Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial.

IMPORTANCE: Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients. OBJECTIVE: To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI). DESIGN, SETTING, AND PARTICIPANTS: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe. INTERVENTIONS: Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). MAIN OUTCOMES AND MEASURES: The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6. RESULTS: Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259726.

Coffee grounds emesis: not just an upper GI bleed.

BACKGROUND: Acute upper gastrointestinal (UGI) bleeding manifests as hematemesis, melena, or hematochezia. Initial management is identical, irrespective of nasogastric (NG) aspirate results. Current practice includes early upper endoscopy. Significantly fewer high-risk bleeding lesions are found on endoscopy in patients with coffee grounds vs. bloody NG aspirates. OBJECTIVE: We present a case series to illustrate that patients with coffee grounds emesis (CGE) often have other unsuspected illnesses that may be overlooked due to preoccupation with the GI bleed. CASE REPORTS: A retrospective chart review of a series of 6 patients presenting with CGE and admitted for upper GI bleeding was performed. All 6 patients were hemodynamically stable at admission. NG lavage showed coffee grounds that cleared easily. None of the patients required blood transfusions during their hospital stay. Endoscopy in 3 of 6 patients failed to find any significant UGI lesions or stigmata of recent bleed. CONCLUSION: Although patients were admitted for UGI bleeding, the more significant associated diagnoses included acute myocardial infarction, urosepsis, small bowel obstruction, bilateral pulmonary emboli, and acute renal failure. Hemodynamically stable patients presenting with coffee grounds NG aspirate and no fall in hemoglobin/hematocrit should be evaluated for other non-GI bleeding-related conditions even as the GI bleed is being managed.

Postpolypectomy bleeding in patients undergoing colonoscopy on uninterrupted clopidogrel therapy.

BACKGROUND: The risk of postpolypectomy bleeding (PPB) in patients undergoing colonoscopy on uninterrupted clopidogrel therapy has not been established. OBJECTIVE: To assess the PPB rate and outcome and identify risk factors associated with PPB in patients taking clopidogrel. DESIGN: Single-center, retrospective study. Demographics, clinical parameters, polyp characteristics, polypectomy techniques, and postpolypectomy events in the groups were compared by univariate analysis. Stepwise logistic regression analyses identified independent risk factors associated with PPB. SETTING: Veterans Affairs Medical Center. PATIENTS: A total of 142 patients (375 polypectomies) taking clopidogrel (cases) and 1243 patients (3226 polypectomies) not taking clopidogrel (controls). INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Postpolypectomy bleeding, hospitalization, and mortality. RESULTS: The immediate (intraprocedural) bleeding rate was similar in the 2 groups (2.1% vs 2.1%). Delayed (postprocedural) PPB rate was higher in the group taking clopidogrel (3.5% vs 1.0%, P = .02). Delayed bleeding of significance requiring hospitalization and transfusion/intervention was also higher in patients taking clopidogrel (2.1% vs 0.4%, P = .04). The length of hospital stay and interventions for PPB were comparable between the 2 groups. There was no mortality. Concomitant use of clopidogrel and aspirin/other nonsteroidal anti-inflammatory drugs (odds ratio 3.7; 95% CI, 1.6-8.5) and the number of polyps removed (OR 1.3; 95% CI, 1.2-1.4) were the only significant risk factors associated with PPB. Clopidogrel alone was not an independent risk factor for PPB. LIMITATIONS: Retrospective study and small number of patients with PPB. CONCLUSIONS: The PPB rate is significantly higher in patients undergoing polypectomy while taking clopidogrel and concomitant aspirin/nonsteroidal anti-inflammatory drugs; however, the risk is small and the outcome is favorable. Routine cessation of clopidogrel in patients before colonoscopy/polypectomy is not necessary.

Outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin.

The purpose of this study is to evaluate the incidence and outcome of retinopathy in chronic hepatitis C patients treated with peginterferon and ribavirin. A total of 74 hepatitis C patients with baseline eye exams and eye exams during therapy were included. Retinopathy was defined as development of cotton wool spots and/or intra-retinal hemorrhage. Demographics, hepatitis C viral characteristics, treatment and laboratory data, and eye exam findings were compared in groups with and without retinopathy. Retinopathy developed in 28 (38%), early in therapy. Pre-treatment eye exams did not predict risk of retinopathy. Therapy was continued in all but one; cotton wool spots resolved in 24 of 26. All nine patients with intra-retinal hemorrhage had resolution. No patient had retinopathy-related visual deterioration. Retinopathy is common with peginterferon therapy, but the outcome is favorable. Cessation of therapy for retinopathy is not warranted. Severe visual disturbances and scotomas deserve further evaluation.

Hunt for the Shunt: An Unusual Case of Late-onset Hydrothorax in a Patient on Peritoneal Dialysis.

