Abstract
Background
Recently, the European Crohn’s and Colitis Organisation (ECCO) Consensus on Quality-of-Care (QoC) Standards proposed essential criteria on the structure of units who manage ...patients with inflammatory bowel disease (IBD)1. The E-QUALITY taskforce investigated whether there is a gap between the given recommendations and the real-world structure of IBD units across ECCO-affiliated countries.
Methods
The E-QUALITY task force developed a web survey accessible to all institutions affiliated to ECCO across Europe. Each institution was invited by email to participate. Only one delegate per institution was requested to respond to the 48 questions listed in the web questionnaire. A descriptive analysis was done.
Results
Data were collected from September 2022 to December 2022. One-hundred nineteen institutions from 24 countries responded (Figure 1). Characteristics of the institutions are shown in Figure 2. Overall, 80 (67%) institutions identified their hospital as an IBD Unit, 75 (63%) had identified IBD sub-specialists (4 on average per hospital), 66 (55%) had a dedicated IBD nurse, 69 (58%) had an IBD surgeon, and 92 (77%) had a referral pathway for complex IBD surgery. In 81 (68%) institutions there was a regular MDT discussion of IBD cases. The multidisciplinary team (MDT) included at least one pathologist in 80 (67%) institutions, a radiologist in 86 (72%), a dietitian in 69 (58%), and a stoma specialist in 79 (66%). In 107 (90%) institutions, timely access to another sub-specialist (i.e., dermatologist, rheumatologist) was provided. Paediatric-to-adult transition clinics were available in 66 (55%) institutions. In 77 (64%) institutions, departmental IBD management guidelines were reported however, only 56 (47%) developed and applied quality indicators. Almost all institutions (113, 95%) provide direct contact to patients, mainly by telephone and email, and 105 (88%) provide remote follow-up to their IBD patients. In 111 (93%) institutions, there were facilities to administer intravenous therapies, 103 (86%) had an integrated hospital emergency department, 107 (90%) had inpatient admission rights, and 86 (82%) defined a pathway for early recognition of flares. Collaboration with patients’ associations was present in 99 (83%) of institutions, and a patient database was available in 88 (74%). Lack of dedicated funds, protected time and shortage of personnel were regarded as the three main challenges to achieving and maintaining QoC.
Conclusion
Our survey has revealed that the structure of IBD units across Europe seems to be consistent with the ECCO standards, although some gaps still exist. ECCO will improve programs and initiatives to help institutions provide standard QoC across countries.
References:
1. Fiorino G, Lytras T, Younge L, et al. Quality of care standards in inflammatory bowel diseases: A european crohn's and colitis organisation ecco position paper. Journal of Crohn's & colitis 2020;14:1037-48.
Leaching using EDTA applied to a Pb, Zn and Cd polluted soil significantly reduced soil metal concentrations and the pool of metals in labile soil fractions. Metal mobility (Toxicity Characteristic ...Leaching Procedure), phytoavailability (diethylenetriaminepentaacetic acid extraction) and human oral-bioavailability (Physiologically Based Extraction Test) were reduced by 85–92%, 68–91% and 88–95%, respectively. The metal accumulation capacity of the terrestrial isopod
Porcellio scaber (Crustacea) was used as in vivo assay of metal bioavailability, before and after soil remediation. After feeding on metal contaminated soil for two weeks,
P. scaber accumulated Pb, Zn and Cd in a concentration dependent manner. The amounts of accumulated metals were, however, higher than expected on the basis of extraction (in vitro) tests. The combined results of chemical extractions and the in vivo test with
P. scaber provide a more relevant picture of the availability stripping of metals after soil remediation.
Bioaccumulation tests with
Porcellio scaber isopods are proposed as a supplement to chemical extraction in assessing metal bioavailability before and after soil remediation.
Abstract
Background
From the PURSUIT programme, it is known that golimumab (GLM) trough concentrations (TC) >2.5 mg/l at week (w)6 of induction therapy are associated with clinical response in ...patients with ulcerative colitis (UC).1 No TC threshold has been established for mucosal healing (MH; Mayo endoscopic score ≤1). A population pharmacokinetic (popPK) model may support dose optimisation to improve attainment of a predefined TC target.
Methods
GLM concentration–time data of 56 patients with UC (335 venepuncture and 296 dried bloodspot (DBS) samples) were obtained from 2 study centres (University Hospitals Leuven, Belgium and Ljubljana University Medical Centre, Slovenia).2,3 A popPK model was developed using NONMEM 7.4. Exposure during GLM induction therapy was linked to MH at w14.
