5015 articles - 08.09.10
1: Am J Gastroenterol. 2010 Sep;105(9):1917-21.
Tandon P, Saez R, Berzigotti A, Abraldes JG, Garcia-Pagan JC, Bosch J.
Hospital Clinic, University of Barcelona, Barcelona, Spain.
OBJECTIVES:Randomized controlled trials of variceal bleeding prophylaxis demonstrate beta-blocker (BB) withdrawal rates of about 15%. We aimed to evaluate the dosing and tolerance of BBs achievable in a specialized, nurse-run BB titration clinic with non-trial participants.METHODS:We analyzed prospectively collected data from 154 patients seen at the clinic between 2004 and 2009. BBs were titrated to patient tolerance. The therapeutic target (TT) was defined as a heart rate between 50 and 60 beats per minute (bpm) on the last clinic visit and/or maximum doses of BBs (propranolol 320 mg, nadolol 160 mg).RESULTS:Eight of 154 patients were lost to follow-up, leaving 146. Fifty-five percent were male (mean age, 55; mean model for end-stage liver disease (MELD) score, 9), with 74% Child-Pugh class A. Median end-of-study doses were 120 mg propranolol and 60 mg nadolol. Seventy-nine percent of patients reached the TT before they were discharged from the clinic. Side effects were experienced by 72% of patients. Thirty-four percent had no need for dose reduction; 17% required transient dose reduction, 16% permanent dose reduction, and 5% BB discontinuation. Among patients requiring permanent dose reduction or discontinuation, the top reasons were fatigue and orthostatic symptoms. Independent predictors of achieving higher doses of BB were the absence of side effects, younger age, and diabetes.CONCLUSIONS:This study provides evidence that a specialized BB titration clinic attains low withdrawal rates and higher doses, similar to those in clinical trials. Nurse-led clinics can contribute to successful titration of these important medications.
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PMID: 20818346 [PubMed - in process]2: Hepatology. 2010 Jul 16; [Epub ahead of print]
Asrani SK, Leise MD, West CP, Murad MH, Pedersen RA, Erwin PJ, Tian J, Wiesner RH, Kim WR.
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN.
Sirolimus is used in patients with renal insufficiency after liver transplantation (LT) and especially in those with calcineurin inhibitor (CNI)-associated nephrotoxicity. We conducted a systematic review of all randomized controlled trials and observational studies to test the hypothesis that the use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency [glomerular filtration rate (GFR) < 60 mL/minute or creatinine level >/= 1.5 mg/dL]. We performed a search of all major databases, conference proceedings, and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was used to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus-based therapy at 1 year. Eleven studies (three randomized controlled trials and eight observational studies) met the final inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95% confidence interval (CI) = -2.93 to 9.69] was observed in methodologically sound observational studies and controlled trials reporting the primary outcome. In controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an improvement of 10.35 mL/minute (95% CI = 3.98-16.77) in GFR or creatinine clearance. Sirolimus was not significantly associated with death [relative risk (RR) = 1.12, 95% CI = 0.66-1.88] or graft failure (RR = 0.80, 95% CI = 0.45-1.41), although reporting was incomplete. It was associated with a statistically significant risk of infection (RR = 2.47, 95% CI = 1.14-5.36), rash (RR = 7.57, 95% CI = 1.75-32.70), ulcers (RR = 7.44, 95% CI = 2.03-27.28), and discontinuation of therapy (RR = 3.61, 95% CI = 1.32-9.89). Conclusion: Conversion to sirolimus from CNIs is associated with a nonsignificant improvement in renal function in LT recipients with renal insufficiency, although the results are limited by heterogeneity, a risk of bias, and a lack of standardized reporting. (HEPATOLOGY 2010;).
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PMID: 20815021 [PubMed - as supplied by publisher]3: Hepatology. 2010 Sep;52(3):1143-55.
Nunez M.
