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infections are prevalent amongst chronic rhinosinusitis (CRS) sufferers. Many strains form biofilms, leading to treatment failure. Lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. To assess the activity of a phage cocktail in eradicating biofilms of .aeruginosa isolates from CRS patients. : . isolates from CRS patients with and without cystic fibrosis (CF) across three continents were multi-locus sequence typed and tested for antibiotic resistance. Biofilms grown were treated with a cocktail of four phages (CT-PA). Biofilm biomass was measured after 24 and 48 h, using a crystal violet assay. Phage titrations were performed to confirm replication of the phages. A linear mixed effects model was applied to assess the effects of treatment, time, CF status, and multidrug resistance on the biomass of the biofilm. The isolates included 44 strain types. CT-PA treatment significantly reduced biofilm biomass at both 24 and 48 h post-treatment ( < 0.0001), regardless of CF status or antibiotic resistance. Biomass was decreased by a median of 76% at 48 h. Decrease in biofilm was accompanied by a rise in phage titres for all except one strain. A single dose of phages is able to significantly reduce biofilms formed by a range of .aeruginosa isolates from CRS patients. This represents an exciting potential and novel targeted treatment for biofilm infections and multidrug resistant bacteria.

Recent literature demonstrates that a learning curve exists for endoscopic pituitary surgery. However, there is significant variability in the way these studies report their outcomes. This study aims to systematically review the literature regarding outcomes for endoscopic pituitary surgery and how this may be related to a surgical learning curve. An electronic search of the databases Medline, Scopus, Embase, Web of Science and Cochrane Library databases was performed and data extracted according 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Ten articles were included in the review as they examined the following: rates of gross total resection, average operative time, CSF leak rate, visual outcomes, endocrine outcomes and how these results were influenced by surgical experience. We have demonstrated that a learning curve exists for some outcome variables for endoscopic pituitary surgery. However, there is significant heterogeneity in the current body of literature which makes clear comparisons difficult.

Purpose of Review Perturbations in local microbiota have been demonstrated in many chronic inflammatory diseases including chronic rhinosinusitis (CRS). The purpose of this paper is to review the latest microbiome research as it pertains to CRS and establish whether there is any evidence supporting the microbiome hypothesis for CRS. Treatment factors that may influence the sinonasal microbiome as well as the role of probiotics are also discussed. Recent Findings Despite significant heterogeneity in study design, tissue sampling, processing and bioinformatics analysis, consistent findings have emerged from the recent literature. Healthy individuals and CRS patients have similar overall bacterial burden of disease and share many common phylum. CRS patients, however, routinely show reductions in markers of biodiversity. Both medical and surgical treatments appear to influence the sinonasal microbiome, with certain bacterial strains associated with better treatment outcomes. Summary The presence of microbial dysbiosis in CRS is now supported by numerous studies. Whether this dysbiosis is a cause or rather an association of the disease process still remains unclear. Although probiotic therapies show early promise, much larger studies are required to establish their real role as a treatment for CRS.

Olfactory groove meningiomas (OGM) are a skull base neoplasm that represents between 8 and 13% of all intracranial meningiomas. Approach selection focuses on achieving frontal lobe decompression, gross total resection and vision preservation. Recently, there has been a focus on olfaction and considering its preservation as a quality-of-life outcome measure. An electronic search of the databases Medline, Scopus, Embase, Web of Science and Cochrane library databases was performed and data extracted according 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Six articles were selected for inclusion mainly based due to reporting quantitative outcomes for olfaction assessed by a smell identification test (e.g. sniffin’ sticks). Objective olfaction preservation can be achieved with a variety of surgical approaches. More research which includes objective assessment of olfactory function and ideally as well QoL outcome measures is needed to further optimize the treatment pathways in OGM patients.

Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery. 112 adult (8-10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups. Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats. Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.

Antibiotics are often administered to patients perioperatively and have been shown to affect ROS production of nasal cells , but their effect in the setting of active wound healing remains unclear. Reactive oxygen species (ROS) are known to play a significant role in wound healing. This study analyzed a broad array of antibiotics used after sinus surgery to assess their effect on wound healing and ROS production . It was hypothesized that ROS production would be affected by these antibiotics and there would be a negative relationship between ROS activity and cell migration speed. Monolayers of primary human nasal epithelial cells (HNEC) and primary fibroblasts were disrupted with a linear wound, treated with 10 different antibiotics or a ROS inhibitor and observed over 36 h in a controlled environment using confocal microscopy. ROS activity and migration speed of the wound edge were measured at regular intervals. The relationship between the two parameters was analyzed using mixed linear modeling. Performing a linear scratch over the cell monolayers produced an immediate increase in ROS production of ~35% compared to unscratched controls in both cell types. Incubation with mitoquinone and the oxazolidinone antibiotic linezolid inhibited ROS activity in both fibroblasts and HNEC in association with slowed fibroblast cell migration ( < 0.05). Fibroblast cell migration was also reduced in the presence of clarithromycin and mupirocin ( < 0.05). A significant correlation was seen between ROS suppression and cell migration rate in fibroblasts for mitoquinone and all antibiotics except for azithromycin and doxycycline, where no clear relationship was seen. Treatments that slowed fibroblast cell migration compared to untreated controls showed a significant correlation with ROS suppression ( < 0.05). Increased ROS production in freshly wounded HNEC and fibroblast cell monolayers was suppressed in the presence of antibiotics, in correlation with reduced fibroblast cell migration. In contrast, HNEC cell migration was not significantly affected by any of the antibiotics tested. This differential effect of antibiotics on fibroblast and HNEC migration might have clinical relevance by reducing adhesion formation without affecting epithelial healing in the postoperative setting.

