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Introduction: The COVID-19 pandemic has led to changes in society, affecting the mental health of the population, particularly in childhood and adolescence. Minors with previous psychiatric pathology may show increased symptomatology (depression, anxiety or stress) both during confinement and persistently after it. Objective: To assess the evolution of clinical symptomatology and the emotional impact on minors attending our Day Hospital and their caregivers one year after the end of COVID-19 confinement. Method: Clinical symptoms (emotional and behavioural) were assessed during confinement and/or one year later in 81 participating families. Clinical differences between both time points were analyzed, firstly, for two groups of minors and independent caregivers and, secondly, for the same group of minors and caregivers evaluated on both occasions. Results: Longitudinal analyses showed trends to an increase in symptomatology in the dimensions of depression, anxiety, and affective and behavioral control. However, these significant differences weren't maintained after correction for multiple comparisons. Their family members and caregivers also showed no significant changes between the two time points. Conclusions: The clinical symptomatology of minors with psychiatric pathology has been maintained one year after the end of the confinement due to COVID-19. Regular follow-up, good parent-child communication and adequate social support on the minor-caregiver dyad should be encouraged to promote proper emotional management. [ABSTRACT FROM AUTHOR]

Data regarding bowel preparation in patients with Inflammatory Bowel Disease (IBD) are scarce. To compare efficacy, safety, and tolerability of low-volume preparations in patients with IBD. Single-center, randomized, prescriber, and colonoscopist-blinded clinical trial. IBD outpatients undergoing colonoscopy were randomized 1:1:1 to receive 1 Liter-polyethylene glycol-ascorbate (1L-PEG), 2 Liters-PEG, or sodium picosulfate (SP). The primary endpoint was percentage of quality cleansing assessed via the Boston Bowel Preparation Scale (BBPS ≥6, segments ≥2). Secondary endpoints were total high quality cleansing (BBPS 8 or 9), high-quality segmental BBPS (≥2), and patients' tolerability, symptoms, and satisfaction, assessed by questionnaires. Safety was monitored by adverse event reporting, laboratory evaluation at colonoscopy, and telephonic follow-up. Ninety-two patients were included (33 1L-PEG, 28 2L-PEG, and 31 SP). No significant differences between preparations were observed in quality or high-quality total BBPS or high-quality segmental BBPS. Complete intake of the solution was higher for SP (p = 0.006) and lower for 1L-PEG (p = 0.02) compared to 2L-PEG intake (p = 0.55). Clinically irrelevant hyponatremia was higher in the SP group (p < 0.0001). SP instructions were easier to understand from patient's point of view (p = 0.01). Willingness to retake was higher with SP (p < 0.0001) and less for 1L-PEG (p < 0.0001). No serious adverse events were reported. We observed no differences in efficacy between low-volume preparations in patients with IBD. Complete intake was higher for SP and lower for 1L-PEG. SP and 2L-PEG instructions were better understood and graded, and SP was more likely to be retaken. Willingness to retake was lower for 1L-PEG. No serious adverse events were reported. No differences in terms of efficacy were regarded in this clinical trial comparing low-volume preparations for colonoscopy in patients with IBD: however, Sodium Pisoculfate is better tolerated and accepted from patient's point of view. No serious adverse events were reported. [ABSTRACT FROM AUTHOR]

Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients. [ABSTRACT FROM AUTHOR]

HLA-DQA1*05 was not significantly associated with ADA positivity (Model-1 [IM-UNITI, P = 0.25; UNIFI, P = 0.85]), regardless of immunomodulator use (Model-2 [IM-UNITI, P = 0.23; UNIFI, P = 0.84]) or anti-TNF failure history (Model-3 [IM-UNITI, P = 0.96; UNIFI, P = 0.44]). Crohn's disease (CD) and ulcerative colitis (UC) patients carrying the human leukocyte antigen (HLA)-DQA1*05 allele and treated with infliximab/adalimumab have a 2-fold risk of anti-drug antibody (ADA) formation and potential loss of response (LOR). We investigated the relationship between HLA-DQA1*05 and ustekinumab LOR, ADA formation, and serum trough drug concentrations in the pivotal IM-UNITI (CD) and UNIFI (UC) studies. [Extracted from the article]

