John Vlachogiannakos

Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis

Background  Endotoxaemia is commonly seen in cirrhotic patients with ascites and this may be associated with increased portal pressure.

Is there a role for second-look capsule endoscopy in patients with obscure GI bleeding after a nondiagnostic first test?

BACKGROUND Long-term follow-up data on patients with obscure GI bleeding subjected to capsule endoscopy (CE) are missing. OBJECTIVE Our purpose was to follow up patients with a nondiagnostic test and determine whether a second-look CE would be beneficial. PATIENTS We enrolled 293 subjects. CE studies were classified as diagnostic (positive findings) or nondiagnostic (findings of uncertain significance/no findings). Patients were followed up for a mean (SD) 24.8 (5.2) months. Outcome was defined as continued or complete resolution of bleeding. INTERVENTIONS Patients with a nondiagnostic test were subjected to a repeat CE if they manifested a new bleeding episode or a drop in hemoglobin >or=2 g/dL. RESULTS Positive findings, findings of uncertain significance, and no findings were identified in 41.6%, 16.0%, and 42.3% of our patients, respectively. Therapeutic intervention was possible in 72.1% of those with positive findings and in 30% of those with findings of uncertain significance. Complete resolution of bleeding occurred more often in patients with a diagnostic test (65.2%) compared with those with a nondiagnostic test (35.4%, P < .001). Second-look CE was performed in a subgroup of our patients (n = 76) and was diagnostic in those whose presentation changed from occult to overt or those whose hemoglobin dropped >or=4 g/dL. CONCLUSIONS In patients with obscure GI bleeding, a diagnostic CE leads to therapeutic interventions and a favorable outcome. Patients with a nondiagnostic test would definitely benefit from a second-look CE if the bleeding presentation changes from occult to overt or if the hemoglobin value drops >or=4 g/dL.

Selective Serotonin Reuptake Inhibitors for the Treatment of Hypersensitive Esophagus: A Randomized, Double-Blind, Placebo-Controlled Study

OBJECTIVES:Ambulatory 24-h pH–impedance monitoring can be used to assess the relationship of persistent symptoms and reflux episodes, despite proton pump inhibitor (PPI) therapy. Using this technique, we aimed to identify patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on their symptoms.METHODS:Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, and regurgitation), despite PPI therapy twice daily, underwent 24-h pH–impedance monitoring. Distal esophageal acid exposure (% time pH <4) was measured and reflux episodes were classified into acid or non-acid. A positive symptom index (SI) was declared if at least half of the symptom events were preceded by reflux episodes. Patients with a normal distal esophageal acid exposure time, but with a positive SI were classified as having hypersensitive esophagus and were randomized to receive citalopram 20 mg or placebo once daily for 6 months.RESULTS:A total of 252 patients (150 females (59.5%); mean age 55 (range 18–75) years) underwent 24-h pH–impedance monitoring. Two hundred and nineteen patients (86.9%) recorded symptoms during the study day, while 105 (47.9%) of those had a positive SI (22 (20.95%) with acid, 5 (4.76%) with both acid and non-acid, and 78 (74.29%) with non-acid reflux). Among those 105 patients, 75 (71.4%) had normal distal esophageal acid exposure time and were randomized to receive citalopram 20 mg (group A, n=39) or placebo (group B, n=36). At the end of the follow-up period, 15 out of the 39 patients of group A (38.5%) and 24 out of the 36 patients of group B (66.7%) continue to report reflux symptoms (P=0.021).CONCLUSIONS:Treatment with SSRIs is effective in a select group of patients with hypersensitive esophagus.

Sedation in digestive endoscopy: the Athens international position statements

Aliment Pharmacol Ther 2010; 32: 425–442

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine

Background  The efficacy of long‐term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe‐Ag)‐negative lamivudine‐resistant chronic hepatitis B (CHB) patients is still under investigation.

Course of inflammatory bowel disease in patients infected with human immunodeficiency virus.

