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Background A substantial group of patients with inflammatory bowel disease (IBD) experience fatigue, even while in clinical remission. At present, disease-specific behaviours that maintain or worsen symptom burden including fatigue have not been explored. We developed a questionnaire evaluating IBD-specific avoidance behaviour and investigated how this relates to self-reported fatigue. Methods This study was a close collaboration between the psychology and gastroenterology department of our tertiary referral centre. A 72-item IBD-specific avoidance behaviour questionnaire (IBD-B) was generated based on literature review and input from clinicians and a patient focus group (n = 10). Between July 2018 and March 2019, 500 consecutive IBD patients were included at our infusion unit (wave 1) (participation rate 79%, 48% male, 66% Crohn’s disease (CD), median age 40). Patients completed the 72-item IBD-B, a demographic questionnaire, patient-reported outcome assessing disease activity (PRO2) and a Visual Analogue Scale (VAS) for fatigue. Test–retest reliability was assessed in 89 patients (54% male, 70% CD, median age of 40) who completed the IBD-B, PRO2 and VAS fatigue scale a second time after 4–12 weeks (wave 2). Clinical remission was defined as an abdominal pain score ≤1 and a liquid to very soft stool frequency ≤1.5 in CD patients and as no rectal bleeding and a stool frequency ≤1 in patients with ulcerative colitis (UC). A principal component analysis (PCA) was then used to reduce the number of items and investigate the underlying factor structure of the IBD-B. The predictive value of IBD-specific behaviours for fatigue was finally investigated both cross-sectionally and prospectively. Results At wave 1, 46% and 69% of CD and UC patients, respectively, were in clinical remission. PCA suggested a reduction of the 72-item to a final 25-item IBD-B and a seven-factor solution for use in clinical practice (loading factors >0.5, Table 1). The final 25-item IBD-B showed good psychometric properties. The median (IQR) total IBD-B and fatigue scores were, respectively, 29 (40-20) and 52 (77-25) for patients in clinical remission compared with 38 (48-28) and 74 (87-50) for patients not in clinical remission (both p < 0.01). Both cross-sectional and prospective significant correlations between IBD-B factors and fatigue were demonstrated (Table 2). Conclusion The IBD-B is a valuable tool to accurately measure IBD-specific avoidance behaviour in IBD patients. IBD patients without clinical remission report higher IBD-B values and show a higher correlation between avoidance behaviour and fatigue. Further research should now focus on identifying predictors for fatigue in IBD patients in clinical remission.

The objective of this work is to develop and evaluate experimental approaches with different analytical techniques to measure the permeability, diffusivity, and solubility of water in model coatings. These properties are of primary relevance in studies of coatings for corrosion protection. For water permeation measurements, setups were designed and prepared to facilitate measurements by microcalorimetry, gravimetry, and thermogravimetric analysis. For sorption measurements, films were prepared in various thicknesses to allow a proper analysis with Fourier-transform infrared spectroscopy in transmission mode and gravimetry. Both methods are successful in following water uptake kinetic curves, being complementary in film thickness ranges that can be analyzed. The validity of the permeabilities calculated from permeation measurements is compared to results from group contribution methods and reported values in the literature. Diffusivities were determined using data from the transient region in sorption and permeation measurements, as well as from the steady-state permeation rate and equilibrium solubility in permeation and sorption measurements, respectively.

Quality of care is a very timely topic in medicine. We designed a questionnaire to measure perceived quality of care and to explore areas of improvement.In this prospective study a questionnaire was developed and administered to all patients with inflammatory bowel disease participating in a randomized clinical trial. The questionnaire was based on validated surveys and supplemented with novel, relevant questions. Factors associated with (poor) quality of care were identified.Between October 2016 and January 2017, all 107 patients participating in a randomized controlled trial completed the questionnaire (63% male, 76% ulcerative colitis, median age of 47 years). The median satisfaction score was 9 out of 10. Areas of improvement were that too little attention was paid to the disease impact on family and work, dietary and exercise pattern, daily activities and quality of life. Multivariate analysis showed that clinical remission [5.77 (2.03-16.39), p=0.001] was a predictor of good quality of care.In this large IBD trial bureau, inflammatory bowel disease patients were very satisfied with the quality of care. Domains for quality improvement, such as attention to the impact of IBD on family and work, were identified.