INTRODUCTION: Crohn’s disease (CD) varies by location, potentially affecting therapy efficacy and surgery risk, although research on this topic is conflicting. This study aims to investigate the independent association between CD location and therapeutic patterns. METHODS: We analyzed patients with CD diagnosed from January 2005 to May 2023 registered in the nationwide ENEIDA registry. A univariate Cox regression analysis assessed the association of disease location with biologic use and persistence (with treatment discontinuation as a failure event), as well as the use of intestinal resections. A multivariate model was constructed to evaluate the independent association of disease location with therapeutic patterns, controlling for potential confounders such as sex, age at inclusion and diagnosis, disease duration and behavior, previous surgery or biological therapy, extraintestinal manifestations, and perianal disease. RESULTS: The study included 17,292 patients with a median follow-up period of 6 years (interquartile range 2–10 years). Ileocolonic location was associated with a higher biologic use than colonic location (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.22–1.38) and ileal disease (HR 1.21, 95% CI 1.16–1.27), independently predicting biologic use (P < 0.001). Ileal location was associated with a lower biologic persistence than ileocolonic location (HR 1.14, 95% CI 1.07–1.21) and colonic disease (HR 1.10, 95% CI 1.01–1.20), independently predicting biologic persistence (P 5 0.019). Ileal disease was associated with a higherlikelihood of intestinal resections than colonic (HR 2.82, 95% CI 2.45–3.25) and ileocolonic location (HR 1.13, 95% CI 1.05–1.22), independently predicting the use of surgery (P < 0.001). DISCUSSION: CD location with ileal predominance is associated with a distinct therapeutic pattern, including higher biologic use, lower treatment persistence, and increased rates of intestinal resections. [ABSTRACT FROM AUTHOR]

Table olives are the most important fermented vegetable in the Mediterranean countries. In a continuous effort to improve the quality of this food, this work applies an experimental design with four variables to study the use of 1-methylcyclopropene (1-MCP, 2.85 µL/L) in combination with a light heat shock (65 °C, 5 min) and dimethyl dicarbonate (DMDC, 83 mg/L), during the processing of Spanish style and natural table olives. Fruits processed in the Spanish style exhibited higher moisture levels, luminance, and combined acidity. On the contrary, natural olives contained more sugars, had a firmer texture, and displayed a greener colour. Our results show that applying 1-MCP, heat shock, and DMDC can positively impact the processing of Spanish style and natural table olives and influence their physicochemical characteristics. Adding DMDC to the initial brine caused colour degradation but lowered the pH. Using 1-MCP with a light heat shock improved the sugar content and luminance of olives and increased the titratable acidity in the brine. Applying 1-MCP to the Spanish style enhanced the luminosity (brightness) and, when combined with DMDC, led to the lowest pH levels. Further research at an industrial scale is necessary to validate these results and study their influence on microorganisms. These treatments could have applications in developing new table olive processing methods that allow for more predictable products. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats. Methods: Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (107 cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed. Results: Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (− 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (− 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment. Conclusions: ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis. [ABSTRACT FROM AUTHOR]

Aims: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid‐dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. Methods: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. Results: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15–25 mg) and a median time of 14 months (interquartile range, 4–52 months). Thirty‐seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX‐related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22–7.69; P =.017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23–6.68; P =.015) variants, and smoking (OR 2.61, 95% CI 1.12–6.05; P =.026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX‐related adverse effects (OR 2.78, 95% CI 1.26–6.13, P =.011). Conclusion: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD. [ABSTRACT FROM AUTHOR]

