Re-resection Rates and Disease Recurrence in Crohn's Disease - A Population-Based Study Using Individual-Level Patient Data.

BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.

Non-TGFß profibrotic signaling in ulcerative colitis after in vivo experimental intestinal injury in humans.

Although impaired regeneration is important in many gastrointestinal diseases including ulcerative colitis (UC), the dynamics of mucosal regeneration in humans are poorly investigated. We have developed a model to study these processes in vivo in humans. Epithelial restitution (ER) and extracellular matrix (ECM) regulation after an experimental injury of the sigmoid colonic mucosa was assessed by repeated high resolution endoscopic imaging, histologic assessment, RNA sequencing, deconvolution analysis, and 16S rDNA sequencing of the injury niche microbiome of 19 UC patients in remission and 20 control subjects. Human ER had a 48-hour lag before induction of regenerative epithelial cells (WAE and TA cells) along with increase of fibroblast derived stem cell growth factor Gremlin 1 mRNA (GREM1). However, in UC deconvolution data showed aby rapid induction of inflammatory fibroblasts, and upregulation of major structural ECM collagen mRNAs and along with tissue inhibitor of metalloproteinase 1 (TIMP1) suggesting increased profibrotic ECM deposition. No change was seen in transforming growth factor ß (TGFß) mRNA whereas and the profibrotic cytokines interleukin 13 (IL13) and IL11 were upregulated in UC suggesting that human post injury responses could be TGFß-independent. In conclusion, we found distinct regulatory layers of regeneration in the normal human colon and a potential targetable profibrotic dysregulation in UC that could lead to long-term end organ failure - i.e., intestinal damage.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy.

BACKGROUND: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. METHODS: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. RESULTS: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69-2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1-7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 µg/mL (range 0.005-0.12 µg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4-6.9] µg/mL) and without (3.1 [range 0.7-11.0] µg/mL) infections during the first year of life (P = .41). CONCLUSIONS: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review.

Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis α monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.

The effect of induced hyperammonaemia on sleep and melanopsin-mediated pupillary light response in patients with liver cirrhosis: A single-blinded randomized crossover trial.

BACKGROUND & AIMS: Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis. METHODS: The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days. RESULTS: The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS. CONCLUSIONS: Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests. TRIAL REGISTRATION: Registration number: NCT04771104.

Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study.

INTRODUCTION: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement.

BACKGROUND AND AIMS: No consensus exists on defining intestinal ultrasound response, transmural healing, or transmural remission in inflammatory bowel disease, nor clear guidance for optimal timing of assessment during treatment. This systematic review and expert consensus study aimed to define such recommendations, along with key parameters included in response reporting. METHODS: Electronic databases were searched from inception to July 26, 2021, using pre-defined terms. Studies were eligible if at least two intestinal ultrasound [IUS] assessments at different time points during treatment were reported, along with an appropriate reference standard. The QUADAS-2 tool was used to examine study-level risk of bias. An international panel of experts [n = 18] rated an initial 196 statements [RAND/UCLA process, scale 1-9]. Two videoconferences were conducted, resulting in additional ratings of 149 and 13 statements, respectively. RESULTS: Out of 5826 records, 31 full-text articles, 16 abstracts, and one research letter were included; 83% [40/48] of included studies showed a low concern of applicability, and 96% [46/48] had a high risk of bias. A consensus was reached on 41 statements, with clear definitions of IUS treatment response, transmural healing, transmural remission, timing of assessment, and general considerations when using intestinal ultrasound in inflammatory bowel disease. CONCLUSIONS: Response criteria and time points of response assessment varied between studies, complicating direct comparison of parameter changes and their relation to treatment outcomes. To ensure a unified approach in routine care and clinical trials, we provide recommendations and definitions for key parameters for intestinal ultrasound response, to incorporate into future prospective studies.

Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.

IBD metabonomics predicts phenotype, disease course, and treatment response.

