Publications
143 results found
Triantafyllou E, Woollard K, McPhail M, et al., 2018, The role of monocytes and macrophages in acute and acute-on-chronic liver failure, Frontiers in Immunology, Vol: 9, ISSN: 1664-3224
Acute and acute-on-chronic liver failure (ALF and ACLF), though distinct clinical entities, are considered syndromes of innate immune dysfunction. Patients with ALF and ACLF display evidence of a pro-inflammatory state with local liver inflammation, features of systemic inflammatory response syndrome (SIRS) and vascular endothelial dysfunction that drive progression to multi-organ failure. In an apparent paradox, these patients are concurrently immunosuppressed, exhibiting acquired immune defects that render them highly susceptible to infections. This paradigm of tissue injury succeeded by immunosuppression is seen in other inflammatory conditions such as sepsis, which share poor outcomes and infective complications that account for high morbidity and mortality. Monocyte and macrophage dysfunction are central to disease progression of ALF and ACLF. Activation of liver-resident macrophages (Kupffer cells) by pathogen and damage associated molecular patterns leads to the recruitment of innate effector cells to the injured liver. Early monocyte infiltration may contribute to local tissue destruction during the propagation phase and results in secretion of pro-inflammatory cytokines that drive SIRS. In the hepatic microenvironment, recruited monocytes mature into macrophages following local reprogramming so as to promote resolution responses in a drive to maintain tissue integrity. Intra-hepatic events may affect circulating monocytes through spill over of soluble mediators and exposure to apoptotic cell debris during passage through the liver. Hence, peripheral monocytes show numerous acquired defects in acute liver failure syndromes that impair their anti-microbial programmes and contribute to enhanced susceptibility to sepsis. This review will highlight the cellular and molecular mechanisms by which monocytes and macrophages contribute to the pathophysiology of ALF and ACLF, considering both hepatic inflammation and systemic immunosuppression. We identify areas for f
Malik SS, Lythgoe MP, McPhail M, et al., 2018, Metachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: a systematic review and meta-analysis, Familial Cancer, Vol: 17, Pages: 557-564, ISSN: 1389-9600
Around 5% of colorectal cancers are due to mutations within DNA mismatch repair genes, resulting in Lynch syndrome (LS). These mutations have a high penetrance with early onset of colorectal cancer at a mean age of 45 years. The mainstay of surgical management is either a segmental or extensive colectomy. Currently there is no unified agreement as to which management strategy is superior due to limited conclusive empirical evidence available. A systematic review and meta- analysis to evaluate the risk of metachronous colorectal cancer (MCC) and mortality in LS following segmental and extensive colectomy. A systematic review of the PubMed database was conducted. Studies were included/ excluded based on pre-specified criteria. To assess the risk of MCC and mortality attributed to segmental or extensive colectomies, relative risks (RR) were calculated and corresponding 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Data about mortality, as well as patient ascertainment [Amsterdam criteria (AC), germline mutation (GM)] were also extracted. Statistical analysis was conducted using the R program (version 3.2.3). The literature search identified 85 studies. After further analysis ten studies were eligible for inclusion in data synthesis. Pooled data identified 1389 patients followed up for a mean of 100.7 months with a mean age of onset of 45.5 years of age. A total 1119 patients underwent segmental colectomies with an absolute risk of MCC in this group of 22.4% at the end of follow-up. The 270 patients who had extensive colectomies had a MCC absolute risk of 4.7% (0% in those with a panproctocolecomy). Segmental colectomy was significantly associated with an increased relative risk of MCC (RR = 5.12; 95% CI 2.88–9.11; Fig. 1), although no significant association with mortality was identified (RR = 1.65; 95% CI 0.90–3.02). There was no statistically significant difference in the risk of MCC betwe
Lythgoe MP, Malik SS, McPhail M, et al., 2018, Response to letter to editor regarding published articlemetachronous colorectal cancer following segmental or extended colectomy in Lynch syndrome: A systematic review and meta-analysis, Familial Cancer, Vol: 17, Pages: 545-546, ISSN: 1389-9600
Puthucheary ZA, Astin R, Mcphail MJW, et al., 2018, Metabolic phenotype of skeletal muscle in early critical illness, THORAX, Vol: 73, Pages: 926-935, ISSN: 0040-6376
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- Citations: 95
Bernal W, Wallace D, McPhail MJW, et al., 2018, Changes in Performance Status after Liver Transplantation; A National Cohort Study, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 673A-673A, ISSN: 0270-9139
Singanayagam A, Nathwani R, Triantafyllou E, et al., 2018, PLASMA S100A8/A9: A NOVEL MECHANISTIC BIOMARKER IN INNATE IMMUNE ACTIVATION IN ACUTE-ON-CHRONIC LIVER FAILURE, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A131-A132, ISSN: 0017-5749
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- Citations: 2
McPhail MJW, Parrott F, Wendon JA, et al., 2018, Incidence and outcomes for patients with cirrhosis admitted to the United Kingdom Critical Care Unitsa, Critical Care Medicine, Vol: 46, Pages: 705-712, ISSN: 0090-3493
OBJECTIVE: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. DESIGN: Retrospective cohort study. SETTING: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. PATIENTS: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]). CONCLUSIONS: More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.