Current study screened additives which could modify the drug release from prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension, without negatively influencing the processability and/or stability of the formulation. Therefore, 11 additives (i.e. emulsifiers, pore-formers and FA-based lubricants) were added in a 20% concentration to a paracetamol/behenic acid formulation. Two additives, Kolliphor® P338 and P407 provided complete drug release in less than 1 h, as their thermoreversible gel formation resulted in a disintegration of the prills. Lower Kolliphor® P338 or P407 concentrations (2.5–10%) resulted in a complete but slower drug release in 24 h as the prills no longer disintegrated and the release mechanism was dominated by pore-formation. Prills with a robust drug release profile (i.e. independent of pH and surfactant concentration of the dissolution medium) were obtained after the addition of ≥5% Kolliphor® P338 or P407 to the FA-based formulation. Based on a 6-month stability study, it was concluded that Kolliphor® P407 was a suitable additive to modify the drug release profile of API/FA suspension-based prills when formulations were stored below 25 °C at low relative humidity.

The healing behavior of a dynamically reversible covalent polymer network with a Tg of 3 °C, based on the reversible Diels-Alder (DA) cycloaddition between furan and maleimide moieties is reported, for both room-temperature and heating-mediated healing. In previous work the dynamic character of the DA cycloaddition reaction in a polymer network was studied, those findings are used to understand its healing ability. The recovery of mechanical properties by intrinsic healing is studied by Dynamic Mechanical Analysis, quantifying the loss in properties due to incurred damage and assessing their recovery with respect to the original material. The DA cycloadduct bonds in the network can be mechanically activated to autonomously heal damage at room temperature if the damage surfaces remain activated. If the damage surfaces are not brought in contact fast enough they reestablish equilibrium (aging) and lose their autonomous healing potential. In the latter case, only heating-mediated healing can occur, reactivating the healing ability. Controlled damage formation and subsequent sealing of the damage of network coatings is monitored by Atomic Force Microscopy and optical microscopy. The repeatability for both mechanical activation, studied by tensile testing, and thermal cycling, studied by Differential Scanning Calorimetry, is reported.

Current study evaluated the processability and characteristics of prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension instead of previously studied API/FA solutions to enlarge the application field of prilling. Metformin hydrochloride (MET) and paracetamol (PAR) were used as model APIs while both the effect of drug load (10–40%) and FA chain length (C14–C22) were evaluated. API/FA suspensions were processable on lab-scale prilling equipment without thermal degradation, nozzle obstruction or sedimentation in function of processing time. The collected prills were spherical (AR ≥ 0.898) with a smooth surface (sphericity ≥ 0.914) and a particle size of ±2.3 mm and 2.4 mm for MET and PAR prills, respectively, independent of drug load and/or FA chain length. In vitro drug release evaluation revealed a faster drug release at higher drug load, higher API water solubility and shorter FA chain length. Solid state characterisation via XRD and Raman spectroscopy showed that API and FA crystallinity was maintained after thermal processing via prilling and during storage. Evaluation of the similarity factor indicated a stable drug release (f2 > 50) from MET and PAR prills after 6 months storage at 25 °C or 40 °C.

