Endoscopic Ultrasound-Guided Transmural and Percutaneous Transhepatic Gallbladder Drainag…

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Effects of Fractionated Plasma Separation and Adsorption on Survival in Patients with Acu…

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A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome.
Gastroenterology. 2011 Jul 7;
Authors: van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ali UA, Schrijver AM, Boermeester MA, va…

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Pregabalin Reduces Pain in Patients With Chronic Pancreatitis in a Randomized, Controlled Trial.
Gastroenterology. 2011 Apr 14;
Authors: Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM
BACKGROUND & A…

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Reductions in 28-Day Mortality Following Hospital Admission for Upper-Gastrointestinal Hemorrhage.
Gastroenterology. 2011 Mar 26;
Authors: Crooks C, Card T, West J
BACKGROUND & AIMS: It is unclear whether mortality…

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Acid Suppressants Reduce Risk of Gastrointestinal Bleeding in Patients on Antithrombotic or Anti-Inflammatory Therapy.
Gastroenterology. 2011 Mar 30;
Authors: Lin KJ, Hernández-Díaz S, Rodríguez LA
BACKGROUND & …

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Safety of Proton Pump Inhibitor Exposure.

Gastroenterology. 2010 Aug 18;

Authors: Yang YX, Metz DC

Proton pump (H+/K+-ATPase) inhibitors (PPIs) are widely used to treat patients with acid-related disorders because they are generally perceived to be safe and effective. However, as with any pharmacological agent, they have the potential for side effects. Many studies have examined the side effects of long- or short-term PPI exposure. We review the mechanism of action of PPIs, focusing on recently released products that might have greater risks of adverse effects than older products because of increased potency and/or duration of action. We summarize the data available on the putative adverse effects of PPI therapy and propose guidelines for clinicians who prescribe these agents, to limit the potential for adverse outcomes in users of these effective therapeutic agents.

PMID: 20727892 [PubMed - as supplied by publisher]

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Prognostic Importance of the Cause of Renal Failure in Patients with Cirrhosis.

Gastroenterology. 2010 Jul 31;

Authors: Martín-Llahí M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R, Solá E, Pereira G, Marinelli M, Pavesi M, Fernández J, Rodés J, Arroyo V, Ginès P

BACKGROUND AND AIM:: The prognostic value of the different causes of renal failure in cirrhosis is not well established. The aim of this study was to investigate the predictive value of the cause of renal failure in cirrhosis. METHODS:: Five-hundred and sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine>1.5 mg/dL on two successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into four groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end-point was survival at 3 months. RESULTS:: Four-hundred and sixty-three patients (82.4%) had renal failure that could be classified in one of the four groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to the cause of renal failure, the 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (p<0.0005). In a multivariate analysis adjusted for potentially-confounding variables, the cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at the time of diagnosis of renal failure. CONCLUSIONS:: A simple classification of patients with cirrhosis according to the cause of renal failure is useful in the assessment of prognosis and may help in decision making in liver transplantation.

PMID: 20682324 [PubMed - as supplied by publisher]

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Inflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism.

Gastroenterology. 2010 Jun 11;

Authors: Novacek G, Weltermann A, Sobala A, Tilg H, Petritsch W, Reinisch W, Mayer A, Haas T, Kaser A, Feichtenschlager T, Fuchssteiner H, Knoflach P, Vogelsang H, Miehsler W, Platzer R, Tillinger W, Jaritz B, Schmid A, Blaha B, Dejaco C, Eichinger S

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD. METHODS: We assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006-December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE. RESULTS: Overall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8-45.0 vs 21.7%; 95% CI: 18.8-24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4-4.2; P = .001). CONCLUSIONS: Patients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

PMID: 20546736 [PubMed - as supplied by publisher]

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Equal Efficacy of Endoscopic Variceal Ligation and Propranolol in Preventing Variceal Bleeding in Patients with Non-Cirrhotic Portal Hypertension.

