Interleukin 12 (IL-12) is increased in tumour bearing human liver and expands CD8C and CD56C T cells in vitro but not in vivo

Human liver is enriched with CD8CT- and CD3CCD56C natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56C/CD8CT lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n ¼ 13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n ¼ 9, 3678 pg, p!0:01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8CT and CD3CCD56CNT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8CT and CD56CNT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes

Interleukin 12 (IL-12) is increased in tumour bearing human liver and expands CD8C and CD56C T cells in vitro but not in vivo

Human liver is enriched with CD8CT- and CD3CCD56C natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56C/CD8CT lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n ¼ 13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n ¼ 9, 3678 pg, p!0:01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8CT and CD3CCD56CNT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8CT and CD56CNT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Towards the ACWP Questionnaire : the Australian Child Wellbeing Project : Final Phase Two Report

This is the Phase Two report of the Australian Child Wellbeing Project (ACWP) which is a child-centred study that started with young people’s perspectives to design a major nationally representative survey of wellbeing among 8 - 14 year olds. The survey will benchmark child wellbeing in Australia and provide information that contributes to the development of effective services for young people’s healthy development. This document reports on Phase Two of the project: development of the wellbeing indicators. The development of indicators was informed by the findings of the first qualitative phase of the project, a review of literature and existing wellbeing measures, considerations related to online implementation, two stages of feedback from the Project Steering Group as well as cognitive interviews with children in the target population (i.e. Years 4, 6, and 8) who responded to various versions of the field trial questionnaire

Interleukin 12 (IL-12) is increased in tumour bearing human liver and expands CD8C and CD56C T cells in vitro but not in vivo

Human liver is enriched with CD8CT- and CD3CCD56C natural T (NT)-lymphocytes, important anti-tumour effectors, similar to murine NKTs. IL-12 promotes anti-tumour functions of NKTs. We quantified IL-12 and CD56C/CD8CT lymphocytes in normal and tumour bearing liver. We also examined the effect of IL-12 on the expansion/activation of peripheral blood cells in vitro. IL-12 was detected in normal (n ¼ 13, median 2032 pg/100 mg protein) and increased in tumour bearing liver (n ¼ 9, 3678 pg, p!0:01). Infiltrating monocytes appear to be the principal producers. Culture with IL-12 selectively expanded CD8CT and CD3CCD56CNT cells and polarised their cytokine responses to Th1-type. However, there was no in vivo expansion of these cells in tumour bearing liver. Changes observed in culture required addition of IL-2. We therefore quantified IL-2 in hepatic tissue. IL-2 was detected in normal liver (median 4700 pg/100 mg protein). Surprisingly, there was no increase in tumour-infiltrated liver (4910 pg). The presence of IL-12 may create an environment in healthy liver that promotes the accumulation of CD8CT and CD56CNT cells. Therefore, the development of metastases in the presence of high levels of IL-12 may be due to an insufficient IL-12 response. Alternatively, lack of IL-2 rather than a defect in IL-12, may be responsible for insufficient expansion/activation of tumour specific cytotoxic T lymphocytes

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. To determine the association between mortality and the development of early IPN. International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p  0.05). Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality