of Technical Skills (OSATS) score for ESS and time was taken to complete an ESS procedure. Their performance on the 3D models and cadavers was compared. Results: There were no significant differences in the OSATS score between 3D models and cadavers (50.41 ± 13.31 vs. 48.29 ± 16.01, p = 0.36). There was a strong positive correlation between the score in 3D models and those in cadavers (r = 0.84, p < 0.001). No significant differences were found in time for a mini-ESS (21:29 ± 0:10 vs. 20:33 ± 0:07, p = 0.53). There were positive correlations between 3D models and cadavers in time taken for a mini-ESS (r = 0.55, p = 0.04). Conclusion: The surgical performance on the 3D models was comparable to that on cadavers. This supports the utility of the 3D models as an inexhaustible alternative for cadavers in ESS surgical skill assessment.

Mental workload during endoscopic sinus surgery is associated with surgeons' skill levels.

Introduction: Surgeons' mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient's anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models. Materials and methods: Forty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons' mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training. Results: The total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons' mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = -2.3664, p = 0.0091, effort; z = -2.1704, p = 0.0346, and performance; z = -2.5992, p = 0.0017), the independent factors were increased (mental demand; z = -2.5992, p = 0.0023 and physical demand; z = -2.2509, p = 0.0213), and frustration did not change (p = 0.3625). Conclusion: Some of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars' mental burdens would be necessary during surgical training to sustain their mental health.

Adaptive immune responses in Staphylococcus aureus biofilm-associated chronic rhinosinusitis.

BACKGROUND: The etiopathogenesis of chronic rhinosinusitis (CRS) is currently an area of intense debate. Recently, biofilms have been proposed as a potential environmental trigger in this disease. In particular, Staphylococcus aureus biofilms appear to be a predictor of severe disease recalcitrant to current treatment paradigms. However, direct causal links between biofilms and host immune activation are currently lacking. This study aimed to document both the adaptive immune responses that characterize S. aureus biofilm-associated CRS and the relative contributions of staphylococcal superantigens and S. aureus biofilms in the inflammatory make-up of this disease. METHODS: A total of 53 disease subjects and 15 controls were recruited. Sinonasal mucosa was collected for the determination of S. aureus and Haemophilus influenzae biofilms and presence of total and superantigen-specific IgE and for the measurement of cytokines that characterize the T-helper pathways. RESULTS: Staphylococcus aureus biofilms and superantigens are significantly associated in CRS patients, suggesting the biofilm may be a nidus for superantigen-eluting bacteria. The presence of S. aureus biofilms is associated with eosinophilic inflammation, across the spectrum of CRS, on the back of a T-helper(2) skewing of the host's adaptive immune response (elevated Eosinophilic Cationic Protein and IL-5). This can be distinguished from the superantigenic effect resulting in the induction of IgE. CONCLUSION: This study provides novel evidence of a link between S. aureus biofilms and skewing of the T-cell response toward the T-helper(2) pathway that is independent of superantigen activities. Further research is required to confirm the cause-effect relationship of this association.