Weil D, Levesque E, McPhail M, et al., 2017, Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis., Ann Intensive Care, Vol: 7, ISSN: 2110-5820
BACKGROUND: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. METHODS: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). RESULTS: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mo
Zia R, Patel VC, Gray N, et al., 2017, Multi-platform metabonomics reveals a distinct metabolic phenotype of acute-on-chronic liver failure, 68th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: Wiley, Pages: 675A-675A, ISSN: 0270-9139
Aggarwal N, Donald ND, Malik S, et al., 2017, The Association of Low-Penetrance Variants in DNA Repair Genes with Colorectal Cancer: A Systematic Review and Meta-Analysis, Clinical and Translational Gastroenterology, Vol: 8, ISSN: 2155-384X
OBJECTIVES: Approximately 35% of colorectal cancer (CRC) risk is attributable to heritable factors known hereditary syndromes,accounting for 6%. The remainder may be due to lower penetrance polymorphisms particularly of DNA repair genes. DNA repairpathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), direct reversal repair(DRR), and double-strand break repair are complex, evolutionarily conserved, and critical in carcinogenesis. Germline mutations inthese genes are associated with high-penetrance CRC syndromes such as Lynch syndrome. However, the association of lowpenetrancepolymorphisms of DNA repair genes with CRC risk remains unclear.METHODS: A systematic literature review of PubMed, Embase, and HuGENet databases was conducted. Pre-specified criteriadetermined study inclusion/exclusion. Per-allele, pooled odds ratios disclosed the risk attributed to each variant. Heterogeneitywas investigated by subgroup analyses for ethnicity and tumor location; funnel plots and Egger’s test assessed publication bias.RESULTS: Sixty-one polymorphisms in 26 different DNA repair genes were identified. Meta-analyses for 22 polymorphisms in 17genes revealed that six polymorphisms were significantly associated with CRC risk within BER (APE1, PARP1), NER (ERCC5, XPC),double-strand break (RAD18), and DRR (MGMT), but none within MMR. Subgroup analyses revealed significant association ofOGG1 rs1052133 with rectal cancer risk. Egger’s test revealed no publication bias.CONCLUSIONS: Low-penetrance polymorphisms in DNA repair genes alter susceptibility to CRC. Future studies should thereforeanalyze whole-genome polymorphisms and any synergistic effects on CRC risk.TRANSLATIONAL IMPACT: This knowledge may enhance CRC risk assessment and facilitate a more personalized approach tocancer prevention.