Metabonomics in inflammatory bowel disease (IBD) characterizes the effector molecules of biological systems and thus aims to describe the molecular phenotype, generate insight into the pathology, and predict disease course and response to treatment. Nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and integrated NMR and MS platforms coupled with multivariate analyses have been applied to create such metabolic profiles. Recent advances have identified quiescent ulcerative colitis as a distinct molecular phenotype and demonstrated metabonomics as a promising clinical tool for predicting relapse and response to treatment with biologics as well as fecal microbiome transplantation, thus facilitating much needed precision medicine. However, understanding this complex research field and how it translates into clinical settings is a challenge. This review aims to describe the current workflow, analytical strategies, and associated bioinformatics, and translate current IBD metabonomic knowledge into new potential clinically applicable treatment strategies, and outline future key translational perspectives.

Fluorescence-based tracing of transplanted intestinal epithelial cells using confocal laser endomicroscopy.

BACKGROUND: Intestinal stem cell transplantation has been shown to promote mucosal healing and to engender fully functional epithelium in experimental colitis. Hence, stem cell therapies may provide an innovative approach to accomplish mucosal healing in patients with debilitating conditions such as inflammatory bowel disease. However, an approach to label and trace transplanted cells, in order to assess engraftment efficiency and to monitor wound healing, is a key hurdle to overcome prior to initiating human studies. Genetic engineering is commonly employed in animal studies, but may be problematic in humans due to potential off-target and long-term adverse effects. METHODS: We investigated the applicability of a panel of fluorescent dyes and nanoparticles to label intestinal organoids for visualization using the clinically approved imaging modality, confocal laser endomicroscopy (CLE). Staining homogeneity, durability, cell viability, differentiation capacity, and organoid forming efficiency were evaluated, together with visualization of labeled organoids in vitro and ex vivo using CLE. RESULTS: 5-Chloromethylfluorescein diacetate (CMFDA) proved to be suitable as it efficiently stained all organoids without transfer to unstained organoids in co-cultures. No noticeable adverse effects on viability, organoid growth, or stem cell differentiation capacity were observed, although single-cell reseeding revealed a dose-dependent reduction in organoid forming efficiency. Labeled organoids were easily identified in vitro using CLE for a duration of at least 3 days and could additionally be detected ex vivo following transplantation into murine experimental colitis. CONCLUSIONS: It is highly feasible to use fluorescent dye-based labeling in combination with CLE to trace intestinal organoids following transplantation to confirm implantation at the intestinal target site.

Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease.

Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re-establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grown in vitro in organoid structures, though only a fraction of the cells contained are stem cells with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two-dimensional and three-dimensional culture protocols, as well as co-culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing for efficient clinical application is in progress. In vitro culture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact-dependent stimuli and structural support. The aim of this review was to discuss medium compositions and support matrices for optimal intestinal stem cell culture, as well as potential modifications to advance clinical use in IBD.

Objective Quantification of Immune Cell Infiltrates and Epidermal Proliferation in Psoriatic Skin: A Comparison of Digital Image Analysis and Manual Counting.

Digital pathology and image analysis have developed extensively during the last couple of years. Especially the advance in whole-slide scanning, software, and computer processing makes it possible to apply these methods in tissue-based research. Today this task is dominated by tedious manual assessments by pathologists with the interobserver and intraobserver variation this includes. Automated quantitative assessment of immunohistochemical staining has the potential to objectively extract numerical measures from cell and tissue structures, and allows efficient high throughput analysis in clinical research. Published data of manual cell counts in psoriatic skin samples were in this study reevaluated using the digital image analysis (DIA) software. Whole slides immunohistochemically stained for CD3, CD4, CD8, CD45R0, and Ki-67 were scanned and quantitatively evaluated using simple threshold analysis. Regression analysis with R values in the range of 0.85 to 0.95 indicates a good correlation between the manual count of cell numbers and the staining density obtained by automated DIA. Moreover, we show that the automated image analysis is reliable over a broad range of thresholds and that it is robust to differences in staining intensities and hence useful for high throughput analysis. DIA is a viable technical approach for automated cell quantification. Its output highly correlates to the conventional manual cell counting and hence allows for increasing the throughput and reducing the analysis time significantly.

