Recommended Read March 2014

Recommended Read (March 2014)

  When someone tells you that they are good at DIY, the usual picture that comes to the mind is that of a person trying to assemble flat pack furniture. You may be shocked when you realise that they are talking about DIY faecal transplants. Instructions for do-it-yourself faecal transplants are available online; individuals have posted videos on YouTube with tens of thousands of views and written books advocating at-home procedures using stool from acquaintances or family members. Some have even considered using their pets as donors. An open letter on one Faecal Microbiota Transplantation (FMT) advocacy site urges doctors to recognize that at-home treatments are occurring, partly because physicians are not offering the procedure Faecal transplantation was first described in 1958 Eiseman, B., Silen, W., Bascom, G. S. & Kauvar, A. J. Surgery 44, 854–859. It was only in 2013, first randomised controlled trial was published proving its benefit in recurrent Clostridium difficile infection Van Nood, E. et alN. Engl. J. Med. 368, 407–415. The 43 trial participants had recurrent Clostridium difficile infections. Patients in the control groups received antibiotics alone while patients in the test group received antibiotics along with a fluid derived from filtered faeces, which was delivered into the upper small intestine through nasal tubes. This trial was stopped ahead of schedule because the faecal slurry was more than twice as effective in resolving symptoms as antibiotics alone. Many non-randomised trials in patients with recurrent Clostridium difficile  infection also confirmed the efficacy of Faecal Microbiota Transplantation (FMT) with success rate about 90%.More than a half a dozen clinical trials have been registered to study FMT in inflammatory bowel diseases. The hope of manipulation of the gut microbiome to treat diseases other than C. difficile is still at speculative stages. In May 2013, the US Food and Drug Administration (FDA) issued a public announcement that it had been regulating human faeces as a drug. The FDA revised its position later in 2013 not to enforce the Investigational New Drug (IND) requirement for recurrent C. difficile infections. This means that FMT for recurrent C. difficile infections can be performed without any mandatory screening, whereas FMT for other indications cannot be performed without an IND application. There are potential risks associated with FMT like spread of HIV or hepatitis. It is also possible that FMT could change the microbiome to make people more susceptible to chronic conditions such as obesity or autoimmune disorders. Few human studies have followed patients prospectively to assess for adverse outcomes of FMT. Transient abdominal discomfort and bloating have been observed after FMT, but little long-term safety data exist. Rigorous screening of FMT is essential, however over regulation might encourage DIY enthusiasts to do FMT outside health care setting. Stool banks are proposed as a solution to ensure the quality of FMT and openBiome is one stool bank started in USA in 201, which supplies material for C. difficile treatments.

  Education committee is always at the service of our members if they are in need of a topic for research or audit. Here is one for you. Renal stones are not the usual cause of abdominal pain in children with inflammatory bowel disease. Not many people have looked at this problem in patients with IBD. McConnell N et al have published their experience in British Journal of Urology BJU Int. 2002 Jun;89(9):835-41. They have studied 25 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 17 normal subjects. Renal calculi were found in two patients with CD and in none with UC. Hyperoxaluria was present in 36% of patients with CD but was absent in those with UC. Analysis of covariance showed an association between low urinary citrate/creatinine ratio and renal stones, and between a combined urinary citrate and magnesium deficit relative to calcium, as expressed in the CMC index ((citrate x magnesium)/calcium), and renal stones . Changes in urinary calcium, oxalate, urate, magnesium or the calcium oxalate index were not associated with the presence of stones. There was no independent relationship between any clinical factor and the presence of stones. The authors have concluded that lower urinary concentrations of magnesium and citrate (stone inhibitors), relative to calcium (stone promoter; the CMC index) may be more important in lithogenesis in inflammatory bowel disease than is hyperoxaluria. Avoiding low urinary levels of magnesium and citrate may aid in preventing and treating renal calculi. Trinchieri A  et al have published Urinary patterns of patients with renal stones associated with chronic inflammatory bowel disease in   Arch Ital Urol Androl. 2002 Jun;74(2):61-4 From a cohort of 1941 consecutive patients with renal stones, they have identified 10 patients with Crohn's disease, 12 with ulcerative colitis and one patient with ileal bypass for obesity. Six patients underwent ileal resection and 10 patients total colectomy. Urinary oxalate excretion was significantly higher and urinary citrate lower in stone patients with ileal disease than in idiopathic stone formers and stone patients with ulcerative colitis .Urinary volume was significantly lower in patients with ulcerative colitis. From these two papers it appears that hyperoxaluria and reduced citrate excretion are important factors in renal stone development.

