Gastroenterologist perceptions of faecal microbiota transplantation

© 2015 Baishideng Publishing Group Inc. All rights reserved. AIM: To explore gastroenterologist perceptions towards and experience with faecal microbiota transplantation (FMT). METHODS: A questionnaire survey consisting of 17 questions was created to assess gastroenterologists' attitude towards and experience with FMT. This was anonymously distributed in hard copy format amongst attendees at gastroenterology meetings in Australia between October 2013 and April 2014. Basic descriptive statistical analyses were performed. RESULTS: Fifty-two clinicians participated. Twenty one percent had previously referred patients for FMT, 8% more than once. Ninety percent would refer patients with Clostridium difficile infection (CDI) for FMT if easily available, 37% for ulcerative colitis, 13% for Crohn's disease and 6% for irritable bowel syndrome. Six percent would not refer any indication, including recurrent CDI. Eighty-six percent would enroll patients in FMT clinical trials. Thirty-seven percent considered the optimal mode of FMT administration transcolonoscopic, 17% nasoduodenal, 13% enema and 8% oral capsule. The greatest concerns regarding FMT were: 42% lack of evidence, 12% infection risk, 10% non infectious adverse effects/lack of safety data, 10% aesthetic, 10% lack of efficacy, 4% disease exacerbation, and 2% inappropriate use; 6% had no concerns. Seventy seven percent believed there is a lack of accessibility while 52% had an interest in learning how to provide FMT. Only 6% offered FMT at their institution. CONCLUSION: Despite general enthusiasm, most gastroenterologists have limited experience with, or access to, FMT. The greatest concerns were lack of supportive evidence and safety issues. However a significant proportion would refer indications other than CDI for FMT despite insufficient evidence. These data provide guidance on where education and training are required

Effect of anticomplement agent K-76 COOH in hamster-to-rat and guinea pig- to-rat xenotransplantation

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug's 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9-12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d.i.v. K76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition to K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

An analysis of concordant xenografting

SIGLEAvailable from British Library Document Supply Centre- DSC:D061855 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Bringing Top-End Endoscopy to Regional Australia: Hurdles and Benefits

This paper focuses on recent experience in setting up an endoscopy unit in a large regional hospital. The mix of endoscopy in three smaller hospitals, draining into the large hospital endoscopy unit, has enabled the authors to comment on practical and achievable steps towards creating best practice endoscopy in the regional setting. The challenges of using what is available from an infrastructural equipment and personnel setting are discussed. In a fast moving field such as endoscopy, new techniques have an important role to play, and some are indeed cost effective and have been shown to improve patient care. Some of the new techniques and technologies are easily applicable to smaller endoscopy units and can be easily integrated into the practice of working endoscopists. Cost effectiveness and patient care should always be the final arbiter of what is essential, as opposed to what is nice to have. Close cooperation between referral and peripheral centers should also guide these decisions

Bringing top-end endoscopy to regional Australia: hurdles and benefits

This paper focuses on recent experience in setting up an endoscopy unit in a large regional hospital. The mix of endoscopy in three smaller hospitals, draining into the large hospital endoscopy unit, has enabled the authors to comment on practical and achievable steps towards creating best practice endoscopy in the regional setting. The challenges of using what is available from an infrastructural equipment and personnel setting are discussed. In a fast moving field such as endoscopy, new techniques have an important role to play, and some are indeed cost effective and have been shown to improve patient care. Some of the new techniques and technologies are easily applicable to smaller endoscopy units and can be easily integrated into the practice of working endoscopists. Cost effectiveness and patient care should always be the final arbiter of what is essential, as opposed to what is nice to have. Close cooperation between referral and peripheral centers should also guide these decisions

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Concise Lexicon for Sign Linguistics

This extensive, well-researched and clearly formatted lexicon of a wide variety of linguistic terms is a long overdue. It is an extremely welcome addition to the bookshelves of sign language teachers, interpreters, linguists, learners and other sign language users, and of course of the Deaf themselves

Surgery for Crohn's disease and anti-TNF agents. The changing scenario

Surgery has been a mainstay of therapy for Crohn\u2019s disease for a long time, essentially as a consequence of the fairly modest efficacy of traditional medications such as immunomodulators, 10 antibiotics and 5-ASA, especially in severe cases. However, in the past decade and half, the advent of anti-TNF agents has greatly changed the medical approach to this disease and may modify its general management as well. Here, we have reviewed the current literature on incidence of surgery, timing of surgery and postoperative recurrence of Crohn\u2019s disease before and after the advent of anti-TNF agents. In addition, we have reviewed the risk of perioperative 15 complications in patients on anti-TNF agents before surgery. The data show that the use of these medications is changing or expecting to change shortly a number of surgical aspects of Crohn\u2019s disease managemen