Background: Human immunodeficiency virus (HIV) infection depletes CD4+ lymphocytes, which may benefit patients with inflammatory bowel disease (IBD). The aim was to compare the course of IBD in HIV patients with a matched group of IBD seronegative patients. Methods: A total of 20 IBD (14 Crohns disease, 6 ulcerative colitis) HIV infected patients and 40 matched control seronegative IBD patients (2 controls per case) were compared regarding relapse of their disease. The CD4+ count was followed every 6 months and a value of ≤500 cells/&mgr;L was used to define patients with immunosuppression. Relapse rates per year of follow‐up were compared among the 2 groups and survival curves for cumulative remission rates were compared with a log‐rank test. Multivariate analysis was used to discriminate among the impact of different variables on the risk of IBD relapse. Results: The median duration of follow‐up was 8.4 years (range 0.6–18 years). The mean relapse rate for the HIV+IBD group was 0.016/year of follow‐up as compared to 0.053/year of follow‐up for the IBD‐matched control group (P = 0.032). Regarding the HIV‐positive/IBD group, 14 patients were immunosuppressed at any given time during the follow‐up period. None of these patients experienced an IBD relapse, whereas 3 out of the 6 without immunosuppression relapsed (P = 0.017). According to the multivariate analysis, HIV status was the only risk factor independently associated with a lower probability of IBD relapse. Conclusions: HIV infection reduces the relapse rates in IBD patients and this may be attributed to the lower CD4+ counts seen in these patients. (Inflamm Bowel Dis 2010;)

Somatostatin inhibits gastric acid secretion more effectively than pantoprazole in patients with peptic ulcer bleeding: A prospective, randomized, placebo-controlled trial

Objective Gastric acid inhibition is beneficial in the management of peptic ulcer bleeding (PUB). The aim of this double-blind study was to test whether somatostatin (SST) increases intragastric pH in PUB as compared with pantoprazole (PAN) and placebo (PLA). Material and methods Eligible patients were randomized to receive SST (500 μg/h+250 μg bolus), or PAN (8 mg/h+80 mg bolus) or PLA (normal saline) i.v., for 24 h. All patients underwent gastric pH monitoring during the infusion of the trial drugs. Results The three groups (SST, n=14; PAN, n=14; PLA, n=15) were comparable for age, gender, aetiology of PUB and laboratory data at admission. Mean (±SE) baseline pH levels in the fundus increased during the administration of the trial drugs (SST: 1.94±0.18 to 6.13±0.37, p<0.0001; PAN: 1.93±0.16 to 5.65±0.37, p<0.0001; PLA: 1.86±0.12 to 2.10±0.15, p=0.0917). During the first 12 h of infusion, the mean (±SE) percentage time spent above pH 4.0 and 5.4 was higher with SST versus PAN (84.4%±4.8 versus 55.1%±8.3, p=0.0049 and 74.2%±6.5 versus 47.1%±8.3, p=0.0163, respectively) and there was a trend favouring the SST group regarding the time spent above pH 6.0 and 6.8 (65.7%±6.4 versus 43.3%±8.2, p=0.0669 and 49.2%±7.7 versus 28.4±6.6, p=0.0738, respectively). Conclusions In PUB, both SST and PAN inhibit gastric acid secretion as compared with placebo. However, during the first 12 h of the infusion, SST was more effective than PAN in maintaining high intragastric pH. These results may provide a rationale for the administration of SST in PUB.

Clinical trial: the effect of somatostatin vs. octreotide in preventing post-endoscopic increase in hepatic venous pressure gradient in cirrhotics with bleeding varices

Background Hepatic venous pressure gradient (HVPG) increases significantly after endoscopic therapy in patients with bleeding oesophageal varices, which may precipitate further haemorrhage. Whether vasoactive drugs can suppress these changes remains unknown.

Effect of infliximab on the healing of intestinal anastomosis. An experimental study in rats

BACKGROUND AND AIM Infliximab is effective in the induction and maintenance of remission in Crohns disease. Whether, the perioperative administration of anti-TNF-a compromises intestinal healing leading to anastomotic failure and increased risk of postoperative complications, remains controversial. The aim of the study was to evaluate the effect of Infliximab on intestinal anastomosis healing. METHODS Fifty six wistar rats were divided into 4 groups: (a) 20 rats were subjected to excision of part of the terminal ileum followed by anastomosis which was evaluated on the 3rd or 7th postoperative day; (b) 20 rats received Infliximab and thereafter, the same surgical protocol as group (a) was followed; (c) 8 rats received Infliximab and served as relative control group; and (d) 8 served as absolute control group. Bursting pressure was used for testing intestinal healing. Additionally, the anastomoses were examined macroscopically, histologically and immunohistochemically for TGFb1, MMP1, MMP2 and Collagen V. The results were confirmed by Western blot analysis. RESULTS There were no significant differences in bursting pressures and septic intra-abdominal events among non-Infliximab (a) and Infliximab-treated (b) groups. Infliximab-treated (b) group showed mild to moderate inflammation, whereas the non-Infliximab (a) group exhibited severe inflammation. Expression of TGFb1, MMP2 and collagen V was significantly higher in the Infliximab-treated (b) group. CONCLUSION Infliximab seems to influence intestinal healing in terms of less inflammatory activity and higher tissue remodeling activity.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.