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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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Anemia , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Deficiencias de Hierro , Humanos , Calidad de Vida , Hierro/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Anemia/tratamiento farmacológico , Anemia/etiología , Estrés OxidativoRESUMEN
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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Enfermedades Inflamatorias del Intestino , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Humanos , Femenino , Masculino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Detección Precoz del Cáncer , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Inmunosupresores/efectos adversos , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnósticoRESUMEN
BACKGROUND: Diet plays a pivotal role in the onset and progression of Crohn's disease (CD). Nutritional interventions revealed effects on intestinal inflammation and gut microbial composition. However, data from well-designed and controlled dietary trials are lacking. Therefore, evidence-based dietary recommendations are still unavailable to patients and physicians. Here, we aim to investigate the effects of an evidence-based anti-inflammatory diet, and an ileocolonic-targeted capsule containing vitamin B2, B3 and C (ColoVit) on patients with CD and their healthy household members. METHODS AND ANALYSIS: In this multicentre, randomised, placebo-controlled, partially blinded nutritional intervention trial, we aim to recruit 255 CD patients with Harvey-Bradshaw Index <8 and a faecal calprotectin (FCal) cut-off of ≥100 µg/g at baseline. Participants will be randomised into two experimental intervention groups and one placebo group. In the experimental groups, participants will either adhere to the Groningen anti-inflammatory diet (GrAID) or ingest an ileocolonic-delivered oral vitamin B2/B3/C capsule (ColoVit). The study consists of a 12-week controlled interventional phase, which proceeds to a 9-month observational follow-up phase in which patients allocated to the GrAID group will be requested to continue the intervention on their own accord. Household members of participating patients will be asked to participate in the trial as healthy subjects and are allocated to the same group as their peer. The primary study outcome for patients is the change in FCal level from baseline. The primary outcome for household members is the change in gut microbial composition, which is set as secondary outcome for patients. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board of the Stichting Beoordeling Ethiek Biomedisch Onderzoek in Assen, the Netherlands. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04913467.
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Enfermedad de Crohn , Microbiota , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Dieta , Antiinflamatorios , Vitaminas , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND AND AIMS: Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. METHODS: We conducted a retrospective, multicentre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy. RESULTS: In total, 219 patients starting either methotrexate [nâ =â 105] or tioguanine [nâ =â 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], pâ <0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, pâ =â 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, pâ <0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [pâ <0.001]. CONCLUSIONS: We observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.
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Enfermedad de Crohn , Tioguanina , Enfermedad de Crohn/inducido químicamente , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Inmunosupresores/efectos adversos , Metotrexato/efectos adversos , Estudios Retrospectivos , Tioguanina/efectos adversos , Resultado del TratamientoRESUMEN
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies.We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing.Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing-based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7).HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.
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Heces/química , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/fisiopatología , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/fisiopatología , Complejo de Antígeno L1 de Leucocito/análisis , beta-Defensinas/análisis , Adulto , Biomarcadores/análisis , Biopsia/normas , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND AND AIMS: Women with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors. METHODS: Clinical data from adult IBD women in a multicentre Dutch IBD prospective cohort [PSI] from 2007 onwards were linked to cervical cytology and histology records from the Dutch nationwide cytology and pathology database [PALGA], from 2000 to 2016. Patients were frequency-matched 1:4 to a general population cohort. Standardised detection rates [SDR] were calculated for CIN2+. Longitudinal data were assessed to calculate CIN2+ risk during follow-up using incidence rate ratios [IRR] and risk factors were identified in multivariable analysis. RESULTS: Cervical records were available from 2098 IBD women [77%] and 8379 in the matched cohort; median follow-up was 13 years. CIN2+ detection rate was higher in the IBD cohort than in the matched cohort (SDR 1.27, 95% confidence interval [CI] 1.05-1.52). Women with IBD had an increased risk of CIN2+ [IRR 1.66, 95% CI 1.21-2.25] and persistent or recurrent CIN during follow-up (odds ratio [OR] 1.89, 95% CI 1.06-3.38). Risk factors for CIN2+ in IBD women were smoking and disease location (ileocolonic [L3] or upper gastrointestinal [GI] [L4]). CIN2+ risk was not associated with exposure to immunosuppressants. CONCLUSIONS: Women with IBD are at increased risk for CIN2+ lesions. These results underline the importance of human papillomavirus [HPV] vaccination and adherence to cervical cancer screening guidelines in IBD women, regardless of exposure to immunosuppressants.