SummaryBackground The presence of antibodies towards infliximab (ATI) is associated with lower infliximab (IFX) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease (CD). Aim To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX. Methods A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification. Results Clinical response (physicians' global assessment) and biological response and remission (CRP) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 μg/mL [0.3-3.6] at T0 to 3.6 μg/mL [0.5-10.2] at T+1 (P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r −0.57, P < .0001) and the probability of clinical response (P = 0.034) at T+1. When ATI were quantifiable but

Background Despite improvements in medical therapy, the majority of patients with Crohn's disease still require surgery. The aim of this study was to report safety, and clinical and surgical recurrence rates, including predictors of recurrence, after ileocaecal resection for Crohn's disease. Methods This was a cohort analysis of consecutive patients undergoing a first ileocaecal resection for Crohn's disease between 1998 and 2013 at one of two specialist centres. Anastomotic leak rate and associated risk factors were assessed. Kaplan–Meier estimates were used to describe long-term clinical and surgical recurrence. Univariable and multivariable regression analyses were performed to identify risk factors for both endpoints. Results In total, 538 patients underwent primary ileocaecal resection (40·0 per cent male; median age at surgery 31 (i.q.r. 24–42) years). Median follow-up was 6 (2–9) years. Fifteen of 507 patients (3·0 per cent) developed an anastomotic leak. An ASA fitness grade of III (odds ratio (OR) 4·34, 95 per cent c.i. 1·12 to 16·77; P = 0·033), preoperative antitumour necrosis factor therapy (OR 3·30, 1·09 to 9·99; P = 0·035) and length of resected bowel specimen (OR 1·06, 1·03 to 1·09; P < 0·001) were significant risk factors for anastomotic leak. Rates of clinical recurrence were 17·6, 45·4 and 55·0 per cent after 1, 5 and 10 years respectively. Corresponding rates of requirement for further surgery were 0·6, 6·5 and 19·1 per cent. Smoking (hazard ratio (HR) 1·67, 95 per cent c.i. 1·14 to 2·43; P = 0·008) and a positive microscopic resection margin (HR 2·16, 1·46 to 3·21; P < 0·001) were independent risk factors for clinical recurrence. Microscopic resection margin positivity was also a risk factor for further surgery (HR 2·99, 1·36 to 6·54; P = 0·006). Conclusion Ileocaecal resection achieved durable medium-term remission, but smoking and resection margin positivity were risk factors for recurrence.

Summary Background Data on dose de-escalation in patients with Crohn's disease (CD) are limited. Aim To evaluate outcomes of dose de-escalation from adalimumab (ADM) every other week (EOW) to every three weeks (ETW). Methods We selected patients with CD receiving maintenance therapy with ADM 40 mg ETW with serum levels (SL) available before and after dose de-escalation. Sex- and age-matched controls continuing ADM 40 mg EOW were identified. Patient reported outcome, C-reactive protein (CRP) and serum albumin were collected. Results Out of 898 patients, we identified 40 (11 male, median 37 years) who de-escalated to ADM 40 mg ETW for ADM-related adverse events (AE, n = 1), ADM SL >7 μg/mL (n = 8), or both (n = 31). Compared to controls, ADM SL dropped significantly within 4 months, without associated clinical or biochemical changes. In 53% of patients, dose de-escalation was associated with disappearance of AE (8/16 skin manifestation, 3/6 arthralgia, 5/7 frequent infectious episodes). During a median follow-up of 24 months, 65% of patients maintained clinical response, but 35% needed dose escalation back to ADM 40 mg EOW because of clinical relapse (n = 8), ADM SL

In this work, we introduce single-component self-healing polyurethanes based on reversible maleimide/ furan Diels–Alder reactions with good physical integrity on healing. Diols bearing thermo-reversible furfuryl and maleimide moieties were synthesized by a four-step coupling strategy starting from commercially available 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) and thermo-responsive monoalcohol (with furfuryl or maleimide functions). These diols were reacted in presence of 1,6- hexamethylene diisocyanate and polypropylene glycol (PPG), in order to obtain amorphous polyurethanes with good chain mobility for the self-healing processes (Tg < RT). The cross-linking density, related to the healing process, could be readily tuned with the amount of thermo-responsive moieties as well as the PPG chain length. Swelling test and FTIR spectroscopy confirmed the formation of reversible networks. Qualitative micro-scratch test on thin films indicated tunable healing efficiencies based on the polyurethane composition as a function of the content, the chemical nature of the thermo-responsive moieties (reversible vs. irreversible), the PPG nature (hydroxyl or amino terminated) and chain length. This new structural concept is of great interest for thermally mendable, self-healing and adhesive polyurethanes.

