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Background and Aims The health consequences of coronavirus disease 2019 [COVID-19] among patients with ulcerative colitis [UC] and Crohn’s disease [CD] remain largely unknown. We aimed to investigate the outcomes and long-term effects of COVID-19 in patients with UC or CD. Methods We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28, 2020 and April 1, 2021, through medical records and questionnaires. Results All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 [N = 230 087]. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N = 46 [14.4%], relative risk [RR] = 2.49 [95% confidence interval, CI, 1.91–3.26]) and CD (N = 24 [12.2%], RR = 2.11 [95% CI 1.45–3.07]) as compared with the background population (N = 13 306 [5.8%]). A similar pattern was observed for admission to intensive care (UC: N = 8 [2.51%], RR = 27.88 [95% CI 13.88–56.00]; CD: N = 3 [1.52%], RR = 16.92 [95% CI 5.46–52.46]). After a median of 5.1 months (interquartile range [IQR] 4.5–7.9), 58 [42.3%] and 39 [45.9%] patients with UC and CD, respectively, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (odds ratio [OR] = 1.50 [95% CI 1.07–10.22], p = 0.01) and severe COVID-19 (OR = 2.76 [95% CI 1.05–3.90], p = 0.04), but not with age or presence of comorbidities. Conclusion In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent, affecting 43.7% of COVID-19-infected patients. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

INTRODUCTION: Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation. METHODS: This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value. RESULTS: ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966). DISCUSSION: MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients. ispartof: CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY vol:13 issue:7 ispartof: location:United States status: published

Lay Summary This brief report investigated the impact of clinical, biochemical, and endoscopic activity of IBD on the severity and long-term outcomes of COVID-19 in a prospective population-based cohort. The study did not identify any association between IBD activity and COVID-19 outcomes.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche. ispartof: LANCET GASTROENTEROLOGY & HEPATOLOGY vol:7 issue:1 pages:28-37 ispartof: location:Netherlands status: published

BACKGROUND AND AIMS: Intestinal stenosis is a common complication of Crohn's Disease (CD). Stenosis is associated with alteration of bowel mechanical properties. This study aims to quantitate the mechanical properties of the intestinal stenosis and to explore associations between histology and mechanical remodeling at stenotic intestinal sites in CD patients.METHODS: Intestinal segments from stenotic sites were studied in vitro from 19 CD patients. A luminal catheter with a bag was used to stepwise pressurize the intestinal segments from 0-100 cmH 2O with 10 cmH 2O increments. B-mode ultrasound images were obtained at the narrowest part of the stenosis at each pressure level and morphometric parameters were obtained from ultrasound images. The mechanical behavior of the stenotic tissue were characterized by using an isotropic three dimensional strain energy function in Demiray model form, the mechanical constants were obtained by fitting the model to the recorded intraluminal pressure and the inner radius of the stenotic segment of the small bowel. Grading scores were used for histological analysis of inflammation, fibrosis, muscular hypertrophy and adipocyte proliferation in the intestinal layers. The collagen area fraction in intestinal layers was also calculated. Associations between histological and the mechanical constants (stiffness) were analyzed. RESULTS: Chronic inflammation was mainly located in mucosa whereas fibrosis was found in submucosa. The mechanical remodeling was performed with changed mechanical constants ranged between 0.35-13.68kPa. The mechanical properties changes were associated mainly with chronic inflammation, fibrosis and combination of inflammation and fibrosis (R>0.69, P0.53, PCONCLUSIONS: We quantitated the intestinal stenosis stiffness. Associations were found between bowel mechanical remodeling and histological changes at the stenotic site in CD patients.STATEMENT OF SIGNIFICANCE: Although intestinal ultrasonography, CT and MRI can be used to diagnose Crohn's Disease (CD)-associated bowel strictures, these techniques may not have sufficient accuracy and resolution to differentiate predominantly inflammatory strictures from predominantly fibrotic strictures. The present study aims to quantitate the mechanical remodeling of intestinal stenosis and to explore the associations between histological parameters and mechanical properties at the intestinal stenotic sites in CD patients. For the first time, we quantitatively demonstrated that the mechanical properties of the intestinal wall in CD stenosis are associated with the chronic inflammation, fibrosis and collagen fraction in the intestinal layers. The results of this study may facilitate design and development of artificial biomaterials for gastrointestinal organs. The potential clinical implication of this study is that the histological characteristics in patients with CD can be predicted clinically by means of inflammation and fibrosis assessment in conjunction with tissue stiffness measurement.

