Nazario Caruso

Randomized Study of Two "Rescue" Therapies for Helicobacter pylori-Infected Patients After Failure of Standard Triple Therapies

OBJECTIVES:A novel rifabutin-based therapy is able to cure Helicobacter pylori infection in most patients who have failed eradication after standard proton pump inhibitor (PPI)-based triple therapy. We compared this regimen with the quadruple therapy.METHODS:A total of 135 patients were randomized into three groups who were treated for 10 days with pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d., and rifabutin 150 mg o.d. (RAP150 group), or 300 mg o.d. (RAP300 group), and pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. (QT group). Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori eradication was assessed by the 13C-urea breath test.RESULTS:On intention-to-treat analysis, eradication rates (with 95% confidence intervals [CI]) were 66.6% (53–80%) in the RAP150 and QT groups, respectively, and 86.6% (76–96%) in RAP300 group (p < 0.025). Most patients harboring metronidazole- and clarithromycin-resistant strains were eradicated at an equal rate by each of the three regimens. Side effects were observed in 9% and 11% of rifabutin-treated patients, and in 47% of those on quadruple therapy (p < 0.0001).CONCLUSIONS:In patients who failed standard eradicating treatments, a 10-day course of rifabutin with pantoprazole and amoxycillin is more effective and well tolerated than the quadruple therapy.

Gastrointestinal motor dysfunction, symptoms, and neuropathy in noninsulin-dependent (type 2) diabetes mellitus

Although relatively frequent. diabetic involvement of digestive tract motility has not been investigated extensively in different organs. The authors studied esophageal, gastric, and gallbladder motor function in 35 type 2 (noninsulin-dependent) diabetic patients to determine the extent of gut involvement. Of these patients, 27 (77%) had peripheral neuropathy, 12 (34%) had both peripheral and autonomic neuropathy, and 22 (63%) had gastrointestinal symptoms. Esophageal manometric abnormalities were recorded in 18 patients, and delayed radionuclide emptying of the esophagus was documented in 16 patients, with a 83% concordance between the two tests. Scintigraphic gastric emptying of solids was delayed in 56% of patients, whereas gallbladder emptying after cholecystokinin stimulation was reduced in 69% of them. In 74% of patients at least one of the viscera under investigation showed abnormal motor function; however, only 36% of patients displayed involvement of the three organs. Gastrointestinal symptoms, duration and therapy of diabetes, previous poor glycemic control, and retinopathy did not correlate with the presence or the extent of motor disorders. Neuropathy was not predictive of gastrointestinal involvement and its extent; however, when motor abnormalities were present in patients with neuropathy, these were usually more severe. Gastrointestinal motor disorders are frequent and widespread in type 2 diabetics, regardless of symptoms. Autonomic neuropathy has a poor predictive value on motor disorders (0.75 for the esophagus, 0.5 for the stomach, 0.8 for the gallbladder), thus suggesting the coexistence of other pathophysiologic mechanisms.

Proton-Pump Inhibitors and Outcome of Endoscopic Hemostasis in Bleeding Peptic Ulcers: A Series of Meta-analyses

OBJECTIVE:To perform metaanalyses of studies on outcome of bleeding ulcers of different proton-pump inhibitors (PPIs) regimens, after stratification of patients by endoscopic stigmata, and analysis of studies with and without endotherapy.METHODS:A total of 35 randomized trials comparing PPIs to placebo and/or H2-receptor antagonists (H2RAs) in 4,843 patients with high-risk endoscopic stigmata were retrieved. Outcomes were rebleeding, surgery, and mortality.RESULTS:Monotherapy with oral or bolus PPIs was superior to placebo and H2RAs in reducing rebleeding in both bleeders and nonbleeders at index endoscopy; the need for surgery was reduced only when compared to H2RAs. In nonbleeders, PPI monotherapy was as effective as a combination of endotherapy with H2RAs. A combination of endotherapy with PPIs was superior to monotherapy in reducing bleeding and surgery, and superior to endotherapy alone in minimizing rebleeding, but not surgery; the benefit was lost when confronted to endotherapy plus H2RAs, whether PPIs were given as infusion or bolus. By pooling data from studies comparing high doses of PPIs as continuous infusion versus regular doses as intermittent bolus, rebleeding, surgery, and mortality were not significantly different.CONCLUSIONS:Combination of endotherapy with either PPIs or H2RAs is indicated for nonbleeding ulcers at endoscopy with the intent to reduce rebleeding and surgery. Its value may extend to bleeding lesions, but current data are scanty. The benefit appears to be independent from route and doses of PPIs, as oral, bolus, or infusional methods are all effective.

Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial.

BACKGROUND:In patients with severe attacks of ulcerative colitis (UC), IV steroids represent the first-line treatment, leading to clinical improvement in approximately 50–60% of patients.AIM:The aim of this study was to prospectively compare the efficacy and safety of different modalities of steroid administration, and to evaluate predictors of failure to therapy.MATERIALS AND METHODS:In a single-center, double-blind trial, consecutive patients with a severe attack of UC received 1 mg/kg/day of 6-methyl-prednisolone administered randomly by either a bolus injection (group A) or continuous infusion (group B).RESULTS:Sixty-six patients were enrolled (35 men, mean age 38 ± 15, range 18–75 yr), 15 of them at their first attack of UC; in the remaining cases, the mean duration of disease was 4.5 ± 5 yr. At inclusion, forty patients (60%) had pancolitis and the remainder had left-sided colitis. Overall, thirty-three patients (50%) underwent clinical remission after 7 days of treatment: 16 of 32 in group A and 17 of 34 in group B. Thirty-one patients eventually underwent total colectomy (12 in group A and 9 in group B), which was carried out by the first month in 10 patients (5 in each group). Twenty-eight patients (15 in group A and 13 in group B) experienced steroid-related adverse reactions. All differences between groups were not statistically significant. Previous use of steroids (OR 13.6, CI 2–86) and active smoking (OR 11.6, CI 1.4–107) were independent predictors of nonresponse.CONCLUSIONS:In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