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Enfermedades Inflamatorias del Intestino/complicaciones , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Detección Precoz del Cáncer , Femenino , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Enfermedades Inflamatorias del Intestino/patología , Persona de Mediana Edad , Clasificación del Tumor , Países Bajos , Prueba de Papanicolaou , Cooperación del Paciente , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes. METHODS: Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, nâ =â 1097; cohort B, nâ =â 2156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS-phenotype (false-discovery rate [FDR] corrected pâ <0.05) associations identified in cohort A were put forward for replication in cohort B. RESULTS: Crohn's disease [CD] GRS were associated with fibrostenotic CD [R2â =â 7.4%, FDRâ =â 0.02] and ileocaecal resection [R2â =â 4.1%, FDRâ =â 1.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R2â =â 7.1%, FDRâ =â 0.02] and primary sclerosing cholangitis [PSC] GRS [R2â =â 3.6%, FDRâ =â 0.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R2â =â 1.7%, FDRâ =â 0.04]. CONCLUSIONS: Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes.
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Colangitis Esclerosante , Colitis Ulcerosa , Enfermedad de Crohn , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Manejo de Atención al Paciente/métodos , Adulto , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/genética , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/genética , Colitis Ulcerosa/terapia , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/genética , Enfermedad de Crohn/terapia , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Femenino , Estudios de Asociación Genética , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Farmacogenética/métodos , Factores de Riesgo , Evaluación de Síntomas/estadística & datos numéricosRESUMEN
A 73-year-old man with a history of type 2 diabetes mellitus, nephrolithiasis, and recurrent urinary tract infections caused by Candida glabrata was admitted to our hospital. Urosepsis was diagnosed and C. glabrata was isolated from urine and blood cultures. Computed tomography intravenous pyelography (CT-IVP) revealed bilateral filling defects caused by renal fungal balls. Treatment initially comprised intravenous anidulafungin coupled with continuous local anidulafungin irrigation via bilateral nephrostomy tubes, which was followed by high-dose oral fluconazole. This regimen successfully eradicated the C. glabrata in follow-up cultures.
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Intestinal fibrosis and stenosis are common complications of Crohn's disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.
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Intestinos/patología , Oxiesteroles/metabolismo , Esteroide Hidroxilasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Colitis/inducido químicamente , Colitis/enzimología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/patología , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Femenino , Fibrosis , Humanos , Intestinos/enzimología , Intestinos/trasplante , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Esteroide Hidroxilasas/deficienciaRESUMEN
Following publication of the original article [1], the authors.
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BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.
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Enfermedades Inflamatorias del Intestino/clasificación , Enfermedades Inflamatorias del Intestino/genética , Adolescente , Adulto , Anciano , Biomarcadores , Biopsia , Dieta , Ambiente , Femenino , Microbioma Gastrointestinal , Genotipo , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Países Bajos , Fenotipo , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Transcriptoma , Secuenciación del Exoma , Adulto JovenRESUMEN
INTRODUCTION: TNF-α-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-α antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues. AIM: To determine the neutralizing capacity of first- and second generation anti-TNF-α antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra). METHODS: TNF-α neutralization was measured using a quantitative TNF-α sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF-кB response element. All available anti-TNF-α drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-α-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab2-fragment, biosimilar CT-P13 (Inflectra) and ADA. RESULTS: TNF-α strongly induced GFP expression in Hela 8D8 cells. Higher concentrations of first-generation anti-TNF-α drugs were required to neutralize TNF-α compared to the second-generation anti-TNF-α drugs. Serum of IBD patients with proven ATI blocked TNF-α-neutralizing properties of IFX biosimilar CT-P13 (Inflectra), whereas such sera did not block the effect of ADA. CONCLUSION: The second-generation anti-TNF-α drugs show increased TNF-α-neutralizing potential compared to first-generation variants. ATI show cross-reactivity toward IFX biosimilar CT-P13 (Inflectra), consequently patients with ATI are unlikely to benefit from treatment with this IFX biosimilar.