Abdominal cancers represent 30% of all diagnosed cancers. Nevertheless, it is unknown if the general practitioner's (GP's) initial cancer suspicion varies for different abdominal cancer types and how this is associated with referrals to standardized cancer patient pathways (CPPs).To explore initial cancer suspicion in GPs and to investigate how this was associated with GP referrals to CPPs and the duration of the primary care interval (PCI) in 10 different abdominal cancer types.We conducted a cohort study on 1104 incident abdominal cancer patients diagnosed in Denmark in 2016 using a combination of survey and register-based data. Poisson regression was used to estimate associations between GP cancer suspicion, CPP referral and PCI duration.The GPs initially suspected cancer or other serious disease in 46-78% of cases, lowest in kidney cancer, and referred 35-65% to a CPP, lowest in oesophageal cancer. The GP's suspicion at the first presentation was strongly associated with referral to a CPP. The median (0-11 days) and 75th percentile (3-32 days) PCIs varied between the abdominal cancer types. The likelihood of a long PCI was more than 3-fold higher when the GP did not initially suspect cancer.In up to half of abdominal cancer patients, there is no initial suspicion of cancer or serious disease. CPPs were used in only one-third to two-thirds of patients, depending on cancer type. For kidney cancer, as well as several abdominal cancers, we need better diagnostic strategies to support GPs to enable effective and efficient referral.This study investigates how often a suspicion of cancer is raised by the general practitioner (GP) at the first consultation leading up to a diagnosis for several abdominal cancer types. The study also explores how often the GPs refer these patients to a cancer patient pathway (CPP). Moreover, the length of the primary care interval is measured, that is, the interval from the first time when the patient presents with symptoms to their GP until referral to a hospital or another specialist. The results show that the GPs initially suspected cancer or other serious disease in 46–78% of 10 selected types of abdominal cancer; lowest suspicion was seen for kidney cancer, and referred 35–65% to a CPP; lowest CPP use was seen for oesophageal cancer. The median time from the first visit to the GP until referral to a hospital or another specialist was 0–11 days, depending on the cancer type. The most important factor for a prompt referral was the GP’s initial cancer suspicion; this was seen independent of the diagnosed cancer type. These findings call for the development of new cancer pathways that better target the patients in whom the GP does not initially suspect cancer.

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p

Background More than 11,500 abdominal cancers are yearly diagnosed in Denmark. Nevertheless, little is known about which investigations the patients undergo before a diagnosis of abdominal cancer. We aimed to investigate the frequency and timing of selected diagnostic investigations during the year preceding an abdominal cancer diagnosis. Methods We conducted a nationwide registry-based cohort study of patients aged ≥ 18 years who were diagnosed with a first-time abdominal cancer in 2014−2018. We included the following cancer types: oesophageal, gastric, colon, rectal, liver, gall bladder/biliary tract, pancreatic, endometrial, ovarian, kidney, and bladder cancer. Investigations of interest were transvaginal ultrasound, abdominal ultrasound, colonoscopy, gastroscopy, endoscopic retrograde cholangiopancreatography, cystoscopy, hysteroscopy, abdominal computed tomography and abdominal magnetic resonance imaging. Generalised linear models were used to calculate incidence rate ratios to enable comparison of monthly rates of investigations. Results All types of investigations were performed, with varying frequency, across the 11 abdominal cancer types in the year preceding the diagnosis. Increased use of investigations revealed that the timing of the onset differed for the different abdominal cancers, with increases seen 2–6 months before the diagnosis. Abdominal ultrasound, colonoscopy and computed tomography were the investigations with the earliest increase. Conclusion In the year before a diagnosis of an abdominal cancer, some patients appear to undergo investigations typically used to detect another cancer type. This indicates that a window of opportunity exists to diagnose some abdominal cancers at an earlier time point. Future studies should explore an alternative clinical pathway to promote earlier diagnosis of abdominal cancers.