Background Intestinal fibrosis represents a significant complication of inflammatory bowel disease (IBD). An urgent need is present for the identification of pathways and markers involved in fibrogenesis to prevent and intervene with intestinal fibrosis. As intestinal fibrosis mainly occurs in the intestinal deeper layers, mucosal biopsies for studies in intestinal fibrosis are of limited information. Therefore, characterisation of the relative contribution of innate and adaptive immune cells in the mucosa and deeper layers in fibrotic distal ileum of Crohn’s disease (CD) patients was performed. Methods Seventeen CD patients undergoing right hemicolectomy (RHC) for stricturing disease and 6 colorectal cancer (CRC) patients undergoing RHC were recruited. The resected ileum was divided in macroscopically inflamed and fibrotic tissue and single-cell suspensions were made from mucosal and deeper intestinal layers for immune cell characterisation with flow cytometry. For comparison, proximal unaffected CD tissue and control ileum from CRC patients was included. Fibrosis and inflammation were confirmed on HE stained histological sections. Wilcoxon matched-pairs signed-rank test between CD samples and Kruskal–Wallis testing with Dunn’s multiple comparisons test compared with CRC ileum were performed. Results From 12 CD patients, an additional macroscopically inflamed region could be identified next to the fibrotic area, with a decreased fibrosis score as compared with the fibrotic area (4.00 vs. 6.00, p = 0.016) (Figure 1). Both fibrotic and inflamed regions had increased inflammation as compared with proximal unaffected CD and control non-IBD ileum (score: 4.00 and 4.50 vs. 1.00 and 0.00, p < 0.001 for all). In the inflamed ileum, no differences in immune populations were observed between mucosa and deeper layers, reflecting the transmural nature of CD. In contrast, CD19+ B cells were specifically enriched in the mucosa of fibrotic ileum, as compared with proximal CD mucosa (32.20 vs. 20.40% of CD45+ cells, p = 0.008) (Figure 2). In the deeper layers of fibrostenotic CD ileum FcεR+ Siglec 8+ eosinophils (1.13 vs. 1.17 % of CD45+ cells, p = 0.027), mature CD11c+ dendritic cells (3.95 vs. 2.96 % of CD45+ cells, p = 0.042) and M2 CD206+ macrophages (0.35 vs. 0.18% of CD45+ cells, p < 0.001) were enriched as compared with the mucosa overlying the fibrotic tissue (Figure 3). Conclusion These results argue that inflammation in the deeper intestinal layers is different from the inflammatory signature seen in mucosal inflamed regions. We here report alternative innate immune cells expanded specifically in the deeper intestinal layers of fibrostenotic CD ileum that could identify targets for new anti-fibrotic therapies.

