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Search Results (345)

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Keywords = extraintestinal disease

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15 pages, 664 KiB  
Article
Real-World Safety of Vedolizumab in Inflammatory Bowel Disease: A Retrospective Cohort Study Supported by FAERS Signal Analysis
by Bojana Milašinović, Sandra Vezmar Kovačević, Srđan Marković, Marija Jovanović, Tamara Knežević Ivanovski, Đorđe Kralj, Petar Svorcan, Branislava Miljković and Katarina Vučićević
Pharmaceuticals 2025, 18(8), 1127; https://doi.org/10.3390/ph18081127 - 28 Jul 2025
Viewed by 410
Abstract
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study [...] Read more.
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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13 pages, 1732 KiB  
Article
Clinical and Phenotypic Characteristics of Early-Onset Inflammatory Bowel Disease: A Five-Year Observational Study
by Ivan S. Samolygo, Marina A. Manina, Ekaterina A. Yablokova, Pavel A. Stribul, Alexander V. Novikov, Anton S. Antishin, Albina S. Pestova, Alexander S. Tertychnyy, Daniel Munblit and Svetlana I. Erdes
Children 2025, 12(7), 952; https://doi.org/10.3390/children12070952 - 18 Jul 2025
Viewed by 360
Abstract
Background: Inflammatory bowel diseases with an early-onset form (EO-IBDs) make up a special disease group with certain clinical and phenotypic characteristics. This article discusses the features of such early onset in a group of children, based on five years of monitoring a registry [...] Read more.
Background: Inflammatory bowel diseases with an early-onset form (EO-IBDs) make up a special disease group with certain clinical and phenotypic characteristics. This article discusses the features of such early onset in a group of children, based on five years of monitoring a registry of children with IBD from a specialized center. Methods: This retrospective single-center cohort study included pediatric patients diagnosed with EO-IBD between 2019 and 2024. Clinical, laboratory, and endoscopic data were collected from medical records, including fecal calprotectin, inflammatory markers, disease activity indices, and endoscopic severity scores. Localization was classified according to the Paris system, and histological activity was assessed using the IBD-DCA score. Results: There were 20 patients with ulcerative colitis (UC) and 17 with Crohn’s disease (CD). Clinical activity was moderate or high (p = 0.179). UC was more characterized by diarrhea and rectal bleeding. CD was more often accompanied by abdominal pain, weight loss, and fever. In total, 82.4% of patients with CD had an inflammatory form. UC-like intestinal lesion was typical of both nosologies—L3 64.7% and E4 60% forms in CD and UC, respectively. Morphological activity was moderate for both nosologies (p = 0.54). IBD-U was present in 43.2% of patients. The median time after which it was possible to diagnose UC was 24 weeks (IQR 20–48) and 40 weeks (IQR 30–45.5) for CD (p = 0.56). Conclusions: Our study confirms the presence of characteristic signs of EO-IBD development, such as a frequent family history of IBD, high or moderate clinical activity during diagnosis verification, colon damage, and a high frequency of extraintestinal manifestations. Full article
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16 pages, 1767 KiB  
Article
Population Structure, Genomic Features, and Antibiotic Resistance of Avian Pathogenic Escherichia coli in Shandong Province and Adjacent Regions, China (2008–2023)
by Shikai Song, Yao Wang, Zhihai Liu, Rongling Zhang, Kaiyuan Li, Bin Yin, Zunxiang Yan, Shifa Yang, Shuqian Lin and Yunpeng Yi
Microorganisms 2025, 13(7), 1655; https://doi.org/10.3390/microorganisms13071655 - 13 Jul 2025
Viewed by 655
Abstract
Avian pathogenic Escherichia coli (APEC) poses a global threat to poultry health and public safety due to its high lethality, limited treatment options, and potential for zoonotic transmission via the food chain. However, long-term genomic surveillance remains limited, especially in countries like China [...] Read more.
