Effect of dimethyl fumarate on lymphocytes in RRMS: Implications for clinical practice.

OBJECTIVE: To assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis. METHODS: Using peripheral blood from several clinical trials of DMF, immune cell subsets were quantified using flow cytometry. For some patients, lymphocyte counts were assessed after DMF discontinuation. Incidence of adverse events, including serious and opportunistic infections, was assessed. RESULTS: In DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a pattern of decline followed by stabilization, which also was reflected in the global reduction in numbers of circulating functional lymphocyte subsets. The relative frequencies of circulating memory T- and B-cell populations declined and naive cells increased. No increased incidence of serious infection or malignancy was observed for patients treated with DMF, even when stratified by ALC or T-cell subset frequencies. For patients who discontinued DMF due to lymphopenia, ALCs increased after DMF discontinuation; recovery time varied by ALC level at discontinuation. T-cell subsets closely correlated with ALCs in both longitudinal and cross-sectional analyses. CONCLUSIONS: DMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not required for safety vigilance. No increased risk of serious infection was observed in patients with low T-cell subset counts. Monitoring ALC remains the most effective way of identifying patients at risk of subsequently developing prolonged moderate to severe lymphopenia, a risk factor for progressive multifocal leukoencephalopathy in DMF-treated patients. TRIAL REGISTRATION NUMBERS: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770.

Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the road ahead.

At its height, the Clostridium difficile infection epidemic caused approximately 7000 infections and 300 deaths per day in the USA. Fecal microbiota transplantation (FMT) has demonstrated extraordinary clinical resolution, C. difficile infection cure rates of over 90%, and low recurrence. In tandem with the rise of FMT, the gastrointestinal microbiome has emerged as a 'vital' organ armed with a wealth of microbe 'soldiers' more powerful than known antibiotics. FMTs' reputation has diffused into many new 'indications' yet these appear to be merely the tip of the iceberg when considering its potential applications. FMT as a therapeutic tool has evolved from the original format of blended donor stool and moved towards a refined product comprising a myriad of microbial components, presented aesthetically as encapsulated lyophilized powder.

Combining infliximab, anti-MAP and hyperbaric oxygen therapy for resistant fistulizing Crohn's disease.

BACKGROUND: Fistulizing Crohn's disease (CD) presents a therapeutic challenge as fistulae are notoriously difficult to heal. Mycobacterium avium ss paratuberculosis (MAP) treatment in CD is gaining attention. AIM: We evaluated healing of CD fistula(e) using a novel combination therapy. STUDY: Nine consecutive patients who failed to heal fistulae on conventional treatment including anti-TNF, were treated with at least three doses of infliximab, 18-30 courses of hyperbaric oxygen therapy and anti-MAP antibiotics comprising rifabutin, clarithromycin and clofazimine. RESULTS: All patients achieved complete healing of fistulae by 6-28 weeks and follow-up for mean 18 months. CONCLUSION: Combining infliximab, hyperbaric oxygen therapy and anti-MAP, seems to enable healing of recalcitrant fistulae and although a small case series, all nine patients achieved complete healing.

Fecal microbiota transplantation: A 'How-To' guide for nurses.

Fecal microbiota transplantation is emerging as one of the most exciting treatments of this century. Rarely has one treatment provided the opportunity to treat a myriad of diseases, not only within the gastrointestinal tract but also in extra-intestinal organs; such is the power of the gastrointestinal microbiota to modulate the immune system and eradicate infections, even where antibiotics have previously failed. The demand for this therapy, both among patients and physicians, is increasing, and a search of the literature reveals numerous reviews, case reports and discussion on the topic. However, to date, much of the literature addresses the procedure from a physician's point of view, and can therefore be lacking in practical detail. As nurses are often the 'unsung heroes' of the procedure, it is timely to address the subject from a nursing perspective.

Fecal microbiota transplantation: techniques, applications, and issues.

Fecal microbiota transplantation (FMT) has gained widespread recognition in light of the recent Clostridium difficile infection (CDI) epidemic, responsible for almost 110,000 deaths per year. The procedure's success rate has caused experts to reflect on what other conditions may benefit. This article provides an overview of (1) description and history of FMT, (2) FMT publications in CDI, (3) the concept of the gut microbiota as a virtual organ, (4) rationale for FMT use, (5) FMT use in inflammatory bowel disease, (6) emerging FMT applications, (7) how FMT is currently performed, and (8) how FMT may be performed in the future.

Mycobacterium avium ss paratuberculosis-associated diseases: piecing the Crohn's puzzle together.

The relation of Mycobacterium avium ss paratuberculosis (MAP) to Crohn's Disease (CD) and other MAP-associated conditions remains controversial. New data, coupled with the analogous Helicobacter pylori (H. pylori) story, has permitted us to piece together the MAP puzzle and move forward with a more scientific way of treating inflammatory bowel disease, particularly CD. As infection moves centre stage in inflammatory bowel disease, the dated "aberrant reaction" etiology has lost scientific credibility. Now, our growing understanding of MAP-associated diseases demands review and articulation. We focus here on (1) the concept of MAP-associated diseases; (2) causality, Johne Disease, the "aberrant reaction" hypothesis; and (3) responses to published misconceptions questioning MAP as a pathogen in CD.

Primary treatment of Crohn's disease: combined antibiotics taking center stage.

Although controversial, the use of properly chosen antibiotics in Crohn's disease appears beneficial. Evidence supporting the use of targeted antibiotic therapy comes in two forms: statistical evidence derived from meta-analyses of multiple formal studies and the documented clinical and endoscopic responses in patients treated with antibiotic combinations outside of formal clinical studies. This article reviews evidence from both categories that support the use of properly chosen antibiotic regimens in treating Crohn's disease, comments on the advantages and disadvantages of antibiotic therapy, and attempts to present a unifying hypothesis related to the role of enteric bacteria, mucosal immunity and antibiotic therapy. Relevant studies identified through a Medline search from 1976 to 2011 were assessed for inclusion by two independent observers who resolved any disagreements by consensus. References from all identified articles and recent review articles were cross-checked to ensure a thorough search. Papers were selected based on scientific merit as to which presented original contributions to the results.

Durable alteration of the colonic microbiota by the administration of donor fecal flora.

GOALS: To determine whether fecal bacteriotherapy results in a durable beneficial change in the colonic microbiota of patients with flora-related disorders. BACKGROUND: Earlier studies have implicated the colonic microbiota in a number of conditions. Administration of a fecal suspension from a healthy individual to an ill individual (fecal bacteriotherapy) can cure Clostridium difficile infection and potentially other diseases. Oral probiotics do not work in this condition, yet there has been no study to determine whether fecal bacteriotherapy results in prolonged implantation. STUDY: Fecal samples were collected from 10 patients undergoing fecal bacteriotherapy. Patients completed an antibiotic schedule and bowel lavage before the infusion of healthy donor feces. Using a molecular approach, the bacterial populations in patient fecal samples were followed from pretreatment to 24 weeks post-initial infusion and compared with the initial infused donor fecal suspension. RESULTS: At intervals of 4, 8, and 24 weeks after the procedure, the bacterial populations in the patients' fecal samples consisted predominantly of bacteria derived from the healthy donor samples. Comparisons of similarity at 4, 8, and 24 week samples to the donor-infused sample were made and each recipient's baseline sample was statistically significant with Friedman test. CONCLUSIONS: This study demonstrates a durable beneficial change in the patients' bacterial populations of the colon to represent those of the healthy donor's microbiota. Manipulation of the colonic microbiota to improve its protective and beneficial role represents a promising field of new therapeutic strategies for the treatment of gastrointestinal conditions.