Background Obtaining insights in the pathogenesis of intestinal fibrosis is a priority for improving outcomes in inflammatory bowel diseases (IBD). Studies in murine models and human organ fibrosis indicate a role for innate immunity pathways in fibrosis. The aim of this study was to dissect the role of innate lymphoid cells (ILC) in chronic intestinal inflammation and fibrosis. Methods A chronic 3-cycles dextran sulphate sodium (DSS) model was induced in wild-type (WT), recombinant activating gene (RAG)-deficient (lacking adaptive immunity), RAG−/− common γ-chain (ɣc)−/− (lacking ILC) and anti-CD90.2 treated (ILC depleted) C57Bl/6 RAG−/− mice. One cycle of DSS comprised 1 week of DSS administration followed by 2 weeks of recovery with normal drinking water. Colonic lamina propria cells were isolated and CD45+Lineage−CD127+CD90.2+ ILC, Ly6C+ monocytes and Ly6G+ neutrophils were identified after staining by flow cytometry. Inflammation and fibrosis were scored by macroscopic and HE and Martius Scarlet Blue staining and fibrosis was evaluated by hydroxyproline quantification. For analysis Kruskal–Wallis testing with multiple Dunn’s comparisons was performed. Results In RAG-1−/− mice chronic inflammation and fibrosis developed similarly as in WT mice, with elevated KLRG-1+ ILC2 (68.90 vs. 48.00% of ILC, p = 0.012) after repeated DSS exposure as compared with control mice (Figure 1). Chronic colitis could also be induced in RAG−/−ɣc−/− or ILC depleted RAG−/− mice (ILC: 0.99 vs. 25.70% of CD45+ cells, p = 0.029), with no attenuation of fibrosis (p > 0.99) as compared with chronic DSS exposed RAG-1−/− mice despite the absence of ILC (Figure 2). Colon length decrease was more pronounced in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS colitis (7.15 vs. 8.30 cm, p = 0.046), while hydroxyproline levels and thickness of mucosa and muscularis propria were not different in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS. Moreover, after the second cycle of DSS a slower recovery of weight was seen in RAG−/−yc−/− mice as compared with RAG-1−/− mice (d31: 88.64 vs. 111.0% of initial weight, p < 0.001; d35 p = 0.001; d39 p = 0.006 and d42 p = 0.002) (Figure 3). In absence of ILC, RAG−/−yc−/− mice increased lamina propria neutrophils (19.10 vs. 5.91% of CD45+ cells, p = 0.004) and monocytes (11.80 vs. 3.25% of CD45+ cells, p = 0.004) may represent an alternative source of inflammation. Conclusion These data argue against a pro-fibrotic role of ILC in the induction of fibrosis in chronic DSS colitis, and suggest a protective and recovery-enhancing role of ILC after repeated intestinal injury.

SummaryBackground The long-term efficacy of infliximab in patients with Crohn's disease is suboptimal. Aim To study prognostic factors for real-life long-term effcacy of infliximab in Crohn's disease. Methods All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient- and disease-related factors were used to identify independent predictors of infliximab failure-free survival using Cox proportional hazards regression. Results Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4–4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year infliximab failure-free survival was 65.9% (95% CI 58.3–73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2–5.2), P = 0.02), L1 disease location [HR 2.0 (1.1–3.5), P = 0.02], prior anti-TNF use [HR 2.3 (1.1–4.8), P = 0.03], haemoglobin

BACKGROUND: Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti‐fibrotic therapies are available; however, several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD. AIM: To standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Chron's disease. METHODS: An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting. RESULTS: Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre‐stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naive small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post‐prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24‐48 weeks is considered the appropriate endpoint in pharmacological trials. CONCLUSIONS: Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.

The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting.To assess the efficacy and safety of anti-TNF therapy in elderly patients taking into account eventual comorbidity.Observational and retrospective single-centred study where 66 IBD patients initiating anti-TNF treatment at age ≥65 years (cases: ≥65 anti-TNF) were compared with 112 IBD patients initiating anti-TNF65 years (controls65 anti-TNF) and 61 anti-TNF naïve IBD patients treated with immunosuppressants (IMS) and/or corticosteroids (CS) ≥65 years (controls ≥65 IMS/CS). Controls were matched to cases for IBD type, follow-up, disease duration and anti-TNF type. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Both efficacy and safety of treatment were adjusted for comorbidity.The short-term clinical response to anti-TNF at 10 weeks was significantly lower in cases: ≥65 anti-TNF (68% vs. 89%; P0.001), whereas at ≥6 months, differences were not significant (79.5% vs. 82.8%; P = 0.639). The risk for any severe adverse events was higher in cases: ≥65 anti-TNF than in controls65 anti-TNF (RR = 4.7; P0.001) or controls ≥65 IMS/CS (RR = 3.09; P = 0.0008). Age older than 65 and CCI0 were independent risk factors for malignancy and mortality regardless of the medication.Elderly patients treated with anti-TNF have a lower rate of short-term clinical response and a higher rate of severe adverse events than the younger patients under the same treatment.

