Regular monitoring of airway microbiology is key in CF management. Standards recommend prompt sample processing. Increasingly, care is delivered remotely with limited evidence for sputum sample quality following postal delivery and absent data for postal acid-fast bacilli (AFB) and cough samples. We evaluated airway samples sent by post in CF patients against those processed the same day.

PRESENTATIONSwhether altered levels of various lipid metabolism and transport related proteins could predict the severity of ACLF.Aim: To identify candidate circulating biomarkers using proteomics, to assess the severity and prognosis in ACLF patients.Methods: After depleting major plasma proteins, low abundant protein fraction was trypsin digested, iTRAQ labeled and fractionated using (SCX,RP) HPLC subjected to high resolution mass spectrometry for quantitative expression profiling.Validation of protein expression profiling were performed in; Gr. 1 ACLF (n = 40), Gr. 2 compensated cirrhosis (n = 20) and Gr. 3 healthy controls (n = 20).Results: 305 differentially regulated proteins were identified of which 120 were more than 2 fold differentially regulated.Proteins involved in transport and metabolism of lipids were significantly reduced in Gr. 1 (Pon1, ApoA1, ApoA2, and ApoC3; >2 folds).Pon 1 was significantly reduced in Gr. 1 (25ug/ml), vs. Gr. 2 (45ug/ml), Gr. 3 (140ug/ml) (p = 0.02, p = 0.0001).Levels of other lipid transporters (Apo A1, Apo A2, Apo C1 Apo C3, Apo B, Apo E) were significantly reduced in Gr. 1 vs. Gr.2, Gr. 3 (p < 0.05).Levels of of Pon1 and Apo B were significantly reduced in the non survivors compared to survivor in Gr. 1 (p < 0.05).Ratios of Pon1/ApoA1, Apo A2, ApoC1 were severely deranged in non survivors in Gr. 1 (p < 0.05).The level of Pon 1 and the ratio of Pon 1/A1, A2, C1 correlated inversely with the MELD, SOFA and CTP scores (p < 0.05).Moreover, level of Pon1 and the ratio of Pon1/Apo A1, A2 and C1 showed a direct correlation with survival in ACLF patients (p < 0.03, r 2 >0.3).Conclusions: In the ACLF patients, circulating Pon1 level and the ratio of Pon1/Apo A1, A2, C1 were significantly reduced in the nonsurvivors compared to survivors.These lipid transporter proteins could serve as biomarkers for assessing the outcome of patients with ACLF.

Patients with chronic liver disease requiring intensive care are thought to carry a poor prognosis in comparison with noncirrhotic patients with similar severity of illness. During the last decade improvements in multiple areas of management in patients in the ICU have occurred but improvement in outcomes in patients with cirrhosis has not been shown.

Present outcome prediction tools for patients with acute-on-chronic liver failure during critical illness are only of moderate accuracy. Regression methods on latent variables (usually applied to top-down system biology applications with spectroscopic data) may offer significant advantages over logistic regression techniques as multiple cross-correlations are acceptable in this form of modelling.

BACKGROUND & AIMS:The incidence of cirrhosis and subsequent development of organ dysfunction (OD) requiring intensive care unit (ICU) support is rising. Historically, critically ill cirrhotics are perceived as having poor prognosis and substantial cost of care. METHODS:The aim was to prospectively analyse resource utilisation and cost of a large cohort of patients (n=660) admitted to a Liver ICU from 2000 to 2007 with cirrhosis and OD. Child Pugh, MELD, SOFA, APACHE II, and organ support requirements were collected. The Therapeutic Intervention Scoring System (TISS) score, a validated tool for estimating cost in ICU, was calculated daily. Logistic regression was used to determine independent predictors of increased cost. RESULTS:Alcohol was the most common etiology (47%) and variceal bleeding (VB) the most common reason for admission (35%). Invasive ventilatory support was required in 74% of cases, vasopressors in 49%, and 50% required renal replacement therapy. Forty-nine per cent of non-transplanted patients survived to ICU discharge. Median TISS score and ICU cost per patient were 261 and €14,139, respectively. VB patients had the highest survival rates (53% vs. 24%; p<0.001) and lower associated cost. A combination of VB (OR 0.48), need for ventilation (OR 2.81), low PO(2)/FiO(2) on admission (OR 0.97), and lactate (OR 0.93) improved cost prediction on multivariate analysis (AUROC 0.7; p<0.001) but organ failure scores per se were poor predictors of cost. CONCLUSIONS:Patients with cirrhosis and OD result in considerable resource expenditure but have acceptable hospital survival. Further health economic assessment and outcome prediction tools are required to appropriately target resource utilisation.

