Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.

A Population-Based Cross-Sectional Study of Paediatric Coeliac Disease in Catalonia Showed a Downward Trend in Prevalence Compared to the Previous Decade.

(1) Background: Previous studies showed an increased prevalence and incidence of coeliac disease (CD) over time. The objective is to ascertain whether the CD prevalence in Catalonia (a region of Southern Europe) among children aged 1-5 is as high as previously found in 2004-2009; (2) Methods: From 2013 to 2019, 3659 subjects aged 1-5 years were recruited following the previously used methodology. Factors with a potential impact on CD prevalence were investigated; (3) Results: In 2013-2019, 43/3659 subjects had positive serology, giving a standardised seroprevalence of 12.55/1000 (95% CI: 8.92; 17.40), compared to 23.62 (13.21; 39.40) in 2004-2007. The biopsy-proven crude prevalence was 7.92/1000 (95% CI: 5.50; 11.30), and the crude prevalence based on ESPGHAN criteria was 8.74/1000 (95% CI: 6.20-12.30). In contrast to 2004-2009, we did not find differences in the seroprevalence rates between 1 and 2 years vs. 3 and 4 years of age (age percentage of change -7.0 (-29.5; 22.8) vs. -45.3 (-67.5; -8.0)). Rotavirus vaccination was the most remarkable potential protective factor (48% vs. 9% in 2004-2009; p < 0.0001), but not the time of gluten introduction. (4) Conclusion: The present study did not confirm a worldwide CD prevalence increase and emphasizes the need to perform prevalence studies over time using the same methodology in the same geographical areas.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

BACKGROUND: Previous studies suggested that Interleukin-10 (IL-10) depletion in Crohn's disease (CD) could predict outcome. AIM: To determine IL-10 in blood and at different intestinal locations in patients with active CD and to assess its potential prognostic capacity to identify aggressive CD. METHODS: Twenty-three patients with CD were included. Ulcerative colitis (UC), infectious colitis and healthy individuals acted as controls. Serum and mucosal samples were taken at baseline and 1 month after steroid initiation in CD patients. Patients were classified according to steroid response. Control samples were obtained from different intestinal locations. IL-10 expression was measured with real-time polymerase chain reaction, immunofluorescence (intestine) and ELISA (serum, biopsy cultures' supernatants and tissue homogenates). RESULTS: CD and UC showed an increase in IL-10 messenger RNA (mRNA) versus controls (p < .0001) in mucosa, whereas IL-10 protein secretion was increased in all types of intestinal inflammation (p < .001). No differences in IL-10 mRNA were found in CD at baseline regarding steroid response, but levels decreased in non-responders versus responders (p = .027) and were restored with rescue therapy. Serum IL-10 was increased in steroid-refractory CD at baseline and after treatment. CONCLUSIONS: Abnormal IL-10 levels in refractory patients in both mucosa and blood have physiopathological relevance and may have potential clinical applications.

Efficacy of Hepatitis B Virus Vaccines HBVaxpro40© and Fendrix© in Patients with Chronic Liver Disease in Clinical Practice.

Chronic liver disease results in a low response rate to the hepatitis B virus vaccine. Information on the efficacy of the double adjuvanted vaccine FENDRIX® (3-O-desacyl-4'-monophosphoryl lipid A and aluminum phosphate) and single adjuvant HBVAXPRO®40 (aluminum hydroxyphosphate sulfate) in chronic liver disease is scarce. The primary aim of this prospective study in clinical practice was to evaluate the effectiveness of HBVAXPRO®40 and FENDRIX® in this setting. Patients received HBVAXPRO® (0, 1 and 6 months) or FENDRIX® (0, 1, 2 and 6 months) depending on availability. Clinical data and anti-HBs levels were collected at 2, 6 and 12 months. A total of 125 patients were included (mean age 61.8 years; 57.6% males; 43.2% liver cirrhosis; 75.9% Child A and 24.1% Child B): 76 were vaccinated with HBVAXPRO® and 49 with FENDRIX®. There were no significant differences between the two vaccines. The overall response rates at 2, 6 and 12 months were 76.8, 72.8 and 59.2%, respectively. In the univariate analysis, active alcohol intake, alcohol etiology, liver cirrhosis and ultrasound signs of portal hypertension were associated with a lower response to vaccination, whereas in the multivariate analysis, liver cirrhosis was the only factor that significantly increased the likelihood of nonresponse (OR 10.5). HBVAXPRO® and FENDRIX® are good options for HBV vaccination in patients with chronic liver disease.

Strange coincidence in the gut: pseudomelanosis duodeni diagnosed by capsule endoscopy and active bleeding due to angiodysplasia.