Using the advanced thermal analysis technique of fast scanning chip calorimetry, an isothermal crystallization study was undertaken on poly(3-hexyl thiophene) (P3HT), a workhorse material for organic photovoltaics (OPVs). As a model system, poly(butylene terephthalate) (PBT), a polyester with similar transition temperatures was first analyzed. By using gold foil as a substrate, it was possible to perform this study on thin layers, making the results more applicable for actual OPVs, where thin layers are used for charge generation. Using heating and cooling rates of 30 000 K s−1, all non-isothermal processes could be avoided, and the evolution of isothermally formed crystals could be analyzed. The bell-shaped curve of crystallization rate as a function of isothermal crystallization temperature was constructed for a ca. 550 nm thin P3HT layer.

Vease contenido relacionado en DOI: http://dx.doi.org/10.1016/j.crohns.2012.09.002 Este articulo es una traduccion del articulo publicado en Journal of Crohn’s and Colitis, Vol. 6, Dignass A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management, 991-1030 © 2012 European Crohn’s and Colitis Organisation. Publicado por Elsevier B.V. Todos los derechos reservados. http://dx.doi.org/10.1016/j.crohns.2012.09.002 Citar este articulo como: Dignass A, et al., Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management, Journal of Crohn’s and Colitis (2012), http://dx.doi.org/10.1016/j.crohns.2012.09.002 ∗ Autor para correspondencia. Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, Alemania. Telefono: +49 69 95332201; fax: +49 69 95332291. ∗∗ Autor para correspondencia. Division of Gastroenterology, Department of Medicine, MtSinai Hospital and University Health Network; University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5. Correos electronicos: axel.dignass@fdk.info (A. Dignass), gvanassche@mtsinai.on.ca (G. van Assche). ♦ La afiliacion en nombre de la ECCO puede encontrarse en el anexo 1 al final del manuscrito.

Vease contenido relacionado en DOI: http://dx.doi.org/10.1016/j.crohns.2012.09.005 Este articulo es una traduccion del articulo publicado en Journal of Crohn’s and Colitis, Vol. 6, Dignass A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations, 1-33 © 2012 European Crohn’s and Colitis Organisation. Publicado por Elsevier B.V. Todos los derechos reservados. http://dx.doi.org/10.1016/j.crohns.2012.09.005 Citar este articulo como: Dignass A, et al., Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations, Journal of Crohn’s and Colitis (2012), http://dx.doi.org/10.1016/j.crohns.2012.09.005 ∗ Autor para correspondencia. Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network, University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5. ∗∗ Autor para correspondencia. Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, Alemania. Correos electronicos: gvanassche@mtsinai.on.ca (G. van Assche), axel.dignass@fdk.info (A. Dignass). ♦ La afiliacion a nombre de la ECCO puede encontrarse en el anexo 1, al final del manuscrito.

SummaryBackground Adalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail. Aim To update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs). Methods Treatment-emergent adverse events (AEs; first dose to 70 days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.1). Rates were assessed as events/100 (E/100 PYs). Results The database (16 trials; CD, N = 3606; UC, N = 1739) represented 4145 and 3397 PYs of exposure, respectively. For CD, incidences of any AEs with adalimumab were 60.8%-65.1%, depending on dose, and 71.5% with placebo; for UC, the incidences were 53.5%-54.8% and 56.1%, respectively. Rates of any AEs (CD, 605 E/100 PYs; UC, 361 E/100 PYs), serious AEs (CD, 36.1 E/100 PYs; UC, 18.9 E/100 PYs), and malignancies (CD, 1.2 E/100 PYs; UC, 1.0 E/100 PYs) were similar between current and prior analyses. Apparent rate of opportunistic infections was lowered to 0.3 and 0.2 E/100 PYs for CD and UC, respectively, by recent MedDRA changes excluding oral candidiasis and tuberculosis. Standardised incidence ratios for malignancies were similar to the general population (CD, 1.45 [95% CI, 0.90-2.22]; UC, 1.36 [95% CI, 0.84-2.07]). Demyelinating disorders were uncommon (CD, 0.1 E/100 PYs; UC