Background Population-based data regarding outcomes of coronavirus disease 2019 (COVID-19) among patients with ulcerative colitis (UC) and Crohn’s disease (CD) are limited. Studies on the association of COVID-19 outcomes and immunomodulating therapies, are scarce. Therefore, we aimed to conduct a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. Methods The Danish COVID-19 IBD Database is an extensive population-based database that prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD in Denmark. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death. Regression analysis was adjusted for age, sex, disease type, disease activity, cardiovascular disease, and corticosteroids. Results The study recruited 363 patients (UC: 223; CD: 140) from January 28th, 2020, to February 7th, 2021. A total of 36 (16.1%) and 18 (12.9%) patients with UC and CD, respectively, required a COVID-19 related hospitalization, while eight (3.6%) and three (2.1%) patients required intensive care treatment. Death due to COVID-19 was observed among eight (3.6%) and two (1.4%) patients, respectively. The association between these outcomes and IBD-related treatment is presented in Table 1. As shown, none of the IBD-related medications were associated with severe COVID-19 in univariate and adjusted analysis. However, systemic steroids were found to be associated with the risk of COVID-19 related hospital admission among patients with UC (adjusted odds ratio (aOR)=6.54 (95% CI 1.09-36.39)) and CD (aOR=5.45 (95% CI 2.07-12.24)). Conclusion This ongoing Danish population-based study on COVID-19 outcomes among patients with UC and CD demonstrated severe COVID-19 among only a minority of patients, which was not associated with IBD-related medications. However, use of systemic steroids were associated with COVID-19 necessitating hospital admission among patients with UC and CD.

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

IntroductionChronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes.Methods and analysisThis prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14–16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics.Ethics and disseminationThe principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Trial registration numberNCT03173144; Pre-results.

Background and Aims: Increased small intestinal wall thickness correlates with both inflammatory activity and fibrosis in Crohn's disease [CD]. Assessment of perfusion holds promise as an objective marker distinguishing between the two conditions. Our primary aim was to determine if relative bowel wall perfusion measurements correlate with histopathological scores for inflammation or fibrosis in CD. Methods: A total of 25 patients were investigated before elective surgery for small intestinal CD. Unenhanced ultrasonography [US] and magnetic resonance enterography [MRE] were applied to describe bowel wall thickness. Perfusion was assessed with contrast-enhanced US [CEUS] and dynamic contrast-enhanced MRE [DCE-MRE]. Histopathology was used as gold standard. Results: Compared with histopathology, the mean wall thickness was 0.4 mm greater on US [range -0.3 to 1.0, p = 0.24] and 1.4 mm greater on MR [0.4 to 2.3, p = 0.006]. No correlation was found between the severity of inflammation or fibrosis on histopathology, and either DCE-MRE [r = -0.13, p = 0.54 for inflammation and r = 0.41, p = 0.05 for fibrosis] or CEUS [r = 0.16, p = 0.45 for inflammation and r = -0.28, p = 0.19 for fibrosis]. Wall thickness assessed with US was correlated with both histological inflammation [r = 0.611, p = 0.0012] and fibrosis [r = 0.399, p = 0.048]. The same was not true for MR [r = 0.41, p = 0.047 for inflammation and r = 0.29, p = 0.16 for fibrosis] Conclusions: Bowel wall thickness assessed with US is a valid marker of inflammation in small intestinal CD. However, relative contrast enhancement of US or of MRE cannot distinguish between inflammatory activity and fibrosis.

The datasets presented in this article are related to the research articles entitled “Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies” (Bennike et al., 2015 [1]), and “Proteome Analysis of Rheumatoid Arthritis Gut Mucosa” (Bennike et al., 2017 [2]). The colon mucosa represents the main interacting surface of the gut microbiota and the immune system. Studies have found an altered composition of the gut microbiota in rheumatoid arthritis patients (Zhang et al., 2015; Vaahtovuo et al., 2008; Hazenberg et al., 1992) [5], [6], [7] and inflammatory bowel disease patients (Morgan et al., 2012; Abraham and Medzhitov, 2011; Bennike, 2014) [8], [9], [10]. Therefore, we characterized the proteome of colon mucosa biopsies from 10 inflammatory bowel disease ulcerative colitis (UC) patients, 11 gastrointestinal healthy rheumatoid arthritis (RA) patients, and 10 controls. We conducted the sample preparation and liquid chromatography mass spectrometry (LC-MS/MS) analysis of all samples in one batch, enabling label-free comparison between all biopsies. The datasets are made publicly available to enable critical or extended analyses. The proteomics data and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001608 for ulcerative colitis and control samples, and PXD003082 for rheumatoid arthritis samples., Graphical abstract fx1