Department of Internal Medicine, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA. mnunez@wfubmc.edu
Highly active antiretroviral therapy (HAART)-related hepatotoxicity complicates the management of patients infected with human immunodeficiency virus (HIV), increases medical costs, alters the prescription patterns, and affects the guideline recommendations. Among the clinical consequences derived from HAART-related liver toxicity, hypersensitivity reactions and lactic acidosis are recognized as acute events with potential to evolve into fatal cases, whereas there seems to be other syndromes not as well characterized but of equal concern as possible long-term liver complications. Belonging to the latter category of syndrome, HAART-related nonalcoholic steatohepatitis, liver fibrosis, portal hypertension, and nodular regenerative hyperplasia are discussed in this review. Updated information on liver toxicity of current antiretroviral drugs, including the most recently licensed, is provided. Management and prevention of liver toxicity among HIV-infected patients treated with HAART are reviewed as well.
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PMID: 20812358 [PubMed - in process]4: Am J Gastroenterol. 2010 Aug 24; [Epub ahead of print]
Li Z, Zou D, Ma X, Chen J, Shi X, Gong Y, Man X, Gao L, Zhao Y, Wang R, Yan X, Dent J, Sung JJ, Wernersson B, Johansson S, Liu W, He J.
[1] Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China [2] These authors contributed equally to this work.
OBJECTIVES:Complications of peptic ulcer disease (PUD) are common in China. Population-based estimates of the prevalence of PUD are needed to quantify and characterize the population at risk of these complications.METHODS:As part of a large epidemiological study, 3,600 randomly selected residents of Shanghai (aged 18-80 years) were asked to undergo endoscopy and to provide blood samples for Helicobacter pylori serology. All participants also completed a general information questionnaire and Chinese versions of the reflux disease questionnaire (RDQ) and Rome II questionnaire. Associations between PUD and other factors were analyzed using a multiple logistic regression model.RESULTS:In total, 3,153 individuals (87.6%) completed the survey. All underwent blood tests, and 1,030 patients (32.7%) agreed to undergo endoscopy. Results from 1,022 patients were suitable for analysis. In all, 176 participants (17.2%) had PUD (62 with gastric ulcer; 136 with duodenal ulcer). The prevalence of H. pylori infection was 73.3% in the total population and 92.6% among those with PUD. H. pylori infection was associated with the presence of PUD (odds ratio (OR), 6.77; 95% confidence interval (CI), 2.85-16.10). The majority (72.2%) of individuals with PUD had none of the upper gastrointestinal symptoms assessed by the RDQ. PUD was not significantly associated with symptom-defined gastroesophageal reflux disease (GERD) (OR, 0.80; 95% CI, 0.32-2.03), reflux esophagitis (OR, 1.46; 95% CI, 0.76-2.79) or dyspepsia (OR, 1.69; 95% CI, 0.94-3.04).CONCLUSIONS:The prevalence of endoscopically confirmed PUD in this Shanghai population (17.2%) is substantially higher than in Western populations (4.1%). The majority of individuals with PUD were asymptomatic.Am J Gastroenterol advance online publication, 24 August 2010; doi:10.1038/ajg.2010.324.
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PMID: 20736940 [PubMed - as supplied by publisher]5: Eur J Gastroenterol Hepatol. 2010 Aug 19; [Epub ahead of print]
Lange CM, von Wagner M, Bojunga J, Berg T, Farnik H, Hassler A, Sarrazin C, Herrmann E, Zeuzem S.
aKlinikum der J.W. Goethe-Universitat Frankfurt am Main, Medizinische Klinik bJ.W. Goethe-Universitat Frankfurt am Main, Fachbereich Medizin, fur Biostatistik und Mathematische Modellierung, Theodor-Stern-Kai, Frankfurt am Main cKlinik fur Gastroenterologie und Rheumatologie, Sektion Hepatologie, Universitatsklinikum Leipzig Liebigstr, Leipzig, Germany.