The equilibrium and kinetics of the furan-maleimide Diels-Alder (DA) reaction for the formation of a reversible network were studied by calorimetry between 25 °C and 90 °C using an amorphous bismaleimide eliminating solvent use. The relationship between the equilibrium conversion xeq with temperature and the effect of dilution were simulated. The glass transition-conversion relationship of the reversible network was established. The thermophysical properties of the reversible network were linked to the kinetics and equilibrium of the DA system, and studied by dynamic mechanical analysis (DMA), dielectric analysis (DEA) and rheometry. Below Tg the reversible network behaves like an irreversible network; however, above Tg, a decrease in the rubber tensile storage modulus was observed due to a reduction of cross-link density caused by the retro DA reaction. DEA revealed that above Tg, an interface is formed between released bismaleimide molecules and the remaining network. The rheological behavior is related to xeq and the lifetime of the reversible covalent bonds. When xeq is higher than the gelation conversion xgel (below 90 °C), the system gels at constant xgel. An elastic strengthening effect is observed in a transition region between 90 °C and 115 °C. Above 115 °C the system is reaching a viscous melt behavior. These observations are important for the application of this network as a self-healing material and as a recyclable elastomer or thermoset.

AIM Surgery for ileal pouch-anal anastomosis (IPAA) has evolved over time, especially since the introduction of laparoscopy. The aim of this retrospective study was to report the impact of surgical evolution on outcome over a period of 25 years. METHOD All patients who had IPAA surgery for ulcerative colitis from 1990 to 2015 at the University Hospitals of Leuven were included. Patients were divided into three period arms (period A 1990-1999; period B 2000-2009; period C 2010-2015). The main outcome measure was anastomotic leakage. RESULTS A total of 335 patients (58.8% male) with a median age of 39 years (interquartile range 32-49 years) at surgery were included. Median follow-up was 5 years (interquartile range 2-10 years). Overall anastomotic leakage (grades A-C) was 14.9%. A significant decrease in leakage rate was observed over time (from 21.4% in period A to 12.1% in period B to 10.0% in period C; P = 0.04). The defunctioning ileostomy rate at the time of pouch construction decreased from 91.7% (period A) to 40.3% (period B) to 11.1% (period C) (P

A combination of fast scanning chip calorimetry and X-ray ptychography is explored to study the effects of thermal annealing on the active layer of bulk heterojunction organic photovoltaics. The well-known P3HT/PC 61 BM 1:1 system is investigated as a test case. By using a custom chip calorimetry setup, it is possible to give a thermal treatment at 127 °C (400 K) to P3HT/PC 61 BM 1:1 thin layers, using a heating and cooling rate of 30000 K s −1 , after which the resulting morphology is investigated with X-ray ptychography. Applying only heating and cooling, without isothermal annealing, yields a featureless morphology. This corresponds well with thermal data which indicate a mixed amorphous phase only. For increasing isothermal annealing times, a well-defined morphology appears with increasing domain size, corresponding to the formation of an endothermal melting trajectory. This melting trajectory is expected to consist of both eutectic melting and melting of coarsened crystals. In contrast to chip calorimetry results, large domain sizes are obtained for heating and cooling without isothermal annealing at a conventional rate of 20 K min −1 . This initial morphology then develops further with increased isothermal annealing. The combination of chip calorimetry and ptychography allows separating the effects of each single thermal step on morphology development.

