One in five patients with Inflammatory Bowel Disease (IBD) suffers from anemia, most frequently caused by iron deficiency. Anemia and iron deficiency are associated with worse disease outcomes, ...reduced quality of life, decreased economic participation, and increased healthcare costs. International guidelines and consensus-based recommendations have emphasized the importance of treating anemia and iron deficiency. In this review, we draw attention to the rarely discussed effects of iron deficiency and iron therapy on the redox status, the intestinal microbiota, and the potential interplay between them, focusing on the clinical implications for patients with IBD. Current data are scarce, inconsistent, and do not provide definitive answers. Nevertheless, it is imperative to rule out infections and discern iron deficiency anemia from other types of anemia to prevent untargeted oral or intravenous iron supplementation and potential side effects, including oxidative stress. Further research is necessary to establish the clinical significance of changes in the redox status and the intestinal microbiota following iron supplementation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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 μg/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.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background
Women with inflammatory bowel disease (IBD) are at increased risk of high‐grade cervical intraepithelial neoplasia and cervical cancer (CIN2+).
Aim
To assess the association ...between cumulative exposure to immunomodulators (IM) and biologic agents (BIO) for IBD and CIN2+
Methods
Adult women diagnosed with IBD before December 31st 2016 in the Dutch IBD biobank with available cervical records in the nationwide cytopathology database were identified. CIN2+ incidence rates in IM‐ (i.e., thiopurines, methotrexate, tacrolimus and cyclosporine) and BIO‐ (anti‐tumour necrosis factor, vedolizumab and ustekinumab) exposed patients were compared to unexposed patients and risk factors were assessed. Cumulative exposure to immunosuppressive drugs was evaluated in extended time‐dependent Cox‐regression models.
Results
The study cohort comprised 1981 women with IBD: 99 (5%) developed CIN2+ during median follow‐up of 17.2 years IQR 14.6. In total, 1305 (66%) women were exposed to immunosuppressive drugs (IM 58%, BIO 40%, IM and BIO 33%). CIN2+ risk increased per year of exposure to IM (HR 1.16, 95% CI 1.08–1.25). No association was observed between cumulative exposure to BIO or both BIO and IM and CIN2+. In multivariate analysis, smoking (HR 2.73, 95%CI 1.77–4.37) and 5‐yearly screening frequency (HR 1.74, 95% CI 1.33–2.27) were also risk factors for CIN2+ detection.
Conclusion
Cumulative exposure to IM is associated with increased risk of CIN2+ in women with IBD. In addition to active counselling of women with IBD to participate in cervical screening programs, further assessment of the benefit of intensified screening of women with IBD on long‐term IM exposure is warranted.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA ...methylation biomarkers for blood-based detection of colorectal cancer.
We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection.
Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this ...“off-hours effect” also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands.
Methods
Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT: 2009–2015, EVT: 2014–2017). Office hours were defined as presentation during weekdays between 8 AM and 5 PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle DNT for IVT, door-to-groin DGT for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90 days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values.
Results
In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30 min,
p
= 0.024, adjusted difference 2.5 min, 95% CI 0.7–4.2). Presentation outside office hours was not associated with a longer DGT (median 130 min for both groups, adjusted difference 7.0 min, 95% CI − 4.2 to 18.1). Clinical outcome and sICH rate also did not differ.
Conclusion
Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
This article reports on the sixth scientific workshop of the European Crohn’s and Colitis Organisation ECCO on the pathogenesis of extraintestinal manifestations EIMs in inflammatory bowel ...disease IBD. This paper has been drafted by 15 ECCO members and 6 external experts in rheumatology, dermatology, ophthalmology, and immunology from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.
Background: Although polymyositis and dermatomyositis are regarded as treatable disorders, prognosis is not well known, as in the literature long-term outcome and prognostic factors vary widely. Aim: ...To analyse the prognostic outcome factors in polymyositis and adult dermatomyositis. Methods: We determined mortality, clinical outcome (muscle strength, disability, persistent use of drugs and quality of life) and disease course and analysed prognostic outcome factors. Results: Disease-related death occurred in at least 10% of the patients, mainly because of associated cancer and pulmonary complications. Re-examination of 110 patients after a median follow-up of 5 years showed that 20% remained in remission and were off drugs, whereas 80% had a polycyclic or chronic continuous course. The cumulative risk of incident connective tissue disorder in patients with myositis was significantly increased. 65% of the patients had normal strength at follow-up, 34% had no or slight disability, and 16% had normal physical sickness impact profile scores. Muscle weakness was associated with higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3). Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the patients with a favourable clinical outcome were still using drugs. Jo-1 antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0). Conclusions: Dermatomyositis and polymyositis are serious diseases with a disease-related mortality of at least 10%. In the long term, myositis has a major effect on perceived disability and quality of life, despite the regained muscle strength.
