Author Interviews, Microbiome, Pharmacology / 19.07.2016

MedicalResearch.com Interview with: [caption id="attachment_26264" align="alignleft" width="143"]Mark Pimentel, MD Associate Professor, Medicine Director, GI Motility Program Director, GI Motility Laboratory Cedars-Sinai Dr. Mark Pimentel[/caption] Mark Pimentel, MD Associate Professor, Medicine Director, GI Motility Program Director, GI Motility Laboratory Cedars-Sinai IBS-C Clinical Advisory Board (Chair) at Synthetic Biologics Los Angeles, CA MedicalResearch.com: What is the background for this study? Dr. Pimentel: The SYN-010 program is based on research from my group at Cedars-Sinai Medical Center, and other researchers and collaborators worldwide, investigating the role of intestinal methane production in functional gastrointestinal disorders. Low levels of intestinal methane are a ubiquitous by-product of normal intestinal microbial digestion; however, elevated intestinal methane levels are correlated with decreased intestinal motility and increased symptom severity in patients with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). Methane in humans is produced almost exclusively by the intestinal microorganism Methanobrevibacter smithii (M. smithii). Highest levels of M. smithii are found in the colon; however, overgrowth of M. smithii into the small intestine has also been observed. Previous work from my laboratory demonstrated that methane production by M. smithii in stool samples from IBS-C patients is inhibited by the lactone form of lovastatin. Lovastatin lactone does not appear to eradicate microbial species in the intestine, which should reduce the risk of intestinal dysbiosis and/or the development of microbial resistance. SYN-010 is a proprietary, modified-release, oral formulation of lovastatin lactone, designed to protect lovastatin lactone from the stomach and release the active ingredient in two different locations of the intestinal tract where the M. smithii reside. SYN-010 exerts its therapeutic effect at the level of the intestinal microbiome and does not require absorption into the systemic circulation or conversion of the active ingredient (lovastatin lactone) to the cholesterol lowering β-hydroxyacid form.
Author Interviews, Colon Cancer, Cost of Health Care, Gastrointestinal Disease, Vanderbilt / 06.07.2016

MedicalResearch.com Interview with: Erica R. H. Sutton, MD Assistant Professor Department of Surgery, General Vanderbilt MedicalResearch.com: What is the background for this study? What are the main findings? Response: Colorectal cancer is one of the most preventable diseases that we face; however, despite the great strides that we have made in the realm of early detection, many people still do not undergo screenings. We sought to increase the availability of screenings to those in our community who are at high risk for colorectal cancer and uninsured by providing free colonoscopies to them and to examine the cost-effectiveness of this intervention. Over a 12-month period, 682 uninsured people underwent screening colonoscopies, and 9 cancers were detected. Compared to the Surveillance, Epidemiology, and End Results (SEER) registry, our patient population included more early-stage cancers, and our program was found to be cost-neutral.
Author Interviews, Gastrointestinal Disease, Lancet, Microbiome, Pediatrics / 09.03.2016

MedicalResearch.com Interview with: Phillip I. Tarr, MD Melvin E. Carnahan MD Professor of Pediatrics Director, Pediatric Division of Gastroenterolgy and Nutrition Washington University in St Louis School of Medicine St Louis, MO 63110, USA MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Tarr: There is a longstanding belief that gut bacteria are relevant to the developing necrotising enterocolitis (NEC). We have established dysbiosis in the gut before NEC occurs, suggesting this ecological perturbation might be causal.

Author Interviews, Gastrointestinal Disease, Pain Research / 15.01.2016

[caption id="attachment_20649" align="alignleft" width="150"]Prof. Guy Boeckxstaens Translational Research in GastroIntestinal Disorders KU Leuven, Belgium Prof. Guy Boeckxstaens[/caption] More on Gastroenterology on MedicalResearch.com MedicalResearch.com Interview with: Prof. Guy Boeckxstaens Translational Research in GastroIntestinal Disorders KU Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Prof. Boeckxstaens: Patients with IBS have increased abdominal pain for which no efficient therapy is available, mainly as the underlying cause is unclear. In our study, we checked the hypothesis that pain receptors (in particular TRPV1) in the gut wall of IBS patients are more sensitive (sensitized) than those of control subjects. Based on previous work, we focused on histamine, mainly as we had indications that mast cells releasing histamine may be involved in IBS. Interestingly, we noticed that neurons in rectal biopsies were indeed more sensitive to capsaicin, a substance of which we know it selectively acts on the pain receptors of interest. We could demonstrate that histamine sensitizes TRPV1 via interaction with its histamine 1 receptor (H1R). We next showed that treatment with a H1R blocker was able to prevent TRPV1 sensitization. Based on this observation, we decided to start a pilot study evaluating the effect of a H1R blocker, ebastine, in patients suffering from IBS. This study showed that 12 weeks treatment with ebastine indeed improved abdominal symptoms, in particular pain.
Author Interviews, BMJ, Colon Cancer, Gastrointestinal Disease / 13.12.2015