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Biosimilares Farmacéuticos/administración & dosificación , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/inmunología , Adalimumab/administración & dosificación , Adulto , Anciano , Anticuerpos Antiidiotipos/sangre , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes , Productos Biológicos/administración & dosificación , Biosimilares Farmacéuticos/sangre , Certolizumab Pegol/administración & dosificación , Reacciones Cruzadas/inmunología , Etanercept/administración & dosificación , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/patología , Infliximab/administración & dosificación , Infliximab/efectos adversos , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangreRESUMEN
A spontaneous, non-traumatic, urinary bladder rupture is a rare condition. We describe a case of a 23-year-old male with a spontaneous bladder rupture secondary to urinary retention, due to an urethral stricture. He presented to the emergency department with voiding difficulties, severe abdominal pain and renal failure. Abdominal ultrasound revealed large amounts of ascites. After an unsuccessful attempt to place a Foley catheter a cystoscopy was performed which showed an urethral stricture. On CT-cystogram an intra-peritoneal bladder rupture was diagnosed and the patient underwent laparoscopic repair of the bladder wall. The postoperative course was uneventful.
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BACKGROUND AND AIMS: The number of patients with inflammatory bowel disease [IBD], of non-Caucasian descent in Western Europe, is increasing. We aimed to explore the impact of ethnicity and country of birth on IBD phenotype. METHODS: IBD patients treated in the eight University Medical Centers in The Netherlands [Dutch IBD Biobank] were divided into two groups according to their ethnicity: 1] Caucasian patients of Western and Central European descent [CEU]; and 2] patients of non-Caucasian descent [non-CEU]. The non-CEU group was subdivided according to country of birth, into: born in The Netherlands or Western Europe [non-CEU European born]; or born outside Western-Europe who migrated to The Netherlands [non-CEU non-European born]. Both comparisons were analysed for phenotype differences [by chi-square test]. RESULTS: The Dutch IBD Biobank included 2921 CEU patients and 233 non-CEU patients. Non-CEU Crohn's disease [CD] patients more often had upper gastro-intestinal disease [16% vs 8%, p = 0.001] and anal stenosis [10% vs 4%, p = 0.002] than CEU CD patients. The use of anti-tumour necrosis factor [TNF] agents and immunomodulators was higher in non-CEU IBD patients than in CEU IBD patients [45% vs 38%, p = 0.042] and [77% vs 66%, p = 0.001], respectively. Non-CEU IBD patients born in Europe [n = 116] were diagnosed at a lower age than non-CEU IBD patients born outside Europe [n = 115] [at 22.7 vs 28.9 years old, p < 0.001]. CONCLUSION: Non-Caucasians had more severe disease behaviour than Caucasians. Non-CEU patients born in Europe were diagnosed at a lower age with IBD than those born outside Europe who migrated to The Netherlands.