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) treated with biologic and/or immunosuppressant drugs are at increased risk for opportunistic infections. Seroprevalence studies can confirm the diagnosis of SARS-CoV-2 infections as well as the associated risk factors. This is a descriptive study which primary endpoints were to highlight the prevalence of SARS-CoV-2 antibodies in a cohort of IBD patients in March 2021, and to analyze seroconversion in patients with known COVID-19 infection and its relationship with IBD treatments. Patients filled in a questionnaire about symptoms of COVID-19 infection and clinical information about their IBD. All included patients were tested for SARS-CoV-2 antibodies. 392 patients were included. Among patients with clinical infection, 69 patients (17,65%) were IgG-positive, 286 (73,15%) IgG-negative and 36 (9,21%) indeterminate. In relation to seroconversion among patients under biologic treatment, 13 patients of the 23 with a previous positive CRP developed antibodies (56.5%). However, when the influence of immunosuppressive treatment on the probability of developing antibodies was analyzed, no significant differences were seen between those patients with or without treatment (77.8% vs. 77.1%, p = 0.96). In our cohort of IBD patients, after one year of pandemic, there were 18.64% IgG positive patients, a higher prevalence than the general population (15.7%). [ABSTRACT FROM AUTHOR]

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case–control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March–July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3–5.9), occupational risk (OR: 2.9; 95%CI: 1.8–4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2–2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09–0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated.Aims: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC.Methods: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis.Results: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007).Conclusions: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy. [ABSTRACT FROM AUTHOR]

We present thoughts and considerations about a pilot project that we are doing in a Child and Adolescent Psychiatry Day Hospital with adolescents which are related by symptoms or genetic with psychosis. Because of being a period in which it is needed the searching of identities, from them the group one, and the vulnerability that this period produces; we decided to do this group therapy project in the prodromal phase with preventive purpose. [ABSTRACT FROM AUTHOR]

The study of the table olive biofilms is usually achieved using a stomacher which causes the physical rupture of pitted olives in an osmotic media but does not differentiate between those on the surface and inside the fruits. Besides, the high amount of eukaryotic DNA released from the vegetable cells makes the further molecular study of the detached microbiota complex. This work applies Response Surface Methodology, based on a D-optimal experimental design and glass beads, to recover lactic acid bacteria (LAB) and yeasts from the biofilm of fermented olives without crushing the flesh. The RSM showed that the best simultaneous results were obtained by shelling the olives, at 8 °C, with glass beads (6 mm diameter) in a 0.16 (w/w) bead/olive ratio for 15 min at 330–400 rpm. Its application recovered lower LAB (possibly because of excluding those in the flesh), but similar yeast counts to the stomacher. The metataxonomic analysis of total DNA from biofilms showed that the glass bead-based protocol reduced the chloroplast sequences and improved the genera assignation for bacteria (16S) and yeast (ITS). The new non-destructive procedure enhances biofilm studies and may allow validating table olives as a carrier of probiotic microorganisms. [Display omitted] • A D-optimal design optimized lactic acid bacteria/yeast recovery from olive biofilms. • Glass bead method led to similar/lower lactic acid bacteria recovery than stomacher. • The glass bead microbial recovery improved the further molecular studies of biofilms. • Biofilm chloroplast recovery was lower with the glass bead method than with stomacher. • Glass bead improved bacterial and fungal taxa assignation in metagenomics analysis. [ABSTRACT FROM AUTHOR]

In this study, we used an experimental design to assess the influence of 1-methylcyclopropene (1-MCP), a mild heat shock, and dimethyl dicarbonate (DMDC) on microbial evolution in brines and the biofilm composition of Spanish-style and naturally fermented table olives. Data were statistically analyzed using classical and compositional data analysis (CoDA). In the brines, the natural processing style raised the presence of yeast/fungi, while heat shock increased the populations of lactic acid bacteria populations. The interaction among heat shock, natural fermentation, and DMDC favored the survival of Enterobacteriaceae. Concerning biofilms, the metataxonomic analysis showed that the five most frequently detected bacterial genera were Lactiplantibacillus (66.79%), Secundilactobacillus (15.12%), Pediococcus (7.50%), Marinilactibacillus (4.92%), and Enterobacter (3.88%), while most common fungal genera were Saccharomyces (63.13%), Bannoa (11.49%), Candida (8.34%), Wickerhamomyces (4.15%), and Kluyveromyces (2.04%). Treatments also affected microbial diversity in biofilms. Adding DMDC significantly reduced the number of bacterial taxa compared to untreated olives. Additionally, the Spanish-style processing resulted in lower bacterial diversity. In contrast, fungi displayed an opposite trend, with the highest similarity found in naturally processed olives. CoDA revealed that the bacterial genera Marinilactibacillus and Lactiplantibacillus were characteristic of Spanish-style olives, while Secundilactobacillus and Pediococcus were associated with naturally processed olives. For fungi, Saccharomyces was related to both Spanish-style and naturally processed olives. The results indicate that the treatments influenced bacterial and fungal populations in brines and olive biofilms and their relationships. These effects may help modulate/control the microbial evolution during olive fermentation. • 1-MCP and heat shock promote LAB in brine; natural processing enhances yeast/fungi. • Spanish-style processing promotes Lactiplantibacillus development in brines. • Natural process enhances the presence of Secundilactobacillus and Saccharomyces. • Adding DMDC reduces bacterial diversity in olive biofilms, mainly in Spanish style. [ABSTRACT FROM AUTHOR]