AIMS: Chronic hepatitis C alters the host's lipid metabolism and hepatitis C virus (HCV) eradication may be followed by an increase of serum cholesterol to adverse levels. We therefore aimed to determine the impact of chronic hepatitis C and its treatment on circulating lipids in a large European cohort of HCV genotype 1 patients. METHODS: The serum lipid profile of 575 HCV genotype 1-infected patients was characterized before, during and after treatment with pegylated interferon-alpha-2a (180 mug/week) and ribavirin (1000-1200 mg/day) for 48 weeks within a randomized controlled clinical trial. RESULTS: Total baseline cholesterol levels were significantly higher in patients with sustained virologic response (SVR) compared to nonresponders/relapsers (177 vs. 167 mg/dl, P=0.01), and low-cholesterol levels were an independent negative predictor of SVR (P=0.084). During the antiviral treatment, cholesterol levels substantially decreased as a putative marker of interferon-activity, but rebounded above baseline in patients with SVR (177-188 mg/dl, P=0.02), and to baseline in nonresponders/relapsers. Proportions of patients with cholesterol (>240 mg/dl) at baseline and after HCV eradication were 4 and 6%, respectively. Significant differences of triglyceride levels in patients with and without SVR were only observed at follow-up (136 and 117 mg/dl, respectively, P=0.028) but not at baseline. CONCLUSION: Our study reports a substantial pretreatment hypocholesterolemia in European HCV genotype 1 patients with nonresponse to interferon-alpha-based therapy and lower pretreatment cholesterol levels were an independent predictor of not attaining SVR. After treatment-induced HCV eradication median cholesterol levels increased above baseline, but the proportion of patients with high-risk cholesterol levels remained relatively low.
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PMID: 20729742 [PubMed - as supplied by publisher]6: Am J Gastroenterol. 2010 Aug 17; [Epub ahead of print]
Ford AC, Khan KJ, Talley NJ, Moayyedi P.
Leeds General Infirmary, Leeds Gastroenterology Institute, Leeds, UK.
OBJECTIVES:Evidence from randomized controlled trials (RCTs) for the use of 5-aminosalicylic acid (5-ASA) drugs in Crohn's disease (CD) in remission after a surgical resection is conflicting. We conducted a systematic review and meta-analysis of RCTs to examine this issue.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through April 2010). Eligible trials recruited adults with luminal CD in remission after a surgical resection and compared 5-ASAs with placebo, or no treatment. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference.RESULTS:The search strategy identified 3,061 citations. Eleven RCTs were eligible for inclusion containing 1,282 patients. The RR of relapse of CD in remission after surgery with 5-ASA vs. placebo or no therapy was 0.86 (95% CI=0.74-0.99) (NNT=13). Sulfasalazine was of no benefit in preventing relapse in 448 patients (RR=0.97; 95% CI=0.72-1.31), but mesalamine was more effective than placebo or no therapy (RR=0.80; 95% CI=0.70-0.92) in 834 patients, with an NNT of 10.CONCLUSIONS:Mesalamine is of modest benefit in preventing relapse of CD in remission after surgery. Its use should be considered in those in whom immunosuppressive therapy is either not warranted or contraindicated.Am J Gastroenterol advance online publication, 17 August 2010; doi:10.1038/ajg.2010.317.
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PMID: 20717106 [PubMed - as supplied by publisher]7: Gastroenterology. 2010 Aug 6; [Epub ahead of print]
Tillisch K, Mayer EA, Labus JS.
Center for Neurobiology of Stress, Departments of Medicine, Physiology and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles.
BACKGROUND AND AIMS:: The responsiveness of the central nervous system (CNS) is altered in patients with irritable bowel syndrome (IBS). However, due variations in experimental paradigms, analytic techniques, and reporting practices, little consensus exists on brain responses to visceral stimulation. We aimed to identify brain regions consistently activated by supraliminal rectal stimulation in IBS patients and healthy subjects (controls), by performing a quantitative meta-analysis of published studies. METHODS:: Significant foci from with-in group statistical parametric maps were extracted from published neuroimaging studies that employed rectal distension. Voxel-based activation likelihood estimation was applied, pooling the results and comparing them across groups. RESULTS:: Across studies, there was consistent activation in regions associated with visceral afferent processing (thalamus, insula, anterior mid-cingulate) among IBS patients and controls, but considerable differences in the extent and specific location of foci. IBS patients differed from controls in: 1) More consistent activations in regions associated with emotional arousal [pregenual anterior cingulate cortex (pACC), amygdala]; 2) Activation of a midbrain cluster, a region playing a role in endogenous pain modulation. Controls showed more consistent activation of the medial and lateral prefrontal cortex. CONCLUSIONS:: Patients with IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation, but similar activation of regions involved in processing of visceral afferent information. Controls have greater engagement of cognitive modulatory regions. These results support a role for CNS dysregulation in IBS. These findings provide specific targets for guiding development of future neuroimaging protocols to more clearly define altered brain-gut interactions in IBS. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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PMID: 20696168 [PubMed - as supplied by publisher]8: J Hepatol. 2010 Jul 17; [Epub ahead of print]
Mayr R, Janecke AR, Schranz M, Griffiths WJ, Vogel W, Pietrangelo A, Zoller H.
Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Austria.
BACKGROUND & AIMS: Classical ferroportin disease is characterized by hyperferritinemia, normal transferrin saturation, and iron overload in macrophages. A non-classical form is characterized by additional hepatocellular iron deposits and a high transferrin saturation. Both forms demonstrate autosomal dominant transmission and are associated with ferroportin gene (SLC40A1) mutations. SLC40A1 encodes a cellular iron exporter expressed in macrophages, enterocytes, and hepatocytes. The aim of the analysis is to determine the penetrance of SLC40A1 mutations and to evaluate in silico tools to predict the functional impairment of ferroportin mutations as an alternative to in vitro studies. METHODS: We conducted a systematic review of the literature and meta-analysis of the biochemical presentation, genetics, and pathology of ferroportin disease. RESULTS: Of 176 individuals reported with SLC40A1 mutations, 80 were classified as classical phenotype with hyperferritinemia and normal transferrin saturation. The non-classical phenotype with hyperferritinemia and elevated transferrin saturation was present in 53 patients. The remaining patients had normal serum ferritin or the data were reported incompletely. Despite an increased hepatic iron concentration in all biopsied patients, significant fibrosis or cirrhosis was present in only 11%. Hyperferritinemia was present in 86% of individuals with ferroportin mutations. Bio-informatic analysis of ferroportin mutations showed that the PolyPhen score has a sensitivity of 99% and a specificity of 67% for the discrimination between ferroportin mutations and polymorphisms. CONCLUSIONS: In contrast to HFE hemochromatosis, ferroportin disease has a high penetrance, is genetically heterogeneous and is rarely associated with fibrosis. Non-classical ferroportin disease is associated with a higher risk of fibrosis and a more severe overload of hepatic iron. Copyright (c) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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PMID: 20691492 [PubMed - as supplied by publisher]9: BMC Gastroenterol. 2010 Jul 31;10:85.
Chen B, Fan T, Wang CH.
Department of Gastroenterology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, 610041, China.
BACKGROUND: Glyceryl trinitrate (GTN) has been shown to be able to relax the sphincter of Oddi (SO) both in animals and humans. Theoretically, the use of these compounds during and after endoscopic retrograde cholangiopancreatgraphy (ERCP) could relax the biliary and pancreatic sphincters, facilitating cannulation of common bile duct (CBD) during the procedure, or minimizing potential pancreatic outflow obstruction after the procedure. However, clinical trials evaluating the protective effect of GTN on the post-endoscopic retrograde cholangiopancreatgraphy pancreatitis (PEP) have yielded inconclusive results. This meta-analysis is to systematically assess the effect of prophylactic administration of glyceryl trinitrate (GTN) on the prevention of PEP and the effect on the cannulation of bile ducts. METHODS: By searching PubMed (1966 to September 2009), CENTRAL (Cochrane Controlled trials Register; issue 3, 2009) and EMBASE.com (1984 to September 2009), two independent reviewers systematically identified prospective randomized controlled trials (RCTs) detecting the effect of prophylactic GTN on the incidence of PEP and on the cannulation of bile ducts. A meta-analysis of these clinical trials was then performed. RESULTS: There are 55/899(6.1%) patients suffering PEP in the treatment group versus 95/915(10.4%) patients in the placebo group. The overall pooled risk of PEP was significantly lower in the GTN group than in the placebo group (OR 0.56, 95% CI: 0.40 to 0.79, p = 0.001). Subgroup analyses suggested that GTN administered by the sublingual form (OR 0.34,95% CI:0.16 to 0.75, p = 0.007) is more effective than transdermal route(OR 0.64,95% CI:0.40 to 1.01, p = 0.05), and the protective effect of GTN was far more obvious in the centers with high incidence of PEP (OR 0.40, 95% CI:0.24 to 0.67, p = 0.0006) than those centers with a low incidence of PEP (OR 0.75, 95% CI: 0.47 to 1.20, p = 0.22). Additionally, the meta-analysis suggests that GTN was not helpful for the cannulation of bile ducts. CONCLUSION: We concluded that prophylactic administration of GTN may significantly reduce the incidence of PEP and not be helpful for the cannulation of bile ducts.