Introduction Chronic rhinosinusitis (CRS) pathophysiology and its link to microbiome is an area of ongoing investigation. Certain pathogens, in particular Staphylococcus aureus described to contribute to recalcitrant CRS. In addition, different species of coagulase negative staphylococci (CoNS) are frequently isolated from the sinonasal cavity of CRS patients. However, the influence of Staphylococcal species coexisting in the same niche on the inflammatory process remains unclear. The aim of this study was to explore the impact of exoproteins from various Staphylococcus species isolated from the same patients on the mucosal barrier. Methods Staphylococcal species isolated from CRS and control patients were cultured from sinus swabs in planktonic and biofilm forms, and their exoproteins extracted. Primary human nasal epithelial cells (HNECs) from CRS patients were cultured at an air‐liquid interface (ALI) and exposed to 20 μg/mL exoproteins or control. Barrier disruption and cytotoxicity were assessed by measuring the transepithelial electrical resistance (TEER), passage of fluorescein labeled dextrans and lactate dehydrogenase (LDH) levels. IL‐ 6 concentration was measured employing ELISA. Patient's matched sinonasal tissue samples were analyzed with flow cytometry to detect and quantify immune cells. Results Forty‐four Staphylococcal species were isolated from 22 CRS and control patients including: 22 S. aureus, 12 S. epidermidis, and 10 S. lugdunensis. 15 out of 22 S. aureus exoproteins significantly enhanced cytotoxicity, reduced TEER values and increased paracellular permeability compared to control (p < 0.05). By contrast, S. epidermidis and S. lugdunensis exoproteins caused either mild or negligible effects on the TEER values, cell viability, and paracellular permeability. However, S. lugdunensis exoproteins induced significantly higher IL‐6 compared to control. Correlation analysis indicated S. aureus and S. lugdunensis from the same patient acted in concert to disrupt the nasal epithelial barrier and induce toxicity. Conclusion This study shows the significant and detrimental impact of the presence of S. aureus exoproteins on nasal epithelial cell barrier function. S. aureus and S. lugdunensis isolated from the same patients acted in concert to affect the nasal barrier and inducing toxicity.

causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). exoproteins contain virulence factors and play important roles in the pathogenicity of , however their role in CRS pathophysiology remains unknown. We isolated clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the elastase activity of CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans ( = 0.95, = 0.0004) and decreased TEER ( = -0.9333, < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and β-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the elastase activity of CIs and CRS disease severity (for log phase, = 0.5631, = 0.0097; for stationary phase, = 0.66, = 0.0013) assessed by CT imaging of the paranasal sinuses. Our results implicate exoproteins as playing a major role in the pathophysiology of associated CRS by severely compromising mucosal barrier structure and function.

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal \"microbiotypes\" or \"states\": the first is -dominated, the second is -dominated, and the third dominated by the other core genera of the sinonasal microbiome ( , and ). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between species and , suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

Otitis media with effusion (OME) is a biofilm driven disease and commonly accepted otopathogens, such as , have been demonstrated to form polymicrobial biofilms within the middle ear cleft. However, ( ), which is one of the most commonly found bacteria within middle ear aspirates of children with OME, has not been described to form biofilms. The aim of this study was to investigate whether can form biofilms and investigate the impact on antibiotic susceptibility and survivability in polymicrobial biofilms with . The ability of to form single-species and polymicrobial biofilms with was explored. Clinical and commercial strains of and were incubated in brain heart infusion with and without supplementation. Biofilm was imaged using confocal laser scanning microscopy and scanning electron microscopy. Quantification of biofilm biomass and viable bacterial number was assessed using crystal violet assays and viable cell counting in both optimal growth conditions and in adverse growth conditions (depleted media and sub-optimal growth temperature). Antimicrobial susceptibility and changes in antibiotic resistance of single-species and multi-species co-culture were assessed using a microdilution method to assess minimal bactericidal concentration and E-test for amoxicillin and ciprofloxacin. formed single-species and polymicrobial biofilms with . Additionally, whilst strain dependent, combinations of polymicrobial biofilms decreased antimicrobial susceptibility, albeit a small magnitude, in both planktonic and polymicrobial biofilms. Moreover, promoted survival by increasing biofilm production in depleted media and at suboptimal growth temperature. Our findings suggest that may play an indirect pathogenic role in otitis media by altering antibiotic susceptibility and enhancing growth under adverse conditions.