Summary: Background: Recruitment rates for Crohn's disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD. Aims: Identify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions. Methods: PubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database. Results: Key aspects that may improve recruitment rates were identified. An increasingly patient‐centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non‐invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators. Changes implemented to IBD trials during the COVID‐19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted. Conclusions: To improve recruitment in Crohn's disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct. [ABSTRACT FROM AUTHOR]

This article provides a long-term follow-up of the PROTDILAT study, which compared the efficacy of endoscopic balloon dilatation (EBD) and self-expandable metal stent (SEMS) for the treatment of strictures in Crohn's disease (CD). The study found that EBD was more effective than SEMS in the short term, but the long-term effectiveness was similar between the two treatments. The majority of patients treated with EBD were able to avoid surgery and required fewer endoscopic treatments in the long term. Factors associated with a higher risk of surgery included non-intensification of therapy, treatment with SEMS, and a greater number of stents. Complications were more common in surgical treatment compared to endoscopic treatment. [Extracted from the article]

Summary: Background: Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. Aims: To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD Methods: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. Results: Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2‐3.3], P < 0.0001), strictures [OR 1.8 (1.5‐2.2), P < 0.0001], chronic iron deficiency anaemia [OR 2.2 (1.3‐3.2), P < 0.001] and use of second‐line biologics [OR 1.7 (1.1‐2.6), P = 0.021]. The median stricture‐free time was 14 years (95% CI, 12‐16) for cases vs 21 years (95% CI, 19‐23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease [OR 0.5(0.3‐0.8), P = 0.003] and underwent more endoscopic stricture dilations [OR 2.7(1.3‐5.4), P = 0.006]. Conclusions: The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and during follow‐up. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others.Aims: Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date.Methods: Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018.Results: The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease, p < 0.001), gender (female, p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs.Conclusions: One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear. [ABSTRACT FROM AUTHOR]

Background and Aim: Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). Methods: Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990–1995 and 2007–2012 for CD; 1995–2000 and 2007–2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts. Results: A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high‐volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors. Conclusions: Anti‐TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC. [ABSTRACT FROM AUTHOR]

Summary: Background: Thiopurines are the most widely used immunosuppressants in IBD although drug‐related adverse events (AE) occur in 20%‐30% of cases. Aim: To evaluate the safety of thiopurines in elderly IBD patients Methods: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine‐related AEs registered in the ENEIDA database were compared. Results: Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2‐55] vs 32 [IQR 5‐82] months; P < .001). Patients starting >60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs. Conclusion: In elderly IBD patients, thiopurines are associated with an increased risk of non‐infectious, non‐neoplastic, AEs. [ABSTRACT FROM AUTHOR]