Gastroenterology. 2010 Jun 11;

Authors: Sarin SK, Gupta N, Jha SK, Aggarwal A, Mishra SR, Sharma BC, Kumar A

BACKGROUND:: Variceal bleeding increases morbidity and mortality among patients with non-cirrhotic portal hypertension (NCPH). Blockers of beta-adrenergic receptor signaling and endoscopic variceal ligation (EVL) have been used to prevent recurrence of bleeding, based on data from cirrhotic patients. We compared the efficacy and safety of the beta-blocker propranolol with that of EVL in preventing the recurrence of variceal bleeding in patients with NCPH. METHODS:: Consecutive patients of NCPH with history of variceal bleeding in the past 6 weeks were randomly assigned to groups treated every 3 weeks with EVL (n=51) or propranolol (until they had a resting heart rate of 55 bpm or to a maximum of 320 mg/d; n=50). Primary endpoints were recurrence of variceal bleeding or death. Secondary endpoints were complications of EVL in patients given propranolol, variceal eradication following EVL, variceal recurrence after EVL, or a decrease in variceal grade in patients given propranolol. RESULTS:: After a median follow-up period of 23 months, rates of recurrence of bleeding were similar between the groups (EVL=23.5%, propranolol=18%; P=0.625). The actuarial probability of remaining free bleeding recurrence was similar between the groups. No deaths occurred in either group. Of the patients given propranolol, 47% had a decrease in the grade of varices and none experienced bleeding. Adverse events were minor and comparable between groups (EVL=12%, propranolol=18%; P=0.635). CONCLUSIONS:: EVL was not more effective than the beta-blocker propranolol for the secondary prophylaxis of variceal bleeding in patients with NCPH.

PMID: 20547163 [PubMed - as supplied by publisher]

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Efficacy of linaclotide for patients with chronic constipation.

Gastroenterology. 2010 Mar;138(3):886-95.e1

Authors: Lembo AJ, Kurtz CB, Macdougall JE, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Johnston JM

BACKGROUND & AIMS: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit and reduces pain in animal models. We assessed the safety and efficacy of a range of linaclotide doses in patients with chronic constipation. METHODS: We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 310 patients with chronic constipation. Patients were randomly assigned to groups given 75, 150, 300, or 600 microg oral linaclotide or placebo once daily for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs), complete SBMs, stool consistency, straining, abdominal discomfort, and bloating. Severity of constipation, adequate relief of constipation, global relief of constipation, treatment satisfaction, quality of life, adverse events, clinical laboratory data, and electrocardiogram results were assessed. RESULTS: All doses of linaclotide improved the weekly rate of SBM (primary end point) compared with placebo; the increases in overall weekly number of SBMs from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 microg, respectively, compared with 1.5 for placebo (P < or = .05 for each pair-wise comparison of a linaclotide dose to placebo). Likewise, linaclotide significantly improved the weekly rate of complete SBM, stool consistency, straining, abdominal discomfort, bloating, global assessments, and quality of life. The most common and only dose-related adverse event was diarrhea (only 6 patients discontinued treatment because of diarrhea). CONCLUSIONS: Linaclotide therapy was associated with few adverse events and produced rapid and sustained improvement of bowel habits, abdominal symptoms, global relief, and quality of life in patients with chronic constipation.

PMID: 20045700 [PubMed - indexed for MEDLINE]

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Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple’s Disease.