[caption id="attachment_20060" align="alignleft" width="137"]Dr Franco Radaelli Division of Digestive Endoscopy and Gastroenterology Valduce Hospital Como, Italy Dr. Franco Radaelli[/caption] MedicalResearch.com Interview with: Dr Franco Radaelli Division of Digestive Endoscopy and Gastroenterology Valduce Hospital Como, Italy  Medical Research: What is the background for this study? Dr. Radaelli: Split regimens of bowel preparation are strongly recommended by European and American Guidelines as they have been associated with a higher level of colon cleansing. However, there is still uncertainty on whether the higher level of cleansing associated with a split regimen also results in a higher proportion of subjects with at least one adenoma (adenoma detection rate, ADR), that represents by far a more relevant quality indicator than the level of cleansing itself. On this background, we designed a randomized investigator-blinded controlled trial to evaluate whether a “split regimen” of low-volume 2-L PEG-ascorbate solution was superior to the traditional “full dose, the day before regimen” in terms of ADR. Differently from other studies on bowel preparation, we considered adenoma detection rate  instead of the level of colon cleansing, the primary study end-point, and we designed the sample size accordingly. A precise estimation of the sample size was facilitated by including an homogeneous population of asymptomatic subjects undergoing first colonoscopy after positive-FIT within CRC organized screening program. Besides, ADR represents a very solid end-point due to the very low inter-pathology variability in the differential diagnosis between neoplastic and non-neoplastic lesions, while the assessment of the level of cleansing is hampered by unavoidable degree of subjectivity and higher degree of inter-operator variability.
Annals Internal Medicine, Author Interviews, Dermatology, Gastrointestinal Disease, Immunotherapy / 09.12.2015

[caption id="attachment_19875" align="alignleft" width="180"]Isabelle Cleynen PhD University of Leuven Dr. Cleynen[/caption] MedicalResearch.com Interview with: Isabelle Cleynen  PhD University of Leuven  Medical Research: What is the background for this study? What are the main findings? Dr. Cleynen : Ulcerative colitis and Crohn’s disease, together inflammatory bowel disease (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Treatment for IBD usually involves drug therapy including anti-inflammatory drugs and immune system repressors, amongst which biologics as the anti-TNF antibodies used for patients with moderate to severe IBD. Although these TNF-blocking drugs are effective in many patients with immune-mediated disorders like psoriasis, rheumatoid arthritis and spondylarthropathies, and IBD, several case reports and series showed that some patients developed troubling skin problems (including psoriasis and eczema), causing them to stop the anti-TNF treatment. It is however not clear how often these skin problems develop in IBD patients treated with anti-TNF, and what could be the predisposing factors. In a retrospective cohort of 917 IBD patients initiated on anti-TNF therapy in a single center, we have studied which patients did and did not develop skin problems, what type of skin problems, how they were treated, and whether the lesions resolved upon treatment. We found that about one third of the patients developed skin problems while being treated with anti-TNF drugs. The most common type was psoriasiform eczema, often occurring in flexural regions, the scalp, and genitalia. The time between starting the TNF-blocking drug and the appearance of the skin problem varied from less than half a year to more than 4 years. Quite surprisingly, we found that the cumulative dose of the treatment, or drug serum levels were not different in skin and non-skin lesion patients. Skin lesion patients however seemed to be younger when diagnosed with IBD and when started on anti-TNF agents, more often had anti-nuclear and dsDNA antibodies (both auto-immune factors), and a higher number of skin-disease related genetic risk variants. Most patients had a good response to treatment of their skin problem. About 10% of the patients who developed skin problems, however, stopped the TNF-blocking treatment because of this issue.