Avian pathogenic Escherichia coli (APEC) poses a global threat to poultry health and public safety due to its high lethality, limited treatment options, and potential for zoonotic transmission via the food chain. However, long-term genomic surveillance remains limited, especially in countries like China where poultry farming is highly intensive. This study aimed to characterize the population structure, virulence traits, and antimicrobial resistance of 81 APEC isolates from diseased chickens collected over 16 years from Shandong and neighboring provinces in eastern China. The isolates were grouped into seven Clermont phylogroups, with A and B1 being dominant. MLST revealed 27 STs, and serotyping identified 29 O and 16 H antigens, showing high genetic diversity. The minor phylogroups (B2, C, D, E, G) encoded more virulence genes and had higher virulence-plasmid ColV carriage, with enrichment for iron-uptake, protectins, and extraintestinal toxins. In contrast, the dominant phylogroups A and B1 primarily carried adhesin and enterotoxin genes. Antimicrobial resistance was widespread: 76.5% of isolates were multidrug-resistant. The minor phylogroups exhibited higher tetracycline resistance (mediated by tet(A)), whereas the major phylogroups showed increased resistance to third- and fourth-generation cephalosporins (due to blaCTX-M-type ESBL genes). These findings offer crucial data for APEC prevention and control, safeguarding the poultry industry and public health. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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19 pages, 383 KiB  
Review
Extraintestinal Manifestations of Clostridioides difficile Infections: An Overview
by Konstantinos Mpakogiannis, Fotios S. Fousekis, Stylianos Elemes, Evangelos Mantellos, Eirini Christaki and Konstantinos H. Katsanos
Antibiotics 2025, 14(7), 670; https://doi.org/10.3390/antibiotics14070670 - 2 Jul 2025
Viewed by 878
Abstract
Introduction: Clostridioides difficile (C. difficile) is primarily associated with colonic disease, including pseudomembranous colitis. However, in rare instances, it may cause extraintestinal infectious and non-infectious manifestations, particularly in immunocompromised patients or those with significant underlying conditions. Search Methods: A literature review [...] Read more.
Introduction: Clostridioides difficile (C. difficile) is primarily associated with colonic disease, including pseudomembranous colitis. However, in rare instances, it may cause extraintestinal infectious and non-infectious manifestations, particularly in immunocompromised patients or those with significant underlying conditions. Search Methods: A literature review was performed using PubMed, Embase, and Researchgate databases up to 15 February 2025. The following search strings were used: “extraintestinal manifestations”, “extracolonic manifestations”, “extraintestinal infections”, “extracolonic infections”, “Clostridium difficile”, and “Clostridioides difficile”. Results: Extraintestinal manifestations of C. difficile appear to represent fewer than 1% of all reported infections. The most frequently reported infectious complications include bacteremia and abdominopelvic infections and abscesses, often involving polymicrobial cultures, with the isolation of C. difficile alongside microorganisms typically found in the normal intestinal microbiota. Rare non-infectious cases, such as reactive arthritis, have also been described. The underlying pathogenetic mechanism is believed to involve disruption of the intestinal barrier and translocation of bacteria or toxins to sterile sites. Conclusions: Though rare, extraintestinal C. difficile manifestations pose important clinical challenges. Better understanding of their mechanisms is essential for early recognition and appropriate management. Further research is warranted to define potential mechanisms and therapeutic approaches. Full article
13 pages, 1186 KiB  
Article
Determination of Phylogroups, Pathotypes and Antibiotic Resistance Profiles of E. coli Isolates from Freshwater and Wastewater in the City of Panama
by Gabriela A. Rodríguez Guevara, Emmanuel Michelangelli, Juan R. Medina-Sánchez, Fermín Mejía-Meléndez, Carmen Indira Espino, José E. Moreno P., Alex O. Martínez Torres and Jordi Querol-Audí
Pathogens 2025, 14(7), 617; https://doi.org/10.3390/pathogens14070617 - 20 Jun 2025
Viewed by 704
Abstract
Untreated water bodies are critical ecological niches where environmental conditions can drive the adaptive evolution of bacterial populations, enabling them to acquire new traits such as antibiotic-resistance genes. Escherichia coli is typically a commensal bacterium but can evolve into a pathogenic form, known [...] Read more.