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PMID: 20673365 [PubMed - in process]10: J Hepatol. 2010 Oct;53(4):599-607. Epub 2010 Jun 20.
Gowans EJ, Roberts S, Jones K, Dinatale I, Latour PA, Chua B, Eriksson EM, Chin R, Li S, Wall DM, Sparrow RL, Moloney J, Loudovaris M, Ffrench R, Prince HM, Hart D, Zeng W, Torresi J, Brown LE, Jackson DC.
Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia. gowans@burnet.edu.au
BACKGROUND & AIMS: HCV patients who fail conventional interferon-based therapy have limited treatment options. Dendritic cells are central to the priming and development of antigen-specific CD4(+) and CD8(+) T cell immunity, necessary to elicit effective viral clearance. The aim of the study was to investigate the safety and efficacy of vaccination with autologous dendritic cells loaded with HCV-specific cytotoxic T cell epitopes. METHODS: We examined the potential of autologous monocyte-derived dendritic cells (MoDC), presenting HCV-specific HLA A2.1-restricted cytotoxic T cell epitopes, to influence the course of infection in six patients who failed conventional therapy. Dendritic cells were loaded and activated ex vivo with lipopeptides. In this phase 1 dose escalation study, all patients received a standard dose of cells by the intradermal route while sequential patients received an increased dose by the intravenous route. RESULTS: No patient showed a severe adverse reaction although all experienced transient minor side effects. HCV-specific CD8(+) T cell responses were enumerated in PBMC by ELIspot for interferon-gamma. Patients generated de novo responses, not only to peptides presented by the cellular vaccine but also to additional viral epitopes not represented in the lipopeptides, suggestive of epitope spreading. Despite this, no increases in ALT levels were observed. However, the responses were not sustained and failed to influence the viral load, the anti-HCV core antibody response and the level of circulating cytokines. CONCLUSIONS: Immunotherapy using autologous MoDC pulsed with lipopeptides was safe, but was unable to generate sustained responses or alter the outcome of the infection. Alternative dosing regimens or vaccination routes may need to be considered to achieve therapeutic benefit. Copyright (c) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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PMID: 20667615 [PubMed - in process]11: Gut. 2010 Jul 26; [Epub ahead of print]
Bardou M, Barkun A, Martel M.
Dijon, France.
Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also called statins, are commonly prescribed medications that lower serum cholesterol and decrease cardiac morbidity and mortality. They also possess beneficial effects beyond their cholesterol-lowering properties. Preclinical data suggest statins exhibit pleiotropic antineoplastic effects in a variety of tumours, but clinical studies have provided conflicting data as to whether statins influence the risk of cancer. The biological underpinning of potential effects of statins in colorectal cancer and their role in its prevention or as adjuvant therapy are reviewed. Following a meta-analysis of both randomised clinical trials and epidemiological studies, it is concluded that available clinical data only support a modest, although statistically significant, protective effect of statins in colorectal cancer. Statins may impact on outcomes by decreasing the invasiveness or metastatic properties of colorectal cancer. The data supporting these hypotheses, however, are few and further studies are required to better assess these hypotheses. Statins may also exert a beneficial effect on colorectal cancer by sensitising the tumour to chemotherapeutic agents. Further research is needed to better define the role of statins in overcoming chemoresistance. The combination of statins with other drugs, such as low-dose aspirin or safer non-steroidal anti-inflammatory medications, may be useful in both the prevention and treatment of colorectal cancer.