Regulation of antiapoptotic and cytoprotective pathways in colonic epithelial cells in ulcerative colitis.

Ulcerative colitis is an inflammatory bowel disease involving the colon resulting in bloody diarrhea and increased risk of colorectal cancer in certain patient subgroups. Increased apoptosis in the epithelial cell layer causes increased permeability, especially during flares; this leads to translocation of luminal pathogens resulting in a continued inflammatory drive. The present work investigates how epithelial apoptosis is regulated in ulcerative colitis. The main results are that Fas mediated apoptosis is inhibited during flares of ulcerative colitis, probably by an upregulation of cellular inhibitor of apoptosis protein 2 (cIAP2) and cellular FLICE-like inhibitory protein. cIAP2 is upregulated in regenerative epithelial cells both in ulcerative colitis and in experimental intestinal wounds. Inhibition of cIAP2 decreases wound healing in vitro possibly through inhibition of migration. Altogether, it is shown that epithelial cells in ulcerative colitis responds to the hostile microenvironment by activation of cytoprotective pathways that tend to counteract the cytotoxic effects of inflammation. However, the present studies also show that epithelial cells produce increased amounts of reactive oxygen species during stimulation with tumor necrosis factor-α and interferon-γ resulting in DNA instability. The combined effect of increased DNA-instability and decreased apoptosis responses could lead to neoplasia.

GM6001 Increases Anastomotic Leakage following Colonic Obstruction Possibly by Impeding Epithelialization.

BACKGROUND: Emergency operations performed on an obstructed colon are accompanied by an increased risk of anastomotic insufficiency. Tissue-destructive matrix metalloproteinase (MMP) activity is elevated in the obstructed colon and contributes to a loss of suture-holding submucosal collagen, which may be mediated by tumor necrosis factor (TNF)-α. Our aim was to study the effect of the non-selective MMP and TNF-α converting enzyme (TACE) inhibitor GM6001 (30 mg/kg) on anastomosis repair in obstructed left colon. GM6001 has been proved to be highly efficacious in elective anastomosis rodent models. METHODS: A partial obstruction of the distal colon was induced in male Sprague-Dawley rats. After 4 d the obstructed colonic segment was resected, and an end-to-end anastomosis was constructed. Seven days later, the anastomoses were evaluated for clinical leakage. Histopathological and immunohistochemical assessments were also performed. Finally, the direct effect of GM6001 on epithelialization was studied in cultured colonic epithelial cells. RESULTS: Unlike the robust beneficial effect on anastomosis under uncomplicated conditions, here GM6001 had a negative impact on anastomotic wound healing following colonic obstruction and substantially (p=0.004) more rats in the GM6001 group (75%) than in the control group (11%) had developed anastomotic leakage. In the anastomotic wounds, the myofibroblast abundance and cell proliferation were similar in the two groups. Histologically, GM6001 treatment resulted in wider and minimally epithelialized wounds that were commonly necrotic on the luminal side and infiltrated with numerous granulocytes. In vitro, GM6001 also delayed (p=0.026) epithelialization of denuded intestinal epithelium grown on type I collagen. CONCLUSIONS: Non-selective MMP/TACE inhibition with GM6001 increased the anastomotic complications following colon obstruction. Inhibition of epithelialization is one possible mechanism responsible for the increased leakage following GM6001 treatment.

Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential.

[Ulcerative colitis].

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive years, emphasis is additionally put on the management of pregnant patients with UC.

[Ulcerative colitis]. / Colitis ulcerosa.

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive years, emphasis is additionally put on the management of pregnant patients with UC.