Untreated water bodies are critical ecological niches where environmental conditions can drive the adaptive evolution of bacterial populations, enabling them to acquire new traits such as antibiotic-resistance genes. Escherichia coli is typically a commensal bacterium but can evolve into a pathogenic form, known as Diarrheagenic E. coli, responsible for both intestinal and extraintestinal diseases. This study focuses on the characterization of E. coli isolates from water samples collected from the Matasnillo River and the influence of the Juan Díaz Wastewater Treatment Plant (WWTP). While isolates from the Matasnillo River were classified as commensal, 18% of the isolates from the WWTP belonged to either phylogroups D or B2. Pathotype analysis revealed the presence of Entero-Toxigenic and Entero-Hemorrhagic E. coli in the WWTP. Moreover, Matasnillo River isolates exhibited resistance mainly to the quinolone ciprofloxacin, whereas those from the WWTP influent showed resistance to multiple broad-spectrum antibiotics. Sequencing analysis revealed the prevalence of the transmissible quinolone resistance qnrB19 among the Matasnillo River isolates and mutations conferring resistance to quinolone in gyrA, parC, and parE. These findings highlight the importance of monitoring antibiotic-resistant bacterial contamination in both freshwater and wastewater to mitigate the risk of the spread of resistant pathogens and potential epidemic outbreaks. Full article
(This article belongs to the Special Issue Current Progress on Bacterial Antimicrobial Resistance)
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6 pages, 1660 KiB  
Case Report
Three Autochthonous Cases of Amoebic Liver Abscess Clustered in a Small Village of Tuscany (Central Italy), a Non-Endemic Area
by Giuseppantonio Maisetta, Sara Moneta, Benedetta Tuvo, Cesira Giordano, Paola Alessandra Petrocelli, Giovanni Tincani, Daniela Campani, Davide Ghinolfi, Marco Falcone, Fabrizio Bruschi and Antonella Lupetti
Pathogens 2025, 14(7), 609; https://doi.org/10.3390/pathogens14070609 - 20 Jun 2025
Viewed by 630
Abstract
Amebiasis is a rare condition in industrialised countries but is epidemiologically growing. Clinical manifestations may range from asymptomatic to invasive disease. An amebic abscess can be the result of extraintestinal amebiasis, and it is associated with relatively high morbidity and mortality. We present [...] Read more.
Amebiasis is a rare condition in industrialised countries but is epidemiologically growing. Clinical manifestations may range from asymptomatic to invasive disease. An amebic abscess can be the result of extraintestinal amebiasis, and it is associated with relatively high morbidity and mortality. We present three indigenous cases of amoebic liver abscesses observed within a few weeks (October–November 2023) in patients living in a small area near Lucca in Tuscany, Central Italy. Fever accompanied by abdominal pain and liver abscess was observed in all three patients, and one of them presented necrotising colitis and pleural effusion, too. The parasitological diagnosis was performed by microscopy and confirmed with real-time PCR in liver abscess drainage fluid and stools. Full article
(This article belongs to the Section Parasitic Pathogens)
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23 pages, 1695 KiB  
Article
Prediction of Extraintestinal Manifestations in Inflammatory Bowel Disease Using Clinical and Genetic Variables with Machine Learning in a Latin IBD Group
by Tamara Pérez-Jeldres, Paula Reyes-Pérez, Patricio Gonzalez-Hormazabal, Cristóbal Avendano, Roberto Segovia Melero, Lorena Azocar, Veronica Silva, Andres De La Vega, Elizabeth Arriagada, Elisa Hernandez, Nataly Aguilar, Carolina Pavez-Ovalle, Cristian Hernández-Rocha, Roberto Candia, Juan Francisco Miquel, Manuel Alvarez-Lobos, Ivania Valdes, Alejandra Medina-Rivera and Maria Leonor Bustamante
Int. J. Mol. Sci. 2025, 26(12), 5741; https://doi.org/10.3390/ijms26125741 - 15 Jun 2025
Viewed by 678
Abstract
Extraintestinal manifestations (EIMs) significantly increase morbidity in inflammatory bowel disease (IBD) patients. In this study, we examined clinical and genetic factors associated with EIMs in 414 Latin IBD patients, utilizing machine learning for predictive modeling. In our IBD group (314 ulcerative colitis (UC) [...] Read more.
