Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease.

Quantitative assessment of bacterial growth phase utilizing flow cytometry.

Flow cytometry is currently underutilized for bacterial phenotyping and standard microbiological techniques do not provide phenotypic information about the state of the bacterial disease. Pseudomonas aeruginosa is a human pathogen of increased importance in public health due to both the ability to cause chronic diseases and the prevalence of functionally different subsets that can be difficult to treat and diagnose. In the present study, we used flow cytometry to analyze the growth phase of P. aeruginosa. A simple method for single cell quantitative detection of bacterial biofilm and planktonic cells was established with a combination of membrane permeable (SYTO 60) and impermeable (TOTO-1) dyes plus the addition of polystyrene counting beads. The specificity of the dye combination for biofilm detection was determined by comparison with impaired biofilm forming strains of P. aeruginosa LasI/RhlI-/- and ∆PfPhage. Results suggest that flow cytometric bacterial phenotyping serves as an expandable platform that may be useful for enumeration of population level variation in P. aeruginosa studies.

Long-term quality of life in patients with vestibular schwannoma managed with microsurgery.

OBJECTIVE: Little is known about the long term (greater than 10 years) quality of life in patients with vestibular schwannoma. This study aimed to evaluate long-term outcomes in patients with vestibular schwannoma. METHOD: A retrospective cohort study was performed across 2 academic institutions, with patients followed at least 10 years after vestibular schwannoma surgery (2000 to 2007). Telephone interviews were used to assess quality of life using the Glasgow Benefit Inventory and short form 12 item (version 2) health survey. RESULTS: A total of 99 out of 110 patients were included. Increasing age and symptom burden were associated with poorer quality of life (p = 0.01 and 0.02, respectively). The presence of imbalance, headache and facial nerve dysfunction were all associated with poorer quality of life scores (p = 0.01, 0.04 and 0.02, respectively). CONCLUSION: Identifying and managing post-operative symptoms may improve quality of life in vestibular schwannoma patients and can guide clinical decision making.

Wound healing after tonsillectomy - a review of the literature.

OBJECTIVE: To summarise the available literature related to wound healing post tonsillectomy, including the stages of healing, experimental models for assessing healing (in animals and humans) and the various factors that affect wound healing. METHODS: A search of the English literature was conducted using the Ovid Medline database, with the search terms 'tonsillectomy' or 'tonsil' and 'wound healing'. Thirty-one articles that objectively assessed tonsillectomy wound healing were included for analysis. RESULTS: The majority of assessments in humans investigating tonsillectomy wound healing involve serial direct clinical examinations of the oral cavity. Many patient and surgical factors have been shown to affect wound healing after tonsillectomy. There is some research to suggest that the administration of adjunctive treatment in the post-operative period may be beneficial to tonsillectomy wound healing. CONCLUSION: Wound healing post tonsillectomy has been poorly researched. Having a better understanding of the process of wound healing would allow surgeons to potentially prevent, anticipate and manage complications from the surgery that arise as part of the healing process.

Animal models of acute otitis media - A review with practical implications for laboratory research.

Considerable animal research has focused on developing new strategies for the prevention and treatment of acute otitis media (AOM). Several experimental models of AOM have thus been developed. A PubMed search of the English literature was conducted from 1975 to July 2016 using the search terms "animal model" and "otitis media" from which 91 published studies were included for analysis, yielding 123 animal models. The rat, mouse and chinchilla are the preferred animals for experimental AOM models with their individual advantages and disadvantages. The most common pathogens used to create AOM are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Streptococcus pneumoniae (types 3, 23 and 6A) and non-typeable Haemophilus influenzae (NTHi) are best options for inoculation into rat and mouse models. Adding viral pathogens such as RSV and Influenza A virus, along with creating ET dysfunction, are useful adjuncts in animal models of AOM. Antibiotic prophylaxis may interfere with the inflammatory response without a significant reduction in animal mortality.

Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis.

OBJECTIVES: To investigate the relationship between hearing loss and cardiovascular disease risk factors. DESIGN: Cross-sectional study. METHODS: Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed. SETTING: A community-based population. PARTICIPANTS: A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study. MAIN OUTCOME MEASURES: Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin. RESULTS: Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001). CONCLUSIONS: Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss.

Unique microbiology of chronically unstable canal wall down tympanomastoid cavities: considerations for surgical revision.

OBJECTIVE: To review the microbiology of open tympanomastoid cavities in patients who underwent revision surgery due to chronic instability. METHODS: This paper describes a retrospective chart review of surgical revision cases of chronically unstable open mastoid cavities. Patient records from 2000 to 2010 were reviewed for the type of organism cultured, antimicrobial resistance and the presence of cholesteatoma. RESULTS: In total, 121 revision surgical procedures were performed on 101 patients. Seventy-nine procedures involved culture specimen processing, 37 of which were positive. The most commonly cultured organism was Staphylococcus aureus, which was more than twice as common as any other pathogen. The presence of cholesteatoma had no impact on the likelihood of a positive culture or polymicrobial culture. Antimicrobial-resistant pathogens were uncommon. CONCLUSION: A positive culture was not an overwhelmingly common characteristic of unstable tympanomastoid cavities. Furthermore, antimicrobial resistance did not appear to play an essential role in leading patients towards revision open mastoid surgery.

Sigmoid sinus dehiscence resurfacing as treatment for pulsatile tinnitus.

AIM: To report a case of sigmoid sinus dehiscence presenting with pulsatile tinnitus and treated successfully with resurfacing. CASE REPORT: This patient presented with pulsatile tinnitus due to sigmoid sinus dehiscence. This was successfully treated using only soft tissue resurfacing. CONCLUSION: Sigmoid sinus dehiscence is a rare but treatable cause of pulsatile tinnitus. It can occur in the absence of a diverticulum, and is not necessarily limited to the transverse sigmoid junction. When resurfacing, care must be taken not to significantly alter the extraluminal diameter of the sigmoid in a dominant sinus, as this raises the risk of post-operative hydrocephalus.

Pott's puffy tumour and intracranial complications of frontal sinusitis in pregnancy.

INTRODUCTION: A Pott's puffy tumour is a subperiosteal abscess and osteomyelitis of the frontal bone secondary to frontal sinusitis. Intracranial complications are seen in approximately 40 per cent of cases and are potentially life-threatening; such complications have not previously been reported in pregnancy. CASE REPORT: A 21-year-old woman at 35 weeks' gestation presented with a history of frontal headaches and swelling, periorbital oedema, pain and chemosis. Imaging confirmed Pott's puffy tumour with right-sided epidural empyema and periorbital cellulitis. A multidisciplinary team was involved in the patient's management. Intravenous antibiotics were commenced and initial percutaneous drainage through the frontal sinus skin was performed, followed by endoscopic sinus drainage. A caesarean section was performed 3 days later. Complete resolution of the sinus and intracranial collections was noted on imaging performed six weeks later. CONCLUSION: This case highlights the challenges of managing rare intracranial complications of sinusitis in pregnancy, and the importance of multidisciplinary care.