Results
A two-compartment popPK model with linear absorption and elimination showed good predictive capacity (Figure 1A). The estimated popPK parameters (typical value %RSE) were absorption constant (0.511 day−1 8%), apparent clearance CL/F (0.407 l/day 6%), volume of distribution in the central compartment (9.16 l 5%) and peripheral compartment Vp/F (3.21 l 22%) and inter-compartmental clearance (0.464 l/day 13%). Antibodies to GLM and higher alkaline phosphatase increased GLM CL/F, while prior biological use was associated with a larger Vp/F, all predicting lower GLM exposure. Still, 48% and 147% of the interindividual variability (IIV) on CL/F and Vp/F remained unexplained. A total of 14/40 patients (35%, 16/56 no endoscopy data available) achieved MH after GLM induction therapy. These patients had higher model-predicted GLM TC at w6 (median 7.6 mg/l, interquartile range 5.8–8.0) compared with patients not achieving MH (4.7 mg/l 3.3–6.8) (p = 0.005). A GLM TC threshold at w6 >7.4 mg/l predicted MH (Figure 1B). In addition, the estimated area under the GLM concentration–time curve (AUC) from w0 to w6 was higher when MH was achieved (p = 0.010).
Conclusions
With the currently approved induction dosing of GLM, only 10/40 (25%) reached the proposed 7.4 mg/l TC target at w6, suggesting underexposure in a substantial proportion of patients. This popPK model shows good predictive capacity and may be implemented in a therapeutic drug monitoring software tool to allow better targeting of the here established exposure targets (TC and AUC) in individual patients. Still, Bayesian updating of individuals’ PK parameters using early DBS samples is recommended given the remaining large IIV.
(A) Prediction-corrected visual predictive check. (B) Density plot and receiver-operating characteristic (ROC) curve of pGLM TC at w6 as a predictor of MH at w14.
References
1. Adedokun OJ, Xu Z, Marano CW, et al. Pharmacokinetics and exposure–response relationship of golimumab in patients with moderately-to-severely active ulcerative colitis: results from Phase 2/3 PURSUIT induction and maintenance studies. J Crohns Colitis 2017;11:35–46.
2. Detrez I, Dreesen E, Van Assche G, et al. Golimumab dried blood spot analysis (GOUDA): A prospective trial to validate golimumab concentration analysis using the dried blood spot methodology. Inflamm Bowel Dis 2018; P431.
3. Stefanovic S, Detrez I, Compernolle G, et al. Trough levels of golimumab at Week 6 predict drug retention rate in ulcerative colitis. Inflamm Bowel Dis 2018; P632.
Abstract
Background
To facilitate personalised treatment of inflammatory bowel disease (IBD), biomarkers for disease entity and disease severity in easily accessible samples are required. Therefore, ...we aimed to (i) identify proteins that discriminate Crohn’s disease (CD) from ulcerative colitis (UC), (ii) assess the association of proteomic profiles with disease severity and (iii) assess the potential to use serum samples as a proxy for intestinal biopsies.
Methods
In this prospective cross-sectional study, IBD patients with active endoscopic disease (presence of ≥1 ulcer (CD) or Mayo score ≥1 (UC)) and age matched non IBD controls (normal endoscopy) were included. In IBD, biopsies were taken from inflamed tissue; in CD from the edge of an ulcer and in UC and controls between 20 and 25 cm from the anal verge. Disease severity was dichotomised in mild vs. severe defined as SES CD <10 vs. ≥11 in CD and Mayo endoscopy score 1/2 vs. 3 in UC. Ninety-two inflammatory proteins were measured in biopsies and serum using a proximity extension assay (OLINK). The elastic net algorithm was used to select proteins associated with disease severity. Multiplicity adjustments were done using the Benjamini–Hochberg approach.
