Paediatric focal intracranial suppurative infection: a UK single-centre retrospective cohort study.

BACKGROUND: Paediatric focal intracranial suppurative infections are uncommon but cause significant mortality and morbidity. There are no uniform guidelines regarding antibiotic treatment. This study reviewed management in a tertiary healthcare centre in the United Kingdom and considers suggestions for empirical treatment. METHODS: A retrospective, single-centre cohort review of 95 children (< 18 years of age) with focal intracranial suppurative infection admitted between January 2001 and June 2016 in Newcastle upon Tyne, United Kingdom. Microbiological profiles and empirical antibiotic regimens were analysed for coverage, administration and duration of use. Mortality and neurological morbidity were reviewed. Data was analysed using t-tests, Mann-Whitney U tests, independent-samples median tests, and χ2-tests where appropriate. P-values < 0.05 were considered statistically significant. RESULTS: Estimated annual incidence was 8.79 per million. Age was bimodally distributed. Predisposing factors were identified in 90.5%, most commonly sinusitis (42.1%) and meningitis (23.2%). Sinusitis was associated with older children (p < 0.001) and meningitis with younger children (p < 0.001). The classic triad was present in 14.0%. 43.8% of 114 isolates were Streptococcus spp., most commonly Streptococcus milleri group organisms. Twelve patients cultured anaerobes. Thirty one empirical antibiotic regimens were used, most often a third-generation cephalosporin plus metronidazole and amoxicillin (32.2%). 90.5% would have sufficient cover with a third generation cephalosporin plus metronidazole. 66.3% converted to oral antibiotics. Median total antibiotic treatment duration was 90 days (interquartile range, 60-115.50 days). Mortality was 3.2, 38.5% had short-term and 24.2% long-term neurological sequelae. CONCLUSIONS: Paediatric focal intracranial suppurative infection has a higher regional incidence than predicted from national estimates and still causes significant mortality and morbidity. We recommend a third-generation cephalosporin plus metronidazole as first-choice empirical treatment. In infants with negative anaerobic cultures metronidazole may be discontinued.

The Role of the Fibroblast in Inflammatory Upper Airway Conditions.

Upper airway inflammation is one of the most frequent health care presentations. This is perhaps not surprising with our exposure to a myriad of environmental microbes, pollutants, and allergens. The precise pathophysiological mechanisms that cause persistent, exaggerated, upper airway inflammation rather than acute resolving illness remain unclear. Analysis of upper airway specimens identifies specific inflammatory cells, cytokine signatures, and fibrotic airway remodeling. Recent research has highlighted the role of stromal cells in the generation and persistence of chronic inflammation. Rather than simply being scaffolding or extracellular matrix-secreting cells on which organ systems are built, stromal cells including fibroblasts and osteocytes have their own independent immunologic functions. Here, we review the emerging inflammatory roles of upper airway fibroblasts, the majority of which appear to influence immune cell chemotaxis and amplify the inflammatory response.

How reliable are sino-nasal cell lines for studying the pathophysiology of chronic rhinosinusitis?

BACKGROUND: Well-characterized cell lines represent useful scientific tools to study the pathophysiology of human disease. Chronic rhinosinusitis (CRS) is a very common condition, though the number of CRS cell lines is limited, as are data showing how closely they resemble primary cells. METHODOLOGY: Searches for available human cell lines were performed using the American Type Culture Collection (ATCC) and European Collection of Cell Cultures (ECACC). Identified cells were cultured and characterized with tinctorial and immunohistochemical staining and ELISA to assess their response to common, disease-relevant inflammatory stimuli. Carefully phenotyped CRS patients were recruited with informed consent. Primary nasal epithelial cell (PNEC) brushings were harvested, cultured, and compared to the available cell lines. RESULTS: Searches identified 1 relevant CRS sino-nasal cell line, RPMI 2650. Cultured PNECs showed strong expression of epithelial markers while being negative for mesenchymal markers. However, RPMI 2650 cells show an atypical mixed epithelial/mesenchymal phenotype. When stimulated by pro-inflammatory ligands, PNECs responded in a dose-dependent manner, whereas RPMI 2650 cells showed limited response. CONCLUSIONS: The number and availability of cell lines to study the pathophysiology of CRS greatly underrepresent the disease burden. Additionally, the sole commercially available cell line appears to have a different phenotype and behavior to primary patient-derived cells. The development of further reproducible cell lines would be beneficial in our understanding of CRS.

Autonomic nervous system dysfunction and sinonasal symptoms.

BACKGROUND: The autonomic nervous system (ANS) richly innervates the nose and paranasal sinuses, and has a significant role in lower airway diseases, e.g., asthma. Nonetheless, its contribution to sinonasal symptoms is poorly understood. This review aimed to explore the complex relationship between the ANS and sinonasal symptoms, with reference to systemic diseases and triggers of ANS dysfunction. METHODS: A review of articles published in English was conducted by searching medical literature databases with the key words "autonomic nervous system" and ("sinusitis" or "nose" or "otolaryngology"). All identified abstracts were reviewed, and, from these, relevant published whole articles were selected. RESULTS: The ANS has a significant role in the pathophysiologic mechanisms that produce sinonasal symptoms. There was limited evidence that describes the relationship of the ANS in sinonasal disease with systemic conditions, e.g. hypertension. There was some evidence to support mechanisms related to physical and psychological stressors in this relationship. CONCLUSION: The role of ANS dysfunction in sinonasal disease is highly complex. The ANS sits within a web of multiple factors, including personality and psychological distress, that contribute to sinonasal symptoms. Further research will help to clarify the etiology of ANS dysfunction and its contribution to common systemic conditions.