Extraintestinal manifestations (EIMs) significantly increase morbidity in inflammatory bowel disease (IBD) patients. In this study, we examined clinical and genetic factors associated with EIMs in 414 Latin IBD patients, utilizing machine learning for predictive modeling. In our IBD group (314 ulcerative colitis (UC) and 100 Crohn’s disease (CD) patients), EIM presence was assessed. Clinical differences between patients with and without EIMs were analyzed using Chi-square and Mann–Whitney U tests. Based on the genetic data of 232 patients, we identified variants linked to EIMs, and the polygenic risk score (PRS) was calculated. A machine learning approach based on logistic regression (LR), random forest (RF), and gradient boosting (GB) models was employed for predicting EIMs. EIMs were present in 29% (120/414) of patients. EIM patients were older (52 vs. 45 years, p = 0.01) and were more likely to have a family history of IBD (p = 0.02) or use anti-TNF therapy (p = 0.01). EIMs were more common in patients with CD than in those with UC without reaching statistical significance (p = 0.06). Four genetic variants were associated with EIM risk (rs9936833, rs4410871, rs3132680, and rs3823417). While the PRS showed limited predictive power (AUC = 0.69), the LR, GB, and RF models demonstrated good predictive capabilities. Approximately one-third of IBD patients experienced EIMs. Significant risk factors included genetic variants, family history, age, and anti-TNF therapy, with predictive models effectively identifying EIM risk. Full article
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24 pages, 393 KiB  
Review
Faecal Microbiota Transplantation as an Adjuvant Treatment for Extraintestinal Disorders: Translating Insights from Human Medicine to Veterinary Practice
by Alice Nishigaki, Julian R. Marchesi and Renato L. Previdelli
Vet. Sci. 2025, 12(6), 541; https://doi.org/10.3390/vetsci12060541 - 3 Jun 2025
Viewed by 2651
Abstract
Faecal microbiota transplantation (FMT) has emerged as a transformative therapy in human medicine, particularly for managing recurrent Clostridioides difficile infections and other gastrointestinal (GI) disorders. Beyond the GI tract, FMT has shown potential in addressing extraintestinal conditions in people, including metabolic, immune-mediated, dermatological, [...] Read more.
Faecal microbiota transplantation (FMT) has emerged as a transformative therapy in human medicine, particularly for managing recurrent Clostridioides difficile infections and other gastrointestinal (GI) disorders. Beyond the GI tract, FMT has shown potential in addressing extraintestinal conditions in people, including metabolic, immune-mediated, dermatological, neurological, and infectious diseases. Research in people has highlighted its efficacy in decolonising multidrug-resistant organisms in infection, mitigating autoimmune diseases, and improving outcomes in metabolic disorders such as obesity and diabetes. Furthermore, FMT has also been linked to enhanced responses to immunotherapy in cancer and improved management of hepatic and renal conditions. These findings underscore the intricate connections between the gut microbiome and systemic health, opening novel therapeutic avenues. In veterinary medicine, while FMT has demonstrated benefits for GI disorders, its application in extraintestinal diseases remains largely unexplored. Emerging evidence suggests that conditions such as atopic dermatitis, chronic kidney disease, immune-mediated diseases, and behavioural disorders in companion animals could benefit from microbiome-targeted therapies. However, significant gaps in knowledge persist, particularly regarding the long-term safety and efficacy for veterinary applications. This review synthesises findings from human medicine to assess their relevance for veterinary applications and future research. Full article
(This article belongs to the Section Veterinary Biomedical Sciences)
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17 pages, 1536 KiB  
Systematic Review
Prevalence of Joint Complaints in Patients with Celiac Disease: A Systematic Review and Meta-Analysis
by Dimitri Poddighe, Gulsamal Zhubanova, Dinara Galiyeva, Kamilla Mussina and Anders Forss
J. Clin. Med. 2025, 14(11), 3740; https://doi.org/10.3390/jcm14113740 - 27 May 2025
Viewed by 553
Abstract
Background: Current evidence suggests that joint complaints can represent an extra-intestinal manifestation in patients with Celiac Disease (CD) without any rheumatic comorbidity. However, the prevalence of joint complaints in the context of both CD and rheumatic disease is not known. The aim [...] Read more.
