Hospital General de Tomelloso

Inflammation and oxidative stress are key mechanisms in aging, contributing to neurodegenerative diseases, cardiovascular diseases, type 2 diabetes, obesity, and other conditions. In the aging process, the increase in reactive oxygen species and the decrease in antioxidant pathways damage cellular components, accelerating deterioration. Persistent inflammation and oxidative stress also favor the progression of diseases such as atherosclerosis, where LDL oxidation and infiltration in the arteries generate plaques that can lead to myocardial infarction or stroke. In addition, inflammation and oxidative stress can affect the immune system, as well as the development of chronic inflammatory diseases and nonalcoholic fatty liver disease, and may affect mental health, healthy menopause and muscle recovery. Research from both human studies and laboratory tests indicates that taking 80-320 mg per day of anthocyanin-rich extracts from bilberries and blackcurrants (Anthocyanin-EBB) can moderately enhance cholesterol levels, lower markers of inflammation, boost blood vessel health, increase insulin responsiveness, and reduce indicators linked to cardiovascular and metabolic risks. They also have antioxidant, anti-inflammatory and neuroprotective effects, helping in the prevention and management of chronic diseases. As a result, supplementation with anthocyanin-rich extracts may be a promising strategy to promote healthy aging and reduce the risk of development and progression of conditions related to oxidative stress and chronic inflammation. Nevertheless, due to the limited patient populations and short follow-up periods in most existing studies, long-term clinical trials are necessary to determine the definitive advantages of Anthocyanin-EBB in clinical practice.

To identify clusters of highly correlated genes enriched in biological functions and specific molecular pathways involved in the pathogenesis of radiographic damage in axial spondyloarthritis (axSpA) and to discover molecular biomarkers of radiographic progression and disease severity. A total of 144 patients with axSpA were included. First, RNA from peripheral blood mononuclear cells was sequenced in a cohort of 24 patients with axSpA. Hub genes were measured in a n=60 validation cohort through microfluidic PCR. A 5-year follow-up enabled the classification of the patients into fast/moderate or slow progressors. Machine learning approaches were applied to identify a predictive biomarker of progression by integrating gene expression data with clinical variables. An independent cohort of 60 patients with axSpA, with spine radiographs taken 5 years prior, underwent serum proteomic analysis using a Proximity Extension Assay. Unsupervised clustering analysis using transcriptomics revealed two distinct groups of patients with axSpA, differentiated by their clinical profiles. Weight gene correlation network analysis identified six gene modules differentially expressed between the two clusters. Patients in cluster 2 exhibited higher disease activity, greater functional impairment and more structural damage. Molecular alterations linked to structural damage revealed a specific circulating inflammatory proteome profile associated with disease severity. A predictive model composed of two genes and basal total modified Stoke Ankylosing Spondylitis Spinal Score emerged as a key biomarker for identifying moderate-to-fast radiographic progression. This study identified molecular pathways involved in radiographic damage and discovered potential proteomic biomarkers of disease severity and transcriptomic predictors of radiographic progression in axSpA.

ABSTRACTBackgroundLimited data are available on the management and outcomes of postoperative Crohn's disease (CD) in older patients. We aimed to describe the management of CD in the postoperative setting and assess surgical postoperative recurrence (POR) in this population.MethodsThis was a case‐control study including all adult patients with CD from the ENEIDA registry who had undergone a first intestinal resection with ileo‐colonic anastomosis. Patients were grouped according to their age at the time of the first surgery in older (over 60 years) subjects and controls (between 18 and 60 years of age).ResultsA total of 3982 (535 older subjects and 3454 controls) underwent a first intestinal resection for CD with an ileo‐colonic anastomosis. Time from CD diagnosis to surgery was significantly longer in older patients (114 ± 128 vs. 93 ± 97 months; p < 0.001). Older patients also had a lower proportion of penetrating CD (25% vs. 39%; p < 0.0001) and perianal disease (14% vs. 25%; p < 0.0001). A significantly lower proportion of older patients started preventive therapies for POR (32% vs. 51%; p < 0.0001). The cumulative risk of surgical POR was 3.2%, 5.3% and 10.1% in the older group and 3.6%, 6.6% and 14.2% in the control group at three, five and 10 years, respectively (p = 0.093). In the multivariate logistic regression analysis, only prevention with thiopurines was associated with a lower risk of surgical POR.ConclusionsAlthough postoperative preventive therapy with immunomodulators or biologicals is prescribed less often in older patients after a first intestinal resection, they develop surgical POR as often as younger adult patients.