resonance imaging (fMRI) has not been applied in assessing efficacy of L-ornithine L-aspartate (LOLA).Methods: 21 patients with well compensated biopsy-proven mixed aetiology cirrhosis and previous PHES-defined MHE were treated with LOLA for 4 weeks.Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score (PHES) and Cognitive Drug Research Score (CDRS, United BioSource)) were performed.Images were acquired using a 3-Tesla MR scanner (Achieva, Philips Medical Systems, Best, Netherlands) using a 3D T1-weighted sequence with a GE 8-channel head coil.150 slices were obtained with a slice thickness of 1.2 mm, TR of 9.64ms, TE of 4.60ms and flip angle of 8 o .Volumetric MRI of the brain was paired with fMRI using a highly simplistic visuo-motor task.Regional brain volume (BV) and neural activation change (Blood Oxygenation Level Dependent (BOLD)) was assessed within the MRI software library (FSL, Oxford UK) using regional Structural Image Evaluation, using Normalisation, of Atrophy (SIENAr) and fMRI expert analysis tool (FEAT).Results: No change in clinical or biochemical state was noted.Significant improvements in CDR score and PHES score were observed (PHES Mean difference (MD) +1.2, p = 0.008, CDRS MD +1.2, p = 0.003, Speed of Memory z-score (SoM) MD +0.6, p = 0.005, Quality of Executive Memory z-score (QoEM) MD +0.4,p = 0.002, paired t-testing).Regional assessment of BV did not detect statistically significant modification of local grey matter volume following permutation testing.Significant BOLD signal change was detected in the posterior cingulate and ventral-medial prefrontal cortex.This correlated robustly with SoM and QoEM.There was evidence of increased visual cortex activation accompanying improved psychometric performance.Conclusion: Core metabolic and structural regions of the brain showed altered function following treatment with LOLA.This was associated with improved psychometric performance, but not locoregional change in BV suggesting LOLA may improve performance via mechanisms unrelated to low grade cerebral oedema.

Intracranial hypertension (ICH) complicates around 25% of grade III/IV encephalopathy in acute liver failure. Intracranial pressure (ICP) monitoring is controversial in this coagulopathic population.

Summary Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual but well recognised cause of bone marrow dysfunction and multiple organ failure in young patients. Two 18 year‐old patients were admitted to a tertiary liver unit with features of acute liver failure, cardio‐respiratory collapse and pancytopenia. Serological tests and bone marrow examination with in‐situ hybridisation revealed severe acquired haemophagocytic lymphohistiocytosis secondary to acute Epstein–Barr virus infection. Both patients died despite full supportive therapy; the first due to pulmonary haemorrhage, the second due to acute respiratory distress syndrome refractory to high frequency oscillatory ventilation. The clinical spectrum, diagnostic features and current evidence based recommendations for treatment of this condition are explored. The diagnosis of haemophagocytic lymphohistiocytosis should be considered in young patients with marked bone marrow dysfunction and multiple organ failure. Further research into appropriate therapy for patients with acute severe forms of the disease who require intensive organ support is required.

Gc globulin, a hepatically synthesized actin binding protein, is known to decrease in both acute and chronic liver disease, and low levels are associated with poor prognosis. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family of proteins, has been shown to be an early biomarker of ischaemic renal damage. We prospectively investigated the use of these proteins as markers of severity of illness and prognostication in acute and acute-on-chronic liver failure requiring intensive care.

Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism.Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases.The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass.Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass.After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6).Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters.Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined.Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion.Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05).Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05).Myocardial ATP levels were markedly improved in the sulfide-treated group.Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass.These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.

Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism.Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases.The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass.Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass.After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6).Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters.Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined.Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion.Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05).Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05).Myocardial ATP levels were markedly improved in the sulfide-treated group.Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass.These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.

Conclusions: Noradrenaline seems to be as effective and safe as terlipressin in patients with HRS.If confirmed, these results could support the use of noradrenaline, a cheap and easily available drug, in the management of these patients.