Background: Current evidence suggests that joint complaints can represent an extra-intestinal manifestation in patients with Celiac Disease (CD) without any rheumatic comorbidity. However, the prevalence of joint complaints in the context of both CD and rheumatic disease is not known. The aim of this study was to estimate the prevalence of joint complaints in patients with CD. Methods: We searched Medline, Embase, Cochrane, and Web of Science databases for studies reporting joint complaints in patients with CD between 1 January 1990 and 26 November 2024. Search results were screened by two independent reviewers. The pooled prevalence of joint complaints was estimated in meta-analysis using a random effects model. We conducted stratified analyses by region, age (adults vs. children), and study sample size. The Joanna Briggs Institute Critical Appraisal Tool was used to evaluate the quality of included studies, and publication bias was assessed using a funnel plot and Egger’s test. The study protocol was pre-registered in the PROSPERO database and the results were reported according to the PRISMA guidelines. Results: A total of 7414 publications were rendered in the search. Of these, 226 were reviewed in full text and 27 were included in the meta-analysis. Among 6901 patients with CD without any concomitant rheumatic diagnosis, 530 had joint complaints, yielding a weighted pooled prevalence of 10.7% (95%CI: 6.9–15.1). In meta-regression analysis, no association between the prevalence of joint complaints and patients’ clinical characteristics or demographics was found. Conclusions: This meta-analysis indicates that joint complaints in patients with CD without any specific rheumatic comorbidity are not uncommon. Increased awareness of joint complaints in CD is important to improve the diagnosis and clinical care of these patients. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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15 pages, 293 KiB  
Article
Clinical and Genetic Characteristics of Pediatric Patients with Inflammatory Bowel Disease Transitioning to Adult Medicine: A Single-Center Ten-Year Experience
by Giammarco Mocci, Giorgia Orrù, Francesca Maria Onidi, Mara Corpino, Antonella Marongiu, Giovanni Maria Argiolas, Matteo Runfola, Romina Manunza, Giorgia Locci, Elisabetta Tamponi, Teresa Zolfino, Paolo Usai Satta, Alessandro Muscas, Rossano Rossino, Salvatore Savasta and Mauro Congia
J. Clin. Med. 2025, 14(11), 3741; https://doi.org/10.3390/jcm14113741 - 27 May 2025
Viewed by 632
Abstract
Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis [...] Read more.
Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. Methods: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. Results: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2–17). After a median disease duration of 5 years (IQR: 1–16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1–84)] and CD patients [4.5 months (IQR: 1–48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; p < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (p = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (p < 0.009492), along with a stenosing phenotype (p < 0.024) and increased surgical risk (p < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. Conclusions: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients. Full article
15 pages, 856 KiB  
Review
TL1A as a Target in Inflammatory Bowel Disease: Exploring Mechanisms and Therapeutic Potential
by Enrico Tettoni, Roberto Gabbiadini, Arianna Dal Buono, Giuseppe Privitera, Vincenzo Vadalà, Giulia Migliorisi, Peter Bertoli, Alessandro Quadarella, Cristina Bezzio and Alessandro Armuzzi
Int. J. Mol. Sci. 2025, 26(11), 5017; https://doi.org/10.3390/ijms26115017 - 23 May 2025
Viewed by 2850
Abstract
Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand [...] Read more.
Inflammatory bowel diseases (IBD) are chronic disorders characterized by persistent inflammation of the gastrointestinal tract. Despite advances in treatment, a significant proportion of patients remain refractory to current therapies and develop complications, particularly fibrosis, leading to strictures and fistulae. Tumor necrosis factor-like ligand 1A (TL1A) has emerged as a promising new target for IBD treatment, due to its dual role in inflammatory and fibrotic pathways. TL1A, acting through its receptor death receptor 3 (DR3), orchestrates mucosal inflammation by enhancing T-cell activation and promoting pro-inflammatory mediator secretion. TL1A also drives intestinal fibrosis by activating fibroblasts and increasing collagen deposition. Clinical trials evaluating anti-TL1A monoclonal antibodies have shown encouraging efficacy and safety, with significant improvements in clinical remission rates, endoscopic healing, and histologic outcomes. Beyond IBD, TL1A overexpression has been implicated in other immune-mediated inflammatory diseases, highlighting its broader therapeutic potential. This review explores TL1A’s role in IBD pathogenesis, the latest clinical trial data, and its involvement in extraintestinal inflammatory disorders, underscoring its potential as a novel precision-medicine target across multiple diseases. Full article
(This article belongs to the Special Issue Inflammatory Bowel Diseases: Molecular Mechanism and Therapeutics)
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10 pages, 843 KiB  
Article
Multicenter Evaluation of the First Validated German-Language Fatigue Questionnaire for Patients with Chronic Inflammatory Bowel Diseases
by Magnus Müller, Franziska Schulz, Vidan Tadic, Anna Muzalyova, Johanna Classen, Ulrike Denzer, Irina Blumenstein and Elisabeth Schnoy
J. Clin. Med. 2025, 14(11), 3618; https://doi.org/10.3390/jcm14113618 - 22 May 2025
Viewed by 460
Abstract
Background: Patients with inflammatory bowel disease (IBD) often suffer from extra-intestinal manifestations in addition to intestinal symptoms. One of these is fatigue. Fatigue is described as persistent tiredness with episodes of sudden energy loss, which cannot be relieved by rest or sleep [...] Read more.