Human breast milk is generally regarded as the best nutrition for infants in their first months of life. Whether breastfeeding has a protective effect on food allergy is a point of debate and the ...subject of this study.
This retrospective study was conducted in 649 children who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part of routine care in a tertiary care clinic. Food allergy was defined as having at least one positive DBPCFC to any food. The association between both "any" breastfeeding (yes/no) and its duration in months with food allergy was studied by logistic regression analysis with correction for confounding variables.
The prevalence of food allergy was 58.9% (n = 382). Of all subjects, 75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no significant association between food allergy and breastfeeding versus bottle-feeding after correction for the confounding effect of increased breastfeeding by atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85-1.79, p = 0.27). However, in breastfed children, every additional month of breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93-0.99, p = 0.02). No confounders were identified in this association.
These results show for the first time that in children investigated for possible food allergy, every additional month of breastfeeding is associated with a lower risk of developing clinical food allergy as diagnosed by DBPCFC. However, overall, there was no association between the prevalence of food allergy and breastfeeding versus bottle-feeding in this tertiary care population.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Health-related quality of life (HRQL) may be affected by food allergy. Presently, no disease-specific HRQL questionnaire exists for food allergic adults. Therefore, we developed and validated the ...Food Allergy Quality of Life Questionnaire - Adult Form (FAQLQ-AF) in the Dutch language. Twenty-two food allergic patients (greater-than-or-equal18 years) were interviewed and generated 180 HRQL items. The most important items were identified by 54 food allergic patients using the clinical impact method resulting in the FAQLQ-AF containing 29 items (score range 1 'not troubled' to 7 'extremely troubled'). The FAQLQ-AF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (RAND-36) were sent to 100 other food allergic adults for cross-sectional validation of the FAQLQ-AF. Cross-sectional validity was assessed by the correlation between FAQLQ-AF and FAIM (ρ = 0.76, P < 0.001). The FAQLQ-AF had excellent internal consistency (Cronbach's α = 0.97). The FAQLQ-AF discriminated between patients who differ in severity of symptoms (anaphylaxis vs no anaphylaxis, total FAQLQ-AF score 4.9 vs 4.1; P = 0.041) and number of food allergies (>3 food allergies vsless-than or equal to3 food allergies, total FAQLQ-AF score 5.2 vs 4.2; P = 0.008). The total FAQLQ-AF score was correlated with one RAND-36 scale (convergent/discriminant validity). The FAQLQ-AF is the first disease-specific HRQL questionnaire for food allergic adults and reflects the most important issues that food allergic patients have to face. The questionnaire is valid, reliable and discriminates between patients with different disease characteristics. The FAQLQ-AF is short and easy to use and may therefore be a useful tool in clinical research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Parkinson’s Disease (PD) is a heterogeneous, progressive neurodegenerative disorder which is characterized by a variety of motor and non-motor symptoms. To date, no disease ...modifying treatment for PD exists. Here, the study protocol of the Dutch Parkinson Cohort (DUPARC) is described. DUPARC is a longitudinal cohort study aimed at deeply phenotyping de novo PD patients who are treatment-naïve at baseline, to discover and validate biomarkers for PD progression, subtypes and pathophysiology.
Methods/design
DUPARC is a prospective cohort study in which 150 de novo PD subjects will be recruited through a collaborative network of PD treating neurologists in the northern part of the Netherlands (Parkinson Platform Northern Netherlands, PPNN). Participants will receive follow-up assessments after 1 year and 3 years, with the intention of an extended follow-up with 3 year intervals. Subjects are extensively characterized to primarily assess objectives within three major domains of PD: cognition, gastrointestinal function and vision. This includes brain magnetic resonance imaging (MRI); brain cholinergic PET-imaging with fluoroethoxybenzovesamicol (FEOBV-PET); brain dopaminergic PET-imaging with fluorodopa (FDOPA-PET); detailed neuropsychological assessments, covering all cognitive domains; gut microbiome composition; intestinal wall permeability; optical coherence tomography (OCT); genotyping; motor and non-motor symptoms; overall clinical status and lifestyle factors, including a dietary assessment; storage of blood and feces for additional analyses of inflammation and metabolic parameters. Since the start of the inclusion, at the end of 2017, over 100 PD subjects with a confirmed dopaminergic deficit on FDOPA-PET have been included.
Discussion
DUPARC is the first study to combine data within, but not limited to, the non-motor domains of cognition, gastrointestinal function and vision in PD subjects over time. As a de novo PD cohort, with treatment naïve subjects at baseline, DUPARC provides a unique opportunity for biomarker discovery and validation without the possible confounding influences of dopaminergic medication.
Trial registration
NCT04180865
; registered retrospectively, November 28th 2019.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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