IntroductionCrohn's disease [CD] is a chronic inflammatory bowel disease [IBD] that can result in progressive bowel damage and disability 1 . CD can affect individuals of any age, from children to the elderly, 2,3 and may cause significant morbidity and impact on quality of life. Up to one-third of patients present with complicated behaviour [strictures, fistula, or abscesses] at diagnosis 4 . Most patients over time will develop a complication, with roughly 50% of patients requiring surgery within 10 years of diagnosis [5][6][7] . As the precise aetiology of CD remains unknown, a curative therapy is not yet available 8 . Several agents are available for the medical treatment of CD. Medical agents include mesalazine [5-ASA], locally active steroids [such as budesonide], systemic steroids, thiopurines such as azathioprine [AZA] and mercaptopurine [MP], methotrexate [MTX], and biological therapies [such as anti-TNF, anti-integrins, and anti-IL12/23].The European Crohn's and Colitis Organisation [ECCO] produces and regularly updates several guidelines aimed at providing evidence-based guidance on critical aspects of IBD care to all healthcare professionals who manage patients with IBD. To provide high-quality evidence-based recommendations on medical and surgical treatment in CD, ECCO decided to develop these guidelines by adopting the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] approach 9 . GRADE is a systematic process for developing guidelines that addresses how to frame the healthcare questions, summarize the evidence, formulate the recommendations, and grade their strength and the quality of the associated evidence. GRADE increases transparency at all levels of this process and makes explicit the three considerations that lead to a particular recommendation: the quality of the evidence, the balance of benefits and harms, and the patients' values and preferences. Therefore, ECCO reviewed the available high-quality evidence on the medical management of CD and developed evidence-based recommendations on the medical treatment of adult patients with CD. These guidelines do not cover specific situations, such as post-operative management of adult patients with CD, which was already covered in the last ECCO Guidelines on Crohn's disease 10 . MethodsBased on the GRADE workflow, the Guidelines Committee of ECCO [GuiCom] selected a panel of 48 experts supported by a team of methodologists and librarians. Selection was based on IBD expertise, scientific background, and knowledge of the GRADE methodology. All panellists received adequate training in GRADE before starting the process.Additionally, four patients with CD representing the European Federation of Crohn's and Colitis Associations [EFCCA] were invited to participate in all face-to-face meetings and to provide their experiences and state their preferences.Three domains for medical treatment of CD were identified: 1) induction therapy 2) maintenance therapy 3) therapy of fistulizing perianal disease.All panellists were assigned to...

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This article is the second in a series of two publications relating to the European Crohn’s and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn’s disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn’s disease and an update of previous guidelines.

An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 ؎ 3.4% (SOL) and 164.2 ؎ 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ؎ 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r ‫؍‬ ؊0.98, P < 0.003) and SOL muscle (r ‫؍‬ ؊0.97, P < 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 ؎ 16.9% of baseline; P ‫؍‬ 0.005), but not in SOL muscle (to 114.4 ؎ 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ؎ 5.6% of baseline (P ‫؍‬ 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

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The existence of metabolically relevant intramyocellular lipids (IMCL) as assessed by the noninvasive (1)H-magnetic resonance spectroscopy (MRS) has been established. In the present studies, we analyzed the relationships between IMCL in two muscle types [the predominantly nonoxidative tibialis muscle (tib) and the predominantly oxidative soleus muscle (sol)] and anthropometric data, aerobic capacity (VO(2)max, bicycle ergometry, n = 77) and insulin sensitivity (hyperinsulinemic euglycemic clamp, n = 105) using regression analysis. In univariate regression, IMCL (tib) was weakly but significantly correlated with percentage of body fat (r = 0.28, P = 0.01), whereas IMCL (sol) was better correlated with waist-to-hip ratio (r = 0.41, P < 0.0001). No significant univariate correlation with age or maximal aerobic power was observed. After adjusting for adiposity, IMCL (tib) was positively correlated with measures of aerobic fitness. A significant interaction term between VO(2)max and percentage of body fat on IMCL (tib) (P = 0.04) existed (whole model r(2) = 0.26, P = 0.001). In contrast, aerobic fitness did not influence IMCL (sol). No correlation between insulin sensitivity as such and IMCL (tib) (r = -0.13, P = 0.2) or IMCL (sol) (r = 0.03, P = 0.72) was observed. Nethertheless, a significant interaction term between VO(2)max and IMCL on insulin sensitivity existed [P = 0.04 (tib) and P = 0.02 (sol)]; [whole model (sol) r(2) = 0.61, P < 0.0001, (tib) r(2) = 0.60, P < 0.0001]. In conclusion, obesity and aerobic fitness are important determinants of IMCL. IMCL and insulin sensitivity are negatively correlated in untrained subjects. The correlation between the two parameters is modified by the extent of aerobic fitness and cannot be found in endurance trained subjects. Thus, measurements of aerobic fitness and body fat are indispensable for the interpretation of IMCL and its relationship with insulin sensitivity.

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