Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD161+CD8+ T cell clusters were significantly lower in colonized than in noncolonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide–specific and total plasmablasts in blood. Moreover, increased responses of blood mucosa-associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.

Running head: Experimental pneumococcal colonisation and aging Despite low rates of pneumococcal colonisation detected in older people in previous community surveys, experimental colonisation was established in 39% of volunteers aged ≥ 50 years. The serological and functional immune responses of older adults to challenge and colonisation with live pneumococci were markedly different to those of young adults. Experimental human pneumococcal colonisation was safe, supporting the use of this methodology in clinical trials of pneumococcal vaccines for older people.

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules.Trial registrationThe study was registered on EudraCT (2014-004634-26)FundingThe study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.

A single-centre change of practice audit of pain after coblation intracapsular tonsillectomy compared to standard dissection tonsillectomy in a discrete pediatric population.

Epistaxis is a common cause of emergency admissions in ENT. The use of Floseal haemostatic matrix in the treatment of epistaxis has been investigated in a number of studies in North America. We aimed to report a UK-based experience in the context of the current UK management paradigm. The study was designed as a prospective, unrandomised, control-matched longitudinal study. Cases were matched to controls in order to reduce the risk of bias. The overall treatment success rate for Floseal was 75 %, similar to the rates reported by studies based in North America. Nasal packing carried a success rate of 85 % and there was no statistically significant difference between the success rates of both treatments. Anecdotally Floseal can also be used successfully in thrombocyctopenic patients. There was a trend towards a shorter length of stay in the Floseal group, but this was not statistically significant. The 7-day readmission rate was 10 % for both the groups. This controlled study demonstrates that Floseal has a similar treatment success rate to nasal packing and that there may be a trend towards a shorter length of stay.

Rationale: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonisation in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Measurements and Main Results: Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged 70 years and older. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7ug/mL (1.9-3.8) pre-challenge versus 3.0 (1.9-4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8ug/mL (2.0-3.9) to 2.2ug/mL (1.6-3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7-10.1) led to recolonisation in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.

Treatment of midfacial segment facial pain is complex and requires follow-up to achieve any meaningful clinical outcome.

Background: Evidence-based interventions may reduce mortality in surgical patients. This study documented the prevalence of sepsis, adherence to guidelines in its management, and timing of source control in general surgical patients presenting as an emergency.Methods: Patients aged 16 years or more presenting with emergency general surgery problems were identified over a 7-day period and then screened for sepsis compliance (using the Sepsis Six standards, devised for severe sepsis) and the timing of source control (whether radiological or surgical). Exploratory analyses examined associations between the mode (emergency department or general practitioner) and time of admission, adherence to the sepsis guidelines, and outcomes (complications or death within 30 days).Results: Of a total of 5067 patients from 97 hospitals across the UK, 911 (18⋅0 per cent) fulfilled the criteria for sepsis, 165 (3⋅3 per cent) for severe sepsis and 24 (0⋅5 per cent) for septic shock. Timely delivery of all Sepsis Six guidelines for patients with severe sepsis was achieved in four patients. For patients with severe sepsis, 17⋅6-94⋅5 per cent of individual guidelines within the Sepsis Six were delivered. Oxygen was the criterion most likely to be missed, followed by blood cultures in all sepsis severity categories. Surgery for source control occurred a median of 19⋅8 (i.q.r. 10⋅0-35⋅4) h after diagnosis. Omission of Sepsis Six parameters did not appear to be associated with an increase in morbidity or mortality. Conclusion:Although sepsis was common in general surgical patients presenting as an emergency, adherence to severe sepsis guidelines was incomplete in the majority. Despite this, no evidence of harm was apparent. * Members of the UK National Surgical Research Collaborative are co-authors of this study and can be found under the heading Collaborators Paper accepted 25 October 2016Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.10432 IntroductionGeneral surgical patients presenting as an emergency account for over 7 per cent of hospital episodes in the USA and 14 000 ICU admissions per year in the UK 1 -3 . Sepsis is prevalent in this patient group. Early diagnosis of severe sepsis and initiation of goal-directed therapy can reduce mortality, irrespective of the need for surgery 4,5 . This evidence was used to develop a care bundle known as the Sepsis Six for managing patients with severe sepsis (Table 1) 6,7 . These standards have been endorsed by many professional organizations, including the Society of Critical Care Medicine, the European Society of Intensive Care Medicine and the Royal Colleges of Surgeons of England and Ireland 1,2,8,9 . Complete application of these interventions is thought to be associated with as much as a one-third reduction in mortality from sepsis, although uptake is uncertain amongst surgical patients presenting as an emergency 4,6 .The main aims of the present study were to assess adherence to the Sepsis Six guidelines and identify the timing of source control in general su...