  Most paediatric gastroenterologists in the UK perform colonoscopies in children using anaesthesia rather than sedation to reduce discomfort associated with the procedure. Endoscopy with anaesthesia has several advantages including less pain, higher completion rates, shorter examination and recovery times, and improved caecal intubation rates for less-experienced endoscopists. By doing the colonoscopy in this way, are we getting less skilled? Are we more likely to push through loops and angulated segments because there is no pain feedback from the patient. There are no studies conducted in children to look into this issue. Louis Korman et al have published their study on 114 adult patients in Gastrointestinal Endoscopy Volume 79, Issue 4 , 657-662 April 2014. Forces applied during colonoscopy were measured by using the colonoscopy force monitor, which is a wireless, handheld device that attaches to the insertion tube of the colonoscope. They have found that axial and radial forces increase and examination time decreases significantly when propofol is used as the method of anaesthesia compared to sedation using Meperidine or Fentanyl and Midazolam. This study did not link force to an adverse clinical outcome, however the magnitude of forces observed were significant and, in some cases, exceeded tear and perforation forces identified on surgical and cadaveric specimens. The absence of patient feedback and the limitation of patient position affected the method of insertion and withdrawal. This study demonstrated a higher peak force with propofol, suggesting that trainees and experienced endoscopists alike may use push-through techniques to reach the caecum.

  Westernisation of the diet has been suggested as an important factor for the increased incidence of inflammatory bowel disease in developing countries. It is not easy to test this hypothesis in humans partly because of the difficulty of caging humans and feeding them specific diets. Margarita Martinez-Medina et al have published their study on mice models in Gut  2014;63:116-124 doi:10.1136/gutjnl-2012-30411. They have studied the effects of a high fat/high sugar (HF/HS) Western diet on gut microbiota composition, barrier integrity and susceptibility to infection in transgenic CEABAC10 mice expressing human Carcino- embryonic antigen related cell adhesion molecule 6 (CEACAMs). CEACAM6 is abnormally expressed in CD patients.  This allows adherent-invasive Escherichia coli (AIEC) to colonise the gut mucosa and leads to inflammation. HF/HS diet led to dysbiosis in wild type and transgenic CEABAC10 mice, with a particular increase in E coli population in HF/HS-fed CEABAC10 mice. These mice showed decreased mucus layer thickness, increased intestinal permeability, induction of Nod2 and Tlr5 gene transcription, and increased TNFα secretion. These modifications led to a higher ability of adherent-invasive Escherichia coli (AIEC) bacteria to colonise the gut mucosa and to induce inflammation. These data support the multifactorial aetiology of CD, which involves pathogen colonisation in a genetically predisposed patient having a Westernised lifestyle. Food intake is strongly involved in gut microbiota composition and thus changes in eating habits could decrease the proportion of invasive bacteria in the gut mucosa of susceptible CD patients.

  For children in the UK, the ability to swallow tablets seems to arrive alongside puberty, sometimes even later, but it seems to arrive much sooner in the Netherlands. Diana A van Riet-Nales et al have published their study in Arch Dis Child 2013;98:725-731 doi:10.1136/archdischild-2012-303303. Parents administered four oral placebo dosage forms that were aimed at a neutral taste, at home, to their child (1–4 years of age) twice on one day following a randomised cross-over design: small (4 mm) tablet, powder, suspension and syrup. They were asked to report the child's acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the result of the intake. At the end of the study, they were asked to report the preference of the child and themselves. Mini tablets (4 mm diameter) were the most acceptable formulation to healthy Dutch infants and preschool children. Both parents and children preferred the mini tablets and syrups to the suspensions and powders.

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Education Committee
March 2014