Background: Swallowed topical corticosteroids (STCs) are used as the first-line therapy for eosinophilic esophagitis (EoE) and have been extensively studied in randomized controlled trials (RCTs); however, the presentation and doses varied widely among the studies. Aim: The goal of this study was to compare the safety and effectiveness of the different STC-based options in EoE patients. Methods: We performed a literature search for RCTs, spanning a time period from database inception to July 2024, in order to compare the efficacy and safety of all STCs used to induce or maintain EoE remission each other and also with placebo or proton pump inhibitors (PPIs) in a network meta-analysis. Outcomes are expressed as pooled risk ratios (RRs) of failure and 95% confidence intervals (CIs), and we aimed to evaluate histological remission at <15–20 eosinophils per high-power field (eos/hpf), <5–6 eos/hpf, and <1 eos/hpf. The effect sizes for symptomatic improvement and the mean differences for endoscopic EREFS improvement with 95% CIs were also measured. Adverse events were evaluated using RRs, and these included oropharyngeal and esophageal candidiasis and adrenal suppression. Results: Twenty studies involving 1455 patients with active EoE reported on STC effectiveness to induce remission; three additional studies on 232 patients assessed the maintenance of remission. Budesonide 1 mg orodispersible tablets ranked highest in SUCRA in terms of all histological remission endpoints. Budesonide from inhalation devices was the only option superior to placebo in improving symptoms. Budesonide viscous suspension was the only option superior to placebo in improving endoscopy. No therapy was significantly associated with the risk of any adverse event. Significant inconsistencies and small study effects were detected in multiple comparisons. Conclusions: Budesonide orodispersible tablets were the best option for achieving EoE histological remission, but not symptomatic or endoscopic improvement. STC formulations were as safe as placebo or PPI.

The disease course of microscopic colitis is largely unknown and current knowledge is based on retrospective data. The aim of the PRO-MC Collaboration is to prospectively describe the long-term disease course and prognostic factors. Incident patients of microscopic colitis were included in a prospective, European, multicenter, web-based registry. Data on patient characteristics, symptoms, treatment, and quality of life were systematically registered at baseline and during fixed follow-up intervals. Four disease course phenotypes were defined. Of 422 registered incident patients, 220 had a complete 5-year follow-up. After 5 years, 6% had a quiescent disease course, 54% achieved remission after treatment, 33% had a relapsing disease course, and 7% a chronic active disease course. Patients with a relapsing or chronic active disease course had a more impaired quality of life and were more often in need for long-term budesonide treatment. The disease course in the first year after diagnosis was the only predictor of the disease course. Microscopic colitis is a chronic condition with relapsing or continuous disease course in nearly half of the patients during the first 5 years after diagnosis. The disease course in the first year predicts the long-term disease course.

Abstract Background The therapeutic goal in inflammatory bowel disease (IBD), which includes Crohn´s disease (CD) and ulcerative colitis (UC), is the control of the inflammatory process frequently through biologic and JAK-inhibitor therapies, which are generally expensive and may induce adverse effects. Unfortunately, only one-third of patients respond to these treatments, and there are no markers that accurately predict this response. The aim of this study was to identify potential serum and urinary metabolic biomarkers predictive of IBD response to different drugs at baseline (before treatment), which could facilitate the selection of the most appropriate therapy for each patient. Methods A prospective multicenter study was conducted including CD and UC patients who initiated biologic (anti-TNF, ustekinumab or vedolizumab) or JAK-inhibitor (tofacitinib) therapies. Patients were assessed at 14 weeks to determine if they had achieved an endoscopic response, based on the SES-CD and on the endoscopic sub-score of the Partial Mayo Score. The analyses of the serum and urine metabolome, along with the deconvolution of the serum lipoprotein profile into 110 subfractions, were performed using nuclear magnetic resonance for a quantitative differential analysis comparing the baseline serum samples of responders and non-responders. Results A total of 150 patients were included (30 CD anti-TNF, 30 UC anti-TNF, 30 CD ustekinumab, 30 UC vedolizumab and 30 UC tofacitinib). Metabolomics analysis identified 55 potential predictive biomarkers of IBD treatment response (11 common and 44 drug-specific), with significantly altered levels (p&amp;lt;0.05) in the baseline urine and serum samples of subsequent responders compared to non-responders (Figure 1). Moreover, based on ROC curves, some of these biomarkers showed good sensitivity and specificity for distinguishing between responders and non-responders before treatment (Figure 2). Finally, metabolite set enrichment analysis identified different biological pathways associated with the response to each of the treatments for IBD. Among the common ones, the citrate cycle and the metabolism of butanoate, alanine, aspartate, glutamate, and arginine stood out. Conclusion The present study represents a step towards personalized medicine in the selection of targeted therapies for IBD patients, addressing an important unmet need. Although further validation is needed, we have identified serum and urinary metabolic biomarkers with the potential to predict response to biologic and JAK-inhibitor therapies.

