A Retrospective Comparison of Fecal Microbial Transplantation Methods for Recurrent Clostridium Difficile Infection.

BACKGROUND: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. OBJECTIVES: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior. METHODS: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract. RESULTS: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period. CONCLUSIONS: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT.

Fecal Microbiota Transplantation for Clostridium difficile-Associated Diarrhea.

Clostridium difficile-associated diarrhea is a problem most hospital-based physicians will face in their career. This review aims to refresh current knowledge with regard to Clostridium difficile infection and bring physicians up to date with the latest developments in the growing field of fecal microbiota transplantation, the benefits it offers, and the promise this and other developments hold for the future.

Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis.

GOALS: To understand the relationship between acute recurrent pancreatitis and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. BACKGROUND: An emerging number of patients present with a nonclassic phenotype of cystic fibrosis (CF) with partial features or single-organ disease only. The association between the phenotype of recurrent pancreatitis CFTR dysfunction is unclear. METHODS: Patients with idiopathic recurrent pancreatitis were referred for electrophysiologic investigation. RESULTS: Thirty-three patients (18 males) aged 20+/-12 years with recurrent pancreatitis were studied. Three patients had mild asthma and 1 patient had mild ulcerative colitis. There was no family history of CF. All patients had normal imaging of the pancreatic duct by endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. No patient was pancreatic insufficient. Mean sweat chloride values were 41+/-14 meq/L (range: 18 to 64). Nasal potential difference (NPD) measurement was pathologic in 7 patients. Mean basal potential difference in these 7 patients was -33+/-13 mV and there was an abnormal response to chloride-free and isoproterenol solutions. There was no difference in sweat chloride concentration between the 2 groups. Mutation analysis revealed W1282X/5T, D1152H/5T, and W1282X/- in 3 patients with abnormal NPD and 1 W1282X allele was found in 1 patient with normal NPD. CONCLUSIONS: In this series, 21% of patients with recurrent pancreatitis have abnormalities of CFTR function. Patients presenting with recurrent, "idiopathic" pancreatitis require CFTR function testing.

A secreted form of the asialoglycoprotein receptor, sH2a, as a novel potential noninvasive marker for liver fibrosis.

BACKGROUND AND AIM: The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. METHODS: We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. RESULTS: sH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86. CONCLUSIONS: sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein assessed the effect of orlistat in patients with NAFLD. METHODS: We performed a randomized, double-blind, placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The patients were randomized to receive either orlistat (120 mg 3 times daily for 6 months) or placebo. All patients participated in an identical behavioral weight loss program. All patients underwent monthly evaluation by abdominal US; liver enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were monitored, and all patients underwent nutritional follow-up evaluation. Twenty-two patients underwent a second liver biopsy examination at the end of the study. RESULTS: Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body mass index, 33) completed the study. Serum glucose and insulin levels (P<.03) were significantly higher in the orlistat group, which also presented a higher degree of fibrosis. Body mass index was reduced significantly in each group, with a nonsignificant difference between the groups. Serum alanine transaminase (ALT) levels decreased significantly in both groups, with an almost 2-fold reduction in the orlistat group (48% vs 26.4%). There was a statistically significant reversal of fatty liver by US only in the orlistat group (P<.05). CONCLUSIONS: Orlistat improves serum ALT levels and steatosis on US in NAFLD patients, beyond its effect on weight reduction.

The prevalence rate and anatomic location of colorectal adenoma and cancer detected by colonoscopy in average-risk individuals aged 40-80 years.

BACKGROUND: The role of screening colonoscopy for colorectal (CR) neoplasia in average-risk population, remains to be determined. OBJECTIVES: To evaluate the prevalence and anatomic location of CR adenoma and carcinoma and the morbidity of colonoscopy in individuals at average risk for CR cancer (CRC). METHODS: A retrospective prevalence study of subjects aged 40-80 yr, with no cancer-related symptoms, personal or family history of CR neoplasia, who underwent a colonoscopy. RESULTS: Enrolled were 1,177 persons; 183 aged 40-49 yr (young), 917 aged 50-75 yr, and 77 aged 76-80 yr (elderly). The prevalence of overall CR neoplasia, advanced neoplasia, and cancer was 20.9%, 6.3%, and 1.1%, respectively. In the 50-75 age group, the prevalence of overall adenoma, advanced neoplasia, and cancer was 21.3%, 6.7%, and 1.2%, respectively. Of the 206 neoplasia cases, 21-43% harbored proximal neoplasia beyond the reach of sigmoidoscopy, without distal lesions. Among the elderly, the prevalence of overall adenoma, advanced neoplasia, and cancer reached 26.0%, 14.3%, and 2.6%, respectively. In the young group, 9.8% had overall neoplasia, 1.1% had advanced adenoma, and none had CRC. Procedure-related morbidity rate was 0.1%, with no perforations, bleedings, or mortality. CONCLUSIONS: Screening colonoscopy in average-risk subjects demonstrated a considerable prevalence of CR neoplasia and proximal lesions beyond the reach of sigmoidoscopy. The morbidity rate was negligible. Primary screening colonoscopy should be considered in health programs for the average-risk population, beginning at the age of 50 yr. The significantly high rate of advanced and proximal neoplasia in the elderly, encourages the inclusion of healthy subjects aged 76-80 yr in future prospective studies.