Aggarwal N, Donald ND, Malik S, et al., 2017, THE ASSOCIATION OF LOW PENETRANCE VARIANTS IN DNA REPAIR GENES WITH COLORECTAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A126-A126, ISSN: 0017-5749
Aggarwal N, Donald ND, Malik S, et al., 2017, MDM2 T309G POLYMORPHISM AND RISK OF COLORECTAL CANCER, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A126-A127, ISSN: 0017-5749
Al-Freah MAB, McPhail MJW, Dionigi E, et al., 2017, Improving the Diagnostic Criteria for Primary Liver Graft Nonfunction in Adults Utilizing Standard and Transportable Laboratory Parameters: An Outcome-Based Analysis, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 17, Pages: 1255-1266, ISSN: 1600-6135
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- Citations: 21
Audimoolam VK, McPhail MJW, Willars C, et al., 2017, Predicting Fluid Responsiveness in Acute Liver Failure: A Prospective Study, ANESTHESIA AND ANALGESIA, Vol: 124, Pages: 480-486, ISSN: 0003-2999
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- Citations: 11
Gray N, Zia R, King A, et al., 2017, High speed quantitative UPLC-MS analysis of multiple amines in human plasma and serum via pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate: Application to acetaminophen-induced liver failure, Analytical Chemistry, Vol: 89, Pages: 2478-2487, ISSN: 1520-6882
A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification/monitoring of amino acids and amino-containing compounds in human plasma and serum using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag UltraTM). Derivatization of the target amino-containing compounds reagent required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric properties. The resulting method, which requires only 10 µl of sample, provides the reproducible and robust separation of 66 analytes in 7.5 minutes, including baseline resolution of isomers such as e.g. leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2-20 and 800µM. Intra- and inter-day accuracy of between 0.05-15.6 and 0.78 -13.7 % and precision between 0.91-16.9 % and 2.12-15.9 % were obtained. A further 33 biogenic amines can be monitored in samples for relative changes in concentration rather than quantification. Application of the assay to samples derived from healthy controls and patients suffering from acetaminophen (APAP, paracetamol) induced acute liver failure (ALF) showed significant differences in the amounts of aromatic and branched chain amino acids between the groups as well as a number of other analytes, including the novel observation of increased concentrations of sarcosine in ALF patients. The properties of the developed assay, including short analysis time, make it suitable for high throughput targeted UPLC-ESI-MS/MS metabonomic analysis in clinical and epidemiological environments.
Velasquez T, Mackey G, Lusk J, et al., 2016, ESICM LIVES 2016: part three : Milan, Italy. 1-5 October 2016., Intensive Care Med Exp, Vol: 4, Pages: 28-28
McPhail MJW, Montagnese S, Villaneuva M, et al., 2016, Urinary metabolic profiling by 1H NMR spectroscopy in patients with cirrhosis may discriminate overt but not covert hepatic encephalopathy, Metabolic Brain Disease, Vol: 32, Pages: 331-341, ISSN: 1573-7365
To date urinary metabolic profiling has been applied to define a specific metabolic fingerprintof hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of othercomplications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinaryproton nuclear magnetic resonance (1H-NMR) spectra were acquired and NMR data from 52 patientswith cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls werecompared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stageliver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, PsychometricHepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE(OHE, n=21), covert HE (cHE, n=7) or no HE (n=17). Urinary proton nuclear magnetic resonance (1HNMR)spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The resultsshowed good discrimination between patients with cirrhosis (n=52) and healthy controls (n=17)(R2X=0.66, R2Y=0.47, Q2Y=0.31, sensitivity-60%, specificity-100%) as the cirrhosis group hadhigher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinicacid levels. While patients with OHE could be discriminated from those with no HE, with higherhistidine, citrate and creatinine levels, the best models lack robust validity (R2X=0.65, R2Y=0.48,Q2Y=0.12, sensitivity-100%, specificity-64%) with the sample size used. Urinary 1H-NMR metabolicprofiling did not discriminate patients with cHE from those without HE, nor discriminate subjects onthe basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed differenturinary 1H-NMR metabolic profiles compared to healthy controls and those with OHE may bedistinguished from those with no HE although larger studies are required. However, urinary 1H-NMRmetabolic profiling did not discriminate patients with differing grades of
Baumgartner B, McPhail MJ, Semela D, et al., 2016, Neutrophil-to-lymphocyte ratio - a prognostic biomarker for decompensated cirrhosis, Publisher: E M H SWISS MEDICAL PUBLISHERS LTD, Pages: 19S-19S, ISSN: 1424-7860
Grover VP, McPhail M, Wylezinska M, et al., 2016, A longitudinal study of patients with cirrhosis treated with L-ornithine L-aspartate, examined with magnetization transfer, diffusion-weighted imaging and magnetic resonance spectroscopy, Metabolic Brain Disease, Vol: 32, Pages: 77-86, ISSN: 1573-7365
The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T1- and T2-weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50% of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.
