The effect of induction therapy with infliximab or vedolizumab on hepcidin and iron status in patients with Inflammatory Bowel Disease

Background Differentiating absolute iron deficiency from functional iron restriction is challenging in active Inflammatory Bowel Disease (IBD). Hepcidin, the systemic iron regulator, could be the key in the diagnosis and management of absolute iron deficiency. In this study, we assessed hepcidin as a diagnostic iron deficiency marker and we explored the relationship between hepcidin, inflammation, hypoxia, and iron deficiency in patients receiving induction therapy with infliximab (IFX) or vedolizumab (VEDO). Methods 130 patients with IBD, who received induction therapy with IFX or VEDO for active disease, were included in this study. Clinical and biochemical data were extracted from medical records. Serum samples at baseline and week 6 of induction therapy were retrieved from the University Medical Center Groningen (UMCG) biobank and analysed for: hepcidin, inflammation (e.g., interleukins [IL] 6, 10, and Tumour Necrosis Factor-α [TNFα]), oxidative stress (free thiols), and hypoxia (e.g., erythropoietin [EPO], Macrophage Inflammatory Protein-3α [MIP3α]). For comparison, serum samples from 50 age- and gender-matched healthy controls were obtained from pre-donation biobank at the UMCG. Response to therapy was defined by either General Physician’s Assessment at week 14 of induction therapy, normalisation or at least a three-point decrease in clinical scores: Harvey-Bradshaw Index (HBI) for Crohn’s Disease, Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis. Results Hepcidin correlated with ferritin and sTfR/log ferritin index [ρ = 0.74 and ρ = -0.79, respectively; P<0.001 for both markers], while inflammation- and hypoxia-associated markers showed only marginal correlations. Hepcidin accurately identified absolute iron deficiency: AUC(hepcidin) = 0.89 [95% CI: 0.82–0.95; P<0.001]. Induction with either IFX or VEDO decreased hepcidin [13.5 ng/mL vs. 9.5 ng/mL; P<0.001], ferritin [45.5 ug/L vs. 37.0 ug/L, P<0.05], and inflammatory markers at week 6, while transferrin increased [2.4 g/L vs. 2.5 g/L, P<0.001]. In total, 75.4% of patients responded to the induction therapy. Hepcidin and ferritin decreased, while transferrin increased (P<0.001 for all changes) in patients who responded to the therapy. In addition, hypoxia (EPO and MIP3α) and inflammatory markers such as faecal calprotectin, IL-6, IL-22, and TNFα improved significantly. In contrast, none of these improvements were observed in patients who did not respond to the therapy. Conclusion Hepcidin reflects iron deficiency in active IBD, but inflammation masks the severity of the deficiency. Induction therapy with either IFX or VEDO modulates hepcidin and iron indices, especially in patients who respond to the therapy

Children with language delay referred to Dutch speech and hearing centres: caseload characteristics

Background: Early detection and remediation of language disorders are important in helping children to establish appropriate communicative and social behaviour and acquire additional information about the world through the use of language. In the Netherlands, children with (a suspicion of) language disorders are referred to speech and hearing centres for multidisciplinary assessment. Reliable data are needed on the nature of language disorders, as well as the age and source of referral, and the effects of cultural and socioeconomic profiles of the population served in order to plan speech and language therapy service provision. Aims: To provide a detailed description of caseload characteristics of children referred with a possible language disorder by generating more understanding of factors that might influence early identification. Methods & Procedures: A database of 11,450 children was analysed consisting of data on children, aged 2–7 years (70% boys, 30% girls), visiting Dutch speech and hearing centres. The factors analysed were age of referral, ratio of boys to girls, mono- and bilingualism, nature of the language delay, and language profile of the children. Outcomes & Results: Results revealed an age bias in the referral of children with language disorders. On average, boys were referred 5 months earlier than girls, and monolingual children were referred 3 months earlier than bilingual children. In addition, bilingual children seemed to have more complex problems at referral than monolingual children. They more often had both a disorder in both receptive and expressive language, and a language disorder with additional (developmental) problems. Conclusions & Implications: This study revealed a bias in age of referral of young children with language disorders. The results implicate the need for objective language screening instruments and the need to increase the awareness of staff in primary child healthcare of red flags in language development of girls and multilingual children aiming at earlier identification of language disorders in these children. What this paper adds What is already known on the subject Identifying language disorders before children enter school can foster the initiation of early interventions before these problems interfere with formal education and behavioural adjustment. Information on caseload characteristics is important to plan speech and language therapy service provision. There are only a few studies on the caseload characteristics of children at first referral for language assessment. What this paper adds to existing knowle