Purpose e Cross-sectional imaging methods are important for objective evaluationof small intestinal inflammationinCrohn'sdisease(CD).The primary aim was to compare relative parameters of intestinal perfusion between contrast-enhanced ultrasonography (CEUS) and dynamic contrast-enhanced magnetic resonance enterography (DCE-MRE) in CD. Furthermore, we aimed at testing the repeatability of regions of interest (ROIs) for CEUS. Methods This prospective study included 25 patients: 12 females (age: 37, range: 19-66) with moderate to severe CD and a bowel wall thickness>3mm evaluated with DCE-MRE and CEUS. CEUS bolus injection was performed twice for repeatability and analyzed in VueBox®. Correlations between modalities were described with Spearman's rho, limits of agreement(LoA) and intraclass correlation coefficient(ICC). ROIrepeatability for CEUS was assessed. Results s The correlation between modalities was good and very good for bowel wall thickness (ICC=0.71, P

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5,366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared to controls, and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggests that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial- and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular- and membrane proteins, and included known targets of anti-citrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS-data has been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.

Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome. ispartof: Nutrients vol:9 issue:5 ispartof: location:Switzerland status: published

OBJECTIVE The goal of this study was to examine the effects of a single oral dose of 300,000 international units of either ergocalciferol (D₂) or cholecalciferol (D₃) on the plasma levels of 25-hydroxyvitamin D in patients with alcoholic liver cirrhosis. METHODS Inclusion criteria for this study were diagnosis of alcoholic liver cirrhosis and plasma levels of 25-hydroxyvitamin D less than 25 nmol/l. At baseline, patients were divided into Child-Pugh groups A, B, or C and were given one oral dose of 300,000 international units of ergocalciferol (D₂ group, N=23) or cholecalciferol (D₃ group, N=13). Plasma concentrations of 25(OH) vitamin D and vitamin D-binding protein were measured on days 0, 7, 30, and 90. RESULTS On days 7 and 30, patients from the D₃ group had higher vitamin D levels than patients from the D₂ group (P

Udgivelsesdato: 2009-May-1 RATIONALE: Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. OBJECTIVES: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. MEASUREMENTS AND MAIN RESULTS: The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. CONCLUSIONS: Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

Article first published online 19 May 2015., Background: The etiology of the inflammatory bowel diseases, including ulcerative colitis (UC), remains incompletely explained. We hypothesized that an analysis of the UC colon proteome could reveal novel insights into the disease etiology. Methods: Mucosal colon biopsies were taken by endoscopy from noninflamed tissue of 10 patients with UC and 10 controls. The biopsies were either snap-frozen for protein analysis or prepared for histology. The protein content of the biopsies was characterized by high-throughput gel-free quantitative proteomics, and biopsy histology was analyzed by light microscopy and confocal microscopy. Results: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. Conclusions: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate immunity are all increased in abundance in the morphologically normal colon mucosa from patients with UC. The increased abundance of these antimicrobial compounds points to the stimulation of the innate immune system in the etiology of UC.

Vitamin D deficiency is extremely prevalent in the elderly. Most often the first symptoms are caused by myopathy with muscle pain, fatigue, muscular weakness and gait disturbances. More severe deficiency causes osteomalacia with deep bone pain, reduced mineralization of bone matrix and low energy fractures. Recent data also suggest that hypovitaminosis D increases the risk of cancer of the prostate, colon and breast. Thus, hypovitaminosis D is associated with many diseases associated with aging. In order to diagnose hypovitaminosis D, the assessment of serum levels of 25-hydroxy vitamin D is mandatory. Screening based on other markers like alkaline phosphatase and parathyroid hormone (PTH) will be incomplete. The treatment of hypovitaminosis D is simple with administration of combined calcium (1 g) and vitamin D supplements(calciferol, at least 800 IU). Severe cases may demand initial parenteral administration of vitamin D (repeated injections of 300,000 IU 2–3 times with monthly intervals). More potent analogues are rarely needed. One should aim at achieving S-25(OH)D values in the range 50–100 nmol/l.