Summary: Background: Cohort studies comparing the characteristics of childhood‐onset and adulthood‐onset inflammatory bowel disease (IBD) in the biologics era are scarce. Aim: To compare disease characteristics, the use of immunomodulators and biologic agents and the need for surgery between childhood‐ and adulthood‐onset IBD. Methods: Inflammatory bowel disease patients from the ENEIDA registry diagnosed between 2007 and 2017 were included. The childhood‐onset cohort comprised patients diagnosed at ≤16 years of age and the adulthood‐onset cohort those diagnosed at >16 years. The cumulative incidences of immunosuppressive therapy, biologic therapy and surgery were estimated using Kaplan‐Meier curves, compared by the log‐rank test. Cox regression analysis was performed to identify potential predictive factors of treatment with immunosuppressants, biologic agents or surgery. Results: The adulthood‐onset cohort comprised 21 200 patients out of 20 354 (96%) and the childhood‐onset cohort 846 (4%). Median follow‐up was 54 months in the childhood‐onset cohort and 38 months in the adulthood‐onset cohort (P < 0.01). Proportions of Crohn's disease, ileocolonic involvement and inflammatory behaviour at diagnosis were higher in the childhood‐onset cohort. In the multivariate analysis, after adjusting for sex, type of IBD, extraintestinal manifestations, family history and smoking habit, childhood‐onset IBD was associated with higher risk of immunomodulator use (hazard ratio [HR] = 1.2, 95% confidence interval [95% CI] = 1.1‐1.2) and higher probability of receiving biologic treatment (HR = 1.2, 95% CI = 1.1‐1.3). However, childhood‐onset IBD was not associated with higher risk of surgery (HR = 0.9, 95% CI = 0.8‐1.2). Conclusions: Childhood‐onset IBD has differential characteristics and higher risk of treatment with immunomodulators and biologic agents, compared with adulthood‐onset IBD. Nevertheless, paediatric IBD is not associated with higher risk of surgery. [ABSTRACT FROM AUTHOR]

Resumen Objetivos Identificar las comorbilidades prioritarias en la espondiloartritis axial (EspAx) y recomendar cómo hacer su seguimiento desde una perspectiva eminentemente práctica. Métodos Se seleccionó a un grupo multidisciplinar (10 reumatólogos [6 expertos en EspAx], 2 médicos de familia, una internista, una cardióloga, una gastroenteróloga y una psicóloga). En una primera reunión de discusión, se establecieron el alcance y los usuarios, y se votó una lista de comorbilidades sobre la base de la frecuencia y el impacto. Los panelistas debían defender con argumentos consistentes la inclusión de cada comorbilidad/ítem en el documento. Cuatro panelistas y 2 metodólogos, desarrollaron revisiones sistemáticas en temas controvertidos. En una segunda reunión se presentaron los resultados de las revisiones y los argumentos de todos los ítems a incluir. Tras esta reunión se redactó el documento final. Resultados El documento final incluye 2 listas de comprobación (checklist) , una para profesionales sanitarios y otra para pacientes, que recogen: riesgo cardiovascular, comorbilidad renal, riesgo gastrointestinal, estilo de vida, riesgo de infecciones y vacunación, afectación pulmonar, medicación concomitante, trastornos psicoafectivos, osteoporosis y riesgo de fractura. Además, el documento refleja los argumentos para incluir cada ítem y la manera de recoger los ítems. Asimismo, el panel consideró oportuno establecer unas « prácticas a evitar » aplicables a la comorbilidad de la EspAx. Conclusiones Se generaron 2 listas de comprobación y un listado de escenarios a evitar para facilitar el manejo de las comorbilidades de la EspAx. En pasos posteriores probaremos su utilidad y su aceptación por un grupo amplio de usuarios que incluya médicos, pacientes y enfermeras. Abstract Objectives To identify priorities among comorbidities in axial spondyloarthritis (AxSpA) and recommend how to follow them from an eminently practical perspective. Methods A multidisciplinary group was selected (10 rheumatologists—six of them experts in AxSpA—, 2 general practitioners, an internist, a cardiologist, a gastroenterologist and a psychologist). In a first discussion meeting, the scope and users were established and a list of comorbidities was voted based on frequency and impact. The panelists had to defend the inclusion of each comorbidity/item in the document with consistent arguments. Four panelists and two methodologists developed systematic reviews on controversial topics. In a second meeting, the results of the reviews and the arguments concerning the items to be included were presented. After the meeting, the final document was drafted. Results The final document includes two checklists, one for health professionals and another for patients; they incorporate cardiovascular risk, renal comorbidities, gastrointestinal risk, lifestyle, risk of infections and vaccinations, pulmonary involvement, concomitant medication, psycho-affective disorders, osteoporosis, and risk of fracture. In addition, the document reflects the arguments favoring the inclusion of each item and how to record the items for subsequent collection. The panel considered it also appropriate to likewise establish « practices to avoid» applicable to comorbidity in AxSpA. Conclusions Two checklists and a list of situations to avoid were generated to facilitate the management of comorbidities in AxSpA. In a future step, their utility and acceptance will be tested by a broad group of users that includes doctors, patients and nurses. [ABSTRACT FROM AUTHOR]

To turn table olives into appropriate carriers of beneficial bacteria and yeasts to consumers, it is essential to have reliable methods for analysing microorganisms in biofilms. This work validates the application of a non-destructive procedure to study the lactic acid bacteria and yeasts distribution in fruits during Spanish-style green table olive fermentations. Laboratory-scale fermentations were inoculated simultaneously with three Lactiplantibacillus pentosus strains (LPG1, 119, and 13B4) and two yeasts (Wickerhamomyces anomalus Y12 and Saccharomyces cerevisiae Y30), all of them natives of table olive fermentations. Data showed that L. pentosus LPG1 and yeasts W. anomalus Y12 were quite prone to colonise olive biofilms, but only the Lactiplantibacillus strain also can penetrate the epidermis of the fruit and colonise the flesh. Applying a non-destructive treatment consisting in shelling the fruits with glass beads led to obtaining similar lactic acid bacteria and yeast recovery than the classical stomacher destructive method. However, the glass bead procedure improved the quality of the metagenomics analysis (especially when using 16 S rRNA gene-based sequencing). Results show the great utility of procedures that do not destroy the fruit for studying fermented vegetable biofilms. • Glass beads methodology recovered similar lactic acid bacteria and yeast than the destructive method. • The glass bead microbial recovery improved the further molecular studies of biofilms. • Biofilm chloroplast recovery was lower with the glass bead method than with stomacher. • Glass bead improved bacterial and fungal taxa assignation in metagenomics analysis. • Some Lactiplantibacillus strains can penetrate the epidermis of the fruit and colonise the flesh. [ABSTRACT FROM AUTHOR]

Background The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. Methods In this prospective longitudinal multicenter study, 50 IFX-treated Crohn’s disease (CD) patients were followed up for 54 weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Results Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn’s disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3 nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10 nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10 nM) during the observation period (54 weeks). Serum concentration of ATI higher than 10 nM dramatically increased the probability (OR = 51.1; 95% CI: 20.4–128.0; p < 0.0001) of presenting low levels of IFX (⩽1.5 nM) in serum, as observed in some CD patients treated with standard doses of the drug. Conclusions The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug. [ABSTRACT FROM AUTHOR]

Background and Aim In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence. Methods A follow-up study was carried-out including 649 patients, diagnosed with PL between 1995-2004 in 9 participating hospitals from Spain, and who repeated the biopsy during 2011-2013. Medical information and habits were collected through a questionnaire. Based on morphology, IM was sub-classified as complete (small intestinal type, CIM) and incomplete (colonic type, IIM). Analyses were done using Cox (HR) models. Results At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34% IIM, and 4% dysplasia. Mean follow-up was 12 years. 24 patients (3.7%) developed a gastric adenocarcinoma during follow-up. The incidence rate of GC was 2.76 and 5.76 per 1,000 person-years for those with CIM and IIM, respectively. The HR of progression to CG was 2.75 (95% CI 1.06-6.26) for those with IIM compared with those with CIM at baseline, after adjusting for sex, age, smoking, family history of GC and use of NSAIDs. Conclusions IIM is the PL with highest risk to progress to GC. Sub-typing of IM is a valid procedure for the identification of high risk patients that require more intensive surveillance. [ABSTRACT FROM AUTHOR]