Results
Forty-one CD, 39 UC and 10 controls were included. Median SES-CD score IQR was 9 7–16 in CD. In UC, 20 (51.3%), 15 (38.5%) and 4 (10.3%) patients had an endoscopic Mayo score of 3, 2 and 1, respectively. Three proteins differed significantly between UC and CD in tissue (IL-17A, IL13 and CCL4). However, this was not reflected in serum levels of these molecules. For prediction of disease severity in CD, elastic net regression identified a set of 11 serum proteins that discriminated mild from severe disease (accuracy 0.667). Top five proteins were IFNγ (OR 3.03), CCL23 (OR 1.28), Cystatin D (OR 0.61), TNF (OR 1.28) and HGF (OR 1.17) (Figure 1). In tissue, no discriminatory profile was identified. Conversely, in serum of UC, no proteins were selected, while a set of three tissue proteins was associated with disease severity (accuracy 0.725). These proteins were osteoprotegerin (OPG) (OR 1.66), IL8 (OR 1.09) and CCL25 (OR 0.97). The discrepancy between serum and tissue was further supported by correlation analyses. Of all 92 proteins, only three showed significant correlation between tissue and serum: IL17A (r = 0.44), TGF-α (r = 0.42) and IL6 (r = 0.39).
Conclusion
Proteomic profiles between tissue and serum in active IBD correlated poorly. Only in CD, serum markers differentiated mild from severe disease. In UC, no proteins in serum were selected whereas in tissue, expression of OPG, IL-8 and CCL25 was associated with disease severity. These data again emphasise the difference between CD and UC on a molecular level.
Abstract
Background
Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease affecting skin that bears apocrine glands and is characterised by painful, deep-seated, inflamed ...lesions. Treatment includes antibiotics, steroids, surgery, and adalimumab as the only approved biological agent. An association between inflammatory bowel disease (IBD) and HS has been reported, but very limited evidence exists on the efficacy of non-anti-TNF biological agents for the treatment of HS in IBD patients.
Methods
This multicenter case series was performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project by ECCO. Cases of patients with HS and IBD treated with non-anti-TNF biological agents were retrospectively collected through a standardised collection form. Efficacy measures were reported by the local gastroenterologist/dermatologist using physician global assessment (PGA).
Results
Fifty-five patients (65.5% women, median IQR age 40.0 33.1-47.6 years, 50.9% active smokers) were identified (Table 1), all with HS diagnosis confirmed by a dermatologist. We observed a strong CD predominance (90.9%) in the current cohort. HS affected mainly the inguinal (82.0%) and axillary (76.0%) regions, followed by the anogenital region (46.0%). In 42 patients, HS was diagnosed a median of 10.0 4.3-16.4 years after the IBD diagnosis, whereas in 13 HS preceded the IBD diagnosis by 4.1 2.2-5.4 years. Prior to initiating a non-anti-TNF biological agent, all patients had been exposed to at least 1 anti-TNF agent, including (high dose) adalimumab in 83.2% of the cases. In 20% of patients, HS developed while being treated with an anti-TNF agent. After anti-TNF failure (for either IBD and/or HS), physicians opted for ustekinumab (83.6%), vedolizumab (14.5%), or risankizumab (1.8%) as the preferred first non-anti-TNF agent. During ustekinumab treatment (n=46, median time on therapy 2.1 0.8-3.3 years)), 76.1% showed a clinically relevant HS improvement (including 50.0% complete remission), whereas 23.9% did not experience any benefit. With vedolizumab (n=8), 37.5% experienced some benefit (including 25.0% with complete remission), while 62.5% did not report any improvement. The single patient on risankizumab had complete remission. Finally, 6 out of 8 vedolizumab-treated patients were ultimately treated with ustekinumab, reporting a clinical benefit in 5 out of 6.
Conclusion
Ustekinumab is the preferred biological agent after anti-TNF failure in IBD patients with concomitant HS. Although placebo-controlled trials are lacking and ustekinumab is not approved for the treatment of HS, the current multi-centre case series demonstrates a substantial benefit in 78.4% of patients.
A method is described for assessing the effects of metals on the food consumption rate of isopods from measurements of fecal production. The effects of zinc in the diets of two isopod species,
...Porcellio scaber and
Oniscus asellus, were tested. The metal was fed to the isopods on leaves of field maple (
Acer campestre) contaminated with concentrations ranging between 1000 and 10,000 μg Zn g
−1 leaf dry wt. Significant reductions in feeding rates were observed of the highest concentrations of zinc. The test employed in this study is quick, cheap, and relevant for estimating sublethal effects of metals on isopods.
The purpose of this work is to provide experimental evidence on the interactions of suspended nanoparticles with artificial or biological membranes and to assess the possibility of suspended ...nanoparticles interacting with the lipid component of biological membranes.