To increase the durability and reliability of thermosets, self-healing via a vascular network, is developed. A judicious choice of healing agents proves to be necessary to achieve the best recovery of properties. Four low viscosity two-component epoxy-amine healing systems were compared, to check which glass transition temperature range would be best to recover mechanical properties (T g ranging from −8 to 68 °C). Interdiffusion experiments show that all systems react sufficiently slowly at room temperature to allow interdiffusion of epoxy and amine over more than 1 mm before the diffusion is stopped by vitrification. Swelling tests revealed that most of the selected healing agents diffuse into the surrounding matrix and swell it. This might be beneficial for crack closure and improved adhesion between healing system and matrix. Flexural tests demonstrated that, the higher the glass transition temperature of the fully cured healing system, the higher the healing capability.

SummaryBackground Data for adalimumab in ulcerative colitis after prior use of infliximab are scarce. Aims To study adalimumab response rates and predictors of response in ulcerative colitis, including drug concentrations. Methods In this single centre cohort study 73 UC patients, previously exposed to infliximab, were assessed for response to adalimumab at weeks 12 and 52. Serum samples prior to week 12 were available and included in multivariate analysis to predict response. Results Overall clinical response at week 12 and 52 were 75% and 52%, respectively. Adalimumab was continued without need for dose escalation throughout year 1 in 16 patients, 22 needed dose escalation and 35 discontinued treatment within 1 year. Prior response to infliximab and early serum concentrations correlated with response. Receiver operator characteristic curve analysis yielded optimal adalimumab concentrations of 4.58 μg/mL for week 12 and 7.0 μg/mL for week 52. Independent predictors for response at week 12 were primary response to infliximab [odds ratio (OR) 8.33; 95% confidence interval (CI) 1.8–33.3; P = 0.006] and an adalimumab concentration ≥4.58 μg/mL at week 4 (OR 4.85; 95% CI 1.3–18.6; P = 0.009). Positive predictors for week 52 response were primary response to infliximab (OR 5.2; 95% CI 1.14–23.8; P = 0.034) and adalimumab concentration at week 4 of ≥7 μg/mL (OR 3.56; 95% CI 1.17–10.79; P = 0.025). Conclusion Prior response to infliximab and high early adalimumab serum concentrations predict week 12 and year 1 responses to adalimumab in ulcerative colitis.

Este articulo es una traduccion del articulo publicado en Journal of Crohn’s and Colitis, Vol. 6, Dignass A, et al. Second European evidence-based Consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis, 965--990 © 2012 European Crohn’s and Colitis Organisation. Publicado por Elsevier B.V. Todos los derechos reservados. http://dx.doi.org/10.1016/j.crohns.2012.09.003 Citar este articulo como: Dignass A, et al., Second EUROPEAN evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis, Journal of Crohn’s and Colitis (2012), http://dx.doi.org/10.1016/j.crohns.2012.09.003 ∗ Autor para correspondencia. Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, Alemania. Telefono: +49 69 95332201; fax: +49 69 95332291. ∗∗ Autor para correspondencia. Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network; University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5. Correos electronicos: axel.dignass@fdk.info (A. Dignass), gvanassche@mtsinai.on.ca (G. van Assche). ♦ La afiliacion en nombre de la ECCO puede encontrarse en el anexo 1 al final del manuscrito. Definiciones

The interface between donor and acceptor material in organic photovoltaics is of major importance for the functioning of such devices. In this work, the singlet excitation schemes of six polymers used in organic photovoltaics (P3HT, MDMO-PPV, PCDTBT, PCPDTBT, APFO3 and TBDTTPD) at the interface with a PCBM acceptor were studied using TDDFT in combination with the range-separated CAM-B3LYP exchange–correlation functional. By comparing with the excitations in the pure polymer and analyzing the excitation intensities and a measure for orbital overlap, it was possible to identify excitations as either excitation of the polymer or as a charge transfer between donor and acceptor. By combining orbital overlaps between the molecular orbitals involved in charge transfer and the intensity of the polymer excitation a broad correlation was seen with the record efficiencies found in the literature.