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Colitis Ulcerosa/etnología , Enfermedad de Crohn/etnología , Fístula Intestinal/etnología , Fenotipo , Características de la Residencia , Adulto , Edad de Inicio , Anciano , Canal Anal/patología , Colitis Ulcerosa/genética , Colitis Ulcerosa/terapia , Constricción Patológica/etnología , Enfermedad de Crohn/genética , Enfermedad de Crohn/terapia , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Europa (Continente)/etnología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. AIM: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. METHODS: Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro-C3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. RESULTS: C3M and Pro-C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro-C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [P<.001]), C3M (31.6±3.9 vs 26.1±1.6 nmol/L [P=.002] and Pro-C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L [P=.002]) were higher in patients with active inflammation vs without active inflammation. Pro-C3/C3M-ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively. CONCLUSIONS: Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase-9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro-C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease.
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Colágeno Tipo III/metabolismo , Enfermedad de Crohn/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Enfermedad de Crohn/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/sangre , Procolágeno/sangre , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS: In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (7,905 [95% confidence interval 6,234 - 9,864] vs 6,017 [5,186 - 6,946] in never-smokers and 5,710 [4,687 - 6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years ( 5,135 [95% CI 4,122 - 6,303] vs 9,342 [6,010 - 12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS: Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.
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Colitis Ulcerosa/economía , Colitis Ulcerosa/epidemiología , Costo de Enfermedad , Enfermedad de Crohn/economía , Enfermedad de Crohn/epidemiología , Costos de la Atención en Salud , Calidad de Vida , Fumar/economía , Fumar/epidemiología , Adulto , Anciano , Colitis Ulcerosa/tratamiento farmacológico , Comorbilidad , Enfermedad de Crohn/tratamiento farmacológico , Eficiencia , Empleo/estadística & datos numéricos , Femenino , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Cese del Hábito de Fumar/economía , Encuestas y Cuestionarios , Brote de los SíntomasRESUMEN
BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.
Asunto(s)
Enfermedades Inflamatorias del Intestino/complicaciones , Fumar/efectos adversos , Adulto , Artritis/etiología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/etiología , Colitis Ulcerosa/patología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/etiología , Enfermedad de Crohn/patología , Estudios Transversales , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/etiología , Cese del Hábito de FumarRESUMEN
BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT). METHODS: Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for ≥ 4 weeks in children and >50% for ≥3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl). RESULTS: In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died. CONCLUSION: The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making.
Asunto(s)
Enfermedades Intestinales/epidemiología , Intestinos/trasplante , Trasplante de Órganos , Sistema de Registros , Adulto , Niño , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Internet , Enfermedades Intestinales/cirugía , Intestinos/fisiopatología , Masculino , Países Bajos/epidemiología , Necesidades Nutricionales , Nutrición Parenteral en el Domicilio , Complicaciones Posoperatorias/terapia , PrevalenciaRESUMEN
BACKGROUND: Infliximab (IFX) is effective in the treatment of inflammatory bowel diseases (IBD). Currently, IFX is administered at fixed doses and intervals; however, costs are high and optimisation is necessary. Several publications indicate that IFX should be dosed on trough levels ≥3.0 mg/L. For optimising IFX dosing, the use of a pharmacokinetic model is important. Population pharmacokinetics of IFX have been described earlier; however, these models were not used for dose optimising. AIMS: To develop a pharmacokinetic model for IFX in IBD patients that can be used for dose-optimisation of IFX and to predict serum trough levels in this population. METHODS: An observational retrospective study was performed in 42 IFX-treated IBD patients. Serum samples were drawn before infusion at T = 0, 2, 6, 14, 22 and 54 weeks and analysed for IFX and antibodies against IFX (ATI). Relevant covariates were recorded and a population pharmacokinetic model was developed. RESULTS: Individual plots created using the final model showed good correspondence between observed and model predicted values. Serum levels were influenced by ATI, disease activity, sex and albumin. Our results show that in patients without ATI target trough levels ≥3.0 mg/L can be achieved by increasing dosing intervals from 8 to 12 weeks combined with a dose increase. This results in a reduction of 33% in concomitant costs. CONCLUSIONS: In IBD patients without ATI, trough level dosing based on longer intervals can reduce IFX therapy-related visits to the hospital with one-third. Trough level based dose intensification should always be justified by disease activity parameters.