A 27-year-old man of Eritrean origin presented with persistent left-sided abdominal pain. Initial investigation showed signs of liver fibrosis, portal hypertension and splenomegaly. A diagnosis of hepatosplenic schistosomiasis was suspected on grounds of elevated total IgE, grey area antischistosomiasis antibodies and the high endemic status of his native country. However, repeated microscopy of faecal and urine samples, as well as rectal biopsies, failed to demonstrate schistosomal eggs. Finally, the diagnosis of hepatosplenic schistosomiasis was established through demonstration of a Schistosoma mansoni egg in a liver biopsy taken in an attempt to clarify the cause of the above findings. The patient had recently been treated for uncomplicated malaria. Lowered schistosomiasis worm/egg burden and hence reduced sensitivity of classic microscopy-based schistosomiasis testing was attributed to the antischistosomal activity of the antimalarial chemotherapy.

Hydroxyapatite (HA)-coated implants with porous-coated and grit-blasted surface textures were inserted bilaterally in a paired design into the medial femoral condyles of eight dogs for 16 weeks. The implants were weight-loaded and initially subjected to controlled micromotion of 500 μm during each gait cycle. Histology revealed that five implants in each group had bony anchorage, and the remaining implants were surrounded by fibrous tissue. Push-out testing showed no difference in shear stiffness and strength, while energy absorption for porous-coated implants was increased significantly by threefold. The HA coating delaminated on grit-blasted implants during push-out testing, whereas porous-coated implants predominantly failed at the HA-tissue interface. Coverage, surface area, volume, and thickness of the HA coating were significantly reduced in vivo for porous-coated and grit-blasted implants. In conclusion, a plasma-sprayed porous-coated implant surface seems to give better fixation not only of the HA-coating to the implant surface but also of the implant to the surrounding tissues in comparison to a grit-blasted implant surface. The HA coating was reduced more on fibrous-anchored than on bony-anchored implants, suggesting that micromotion accelerates resorption of HA. Resorbed HA coating was replaced by more bone on porous-coated implants than on grit-blasted implants, which suggests that fixation of porous-coated implants will be durable.

The goal of this study was to examine the effects of a single oral dose of 300,000 international units of either ergocalciferol (D₂) or cholecalciferol (D₃) on the plasma levels of 25-hydroxyvitamin D in patients with alcoholic liver cirrhosis.Inclusion criteria for this study were diagnosis of alcoholic liver cirrhosis and plasma levels of 25-hydroxyvitamin D less than 25 nmol/l. At baseline, patients were divided into Child-Pugh groups A, B, or C and were given one oral dose of 300,000 international units of ergocalciferol (D₂ group, N=23) or cholecalciferol (D₃ group, N=13). Plasma concentrations of 25(OH) vitamin D and vitamin D-binding protein were measured on days 0, 7, 30, and 90.On days 7 and 30, patients from the D₃ group had higher vitamin D levels than patients from the D₂ group (P0.05). On day 7, vitamin D levels were found to correlate with Child-Pugh scores from patients in the D₃ group. For patients in the D₂ group, there was a positive correlation between vitamin D and vitamin D-binding protein as indicated by the area under the concentration versus time curves (Spearmen's ρ=0.64 P0.001).In patients with alcoholic liver cirrhosis, a single oral megadose of cholecalciferol was more effective than ergocalciferol in the treatment of vitamin D deficiency. Severe liver disease and low levels of vitamin D-binding protein were predictors for poor treatment outcomes.

Udgivelsesdato: Oct

The primary source of vitamin D in humans is sun exposure to the skin. The incidence of certain autoimmune diseases correlates positively with latitude. As vitamin D production increases with sun exposure, vitamin D insufficiency is hypothesised to influence the development of autoimmune diseases. In experimental animal and cellular studies in vitro 1.25-(OH)2-vitamin D reduces inflammation. This article discusses the role of vitamin D in inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, and rheumatoid arthritis.