1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid vesicles and human red blood cells were incubated in suspensions of magnetic bare cobalt ferrite (CoFe2O4) or citric acid (CA)-adsorbed CoFe2O4 nanoparticles dispersed in phosphate-buffered saline and glucose solution. The stability of POPC giant unilamellar vesicles after incubation in the tested nanoparticle suspensions was assessed by phase-contrast light microscopy and analyzed with computer-aided imaging. Structural changes in the POPC multilamellar vesicles were assessed by small angle X-ray scattering, and the shape transformation of red blood cells after incubation in tested suspensions of nanoparticles was observed using scanning electron microscopy and sedimentation, agglutination, and hemolysis assays.
Artificial lipid membranes were disturbed more by CA-adsorbed CoFe2O4 nanoparticle suspensions than by bare CoFe2O4 nanoparticle suspensions. CA-adsorbed CoFe2O4-CA nanoparticles caused more significant shape transformation in red blood cells than bare CoFe2O4 nanoparticles.
Consistent with their smaller sized agglomerates, CA-adsorbed CoFe2O4 nanoparticles demonstrate more pronounced effects on artificial and biological membranes. Larger agglomerates of nanoparticles were confirmed to be reactive against lipid membranes and thus not acceptable for use with red blood cells. This finding is significant with respect to the efficient and safe application of nanoparticles as medicinal agents.
Abstract
Background
IBD patients treated with infliximab (IFX) develop drug-induced skin lesions in 20–30%. The impact of IFX-induced skin lesions on quality of life (QoL) is unknown.
Methods
In this ...prospective cross-sectional observational study all adult IBD patients on IFX maintenance treatment at our tertiary referral centre were enrolled. Patients with IFX-induced skin lesions were identified and referred to a dermatologist. All skin lesions were documented by photography. Patients filled in a questionnaire on QoL combining The Chronic Urticaria Quality of Life Questionnaire and Dermatology life quality index. The impact of skin lesion on QoL was rated with a score from 1 to 5. Scores >2.5 were considered to have an important impact.
Results
From January to March 2018, 171 patients, aged 20 to 78 years, on IFX maintenance treatment (55.6% men) were included in the study. IFX-induced skin lesions were identified in 40 patients (23.4%): among them eczema (45%), psoriasis (20%), xerosis (10%) and others (25%). Twenty-one patients (52.2%) had skin lesions for more than half a year. Skin lesions did not have an important impact on any of the studied domains (Figure 1).
Conclusions
In our study, we confirmed the high incidence of infliximab-induced skin lesions. However, the new finding is that the impact of these lesions on quality of life is not great.
Abstract
Background
Skin lesions induced by infliximab are an important side effect and lead to drug discontinuation in many cases. It is not known whether these lesions occur more often with ...high-dose treatment or high drug concentrations that are needed to induce and maintain remission of IBD in some patients. We thus investigated whether high-dose infliximab treatment or high trough levels increase the incidence of skin lesions.
Methods
This was a prospective observational cross-sectional study of all patients with IBD on infliximab maintenance treatment at a tertiary referral centre. Every patient’s skin was examined by an experienced gastroenterologist and those with skin lesions were referred to a dermatologist for further evaluation. Furthermore, infliximab trough levels were measured and the dose of infliximab recorded in all patients. High-dose infliximab was defined as a maintenance dose of ≥10 mg/kg q 8 weeks and high trough levels as ≥7 µg/ml.
Results
In total, we included 171 patients (103 CD, 63 UC, 5 IBD-unclassified). Skin lesions were observed in 40/171 (23%) patients (8 psoriatic, 7 psoriasiform eczema, 11 eczema, 4 xerosis, 10 others). Among patients on high-dose infliximab the incidence of skin lesions was not higher than in those with lower dose (9/53 17% vs. 31/118 26%, p = 0.184). Similar was observed for patients with high vs. low trough levels (22/102 22% vs. 18/69 26%, p = 0.493). Moreover, the median dose of administered infliximab was not different in patients with skin lesions compared with those without them (7.45 mg/kg q 8 weeks IQR (interquartile range): 5.71–9.91 vs. 7.85 mg/kg q 8 weeks IQR: 5.88-10.98, p = 0.741); the same was observed for median trough levels (7.46 µg/ml IQR: 4.44–9.69 vs. 8.60 µg/ml IQR: 5.48-12.00, p = 0.389). Finally, no differences were observed for specific skin lesions (Figures 1&2).
Figure 1.
Figure 2.
Conclusions
In this prospective study, high-dose infliximab treatment or high infliximab trough levels were not associated with the occurrence of drug-induced skin lesions. This is a clinically important observation that enables the use of high-dose infliximab maintenance and targeting high trough levels when needed.
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