Gillon S, Wright C, Knott C, et al., 2016, Revision Notes in Intensive Care Medicine, Publisher: Oxford University Press, ISBN: 9780191069642
Revision Notes in Intensive Care Medicine is a key resource for candidates preparing for postgraduate intensive care examinations.
Fitzpatrick JA, Kim JU, Cobbold JFL, et al., 2016, Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy, JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY, Vol: 6, Pages: 15-20, ISSN: 0973-6883
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- Citations: 6
Zia R, Coen M, McPhail M, et al., 2016, Metabonomics: The future of personalized healthcare in liver intensive care?, Biochemist, Vol: 38, Pages: 27-30, ISSN: 0954-982X
Metabonomics involves the use of high-resolution analytical platforms to characterize the low-molecular-mass metabolic composition of biofluids and tissues. The resulting complex metabolic phenotype data are modelled using multivariate statistical approaches to identify systems levels panels of metabolites that discriminate between phenotypes (metabotypes), providing mechanistic insight and candidate biomarkers. With the increasing incidence of liver cirrhosis nationally, the pressures on NHS liver units is set to intensify, with mortality rates in these patients remaining high. This article describes a personalized medicine approach to stratify patients' mortality risk using metabolic phenotyping. This could aid doctors in clinical decision-making for patient transplant candidacy and critical care management to improve current survival rates.
Vijay GKM, Ryan JM, Abeles RD, et al., 2016, Neutrophil Toll-Like Receptor 9 Expression and the Systemic Inflammatory Response in Acetaminophen-Induced Acute Liver Failure, Critical Care Medicine, Vol: 44, Pages: 43-53, ISSN: 1530-0293
Objectives: There is a marked propensity for patients with acetaminophen-induced acute liver failure to develop sepsis, which may culminate in multiple organ failure and death. Toll-like receptors sense pathogens and induce inflammatory responses, but whether this is protective or detrimental in acetaminophen-induced acute liver failure remains unknown.Design, Setting, and Patients: We assessed Toll-like receptor expression on circulating neutrophils and their function in 24 patients with acetaminophen-induced acute liver failure and compared with 10 healthy controls.Interventions: Neutrophil Toll-like receptor 2, -4, and -9 expression and cytokine production and function were studied ex vivo at baseline and following stimulation with lipopolysaccharide, oligodeoxynucleotides, ammonium chloride, and interleukin-8. To examine the influence of acetaminophen-induced acute liver failure plasma and endogenous DNA on Toll-like receptors-9 expression, healthy neutrophils were incubated with acetaminophen-induced acute liver failure plasma with and without deoxyribonuclease-I.Measurements and Main Results: Circulating neutrophil Toll-like receptor 9 expression was increased in acetaminophen-induced acute liver failure on day 1 compared with healthy controls (p = 0.0002), whereas Toll-like receptor 4 expression was decreased compared with healthy controls (p < 0.0001). Toll-like receptor 2 expression was unchanged. Neutrophil phagocytic activity was decreased, and spontaneous oxidative burst increased in all patients with acetaminophen-induced acute liver failure compared with healthy controls (p < 0.0001). Neutrophil Toll-like receptor 9 expression correlated with plasma interleukin-8 and peak ammonia concentration (r = 0.6; p < 0.05) and increased with severity of hepatic encephalopathy (grade 0–2 vs 3/4) and systemic inflammatory response syndrome score (0–1 vs 2–4) (p < 0.05). Those patients with advanced hepatic encephalopathy (grade 3/4) o
McPhail MJW, Shawcross D, Lewis MR, et al., 2016, Mutlivariate metabotyping of plasma accurately predicts survival in decompensated cirrhosis, Journal of Hepatology, Vol: 64, Pages: 1058-1067, ISSN: 1600-0641