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PMID: 20660702 [PubMed - as supplied by publisher]12: Am J Gastroenterol. 2010 Jul 13; [Epub ahead of print]
Bae JC, Cho YK, Lee WY, Seo HI, Rhee EJ, Park SE, Park CY, Oh KW, Sung KC, Kim BI.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
OBJECTIVES:A cross-sectional analysis was conducted in healthy, nondiabetic Korean adults to assess the prevalence of nonalcoholic fatty liver disease (NAFLD), to compare the prevalence of NAFLD across different glycemic ranges as assessed by glycosylated hemoglobin (HbA1c), and to examine the impact of NAFLD on insulin resistance in relation to HbA1c levels.METHODS:After rigorous exclusion criteria, the final number of subjects who participated in a comprehensive health status checkup program was 99,969. All subjects were classified into four categories with respect to HbA1c level (</=4.9, 5.0-5.4, 5.5-5.9, and 6.0-6.4%). We estimated the odds ratio (OR) for prevalence of NAFLD according to the categorized level of HbA1C and evaluated the association of NAFLD with the homeostatic model assessment of insulin resistance (HOMA-IR) in relation to the HbA1c level.RESULTS:Twenty-eight percent (n=28,130, 40.2% of the men, 10.3% of the women) of the study subjects had NAFLD. Men had a 5.83-fold (95% confidence interval 5.63-6.05) increased risk for having NAFLD than did women. The risk for NAFLD increased with increasing level of HbA1c (OR 1.44, 2.62, and 7.18) when compared with the lowest quartile (HbA1C</=4.9%). HOMA-IR increased in the NAFLD subjects as the level of HbA1c increased. The magnitude of association of HOMA-IR with HbA1c level was greater in NAFLD subjects than in non-NAFLD subjects (P<0.001 for interaction). These associations were consistent even after adjustment for body mass index and other metabolic components.CONCLUSIONS:NAFLD had an association with HbA1c level and insulin resistance in nondiabetic individuals, and these associations were independent of obesity and other metabolic components.Am J Gastroenterol advance online publication, 13 July 2010; doi:10.1038/ajg.2010.275.
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PMID: 20628364 [PubMed - as supplied by publisher]13: Gastroenterology. 2010 Sep;139(3):965-74. Epub 2010 Jun 2.
Dahari H, Feinstone SM, Major ME.
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
BACKGROUND & AIMS: Studies in patients and chimpanzees that spontaneously cleared hepatitis C virus (HCV) infections demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism about prophylactic HCV vaccines, and several studies were performed in chimpanzees, although most included fewer than 6 animals. To draw meaningful conclusions about the efficacy of HCV vaccines in chimpanzees, we performed statistical analyses of data from previously published studies from different groups. METHODS: We performed a meta-analysis that compared parameters among naive (n = 63), vaccinated (n = 53), and rechallenged (n = 36) animals, including peak RNA titer postchallenge, time points of peak RNA titer, duration of viremia, and proportion of persistent infections. RESULTS: Each vaccination study induced immune responses that were effective in rapidly controlling HCV replication. Levels of induced T-cell responses did not indicate vaccine success. There was no reduction in the rate of HCV persistence in vaccinated animals, compared with naive animals, when nonstructural proteins were included in the vaccine. Vaccines that contained only structural proteins had clearance rates that were significantly higher than vaccines that contained nonstructural components (P = .015). CONCLUSIONS: The inclusion of nonstructural proteins in HCV vaccines might be detrimental to protective immune responses, and/or structural proteins might activate T-cell responses that mediate viral clearance. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
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PMID: 20621699 [PubMed - in process]14: BMC Gastroenterol. 2010 Jul 9;10:78.
Zhou Y, Zhao Y, Li B, Xu D, Yin Z, Xie F, Yang J.
Department of Hepato-Biliary-Pancreato-Vascular Surgery, the First affiliated Hospital of Xiamen University, Xiamen, China.
BACKGROUND: There is no clear consensus on the better therapy [radiofrequency ablation (RFA) versus hepatic resection (HR)] for small hepatocellular carcinoma (HCC) eligible for surgical treatments. This study is a meta-analysis of the available evidence. METHODS: Systematic review and meta-analysis of trials comparing RFA with HR for small HCC published from 1997 to 2009 in PubMed and Medline. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or random effects model. RESULTS: One randomized controlled trial, and 9 nonrandomized controlled trials studies were included in this analysis. These studies included a total of 1411 patients: 744 treated with RFA and 667 treated with HR. The overall survival was significantly higher in patients treated with HR than in those treated with RFA at 3 years (OR: 0.56, 95% CI: 0.44-0.71), and at 5 year (OR: 0.60, 95% CI: 0.36-1.01). RFA has a higher rates of local intrahepatic recurrence compared to HR (OR: 4.50, 95% CI: 2.45-8.27). In the HR group the 1, 3, and 5 years disease -free survival rates were significantly better than in the HR-treated patients (respectively: OR: 0.54, 95% CI: 0.35-0.84; OR: 0.44, 95% CI: 0.28-0.68; OR: 0.64, 95% CI: 0.42-0.99). The postoperative morbidity was higher with HR (OR: 0.29, 95% CI: 0.13-0.65), but no significant differences were found concerning mortality. For tumors <or= 3 cm HR did not differ significantly from RFA for survival, as reported in three NRCTs . CONCLUSIONS: HR was superior to RFA in the treatment of patients with small HCC eligible for surgical treatments, particularly for tumors > 3 cm. However, the findings have to be carefully interpreted due to the lower level of evidence.