Disease activity in inflammatory bowel disease patients is associated with increased liver fat content and liver fibrosis during follow-up

Purpose Liver steatosis is a frequently reported condition in patients with inflammatory bowel disease (IBD). Different factors, both metabolic and IBD-associated, are believed to contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis and fibrosis in IBD patients and to evaluate which factors influence changes in steatosis and fibrosis during follow-up. Methods From June 2017 to February 2018, demographic and biochemical data was collected at baseline and after 6-12 months. Measured by transient elastography (FibroScan), liver steatosis was defined as Controlled Attenuation Parameter (CAP) >= 248 and fibrosis as liver stiffness value (Emed) >= 7.3 kPa. IBD disease activity was defined as C-reactive protein (CRP) >= 10 mg/l and/or fecal calprotectin (FCP) >= 150 mu g/g. Univariate and multivariate regression analysis was performed; a p-value of <= 0.05 was considered significant. Results Eighty-two out of 112 patients were seen for follow-up; 56% were male. The mean age was 43 +/- 16.0 years, and mean BMI was 25.1 +/- 4.7 kg/m(2). The prevalence of liver steatosis was 40% and of fibrosis was 20%. At baseline, 26 patients (32%) had an active episode of IBD. Using a multivariate analysis, disease activity at baseline was associated with an increase in liver steatosis (B = 37, 95% CI 4.31-69.35, p = 0.027) and liver fibrosis (B = 1.2, 95% CI 0.27-2.14, p = 0.016) during follow-up. Conclusions This study confirms the relatively high prevalence of liver steatosis and fibrosis in IBD patients. We demonstrate that active IBD at baseline is associated with both an increase in liver steatosis and fibrosis during follow-up.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Back/joint Pain, Illness Perceptions and Coping are Important Predictors of Quality of Life and Work Productivity in Patients with Inflammatory Bowel Disease: a 12-month Longitudinal Study

Pathophysiology and treatment of rheumatic disease

Instructions for Authors

Nonadherence to medical therapy is frequently encountered in patients with inflammatory bowel disease (IBD). We aimed to identify predictors for future (non)adherence in IBD

Vedolizumab for Inflammatory Bowel Disease:Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study: ICC Registry - Vedolizumab

Contains fulltext : 220028.pdf (Publisher’s version ) (Open Access)Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression

Mesenchymal Stromal Cell-Derived Exosomes Contribute to Epithelial Regeneration in Experimental Inflammatory Bowel Disease

Microscopic imaging and technolog

Hereditary cancer registries improve the care of patients with a genetic predisposition to cancer:contributions from the Dutch Lynch syndrome registry

The Dutch Hereditary Cancer Registry was established in 1985 with the support of the Ministry of Health (VWS). The aims of the registry are: (1) to promote the identification of families with hereditary cancer, (2) to encourage the participation in surveillance programs of individuals at high risk, (3) to ensure the continuity of lifelong surveillance examinations, and (4) to promote research, in particular the improvement of surveillance protocols. During its early days the registry provided assistance with family investigations and the collection of medical data, and recommended surveillance when a family fulfilled specific diagnostic criteria. Since 2000 the registry has focused on family follow-up, and ensuring the quality of surveillance programs and appropriate clinical management. Since its founding, the registry has identified over 10,000 high-risk individuals with a diverse array of hereditary cancer syndromes. All were encouraged to participate in prevention programmes. The registry has published a number of studies that evaluated the outcome of surveillance protocols for colorectal cancer (CRC) in Lynch syndrome, as well as in familial colorectal cancer. In 2006, evaluation of the effect of registration and colonoscopic surveillance on the mortality rate associated with colorectal cancer (CRC) showed that the policy led to a substantial decrease in the mortality rate associated with CRC. Following discovery of MMR gene defects, the first predictive model that could select families for genetic testing was published by the Leiden group. In addition, over the years the registry has produced many cancer risk studies that have helped to develop appropriate surveillance protocols. Hereditary cancer registries in general, and the Lynch syndrome registry in particular, play an important role in improving the clinical management of affected families.</p

Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2

Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC