Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: In patients with inflammatory bowel disease (IBD), restless legs syndrome (RLS) may occur as an extraintestinal disease manifestation. Iron deficiency (ID) or folate deficiency/vitamin B12 deficiency (FD/VB12D) has previously been described to cause RLS. Here, we determined the prevalence and severity of RLS in IBD patients and evaluated the effect of iron and/or folic acid/vitamin B12 supplementation. METHODS: Patients were screened for ID and RLS by a gastroenterologist. If RLS was suspected, a neurologist was consulted for definitive diagnosis and severity. Patients with RLS and ID, FD, or VB12D received supplementation and were followed-up at weeks 4 and 11 after starting supplementation. RESULTS: A total of 353 IBD patients were included. Prevalence for RLS was 9.4% in Crohn's disease (CD) and 8% in ulcerative colitis (UC). Prevalence for the subgroup of clinically relevant RLS (symptoms ≥ twice/week with at least moderate distress) was 7.1% (n = 16) for CD and 4.8% (n = 6) for UC. 38.7% of RLS patients presented with ID, FD, and/or VB12D. Most frequently ID was seen (25.8%; n = 8). Iron supplementation resulted in RLS improvement (p = 0.029) at week 4 in seven out of eight patients. CONCLUSION: Although the overall prevalence of RLS in IBD did not differ to the general population, clinically relevant RLS was more frequent in IBD patients and, therefore, it is important for clinicians to be aware of RLS symptoms. Though for definite diagnosis and proper treatment of RLS, a neurologist must be consulted. Additionally, iron supplementation of IBD patients with ID can improve RLS symptoms. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03457571.

Pre-study protocol MagPEP: a multicentre randomized controlled trial of magnesium sulphate in the prevention of post-ERCP pancreatitis.

BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In spite of continuing research, no pharmacologic agent capable of effectively reducing the incidence of ERCP-induced pancreatitis has found its way into clinical practise. A number of experimental studies suggest that intrapancreatic calcium concentrations play an important role in the initiation of intracellular protease activation, an initiating step in the course of acute pancreatitis. Magnesium can act as a calcium-antagonist and counteracts effects in calcium signalling. It can thereby attenuate the intracellular activation of proteolytic digestive enzymes in the pancreas and reduces the severity of experimental pancreatitis when administered either intravenously or as a food supplement. METHODS: We designed a randomized, double-blind, placebo-controlled phase III study to test whether the administration of intravenous magnesium sulphate before and after ERCP reduces the incidence and the severity of post-ERCP pancreatitis. A total of 502 adult patients with a medical indication for ERCP are to be randomized to receive either 4930 mg magnesium sulphate (= 20 mmol magnesium) or placebo 60 min before and 6 hours after ERCP. The incidence of clinical post-ERCP pancreatitis, hyperlipasemia, pain levels, use of analgetics and length of hospital stay will be evaluated. CONCLUSIONS: If magnesium sulphate is found to be effective in preventing post-ERCP pancreatitis, this inexpensive agent with limited adverse effects could be used as a routine pharmacological prophylaxis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46556454.

Ulcerative colitis: immune function, tissue fibrosis and current therapeutic considerations.

BACKGROUND: Ulcerative colitis (UC) is a complex disease in which the interaction of genetic, environmental and microbial factors drives chronic intestinal inflammation that finally leads to extensive tissue fibrosis. DISCUSSION: The present review discusses the current knowledge on genetic susceptibility, especially of the IL-12/IL-23 pathway, the pathophysiologic role of the involved cytokines (e.g. IL-13, IL-23, TGFß1) and immune cells (e.g. T cells, epithelial cells, fibroblasts) in UC followed by an overview on actual therapeutic considerations. These future therapies will target selectively the involved cell types by blocking their activation and its downstream signalling, by inhibiting their migration to the inflamed site and by anti-cytokine strategies. This may avoid-when initiated in time-the perpetuation of the inflammatory mechanisms thus preventing fibrosis. With respect to animal models that have guided the most productive efforts for understanding human inflammatory bowel disease, these will be shortly discussed in the respective context.