Substantial proportion of Crohn’s disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A; P=0.05); G0S2 (rs4844486*A/rs1473683*T; P=0.15); TNFAIP6 (rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A; P=0.10); and IL11 (rs1126760*C/rs1042506*G; P=0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway. [ABSTRACT FROM AUTHOR]

We report the case of a 16 year old man whose mother and her partner have transfer delusional ideas; they suffer a "folie à trois" or shared psychotic disorder. It is a rare illness due to the limited help searching of the members and the scarcity evaluation of families with psychotic members. The main treatment is the separation, the teenager was hospitalized in a child and adolescence psychiatry unit, and afterwards a multidisciplinary approach of mental health and social services was done. Nowadays, the etiology of this entity is a challenge, because of lacking of biological markers and the explanations of psychologycal and enviromental mechanisms. [ABSTRACT FROM AUTHOR]

Infliximab (IFX) is a valid treatment for Crohn’s disease (CD), but a relevant percentage of patients do not benefit from this therapy. In the Japanese population, the response to IFX was associated with markers in the TNF receptor superfamily 1A (TNFRSF1A) and 1B (TNFRSF1B) genes. We aimed to replicate the association previously described in the Japanese population and to ascertain the role of TNF receptors as modulators of the response to IFX. We studied 297 white Spanish CD patients with a known response to IFX: 238 responders and 59 primary nonresponders. Four single nucleotide polymorphisms (SNPs) were analyzed: rs767455 in TNFRSF1A and rs1061622, rs1061624, and rs3397 in TNFRSF1B. Comparisons between groups were performed with chi-square tests or the Fisher’s exact test. Different features (sex, age, disease duration, smoking among others) were evaluated as possible confounding factors. No significant association was found between the studied TNFRSF1A polymorphisms and response to IFX. In the TNFRSF1B gene, the haplotype rs1061624_A-rs3397_T was significantly increased in nonresponders: p =0.015, OR=1.78, 95% CI 1.09–2.90; and an increased frequency of rs1061622_G carriers was observed in patients with remission: p =0.033 vs nonresponders and p =0.023 vs patients with a partial response. Our results support a role of TNFRSF1B gene variants in the response to IFX in CD patients. [ABSTRACT FROM AUTHOR]

Background Recently, the notion that smoking may adversely affect Crohn′s disease ( CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti- TNF drugs might offset the adverse effects of tobacco. Aim To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. Methods We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry ( ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. Results In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti- TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease ( HR: 1.5, CI 95% 1.18-1.90) or perianal complications ( HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy ( HR: 1.20, CI 95% 1.05-1.30). Conclusion These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited.METHODS:To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them >3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model.RESULTS:There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies—namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22–2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22–7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25–4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08–9). No infant neoplasms were detected. The proportion of conceptions that needed >1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54–6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17–1.44; OR: 2.82, CI: 0.7–11.38).CONCLUSIONS:Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive. [ABSTRACT FROM AUTHOR]

Background Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. Aim To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. Methods Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid ( n = 5073). Results A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3–9.3; P = 0.012) and Crohn’s disease (CD) (OR 5.8 95% CI: 1.6–20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP ( n = 1477) (OR 5.2 95% CI: 1.8–14; P = 0.002). Conclusions The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Intestinal metaplasia confers an increased risk of progression to gastric cancer. However, some intestinal metaplasia patients do not develop cancer. The development of robust molecular biomarkers to stratify patients with advanced gastric precursor lesions at risk of cancer progression will contribute to guiding programs for prevention. Starting from a genome-wide methylation study, we have simplified the detection method regarding candidate-methylation tests to improve their applicability in the clinical environment. We identified CpG methylation at the ZNF793 and RPRM promoters as a common event in intestinal metaplasia and intestinal forms of gastric cancer. Furthermore, we also showed that Helicobacter pylori infection influences DNA methylation in early precursor lesions but not in intestinal metaplasia, suggesting that therapeutic strategies to prevent epigenome reprogramming toward a cancer signature need to be adopted early in the precursor cascade. To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature. [ABSTRACT FROM AUTHOR]