Pancreatic Duct Stents in the Prophylaxis of Pancreatic Damage after Endoscopic Retrograde Cholangiopancreatography: A Systematic Analysis of Benefits and Associated Risks

Methods: The efficacy of pancreatic stenting in the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) was evaluated by a meta-analysis of 6 controlled studies; 12 additional uncontrolled studies were analyzed for rates of associated risk. Results: Post-ERCP pancreatitis (PEP) developed in 16.5% of controls, and in 5.1 or 9.6% of the stent group at the per-protocol (PP) or intention-to-treat (ITT) analyses. By analyzing only the 4 randomized trials, PEP developed in 24.1% of controls, and in 6.1 or 12.0% of the stented patients at the PP or ITT analyses. Risk was significantly lower in the stent group when compared with controls: OR 0.44 (95% CI 0.24–0.81). The absolute risk reduction is 12.0 (95% CI 3.0–21.0), the number needed to treat 8 (95% CI 5–34), and the publication bias 2. ORs for mild to moderate PEP were reduced in the stent group (OR = 0.537, 95% CI 0.283–1.021), as were those for severe PEP (OR = 0.123, 95% CI 0.021–0.726). Non-pancreatic complications were 4.2%, and included early stent migration (1.4%), perforations (0.4%), bleeding (1.4%), and infections (1.0%). Conclusion: Available trials show benefit for pancreatic stenting in the prophylaxis of PEP, but more randomized studies are needed before endorsing a routine use of this endoscopic procedure.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: A multicentre, randomized study

BACKGROUND:The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain.METHODS:Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy.RESULTS:Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P = 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P = 0.32). Mean units of blood transfused were 1.7 ± 2.1 in the intensive and 1.5 ± 2.1 in the standard regimen group (P = 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P = 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died.CONCLUSIONS:Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Long-Term Outcome After Antiviral Therapy of Patients With Hepatitis C Virus Infection and Decompensated Cirrhosis

BACKGROUND & AIMS We evaluated the long-term outcomes after antiviral therapy of patients with decompensated cirrhosis and hepatitis C virus (HCV) infection. METHODS Seventy-five patients with HCV infection and decompensated cirrhosis received therapy with peginterferon alfa-2b and ribavirin. We compared adverse-event profiles and mortality rates between patients with or without sustained virologic responses (SVRs). The mean follow-up time off therapy was 51 ± 18 months (range, 3-78 months). RESULTS Seven patients with HCV genotypes 1 or 4 (16%) and 17 patients with genotypes 2 or 3 (55%) achieved SVRs. The mean survival times were 53 months among patients who did not achieve SVRs (95% confidence interval [CI], 48-59 months) and 73 months among those who did achieve SVRs (95% CI, 67-80 months) (P = .004). During the study, 25 patients died (2 with and 23 without SVRs). During the follow-up period, 8 of 24 patients with SVRs (33.3%) and 49 of 51 without SVRs (96.1%) experienced further events of decompensation (P < .0001). The hospital readmission rates for patients with and without SVRs were 7.4 and 56 per 1000 person-months, respectively (ratio of 7.5 without/with SVR; 95% CI, 4.0-16.0; P < .0001). At the end of the follow-up period, the incidence of hepatocellular carcinoma was not associated with clearance of HCV. CONCLUSIONS Among patients with cirrhosis that is a result of HCV infection and who have progressed to a stage of liver decompensation, an SVR after antiviral therapy is a positive prognostic factor.

HLA-DRB1 Alleles May Influence Disease Phenotype in Patients With Inflammatory Bowel Disease: A Critical Reappraisal With Review of the Literature

PURPOSEThe HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohn’s disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies.METHODSBlood samples were obtained from 102 Crohn’s disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status.RESULTSAs a whole, after applying Bonferroni’s correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn’s disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohn’s disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohn’s disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic.CONCLUSIONSSome clinical features of Crohn’s disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohn’s disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.

Sustained virological responses following standard anti‐viral therapy in decompensated HCV‐infected cirrhotic patients

Background  Little data is available about predictors of sustained virological response (SVR) during anti‐viral therapy of patients with decompensated HCV cirrhosis.

Gallbladder function and gastric liquid emptying in achalasia

Because of evidence that the abnormalities in achalasia are not restricted to the distal esophagus, we investigated gallbladder function by cholescintigraphy in the steady state and in response to CCK and the scintigraphic gastric emptying of a liquid caloric meal in 10 individuals with achalasia and 10 normal controls. No abnormalities were found during the filling phase of the gallbladder but seven of the 10 patients showed a 50% reduction in the ejection fraction (39.4%±30.4 vs 80.3±8.3 of controls, mean±sd,P=0.007) and a slower than normal ejection phase (9.1%/min±6.6 vs 18.1±4.5,P=0.02. In eight of the 10 patients, gastric liquid emptying was accelerated with a T1/2 of 41.5 min±15.4 vs 74.7 min±11.5 in the controls (P=0.007). It is concluded that in some achalasia patients extraesophageal functional abnormalities of the gastrointestinal tract may be found. Whether these findings are promoted by degenerative changes of extraesophageal nerve fibers as well as their clinical significance require further investigations.