The 'analysis of gene expression and biomarkers for point-of-care decision support in Sepsis' study; temporal clinical parameter analysis and validation of early diagnostic biomarker signatures for severe inflammation andsepsis-SIRS discrimination.

Introduction: Early diagnosis of sepsis and discrimination from SIRS is crucial for clinicians to provide appropriate care, management and treatment to critically ill patients. We describe identification of mRNA biomarkers from peripheral blood leukocytes, able to identify severe, systemic inflammation (irrespective of origin) and differentiate Sepsis from SIRS, in adult patients within a multi-center clinical study. Methods: Participants were recruited in Intensive Care Units (ICUs) from multiple UK hospitals, including fifty-nine patients with abdominal sepsis, eighty-four patients with pulmonary sepsis, forty-two SIRS patients with Out-of-Hospital Cardiac Arrest (OOHCA), sampled at four time points, in addition to thirty healthy control donors. Multiple clinical parameters were measured, including SOFA score, with many differences observed between SIRS and sepsis groups. Differential gene expression analyses were performed using microarray hybridization and data analyzed using a combination of parametric and non-parametric statistical tools. Results: Nineteen high-performance, differentially expressed mRNA biomarkers were identified between control and combined SIRS/Sepsis groups (FC>20.0, p<0.05), termed 'indicators of inflammation' (I°I), including CD177, FAM20A and OLAH. Best-performing minimal signatures e.g. FAM20A/OLAH showed good accuracy for determination of severe, systemic inflammation (AUC>0.99). Twenty entities, termed 'SIRS or Sepsis' (S°S) biomarkers, were differentially expressed between sepsis and SIRS (FC>2·0, p-value<0.05). Discussion: The best performing signature for discriminating sepsis from SIRS was CMTM5/CETP/PLA2G7/MIA/MPP3 (AUC=0.9758). The I°I and S°S signatures performed variably in other independent gene expression datasets, this may be due to technical variation in the study/assay platform.

Report on the incidence of squamous cell carcinomas affecting the eyelids in England over a 15-year period (2000-2014).

AIMS: The authors report on trends in the incidence of squamous cell carcinoma (SCC) affecting the eyelids in England over a 15-year period and identify associations between demographic factors and SCC risk. METHODS: The National Cancer Registration and Analysis Service identified all cases of eyelid SCC in England between 2000 and 2014. The crude and age-standardised rates of eyelid SCCs in England were calculated. The association of SCC with several known demographic risk factors was then examined to assess their importance in periocular cases. RESULTS: Over the 15 years studied, there were 4022 patients in England diagnosed with a first episode of SCC affecting the eyelids. The age-standardised number of reported cases rose between 2000 and 2014 by a mean of 0.0137 cases per 100 000 population per year (equivalent to a rise in SCC incidence of approximately 2% per year). The mean age-standardised incidence rate of SCC during the study period was 0.63 cases per 100 000 population per year.Age was exponentially correlated with incidence, with an approximate doubling of the risk for every decade over the age of 60. The relative risk of eyelid SCC in men compared with women was 1.9. Social deprivation quintile by income was not found to be associated with risk of SCC. CONCLUSION: The incidence of eyelid SCC in England is rising. In addition, the age-standardised and population-standardised rate of SCC is also rising. A higher risk of SCC is strongly correlated with age and male sex but not with deprivation.