Hydrothorax is a rare complication of peritoneal dialysis occurring in about 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. These effusions occur soon after the onset of dialysis and are usually right-sided. We describe an unusual case of late-onset, left-sided, and recurrent effusions in the setting of CAPD. A 67-year-old patient with end-stage renal disease on CAPD for the last three years was admitted to our hospital with acute hypoxic respiratory failure secondary to a left-sided effusion. Although previously asymptomatic, he had three admissions for bilateral (left predominant) effusions in the last year, all of which were found to be transudative on analysis. Therapeutic thoracentesis once again revealed a transudative effusion with an elevated pleural fluid-serum glucose gradient. On this occasion, pleuro-peritoneal scintigraphy with technetium-99m was performed, uncovering a communication between the peritoneal cavity and the left pleural cavity. The peritoneal dialysis was substituted with hemodialysis, and the patient showed an eventual resolution of left-sided effusions within 18 months. Hydrothorax in peritoneal dialysis is due to the transudation of fluid across congenital or acquired pleuro-peritoneal communications. Pleural fluid with protein content less than 3 g/dl, high glucose, and low lactate dehydrogenase (LDH) relative to blood, and the presence of both D and L isomers of lactic acid suggest a transdiaphragmatic leak. Early diagnosis via peritoneal scintigraphy and appropriate management can prevent significant morbidity and mortality.

Bleeding risk after invasive procedures in aspirin/NSAID users: polypectomy study in veterans.

BACKGROUND: Aspirin, by virtue of inhibition of platelet hemostatic function, is withheld before many invasive procedures because of the bleeding risk. American Society of Gastrointestinal Endoscopy guidelines acknowledge the paucity of "high quality data" to make recommendations regarding the use of aspirin (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) before endoscopic procedures. Yet the majority of endoscopists hold ASA/NSAIDs before polypectomy. METHODS: This single-center, retrospective, cohort study was conducted at Veterans Affairs Medical Center, Syracuse, NY. The objectives were to assess the postpolypectomy bleeding risk in ASA/NSAID users in a large cohort of veterans undergoing colonoscopic polypectomy and to identify risk factors associated with postpolypectomy bleeding. All patients undergoing polypectomy between January 2002 and October 2007 were eligible. Patients on anticoagulants/other antiplatelet agents were excluded. Patients were selected randomly by cluster sampling techniques. Electronic medical and pharmacy records were reviewed for patient demographics, polypectomy techniques, and postpolypectomy bleeding rates. Univariate analysis was performed between patients on ASA and NSAIDs (group A) versus those not on ASA or NSAIDs (group B). Multiple regression analysis was performed to identify independent risk factors associated with postpolypectomy bleeding. RESULTS: Five hundred two (43%) of 1174 patients (mean age 66 years, 92% white) were on ASA or NSAIDs, or both. There was no significant difference between postpolypectomy bleeding rates among the 2 groups (3.2% vs 3.0%). Age, sex, polyp characteristics, and polypectomy techniques were comparable between groups A and B. In multiple logistic regression analysis, ASA or NSAID use was not a significant risk factor for postpolypectomy bleeding. Number of polyps removed per patient was the only risk factor significantly associated with postpolypectomy bleeding (P <.01, odds ratio 1.3, 95% confidence interval, 1.18-1.43). CONCLUSIONS: In this large study, use of ASA or NSAIDs did not increase the risk of postpolypectomy bleeding. Cessation of ASA/NSAIDs before colonoscopy/polypectomy is therefore unnecessary.

Successful medical management of emphysematous gastritis with concomitant portal venous air: a case report.

INTRODUCTION: The causes of diffuse abdominal pain following pelvic surgery are numerous. We present a rare case of acute abdominal pain in a woman in the post-partum period. CASE PRESENTATION: A 25-year-old Caucasian woman with neurofibromatosis type 1 presented to our hospital with diffuse abdominal pain immediately after a cesarean section. The patient was acutely ill and toxic with a fever of 38.8 degrees C, a pulse of 120 beats per minute and a distended abdomen with absent bowel sounds. A computed tomography scan showed air in the wall of the stomach and portal venous system. The patient was successfully treated with intravenous antibiotics, bowel rest and total parenteral nutrition. CONCLUSION: It is rare for a case of emphysematous gastritis associated with portal venous air to be treated successfully without surgery. To the best of our knowledge, to date there has been no reported association of emphysematous gastritis with neurofibromatosis.

An unusual presentation of cirrhotic pleural effusion in a patient with no ascites: a case report.

Pleural effusion that develops in a patient with cirrhosis and portal hypertension, in the absence of cardiopulmonary disease, is termed hepatic hydrothorax. Hepatic hydrothorax very rarely presents in the absence of ascites. Although the exact mechanism is somewhat controversial, pleural effusion occurs when ascitic fluid moves through diaphragmatic defects which are opened up by increased intra-abdominal pressure. We report a case report of cirrhotic pleural effusion in a patient with no clinical or radiographic evidence of ascites and discuss the pathogenesis, diagnosis and management of this condition.