OBJECTIVE: A better understanding of the clinical relevance of delayed gastric emptying (e.g. in diabetes) requires a simple, easily accessible and inexpensive method for measuring it. Two "new" methods for measuring gastric emptying of liquids (the paracetamol absorption test and the 13C-acetate breath test) are compared with the gold standard (gastric emptying scintigraphy (GES)). MATERIAL AND METHODS: The three techniques were used simultaneously in 10 healthy subjects. A gastric emptying time-retention curve was drawn for each technique and the results were compared at the 75%, 50% and 25% retention quartiles. RESULTS: Agreement was found between the paracetamol absorption test and GES (p=0.95; Hotelling's T 2 test). Using the Wagner-Nelson one compartment correction produced a retention curve for the 13C-acetate breath test statistically significantly below GES (p Udgivelsesdato: 2007-Oct

Vitamin D deficiency is extremely prevalent in the elderly. Most often the first symptoms are caused by myopathy with muscle pain, fatigue, muscular weakness and gait disturbances. More severe deficiency causes osteomalacia with deep bone pain, reduced mineralization of bone matrix and low energy fractures. Recent data also suggest that hypovitaminosis D increases the risk of cancer of the prostate, colon and breast. Thus, hypovitaminosis D is associated with many diseases associated with aging. In order to diagnose hypovitaminosis D, the assessment of serum levels of 25-hydroxy vitamin D is mandatory. Screening based on other markers like alkaline phosphatase and parathyroid hormone (PTH) will be incomplete. The treatment of hypovitaminosis D is simple with administration of combined calcium (I g) and vitamin D supplements (calciferol, at least 800 IU). Severe cases may demand initial parenteral administration of vitamin D (repeated injections of 300,000 IU 2-3 times with monthly intervals). More potent analogues are rarely needed. One should aim at achieving S-25(OH)D values in the range 50-100 nmol/l.

For many years myopathy has been known to be part of the osteomalacic symptom complex 1–7. Generally, hypovitaminosis D myopathy (HDM) has been considered a symptom occasionally seen in patients suffering from osteomalacic bone disease, rather than an early presenting symptom of vitamin D deficiency. However, already in 1975 in a group of 30 patients with biopsy proven osteomalacia, Skaria et al 5 found that myopathy was the presenting symptom in 30%, but was clinically detectable in 96.7% of patients. Thus, myopathy is a prominent symptom in osteomalacia. Recently it was shown by Glerup et al 8 that HDM precedes bone involvement in osteomalacia caused by vitamin D deficiency.

content of n-3 fatty acids, antioxidants and fiber, and a low content in sugars and saturated fats. The Mediterranean Diet (MD) comprises all the former nutrients, and thus it has been hypothesized that it could be beneficial for patients with Inflammatory Bowel Disease (IBD). The purpose of our study was to evaluate compliance of IBD patients with the MD and assess its impact on disease activity. Methods: A total of 59 patients [41 with Crohn’s disease (CD) and 18 with ulcerative colitis (UC)] with IBD were enrolled in this cross-sectional study. Clinical data and anthropometric measures were recorded. Dietary intake was assessed using a semi-quantitative food frequency questionnaire. Conversion of foodstuffs to nutrient intake was accomplished with the software Food Processor Plus (ESHA Research, Salem, Oregon). Compliance to MD, was analyzed using the Mediterranean Adequacy Index (MAI), which is calculated as a ratio between foodstuffs consumed that characterize MD and others that are not consistent with MD. MAI enables comparison between the estimated nutrient intake and Healthy Reference National Mediterranean Diet. Disease activity was measured using Harvey Bradshaw Index (HBI) for CD and Cinical Activity Index for UC (CAI). Data analysis was performed with SPSS 20 (IBM SPSS statistics). Results: 37.3% (n = 22) of the studied population were overweight, 10.2% (n = 6) obese, 47.5% (n = 28) normal weight and 5% (n = 3) had a low BMI. Patients with no relapse during the last year showed a higher intake of red meat (40.57±20.3 g/d vs 26.4±20.7 g/d; p = 0.022), canned food (12.9±12.9 g/d vs 8.1±11.9 g/d; p = 0.022), and cured meats (5.6±4.2 g/d vs 4.3±6.8 g/d, p = 0.063). Also, patients in remission had a lower intake of skim milk (6.6±40.3mL vs 55.1±151.2mL; p = 0.082) and a higher intake of canned food (12.4±13.2 g/d vs 5.7±9.9 g/d; p = 0.007), sugar (18.1±16.3 g/d vs 11.0±13.4 g/d; p = 0.098) and coffee (78.3±57.5 vs 51.19±60.9; p = 0.052). Only 14% (n = 8) of our population was classified as compliant with MD (MAI 4.6), whereas the mean MAI was 2.46±5.21. Moreover, no correlation was found between MAI and HBI (r = 0.242; p = 0.304) or CAI (r = 0.201; p = 0.44). Conclusions: The studied population with IBD showed a high prevalence of overweight/obesity and only a small number of patients were compliant with the MD. No association was found between MAI and disease activity. Future interventional nutritional studies aiming at investigating the role of MD in the maintenance of remission or relapse frequency are warranted.