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PMID: 20618937 [PubMed - in process]15: Am J Gastroenterol. 2010 Jul 6; [Epub ahead of print]
Hsu J, Abad C, Dinh M, Safdar N.
Section of Infectious Diseases, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
OBJECTIVES:Clostridium difficile is the most common infectious cause of healthcare-associated diarrhea. Because of the increasing incidence and severity of endemic C. difficile infection (CDI), interventions to prevent healthcare-associated CDI are essential. We undertook a systematic review of interventions to reduce healthcare-associated CDI.METHODS:We searched multiple computerized databases, and manually searched for relevant articles to determine which interventions are useful in preventing CDI. Studies were required to be controlled in design and to report the incidence of endemic CDI as an outcome. Data on the patient population, intervention, study design, and outcomes were abstracted and reviewed using established criteria.RESULTS:Few randomized controlled trials exist in the area of CDI prevention. The interventions with the greatest evidence for the prevention of CDI include antimicrobial stewardship, glove use, and disposable thermometers. Environmental decontamination also may decrease CDI rates, although the level of evidence is not as strong as for the other proven interventions. Treatment of asymptomatic carriage of C. difficile is not recommended. There is insufficient evidence to make a recommendation for or against the use of probiotics. In cases of known or suspected CDI, hand hygiene with soap and water is preferred over use of waterless alcohol hand rub. Many nonrandomized trials included in our analysis used multiple interventions concurrently, making the independent role of each preventive strategy difficult to determine. We chose to include only studies that focused on endemic CDI because studies of outbreaks have used multiple strategies, making it difficult to measure the relative efficacy of each strategy. Environmental disinfection and probiotics need to be studied further to evaluate their roles in the prevention of CDI. Although there have been no studies assessing the utility of isolation and cohorting for the prevention of endemic CDI specifically, it is a widely used intervention for containment of this and other similar multidrug-resistant pathogens.CONCLUSIONS:Antimicrobial stewardship, glove use, hand hygiene, and disposable thermometers should be routinely used for the prevention of CDI. Environmental disinfection and probiotics should be studied further for their role in reducing CDI.Am J Gastroenterol advance online publication, 6 July 2010; doi:10.1038/ajg.2010.254.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20606676&dopt=ExternalLink
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PMID: 20606676 [PubMed - as supplied by publisher]16: Am J Gastroenterol. 2010 Jul;105(7):1466-76.
Loveday BP, Srinivasa S, Vather R, Mittal A, Petrov MS, Phillips AR, Windsor JA.
Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
OBJECTIVES: Several clinical guidelines exist for acute pancreatitis, with varying recommendations. The aim of this study was to determine the quality of guidelines for acute pancreatitis. METHODS: A literature search identified relevant guidelines, which were then reviewed to determine their document format and scope and the presence of endorsement by a professional body. The quality of guidelines was determined using the validated Grilli, Shaneyfelt, and AGREE instruments. RESULTS: Twenty-one of the 30 guidelines analyzed were endorsed by professional bodies. Median quality scores were as follows: Grilli, 2; Shaneyfelt, 13; and AGREE, 50. Guideline quality did not improve over time. Guidelines endorsed by a professional body had higher scores than those without official endorsement. Guidelines with tables, a recommendations summary, evidence grading, and audit goals had significantly higher scores than guidelines lacking those features. CONCLUSIONS: The many clinical guidelines for acute pancreatitis range widely in quality. Guidelines developed by professional bodies, and those with tables, a recommendations summary, evidence grading, and audit goals, are of higher quality. Further research is required to determine whether guideline quality alters clinical outcomes.