Biosimilars are replacing originator compounds due to their similar effectiveness, safety and pharmacokinetics. Our objective was to compare the differences in pharmacokinetics and clinical outcomes between the originator infliximab (Ifx) and the biosimilar CT-P13 in a patient cohort with inflammatory bowel disease (IBD). Our cohort study included 86 patients from a historical and a prospective cohort from the start of infliximab treatment to 22 weeks later. Serum infliximab, antidrug antibody levels and other serum biomarkers were measured at weeks 0, 2, 6, 14 and 22. Remission outcomes were evaluated at weeks 14 and 22. Drug levels were measured prospectively and analysed using MANOVA. Of the 86 patients, 44 (51%) and 42 (49%) were administered the originator and CT-P13, respectively. Originator trough levels were higher than the biosimilar trough levels (35 vs. 21, 20.1 vs. 11, 6.6 vs. 2.9 and 4.3 vs. 1.7 μg/mL at weeks 2, 6, 14 and 22, respectively). A post-hoc analysis demonstrated changes in mean serum drug levels over time (p < 0.001) and according to the drug employed (p = 0.001). At week 22, 13 (81%) patients administered the originator achieved clinical remission compared with 5 (19%) patients with the biosimilar (p = 0.02). None of the patients administered the originator withdrew from the treatment compared with 7 for the biosimilar. During the study, there were significant differences in serum infliximab levels between the originator and the CT-P13 in the patients with IBD. The clinical outcomes were influenced by the type of compound administered. [ABSTRACT FROM AUTHOR]

Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn's disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. Methods: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn's Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic enrichment analyses. Results: A total of 41 consecutive CD patients were included; 3250 functional rare variants were identified (2682 damaging and 568 LoF variants). Two homozygous LoF mutations were found in HLA-B and HLA-DRB1 genes associated with lack of response and remission, respectively. Genome-wide LoF variants were enriched in epigenetic marks specific for the gastrointestinal tissue (colon, p = 4.11e–4; duodenum, p = 0.011). The burden of damaging variation in the TNF signaling pathway was associated with response to anti-TNF therapy (p = 0.016); damaging variants were enriched in epigenetic marks from CD8+ (p = 6.01e–4) and CD4+ (p = 0.032) T cells. Conclusions: Functional rare variants are involved in the response to anti-TNF therapy in CD. Cell-type enrichment analysis suggests that the gut mucosa and CD8+ T cells are the main mediators of this response. [ABSTRACT FROM AUTHOR]

Background: The effect of low-frequency functional variation on anti-tumor necrosis factor alpha (TNF) response in Crohn's disease (CD) patients remains unexplored. The objective of this study was to investigate the impact of functional rare variants in clinical response to anti-TNF therapy in CD. Methods: CD anti-TNF naïve patients starting anti-TNF treatment due to active disease [Crohn's Disease Activity Index (CDAI > 150)] were included. The whole genome was sequenced using the Illumina Hiseq4000 platform. Clinical response was defined as a CDAI score <150 at week 14 of anti-TNF treatment. Low-frequency variants were annotated and classified according to their damaging potential. The whole genome of CD patients was screened to identify homozygous loss-of-function (LoF) variants. The TNF signaling pathway was tested for overabundance of damaging variants using the SKAT-O method. Functional implication of the associated rare variation was evaluated using cell-type epigenetic enrichment analyses. Results: A total of 41 consecutive CD patients were included; 3250 functional rare variants were identified (2682 damaging and 568 LoF variants). Two homozygous LoF mutations were found in HLA-B and HLA-DRB1 genes associated with lack of response and remission, respectively. Genome-wide LoF variants were enriched in epigenetic marks specific for the gastrointestinal tissue (colon, p = 4.11e–4; duodenum, p = 0.011). The burden of damaging variation in the TNF signaling pathway was associated with response to anti-TNF therapy (p = 0.016); damaging variants were enriched in epigenetic marks from CD8+ (p = 6.01e–4) and CD4+ (p = 0.032) T cells. Conclusions: Functional rare variants are involved in the response to anti-TNF therapy in CD. Cell-type enrichment analysis suggests that the gut mucosa and CD8+ T cells are the main mediators of this response. [ABSTRACT FROM AUTHOR]