1.
Low FODMAP in 2017: Lessons learned from clinical trials and mechanistic studies.
Eswaran, S
Neurogastroenterology and motility. 2017;(4)
Abstract
Given the prevalence of irritable bowel syndrome (IBS) and the suboptimal response to most therapeutic approaches, there has been increasing interest in and adoption of dietary treatment strategies, such as the low Fermentable Oligo-, Di-, & Mono-Saccharides and Polyols (FODMAP) diet. FODMAPs are a diverse group of carbohydrates that exert effects in the gastrointestinal tract not only via fermentation but likely via alterations in the microbiota, metabolome, permeability, and intestinal immunity as well. Clinical evidence for efficacy of this diet is mounting, but there are significant questions regarding short- and long-term safety and effects on the microbiota and nutrition that remain unanswered. This review article interprets the recent findings reported in this issue of Neurogastroenterology and Motility and summarizes the mechanistic and clinical efficacy data of the low FODMAP diet in IBS patients to date.
2.
Clinical trials in minimal change disease.
Ravani, P, Bertelli, E, Gill, S, Ghiggeri, GM
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(suppl_1):i7-i13
Abstract
Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized against MCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem.
3.
Update in medical therapy of ulcerative colitis: newer concepts and therapies.
Katz, S
Journal of clinical gastroenterology. 2005;(7):557-69
Abstract
Recent advances in the pathogenesis of ulcerative colitis recognize the interface of genetic susceptibility, environmental factors (eg, gut microflora), and an altered host's immune response. The meteoric evolution of new therapies designed to address these pathogenetic factors may lead to confusing and often confounding treatment programs. This review is designed to assist the practitioner when in [corrected] incorporating new or novel therapies into a treatment program. These decisions are based on new clinical trial data and the experience of seasoned gastroenterologists with established remedies. NEWER CONCEPTS AND THERAPIES IN UC 5-ADA-- 1. Remains drug of choice for induction and maintenance of remission in mild to moderate IC.1,2 2. Rare but increased incidence of renal disease exists but benefits outweigh risks.18-20 3. Chemoprevention of colorectal cancer in UC is promising and may be related to higher dose and a lessened degree of inflammation.29-36 4. Bioequivalence of all USA 5-ASA is established. Choice of a 5-ASA preparation is not dependent on superiority of a particular mesalamine.3 Phosphodiesterase Inhibitor (OPC-6525)37: preliminary data promising Immunomodulators 6MP/AZA 1. long-term effect not waning51 2. concerns over lymphoma voiced but overall benefits outweigh risks64-70 3. 6MP metabolites measurements of increasing use52-56 Cyclosporine experience continues but serious adverse events remains.105-114 Biologics Infliximab--somewhat disappointing in CUC, awaiting RCT87-92 Basiliximab--useful as "steroid sensitizer" in previously steroid resistant patients118-120 Visilizumab--promising as alternative to cyclosporin in server U.C.115-117 Apheresis--and emerging "non-drug" treatment alternative121-135 Probiotics--Useful in pouchitis and some mild to moderate U.C.94-98, 154 ISIS topical therapy useful in early pilot study (pouchitis)151 Budesonide (pouchitis)147 Antibiotics (pouchitis)140-146 [corrected]
4.
In search of the magic nutraceutical: problems with current approaches.
Heyland, DK
The Journal of nutrition. 2001;(9 Suppl):2591S-5S
Abstract
Over the last few decades, substrates with immune-modulating properties have been identified in all groups of micro- and macronutrients. Numerous experimental studies have focused on evaluating these substances, either alone or in combination. After hundreds of experiments, no clear, consistent signal exists that any of these agents result in significant treatment benefits in critically ill patients. The current approach to establishing the efficacy of nutritional interventions suffers from several limitations. First, the majority of studies focus on surrogate or substitute end points rather than clinically important end points. Second, the majority of clinical studies are small, and as such are underpowered to detect a significant treatment effect on clinically important end points. Third, the methodological quality of individual randomized trials varies. Methodological limitations, prevalent in nutrition studies, limit the strength of clinical inference that can be made from study results. High quality studies have been shown to differ significantly from low quality studies in their estimation of treatment effect. Fourth, the generalizability of single-site studies is limited. Finally, studies sponsored solely by industry are considered to be less believable than studies conducted under the auspices of peer-review agencies. Future evaluations must be done in the context of large, multicenter, well-designed, randomized trials focusing on clinically important end points that are sponsored from a variety of sources (including peer-reviewed agencies). Although such trials are costly, they are feasible and are much more likely to be believable and generalizable than the current approach.