Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

BACKGROUND: The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known. PURPOSE: To assess the efficacy, comparative effectiveness, and harms of FMT for CDI. DATA SOURCES: MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies. STUDY SELECTION: Any study of FMT to treat adult patients with CDI; case reports were only used to report harms. DATA EXTRACTION: Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence. DATA SYNTHESIS: Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed. LIMITATION: Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis. CONCLUSION: Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Validation of DNA marker-assisted selection for forage biomass productivity under deficit irrigation in alfalfa.

Drought and limited irrigation resources threaten agricultural sustainability in many regions of the world. Application of genomic-based breeding strategies may benefit crop variety development for these environments. Here, we provide a first report on the effect of deploying DNA marker-assisted selection (MAS) for the drought resilience quantitative trait in alfalfa (Medicago sativa L.). The goals of this study were to validate the effect of several quantitative trait loci (QTL) associated with alfalfa forage and crown-root (CR) biomass during drought and to determine their potential to improve forage yield of elite germplasm under water-limited conditions. Marker assisted selection was employed to introgress favorable or unfavorable DNA marker alleles affiliated with 10 biomass QTL into three elite backgrounds. Thirty-two populations were developed and evaluated for forage productivity over 3 yr under continuous deficit irrigation management in New Mexico, USA. Significant yield differences (ranging from -13 to 26%) were detected among some MAS-derived populations in all three elite backgrounds. Application of QTL MAS generally resulted in expected phenotypic responses within an elite genetic background that was similar to that in which the QTL were originally identified. However, relative performance of the populations varied substantially across the three genetic backgrounds. These outcomes indicate that QTL MAS can significantly affect forage productivity of elite alfalfa germplasm in drought-stressed environments. However, if biomass QTL are detected in donor germplasm that is genetically dissimilar to targeted elite populations, characterization of donor alleles may be warranted within elite backgrounds of interest to confirm their phenotypic effects prior to implementing MAS-based breeding.

A pilot study of fecal bile acid and microbiota profiles in inflammatory bowel disease and primary sclerosing cholangitis.

INTRODUCTION: Inflammatory bowel disease (IBD) is thought to arise from an abnormal immune response to the gut microbiota. IBD is associated with altered intestinal microbial community structure and functionality, which may contribute to inflammation and complications such as colon cancer and liver disease. Primary sclerosing cholangitis (PSC) is associated with IBD and markedly increases the risk of colon cancer. We hypothesized that secondary bile acids, which are products of microbial metabolism, are increased in PSC patients. AIM: Here, we profiled the fecal bile acid composition and gut microbiota of participants with IBD and PSC, as well as healthy participants. Additionally, we tested the effects of vancomycin, a proposed treatment for PSC, on gut microbiota and fecal bile acid composition in participants with IBD and PSC. METHODS: Fecal samples were collected from patients with IBD, IBD/PSC and healthy controls and fecal bile acids and DNA for microbiota analysis were extracted. Fecal bile acids were averaged over a seven-day period. For subjects with IBD/PSC, oral vancomycin 500mg twice a day was administered and fecal samples were collected for up to eleven weeks. RESULTS: Participants with IBD and PSC had less fecal microbial diversity at baseline relative to controls. While there was some evidence of altered conversion of cholic acid to deoxycholic acid, no substantial differences were found in the fecal bile acid profiles of patients with IBD and PSC (n=7) compared to IBD alone (n=8) or healthy controls (n=8). Oral vancomycin was a potent inhibitor of secondary bile acid production in participants with IBD and PSC, particularly deoxycholic acid, although no changes in liver biochemistry patterns were noted over a two week period. CONCLUSION: In this pilot study, bile acid profiles were overall similar among patients with IBD and PSC, IBD alone, and healthy controls. Microbiota diversity was reduced in those with PSC and IBD compared to IBD alone or healthy controls.

Identification of Acute Decompensated Heart Failure Hospitalizations Using Administrative Data.

Hospitalization for acute decompensated heart failure (ADHF) is an important outcome in clinical trials and heart failure registries; however, the optimal strategy to identify these hospitalizations using International Classification of Diseases, Ninth Revision (ICD-9) codes is uncertain. We sought to identify diagnostic codes that improve ascertainment of ADHF hospitalizations. Heart failure-related ICD-9 principal discharge codes were used to identify 2,202 hospitalizations within the Minneapolis Veterans Affairs Medical Center from 2009 to 2014. Two independent reviewers adjudicated 447 of these hospitalizations to determine the accuracy of each code. We then applied our findings to an unadjusted nationwide sample containing the same ICD-9 codes of interest, from which overall positive predictive value (PPV), sensitivity, and accuracy were calculated. Use of 428.x alone resulted in a PPV of 91.3% (95% confidence interval [CI] 91.0 to 91.7), sensitivity of 97.5% (95% CI 97.3 to 97.6), and accuracy of 89.7% (95% CI 89.4 to 90.0). Combining 428.x with 402.x1, 404.x1, 415, and 518.4 resulted in improved sensitivity (99.2%; 95% CI 99.0 to 99.3) and accuracy (90.7%; 95% CI 90.4 to 91.1) while maintaining a PPV of 91.1% (95% CI 90.7 to 91.4). Excluding chronic heart failure codes (428.22, 428.32, and 428.42) from the proposed strategy resulted in an improvement of PPV to 92.3% (95% CI 92.0 to 92.6), although sensitivity and accuracy decreased to 96.6% (95% CI 96.3 to 96.8) and 90.0% (95% CI 89.6 to 90.3), respectively. In conclusion, a combination of codes including 428.x, 402.x1, 404.x1, 415, and 518.4 improves sensitivity and overall accuracy in ascertaining ADHF events compared with 428.x alone. This strategy could be further improved by manual adjudication of chronic heart failure codes.