BackgroundBacteria and fungi are believed to influence mucosal inflammation in chronic rhinosinusitis (CRS). However their presence and relationship to disease is debated. This study used multiple detection methods to compare microbial diversity and microbial abundance in healthy and diseased sinonasal mucosa. The utility of contemporary detection methods is also examined.MethodsSinonasal mucosa was analyzed from 38 CRS and 6 controls. Bacterial and fungal analysis was performed using conventional culture, molecular diagnostics (polymerase chain reaction coupled with electrospray ionization time-of-flight mass spectrometry) and fluorescence in situ hybridization.ResultsMicrobes were detected in all samples, including controls, and were often polymicrobial. 33 different bacterial species were detected in CRS, 5 in control patients, with frequent recovery of anaerobes. Staphylococcus aureus and Propionibacterium acnes were the most common organisms in CRS and controls, respectively. Using a model organism, FISH had a sensitivity of 78%, and a specificity of 93%. Many species were detected in both CRS and controls however, microbial abundance was associated with disease manifestation.ConclusionsThis study highlights some cornerstones of microbial variations in healthy and diseased paranasal sinuses. Whilst the healthy sinus is clearly not sterile, it appears prevalence and abundance of organisms is critical in determining disease. Evidence from high-sensitivity techniques, limits the role of fungi in CRS to a small group of patients. Comparison with molecular analysis suggests that the detection threshold of FISH and culture is related to organism abundance and, furthermore, culture tends to select for rapidly growing organisms.

Aims To investigate the effects of incubation conditions on the kinetic constants for zidovudine (AZT) glucuronidation by human liver microsomes, and whether microsomal intrinsic clearance (CL int ) derived for the various conditions predicted hepatic AZT clearance by glucuronidation (CL H ) in vivo . Methods The effects of incubation constituents, particularly buffer type (phosphate, Tris) and activators (Brij58, alamethacin, UDP-N-acetylglucosamine (UDPNAcG)), on the kinetics of AZT glucuronidation by human liver microsomes was investigated. AZT glucuronide (AZTG) formation by microsomal incubations was quantified by h.p.l.c. Microsomal CL int values determined for the various experimental conditions were extrapolated to a whole organ CL int and these data were used to calculate in vivo CL H using the well-stirred, parallel tube and dispersion models. Results Mean CL int values for Brij58 activated microsomes in both phosphate (3.66 ± 1.40 µ l min − 1 mg − 1 , 95% CI 1.92, 5.39) and Tris (3.79 ± 0.74 µ l min − 1 mg − 1 , 95% CI 2.87, 4.71) buffers were higher ( P < 0.05) than the respective values for native microsomes (1.04 ± 0.42, 95% CI 0.53, 1.56 and 1.37 ± 0.30 µ l min − 1 mg − 1 , 95% CI 1.00, 1.73). Extrapolation of the microsomal data to a whole organ CL int and substitution of these values in the expressions for the well-stirred, parallel tube and dispersion models underestimated the known in vivo blood AZT clearance by glucuronidation by 6.5-to 23-fold (3.61-12.71 l h − 1 vs 82 l h − 1 ). There was no significant difference in the CL H predicted by each of the models for each set of conditions. A wide range of incubation constituents and conditions were subsequently investigated to assess their effects on GAZT formation, including alamethacin, UDP-NAcG, MgCl 2 , D -saccharic acid 1,4-lactone, ATP, GTP, and buffer pH and ionic strength. Of these, only decreasing the phosphate buffer concentration from 0.1 M to 0.02 M for Brij58 activated microsomes substantially increased the rate of GAZT formation, but the extrapolated CL H determined for this condition still underestimated known AZT glucuronidation clearance by more than 4-fold. AZT was shown not to bind nonspecifically to microsomes. Analysis of published data for other glucuronidated drugs confirmed a trend for microsomal CL int to underestimate in vivo CL H . Conclusions AZT glucuronidation kinetics by human liver microsomes are markedly dependent on incubation conditions, and there is a need for interlaboratory standardization. Extrapolation of in vitro CL int underestimates in vivo hepatic clearance of drugs eliminated by glucuronidation.

In the sheep model of endoscopic ICA injury, the muscle patch and U-Clip anastomotic device significantly improved survival, reduced blood loss, and achieved primary hemostasis while maintaining vascular patency.

This is the first study to use a highly sensitive pyrosequencing technique to reveal the true diversity of fungi in the sinuses of CRS patients and postoperative changes in richness. The presence of Malassezia, a genus not previously described in the sinuses, is of great interest, and its potential as a disease modifier should see further investigation given its association with atopic disease.

Mupirocin sinonasal rinses are an effective short-term anti-S aureus treatment in surgically recalcitrant CRS as assessed by microbiological and selected rhinological outcomes, although the latter improvements may not be durable with time.

Chronic rhinosinusitis (CRS) is a very common condition that remains poorly understood from a pathogenic standpoint. Recent interest has been sparked by a potential role for biofilms in this process, with a significant body of evidence implicating them in inciting sinonasal inflammation. Biofilms are clearly present on the sinus mucosa of CRS patients, and their presence there is associated with severe disease characteristics and surgical recalcitrance. We are beginning to understand the importance of the species within these biofilms, but there may be other as-yet-unidentified factors at play in influencing disease outcomes. Recent exciting research has emerged documenting the immune response to the presence of biofilms-research that will ultimately solidify the nature and extent of the contribution of biofilms in CRS pathogenesis. Future research should focus on evidence-based antibiofilm treatments with reference to efficacy and timing of treatment.

Objective To provide a summary of the current frailty literature relating to head and neck cancer. Data Sources Ovid MEDLINE, PubMed, Google Scholar. Methods A comprehensive review of the literature was performed from 2000 to 2017 using key words frailty, elderly, geriatric, surgery, otolaryngology, head and neck cancer. Results The aging population has led to an increased diagnosis of head and neck cancer in elderly patients. The prevalence of comorbidities, disabilities, geriatric syndromes and social issues can make treatment planning and management in this population challenging. Chronological age alone may not be the optimal approach to guiding treatment decisions, as there is marked heterogeneity amongst this age group. Individualization of treatment can be achieved by assessing for the presence of frailty, which has growing evidence as an important marker of health status in geriatric oncology. Frailty is a complex geriatric syndrome characterized by a state of increased vulnerability to stressors and is associated with morbidity, mortality, and treatment toxicity. Screening for frailty may provide an efficient method to identify those who would benefit from further assessment or pretreatment optimization, and to provide prognostic information to assist clinicians and patients in formulating the most ideal treatment plan for the elderly individual with head and neck cancer. Conclusions Frailty has emerged as an important concept in geriatric oncology, with wide significance in head and neck cancer. Incorporating frailty assessments into clinical practice may provide otolaryngologists pertinent information regarding health status and outcomes leading to optimal care of the elderly cancer patient. Laryngoscope, 128:E416–E424, 2018

Results indicate that CTSA and EDTA are safe and efficacious for short-term topical application against S. aureus infection in a sheep sinusitis model, and have the potential to be translated to a clinical setting.