Publication Types: Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20606652&dopt=ExternalLink
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PMID: 20606652 [PubMed - indexed for MEDLINE]17: Gastroenterology. 2010 Jun 20; [Epub ahead of print]
Woo G, Tomlinson G, Nishikawa Y, Kowgier M, Sherman M, Wong DK, Pham B, Ungar WJ, Einarson TR, Heathcote EJ, Krahn M.
Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada; Departments of Medicine and Health Policy, Management and Evaluation, and Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
BACKGROUND & AIMS:: The relative efficacies of licensed antiviral therapies for treatment-naive chronic hepatitis B (CHB) infection in randomized controlled trials have not been determined. We evaluated the relative efficacies of the first 12 months of CHB treatments. METHODS:: Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir, telbivudine, and tenofovir, as monotherapies and combination therapies, in treatment-naive individuals. Databases were searched for randomized controlled trials of the first 12 months of therapy in hepatitis B e antigen (HBeAg)-positive and/or HBeAg-negative patients with CHB published in English before October 31, 2009. Bayesian mixed treatment comparisons were used to calculate the odds ratios, including 95% credible intervals and predicted probabilities of surrogate outcomes to determine the relative effects of each treatment. RESULTS:: In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (predicted probability, 88%), normalization of alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and hepatitis B surface antigen loss (5%); it ranked third in histologic improvement of the liver (53%). Entecavir was most effective in improving liver histology (56%), second for inducing undetectable levels of HBV DNA (61%) and normalization of ALT levels (70%), and third in loss of hepatitis B surface antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable levels of HBV DNA (94%) and improving liver histology (65%); it ranked second for normalization of ALT levels (73%). CONCLUSIONS:: In the first year of treatment for CHB, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients. Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20600036&dopt=ExternalLink
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PMID: 20600036 [PubMed - as supplied by publisher]18: Gut. 2010 Jul;59(7):988-1000.
Rossle M, Gerbes AL.
Praxiszentrum, Bertoldstrasse 48, Freiburg, Germany. martin-roessle@t-online.de
Refractory ascites is a frequent complication of advanced cirrhosis and is associated with hepatorenal syndrome and hepatic hydrothorax. Large volume paracentesis and pleurodesis are regarded as first-line treatments in patients who do not respond adequately to diuretics. These treatments, however, do not prevent recurrence and carry the risk of worsening of the circulatory dysfunction leading to hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt (TIPS) has been proposed as an alternative to paracentesis. TIPS reduces the rate of ascites recurrence mainly due to the reduction in the filtration pressure. In addition, TIPS results in a positive effect on renal function, including hepatorenal syndrome, demonstrated by a rapid increase in urinary sodium excretion, urinary volume, and improvement in plasma creatinine concentration. Furthermore, plasma renin activity, aldosterone, and noradrenalin concentrations improve gradually after TIPS insertion suggesting a positive effect on systemic underfilling, the factor of hepatorenal syndrome. As demonstrated recently in two meta-analyses including five randomised studies, TIPS also improves survival when compared with paracentesis. However, the evidence is based on relatively few studies with only 305 patients included. The positive effects of the TIPS are opposed by an increased frequency and severity of episodes of hepatic encephalopathy which may be reduced by both patient selection and reduced shunt diameter. Based on the present knowledge the recommended hierarchy of treatments for refractory ascites may be reconsidered upgrading TIPS in suitable candidates.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20581246&dopt=ExternalLink
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PMID: 20581246 [PubMed - indexed for MEDLINE]19: Gut. 2010 Jul;59(7):975-86.
Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Friedl W, Moller P, Hes FJ, Jarvinen H, Mecklin JP, Nagengast FM, Parc Y, Phillips RK, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen JT, Clark SK, Hodgson SV.
Department of Clinical Genetics, St Georges, University of London, Cranmer Terrace, London, UK.
Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.
Publication Types: Consensus Development Conference
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20581245&dopt=ExternalLink
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PMID: 20581245 [PubMed - indexed for MEDLINE]20: Gut. 2010 Jul;59(7):882-7.
Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T.
Centre for Academic Surgery, Royal London Hospital, London, UK. c.h.knowles@qmul.ac.uk
OBJECTIVE: Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material. DESIGN: Consensual processes undertaken by the IWG and following established guideline decision group methodologies. RESULTS AND CONCLUSION: This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.
Publication Types: Consensus Development Conference Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20581236&dopt=ExternalLink
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PMID: 20581236 [PubMed - indexed for MEDLINE]