Biomechanical Properties of Strictures in Crohn's Disease:Can Dynamic Contrast-Enhanced Ultrasonography and Magnetic Resonance Enterography Predict Stiffness?

Strictures and abdominal pain often complicate Crohn’s disease (CD). The primary aim was to explore whether parameters obtained by preoperative contrast-enhanced (CE) ultrasonography (US) and dynamic CE MR Enterography (DCE-MRE) of strictures associates with biomechanical properties. CD patients undergoing elective small intestinal surgery were preoperatively examined with DCE-MRE and CEUS. The excised intestine was distended utilizing a pressure bag. Luminal and outer bowel wall cross-sectional areas were measured with US. The circumferential stricture stiffness (Young’s modulus E) was computed. Stiffness was associated with the initial slope of enhancement on DCE-MRE (ρ = 0.63, p = 0.007), reflecting active disease, but lacked association with CEUS parameters. For structural imaging parameters, inflammation and stricture stiffness were associated with prestenotic dilatation on US (τ(b) = 0.43, p = 0.02) but not with MRE (τ(b) = 0.01, p = 1.0). Strictures identified by US were stiffer, 16.8 (14.0–20.1) kPa, than those graded as no or uncertain strictures, 12.6 (10.5–15.1) kPa, p = 0.02. MRE global score (activity) was associated with E (ρ = 0.55, p = 0.018). Elastography did not correlate with circumferential stiffness. We conclude that increasing activity defined by the initial slope of enhancement on DCE-MRE and MRE global score were associated with stricture stiffness. Prestenotic dilatation on US could be a potential biomarker of CD small intestinal stricture stiffness

Magnetic Resonance Enterography and Histology in Patients With Fibrostenotic Crohn's Disease: A Multicenter Study

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

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.</p

A proposal for a study on treatment selection and lifestyle recommendations in chronic inflammatory diseases:A danish multidisciplinary collaboration on prognostic factors and personalised medicine

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

Cancer suspicion, referral to cancer patient pathway and primary care interval: a survey and register study exploring 10 different types of abdominal cancer

BACKGROUND: 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). OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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