Background & AimsPredicting survival in decompensated cirrhosis (DC) is important in decision making for liver transplantation and resource allocation. We investigated whether high-resolution metabolic profiling can determine a metabolic phenotype associated with 90-day survival.MethodsTwo hundred and forty-eight subjects underwent plasma metabotyping by 1H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS; DC: 80-derivation set, 101-validation; stable cirrhosis (CLD) 20 and 47 healthy controls (HC)).Results1H NMR metabotyping accurately discriminated between surviving and non-surviving patients with DC. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. This was confirmed on external validation (area under the receiver operating curve [AUROC] = 0.96 (95% CI 0.90–1.00, sensitivity 98%, specificity 89%). UPLC-TOF-MS confirmed that lysophosphatidylcholines and phosphatidylcholines [LPC/PC] were downregulated in non-survivors (UPLC-TOF-MS profiles AUROC of 0.94 (95% CI 0.89–0.98, sensitivity 100%, specificity 85% [positive ion detection])). LPC concentrations negatively correlated with circulating markers of cell death (M30 and M65) levels in DC. Histological examination of liver tissue from DC patients confirmed increased hepatocyte cell death compared to controls. Cross liver sampling at time of liver transplantation demonstrated that hepatic endothelial beds are a source of increased circulating total cytokeratin-18 in DC.ConclusionPlasma metabotyping accurately predicts mortality in DC. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.
Patel VC, Leong LEX, Koller G, et al., 2016, ALTERED GUT MICROBIAL PROFILE IS A PROPONENTOF BACTERIAL TRANSLOCATION IN ACUTE- ON- CHRONIC LIVER FAILURE, EASL International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: S453-S454, ISSN: 0168-8278
Tognarelli JM, Dawood M, Shariff MIF, et al., 2015, Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians, JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY, Vol: 5, Pages: 320-328, ISSN: 0973-6883
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- Citations: 51
McPhail MJW, Farne H, Senvar N, et al., 2015, Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis, Clinical Gastroenterology and Hepatology, Vol: 14, Pages: 516-525.e5, ISSN: 1542-7714
Sarafian MH, Lewis MR, Pechlivanis A, et al., 2015, Bile Acid Profiling and Quantification in Biofluids Using Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry, Analytical Chemistry, Vol: 87, Pages: 9662-9670, ISSN: 1520-6882
Bile acids are important end products of cholesterol metabolism. While they have been identified as key factors in lipid emulsification and absorption due to their detergent properties, bile acids have also been shown to act as signaling molecules and intermediates between the host and the gut microbiota. To further the investigation of bile acid functions in humans, an advanced platform for high throughput analysis is essential. Herein, we describe the development and application of a 15 min UPLC procedure for the separation of bile acid species from human biofluid samples requiring minimal sample preparation. High resolution time-of-flight mass spectrometry was applied for profiling applications, elucidating rich bile acid profiles in both normal and disease state plasma. In parallel, a second mode of detection was developed utilizing tandem mass spectrometry for sensitive and quantitative targeted analysis of 145 bile acid (BA) species including primary, secondary, and tertiary bile acids. The latter system was validated by testing the linearity (lower limit of quantification, LLOQ, 0.25–10 nM and upper limit of quantification, ULOQ, 2.5–5 μM), precision (≈6.5%), and accuracy (81.2–118.9%) on inter- and intraday analysis achieving good recovery of bile acids (serum/plasma 88% and urine 93%). The ultra performance liquid chromatography–mass spectrometry (UPLC-MS)/MS targeted method was successfully applied to plasma, serum, and urine samples in order to compare the bile acid pool compositional difference between preprandial and postprandial states, demonstrating the utility of such analysis on human biofluids.
Phadke R, Puthucheary Z, Rawal I, et al., 2015, Fasciitis frequently accompanies myopathy in acute critical illness muscle wasting: Evidence from qualitative ultrasound and muscle biopsy analysis, 20th International Congress of the World-Muscle-Society, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: S250-S250, ISSN: 0960-8966
Grover VPB, Tognarelli JM, Crossey MME, et al., 2015, Magnetic Resonance Imaging: Principles and Techniques: Lessons for Clinicians, JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY, Vol: 5, Pages: 246-255, ISSN: 0973-6883
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- Citations: 159
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