Vitamin D deficiency in immigrants has been known in the UK for 30-40 years. In Denmark, we have become aware of the problem only recently. Of 69 randomly chosen Palestinian women living in Denmark 85% were found to have very low levels of 25-hydroxyvitamin D (10 nmol/l). Vitamin D deficiency is caused by inadequate exposure to sunlight and a low dietary content of vitamin D and calcium. Typical symptoms are muscle pain, muscle spasms, diminished muscular strength, deep bone pain, and paraesthesias. The diagnosis can be tested by three blood tests: serum 25-hydroxyvitamin D, serum PTH, and serum alkaline phosphatase. If a combination of low 25-hydroxyvitamin D and secondary hyperparathyroidism is found, the treatment should be high-dose ergocalciferol or cholecalciferol (100,000 IU weekly). If only (isolated) low 25-hydroxyvitamin D is found, treatment with 1000 IU of ergocalciferol or cholecalciferol in combination with one gram of calcium daily will be adequate.

Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Thomsen J, Charles P, Eriksen EF (University Hospital of Aarhus, and Primary Health Care Centre, City Vest, Aarhus, Denmark). Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000; 247: 260–268. Objectives. Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. Design. Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. Setting. Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. Subjects. Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. Main outcome measures. Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. Results. Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 ± 1.1 nmol L–1, compared with 17.5 ± 2.3 (P

On the basis of five cases the typical clinical picture of patients with severe vitamin D deficiency is presented. The diagnosis can easily be mistaken and it is not uncommon that rheumatic or malignant diseases are suspected instead. By using a simple screening blood test consisting of 25-OH-vitamin D, PTH and alkaline phosphatase most cases will be diagnosed correctly. Important risk factors are reviewed, the most important being: elderly70 years, persons with low exposure to direct sunlight, gastrointestinal diseases and persons in anti-convulsive treatment. A treatment regimen consisting of oral supplementation of 1000-1500 mg calcium + 1000 IU vitamin D to patients with an isolated low 25-OH-vitamin D (20 nmol/l) is recommended. If the patient also has raised values of PTH or alkaline phosphatase an intramuscular dose of 100,000 IU ergocalciferol pr week for one month is given.

Saccharomyces cerevisiae, known as baker's yeast, is normally considered a non-pathogenic yeast. A genetically very similar subtype, S boulardii, is used in a probioticum (Sacchaflor) to prevent antibiotic-associated diarrhoea and in the treatment of recurrent Clostridium difficile associated diarrhoea. The authors present a case report of a 79-year-old woman with rheumatoid arthritis, who after a bowel resection developed S boulardii fungemia. Her postoperative course was complicated by nutritional problems, anaemia and several nosocomial infections including recurrent C difficile associated diarrhoea. The diarrhoea was treated with metronidazole, vancomycin and Sacchaflor. After 13 days of treatment, the patient developed fungemia with S boulardii. Treatment with Sacchaflor was immediately discontinued and the patient was successfully treated with amphotericin B. Fungemia is a rare, but a serious complication to treatment with probiotics. Accordingly, the authors find it important to remind the clinicians of this risk when prescribing probiotics especially to immunocompromised patients.

The case of an 18-year old man with deep venous thrombosis as a complication of a congenital anomaly of the vena cava inferior is presented. The relevant diagnostic procedures are discussed. It is recommended to screen young patients with idiopathic deep venous thrombosis (DVT) for anomalies of the vessels of the vena cava inferior system. The screening can be done by ultrasound scanning, if necessary followed by cavography or CT-scanning. Other reasons for idiopathic DVT are discussed. It is recommended to screen for cancer, coagulopathy and antiphospholipid antibody. If DVT is found on the basis of congenital anomaly of the vena cava inferior, it is recommended to start life long-term anticoagulant therapy.