(1) Background: Fecal calprotectin (FC) correlates well with colonic inflammatory activity of Crohn’s disease (CD); data about relation of FC and small bowel (SB) lesions are still contradictory. The main aim was to analyze the relationship between FC levels and SB inflammatory activity in patients with established or suspected Crohn’s disease, assessed by small bowel capsule endoscopy (SBCE) or magnetic resonance enterography (MRE). (2) Methods: Two cohorts of patients were included: 1. Prospective data were collected from patients with established or suspected CD who underwent SBCE and FC (Cohort A); 2. A retrospective cohort of patients who underwent MRE and FC determination (Cohort B). Different cutoffs for FC were tested in both cohorts. (3) Results: 83 patients were included and 66 were finally analyzed. A total of 69.6% had SB lesions seen by SBCE (n = 25) or MRE (n = 21). FC mean levels were 605.74 + 607.07 μg/g (IQ range: 99.00–878.75), being significantly higher in patients with SB lesions compared to patients without lesions (735.91 + 639.70 μg/g (IQ range: 107.75–1366.25) vs. 306.35 + 395.26 μg/g (IQ range: 78.25–411.0), p < 0.005). For cohort A, 25 out of 35 patients had SB lesions and a significant correlation between Lewis Score and FC levels was achieved (R²: 0.34; p = 0.04). FC sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive values (NPV) for predicting SB lesions were 80%, 50%, 80%, and 50%, respectively, for FC > 100 µg/g. For cohort B, inflammatory SB activity, measured by MaRIA score, was detected in 21 out of 31 patients (67.7%). Patients with positive findings in MRE had significantly higher values of FC than those with no lesions (944.9 + 672.1 µg/g vs. 221 + 212.2 µg/g, p < 0.05). S, E, PPV, and NPV of FC were 89%, 50%, 77.2%, and 71.4% for FC levels > 100 µg/g. The higher sensitivity and specificity of the FC levels for the detection of SB lesions with SBCE and MRE was obtained for an FC cutoff >265 μg/g and >430 μg/g, respectively. (4) Conclusions: FC has a good correlation with the presence of SB lesions, assessed by SBCE and MRE, in patients with established or suspected Crohn’s disease. However, the ideal cutoff is here proven to be higher than previously reported. Multicenter and large prospective studies are needed in order to establish definitive FC cutoff levels.

Background and Aims: Tofacitinib, a Janus kinase inhibitor, is approved for the treatment of moderate-to-severe ulcerative colitis. Nonetheless, 40-60% of patients will not respond adequately. The mechanisms underlying responses to tofacitinib remain unknown. Methods: We applied single-cell and/or bulk RNA analysis to biopsies (n = 23 and 63, respectively) from ulcerative colitis patients (n = 31) before and after tofacitinib treatment. Response was assessed using endoscopic and clinical criteria. In vitro-derived macrophages and primary intestinal fibroblasts were used to validate our findings. Results: Forty percent of patients responded to tofacitinib. Responders exhibited higher baseline JAK-STAT activity, while non-responders had increased baseline NF-kB pathway activation. Response was associated with significant changes in the abundance and/or activation of immune, epithelial, and stromal cells and the downregulation of S100A9, FCGR3A, MMP12 in resident macrophages. In contrast, non-responders showed a significant increase in the number and activation of macrophages and fibroblasts following tofacitinib treatment, including upregulation of MMP9, IL1B, IL6, CXCL1, CXCL8, and S100A9 compared to baseline. In monocyte-derived macrophages tofacitinib drove the hyperactivation of macrophages in response to lipopolysaccharide, but not TNF or IFNγ. This effect is dependent on the inhibition of IL-10 signaling, which is abundantly induced in response to LPS, but not to TNF or IFNγ. In contrast, cultured fibroblasts, which produced no IL-10 regardless of the stimuli, showed no hyperactivation when pre-treated with tofacitinib. Conclusions: We conclude that resistance to tofacitinib is mediated by the hyperactivation of myeloid cells and we identify IL-10-dependent macrophages as one cellular subset contributing to this resistance.

Background Motorized Spiral Enteroscopy (MSE) reduces procedure time and increases insertion depth into the small bowel; however, there is scarce evidence on factors affecting MSE efficacy. Aims To evaluate diagnostic yield and adverse events of MSE including patients with prior major abdominal surgery. Methods A prospective observational study was conducted on patients undergoing MSE from June 2019 to December 2021. Demographic characteristics, procedure time, depth of maximum insertion (DMI), technical success, diagnostic yield, and adverse events were collected. Results Seventy-four anterograde (54.4%) and 62 retrograde (45.6%) enteroscopies were performed in 117 patients (64 males, median age 67 years). Fifty patients (42.7%) had prior major abdominal surgery. Technical success was 91.9% for anterograde and 90.3% for retrograde route. Diagnostic yield was 71.6% and 61.3%, respectively. The median DMI was 415 cm (264–585) for anterograde and 120 cm (37–225) for retrograde enteroscopy. In patients with prior major abdominal surgery, MSE showed significantly longer small bowel insertion time (38 vs 29 min, p = 0.004), with similar diagnostic yield (61 vs 71.4%, p = 0.201) and DMI (315 vs 204 cm, p = 0.226). The overall adverse event rate was 10.3% (SAE 1.5%), with no differences related to prior abdominal surgery (p = 0.598). Patients with prior surgeries directly involving the gastrointestinal tract showed lower DMI (189 vs 374 cm, p = 0.019) with equal exploration time (37.5 vs 38 min, p = 0.642) compared to those with other abdominal surgeries. Conclusions MSE is effective and safe in patients with major abdominal surgery, although longer procedure times were observed. A lower depth of insertion was detected in patients with gastrointestinal surgery.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017–2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients’ outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March–July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged ≥ 60 years (OR 7.1, 95% CI: 1.8–27 and 4.5, 95% CI: 1.3–15.9), while having ≥2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3–11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.