Gastroenterology. 2009 Oct 28;

Authors: Feurle GE, Junga NS, Marth T

BACKGROUND&AIMS:: Whipple's disease is a chronic infection caused by the actinomycete Tropheryma whipplei. We conducted a randomized controlled trial of the efficacy of antimicrobials that are able to cross the blood brain barrier and to which T. whipplei is susceptible. METHODS:: Patients from central Europe with previously untreated Whipple's disease (n=40) were randomly assigned to groups given daily infusions of either ceftriaxone (1 x 2 g, 20 patients) or meropenem (3 x 1 g, 20 patients) for 14 days, followed by oral trimethoprim-sulfamethoxazole for 12 months. The primary outcome measured was maintenance of remission for 3 years, determined by a composite index of clinical and laboratory data as well as histology. RESULTS:: All patients were observed for the entire follow-up period (median 89 months, range 71-128 months), all achieved clinical and laboratory remission. Remission was maintained in all patients during the time of observation, except for 2 who died from unrelated causes. A single patient with asymptomatic cerebrospinal infection who was resistant to both treatments responded to chloroquine and minocycline. The odds ratio for the endpoint (remission for at least 3 years) was 0.95 (95 % confidence interval 0.05-16.29, P=1.0). CONCLUSION:: This is the first randomized controlled trial to show that treatment with ceftriaxone or meropenem, followed by trimethoprim-sulfamethoxazole, cures patients with Whipple's disease. One asymptomatic individual with infection of the cerebrospinal fluid required additional therapy.

PMID: 19879276 [PubMed - as supplied by publisher]

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Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

Gastroenterology. 2009 Sep;137(3):856-64, 864.e1

Authors: Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ, Murray NG, McCashland T, Reisch JS, Robuck PR,

BACKGROUND & AIMS: N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. METHODS: In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. RESULTS: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). CONCLUSIONS: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

PMID: 19524577 [PubMed - indexed for MEDLINE]

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Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence.

Gastroenterology. 2009 Sep;137(3):892-901, 901.e1

Authors: Kumar A, Jha SK, Sharma P, Dubey S, Tyagi P, Sharma BC, Sarin SK

BACKGROUND & AIMS: Endoscopic variceal ligation (EVL) and propranolol are standard secondary prophylaxis therapies for variceal bleeding. Addition of isosorbide mononitrate (ISMN) to propranolol improves its hemodynamic efficacy; we investigated whether a combination of EVL and propranolol/ISMN was more effective than EVL alone for secondary prophylaxis. METHODS: Patients with a prior variceal bleed were randomly assigned to groups given a combination (n = 88) of EVL, propranolol (dose titrated to reduce heart rate to 55 beats per minute), and ISMN (40 mg/day) or EVL alone (n = 89). Primary end points were rebleeding or death; secondary end points were new complications of portal hypertension or serious adverse effects. RESULTS: The actuarial probabilities of rebleeding 2 years after therapy were 27% in the combination group and 31% in the EVL alone group (P = .822). Two patients in the combination group and 3 patients in the EVL alone group died during the study period (P = .682); no deaths were caused by variceal hemorrhage. In cirrhotic patients, the actuarial probabilities of rebleeding were 24% and 30%, respectively (P = .720). Secondary end points were comparable between groups. In multivariate analyses, presence of ascites (P = .003), serum albumin < 3.3 g/dL (P = .008), and hepatic venous pressure gradients > or = 18 mm Hg (P = .009) were independent risk factors for variceal rebleeding. CONCLUSIONS: EVL alone is sufficient to prevent variceal rebleeding in cirrhotic and noncirrhotic patients with history of variceal bleeding. Addition of propranolol and ISMN to EVL does not reduce the incidence of variceal rebleeding but increases severe adverse effects. Risk factors for rebleeding include ascites, low serum albumin, and high hepatic venous pressure gradients.

PMID: 19481079 [PubMed - indexed for MEDLINE]

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Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.

Gastroenterology. 2009 Jul;137(1):80-7, 87.e1

Authors: Reimer C, Søndergaard B, Hilsted L, Bytzer P

BACKGROUND & AIMS: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. METHODS: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. RESULTS: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .023), week 11 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .009), and week 12 (1.3 +/- 1.2 vs 1.0 +/- 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported > or = 1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

PMID: 19362552 [PubMed - indexed for MEDLINE]

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