Abstract Background Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, with a globally rising incidence. It may result from a complex interaction among genetic predisposition, environmental influences, and alterations in gut microbiota, leading to dysregulation of both innate and adaptive immune responses. Despite advances in understanding CD, the precise immunological mechanisms underlying this disease remain unclear. Currently, biological therapies, such as vedolizumab, are among the most effective options for inducing clinical remission and controlling inflammation in CD. However, approximately two-thirds of patients do not respond adequately to these treatments. Consequently, it is essential to identify immune cell populations that can predict clinical responses to vedolizumab, facilitating more personalized treatment selection for each patient. Methods We characterized peripheral blood mononuclear cells (PBMCs) using spectral flow cytometry with a panel of 40 markers in patients with CD, both before and after 14 weeks of treatment with vedolizumab. Patients were categorized as responders or non-responders based on their SES-CD. Results At baseline Hierarchical phenotypic analysis revealed a total of 39 unique subsets of immune cells within PBMCs (Figure 1). The main populations included T cells (66%), monocytes (0.25%), B cells (12%), and natural killer cells (11%). Within the T cell group, CD4+ cells were twice as prevalent as CD8+ cells. In our evaluation of conventional dendritic cells percentages, we noted an increase in this subset within the responder group, contrasting with the trend observed in macrophages. Furthermore, an unsupervised analysis applying dimensionality reduction algorithms identified 59 clusters (Figure 2), with 37 of them showing differences when comparing responder and non-responder patients. Interestingly, no differences were observed between pre-treatment and post-treatment samples. Conclusion This study presents the first immunophenotyping analysis in CD patients, comparing responders and non-responders to vedolizumab based on SES-CD and highlighting differences between these groups. For the first time, these results reveal circulating immune populations as potential predictors of response to vedolizumab. Although these findings should be validated in a larger cohort to assess their clinical significance in identifying patients most likely to benefit from each therapeutic approach, they open the possibility for changes in clinical practice.

ABSTRACTBackgroundEsoCap is a thin mucoadhesive film designed to target the oesophageal mucosa. The device loaded with mometasone furoate (ESO‐101) is under investigation for the treatment of eosinophilic oesophagitis (EoE).AimsTo evaluate the efficacy, safety and tolerability of ESO‐101 in patients with active EoE.MethodsWe conducted a randomised, placebo‐controlled, phase 2, proof‐of‐concept trial at 14 European sites in adults with EoE. Participants received placebo, uncoated EsoCap (n = 15), or EsoCap loaded with 800 μg of mometasone furoate (n = 28) once daily during 28 days. The primary outcome was the absolute change in the peak eosinophil count; secondary outcomes were histologic, clinical and endoscopic measures.ResultsTreatment with ESO‐101 resulted in reduction (mean ± SD) of 49.1 ± 88.4 eosinophils/high‐power field from baseline, compared with 6.6 ± 65.1 with placebo (p = 0.03). With ESO‐101, 48% and 44% of patients achieved < 15 and < 6 eosinophils/high‐power field, respectively; these were 0% with placebo. EoE Endoscopic Reference Score reduced significantly in patients treated with ESO‐101. In contrast, dysphagia and odynophagia severity decreased similarly in both groups. There were no serious treatment‐emergent adverse events. Mean serum cortisol did not change significantly throughout the trial. Notably, no oropharyngeal or oesophageal candidiasis was documented. The device was well tolerated.ConclusionsESO‐101 was superior to placebo in reducing oesophageal eosinophilia. The device was safe and well tolerated in adults with EoE, supporting the continued development of ESO‐101 for the treatment of EoE (Trials.gov No.: NCT04849390; Eu‐CT No.: 2020–000082‐16).

Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.