We present the case of an 82-year-old male with a medical history of hypertension, dyslipidemia, diabetes mellitus, chronic renal failure, ischemic heart disease and iron deficiency anemia. He was under therapy with hydralazine, furosemide, amlodipine, valsartan, nitroglycerin patches, bisoprolol, omeprazole, doxazosin, human insulin and oral iron. The patient presented at our institution with melena. Initial gastroscopy showed fresh blood and a gastric angiodysplasia that was treated with argon plasma coagulation (APC). Three months later, he suffered a new episode of bleeding and a small bowel capsule endoscopy (SBCE) was subsequently indicated.

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports.

BACKGROUND: SARS-CoV-2 may produce intestinal symptoms that are generally mild, with a small percentage of patients developing more severe symptoms. The involvement of SARS-CoV-2 in the physiopathology of bowel damage is poorly known. Transmission electron microscopy (TEM) is a useful tool that provides an understanding of SARS-CoV-2 invasiveness, replication and dissemination in body cells but information outside the respiratory tract is very limited. We report two cases of severe intestinal complications (intestinal lymphoma and ischaemic colitis) in which the presence of SARS-CoV-2 in intestinal tissue was confirmed by TEM. These are the first two cases reported in the literature of persistence of SARS-CoV-2 demonstrated by TEM in intestinal tissue after COVID 19 recovery and SARS-CoV-2 nasopharyngeal clearance. CASE PRESENTATION: During the first pandemic peak (1st March-30th April 2020) 932 patients were admitted in Hospital Universitari Mútua Terrassa due to COVID-19, 41 (4.4%) required cross-sectional imaging techniques to assess severe abdominal pain and six of them (0.64%) required surgical resection. SARS-CoV-2 in bowel tissue was demonstrated by TEM in two of these patients. The first case presented as an ileocaecal inflammatory mass which turned to be a B-cell lymphoma. Viral particles were found in the cytoplasm of endothelial cells of damaged mucosa. In situ hybridization was negative in tumour cells, thus ruling out an oncogenic role for the virus. SARS-CoV-2 remained in intestinal tissue 6 months after nasopharyngeal clearance, suggesting latent infection. The second patient had a severe ischaemic colitis with perforation and SARS-CoV-2 was also identified in endothelial cells. CONCLUSIONS: Severe intestinal complications associated with COVID-19 are uncommon. SARS-CoV-2 was identified by TEM in two cases, suggesting a causal role in bowel damage.

Long-Term Effect of a Gluten-Free Diet on Diarrhoea- or Bloating-Predominant Functional Bowel Disease: Role of the 'Low-Grade Coeliac Score' and the 'Coeliac Lymphogram' in the Response Rate to the Diet.

1. BACKGROUND: The long-term effect of a gluten-free diet (GFD) on functional bowel disorders (FBDs) has been scarcely studied. The aim was to assess the effect of a GFD on FBD patients, and to assess the role of both the low-grade coeliac score and coeliac lymphogram in the probability of response to a GFD. 2. METHODS: 116 adult patients with either predominant diarrhoea or abdominal bloating, fulfilling Rome IV criteria of FBD, were treated with a GFD. Duodenum biopsies were performed for both pathology studies and intraepithelial lymphocyte subpopulation patterns. Coeliac lymphogram was defined as an increase in TCRγδ+ cells plus a decrease in CD3- cells. A low-grade coeliac score >10 was considered positive. 3. RESULTS: Sustained response to GFD was observed in 72 patients (62%) after a median of 21 months of follow-up, who presented more often with coeliac lymphogram (37.5 vs. 11.4%; p = 0.02) and a score >10 (32 vs. 11.4%; p = 0.027) compared to non-responders. The frequency of low-grade coeliac enteropathy was 19.8%. 4. CONCLUSION: A GFD is effective in the long-term treatment of patients with previously unexplained chronic watery diarrhoea- or bloating-predominant symptoms fulfilling the criteria of FBD. The response rate was much higher in the subgroup of patients defined by the presence of both a positive low-grade coeliac score and coeliac lymphogram.

Clinical outcome after anti-tumour necrosis factor therapy discontinuation in 1000 patients with inflammatory bowel disease: the EVODIS long-term study.

BACKGROUND: The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. AIMS: To assess the risk of relapse in the long-term after anti-TNF discontinuation. METHODS: This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. RESULTS: This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. CONCLUSIONS: A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Clinical impact of endoscopic ultrasound in the study of adrenal gland: cytomegalovirus infection mimicking a neoplasic hypercaptation in PET.

A 71-year-old woman with stage IV follicular lymphoma in complete remission since 2006. In March 2019, chemotherapy treatment was initiated due to a relapse with pulmonary involvement. At three months, the patient presented a bad general condition and fever. A positron emission tomography (PET) showed abnormal metabolic activity in the left adrenal gland (AG), suggestive of lymphoma recurrence.

Real-world long-term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry.

BACKGROUND: Data on the long-term administration of ustekinumab in recommended doses are limited. AIM: To assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn's disease (CD). METHODS: Multi-centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. RESULTS: A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti-TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. CONCLUSION: After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.