Circulating anti-inflammatory adipokines High Molecular Weight Adiponectin and Zinc-α2-glycoprotein (ZAG) are inhibited in early sepsis, but increase with clinical recovery: a pilot study.

BACKGROUND: Adipose tissue has been identified as an endocrine organ secreting adipokines involved in metabolic and inflammatory pathways. Adiponectin, an anti-inflammatory adipokine, is reduced in sepsis. High Molecular Weight (HMW) adiponectin, the biologically most relevant molecule, has been investigated very little in human sepsis. Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine and its expression in adipose tissue is positively correlated with adiponectin expression. It is not yet known whether ZAG has a role in sepsis. In this study we assessed levels of HMW adiponectin and ZAG during different stages of sepsis. METHODS: A prospective observational pilot study was carried out on 21 septic patients. Serum samples were taken on day 1 and 2 post ICU admission and on day of discharge. Samples were analysed for total and HMW adiponectin, HMW/total adiponectin ratio, and ZAG. Results were correlated with clinical and metabolic data. RESULTS: There were no differences in total adiponectin, HMW adiponectin and ZAG plasma concentrations between day 1 (admission) and day 2 of the sepsis episode. Compared to admission, a significant increase in total and HMW adiponectin and ZAG was observed on the day of discharge when clinical improvement had been achieved. There was also an increase in the HMW/total adiponectin ratio at that time. CONCLUSIONS: Our data demonstrate an increase in both HMW adiponectin and total adiponectin in patients who had clinically recovered from sepsis. The increase in HMW/total adiponectin ratio with improvement of the clinical condition suggests that HMW adiponectin may have a greater role in the inflammatory process and insulin resistance seen in sepsis. In this pilot study, we have also demonstrated a significant increase in ZAG in critically ill patients temporally related to recovery from sepsis.

Prediction of invasive candidal infection in critically ill patients with severe acute pancreatitis.

INTRODUCTION: Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients who have a low risk of infection may not benefit and may be harmed. The aim of this study was to assess the validity and discrimination of existing risk scores for invasive candidal infections in patients with severe acute pancreatitis. METHODS: Patients admitted with severe acute pancreatitis to the intensive care unit were analysed. Outcomes and risk factors of admissions with and without candidal infection were compared. Accuracy and discrimination of three existing risk scores for the development of invasive candidal infection (Candida score, Candida Colonisation Index Score and the Invasive Candidiasis Score) were assessed. RESULTS: A total of 101 patients were identified from 2003 to 2011 and 18 (17.8%) of these developed candidal infection. Thirty patients died, giving an overall hospital mortality of 29.7%. Hospital mortality was significantly higher in patients with candidal infection (55.6% compared to 24.1%, P=0.02). Candida colonisation was associated with subsequent candidal infection on multivariate analysis. The Candida Colonisation Index Score was the most accurate test, with specificity of 0.79 (95% confidence interval [CI] 0.68 to 0.88), sensitivity of 0.67 (95% CI 0.41 to 0.87), negative predictive value of 0.91 (95% CI 0.82 to 0.97) and a positive likelihood ratio of 3.2 (95% CI 1.9 to 5.5). The Candida Colonisation Index Score showed the best discrimination with area under the receiver operating characteristic curve of 0.79 (95% CI 0.69 to 0.87). CONCLUSIONS: In this study the Candida Colonisation Index Score was the most accurate and discriminative test at identifying which patients with severe acute pancreatitis are at risk of developing candidal infection. However its low sensitivity may limit its clinical usefulness.