Background: Patients with inflammatory bowel disease (IBD) often suffer from extra-intestinal manifestations in addition to intestinal symptoms. One of these is fatigue. Fatigue is described as persistent tiredness with episodes of sudden energy loss, which cannot be relieved by rest or sleep and has a huge impact on quality of life. The aim of this study is to identify possible risk and influencing factors for the development of fatigue in IBD. Methods: For this purpose, a questionnaire survey was conducted at two German university outpatient clinics for IBD (n = 164). Based on this, the frequency and impact of fatigue on daily life was assessed and analyzed in relation to various health parameters such as patient gender, age, disease activity, and laboratory parameters. Results: Of the 164 patients, 86 were men (52.4%) and 78 were women (47.6%). A total of 75 (45.7%) patients had ulcerative colitis, 84 (51.2%) suffered from Crohn’s disease, and 5 (3.0%) had IBD-unclassified. A total of 17 out of the 164 (10.4%) patients denied that fatigue had affected their daily activities in the past two weeks. None of the examined health parameters had a significant impact on fatigue. Conclusions: Fatigue is a common syndrome in IBD patients and affects their daily activities and quality of life. The results of the present study emphasize the need for further research for a better scientific understanding of fatigue in IBD. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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14 pages, 3409 KiB  
Review
Neutrophils at the Crossroads of Inflammatory Bowel Disease and Atherosclerosis: A State-of-the-Art Review
by Vadim Genkel, Yana Zaripova, Alla Kuznetsova, Alena Sluchanko, Anna Minasova, Maria Zotova, Anna Saenko, Albina Savochkina and Anastasiya Dolgushina
Cells 2025, 14(10), 738; https://doi.org/10.3390/cells14100738 - 18 May 2025
Viewed by 894
Abstract
Inflammatory bowel disease (IBD) is a growing global problem, particularly in regions with low sociodemographic indices and growing populations. IBD incidence is increasing among children and adolescents, leading to a growing economic burden. The prevalence of atherosclerotic cardiovascular diseases among patients with IBD [...] Read more.
Inflammatory bowel disease (IBD) is a growing global problem, particularly in regions with low sociodemographic indices and growing populations. IBD incidence is increasing among children and adolescents, leading to a growing economic burden. The prevalence of atherosclerotic cardiovascular diseases among patients with IBD is also higher than in the general population. While mortality rates have decreased, cardiovascular disease (CVD) remains a significant contributor to mortality and disability in IBD patients. According to the current understanding, neutrophils play an important role in both the atherogenesis and pathogenesis of IBD. This review addresses the state of the art of neutrophil involvement in the development of atherosclerosis and IBD. In the present review, we summarize the currently available evidence regarding neutrophils as a possible key driver of extraintestinal manifestations of IBD and cardiovascular complications. We provide a discussion on the potential role of neutrophil-derived markers in the development of new approaches for the precise diagnosis of atherosclerosis in patients with IBD, as well as new therapeutic targets. Full article
(This article belongs to the Section Cells of the Cardiovascular System)
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16 pages, 1454 KiB  
Article
Meta-Analysis of 16S rRNA Sequencing Reveals Altered Fecal but Not Vaginal Microbial Composition and Function in Women with Endometriosis
by Astrid Torraco, Sara Di Nicolantonio, Martina Cardisciani, Eleonora Ortu, Davide Pietropaoli, Serena Altamura and Rita Del Pinto
Medicina 2025, 61(5), 888; https://doi.org/10.3390/medicina61050888 - 14 May 2025
Viewed by 1041
Abstract
Background and Objectives: Dysbiosis of the oral–gut axis is related to several extraintestinal inflammatory diseases, including endometriosis. This study aims to assess the microbial landscape and pathogenic potential of distinct biological niches during endometriosis. Materials and Methods: A microbiome meta-analysis was [...] Read more.
Background and Objectives: Dysbiosis of the oral–gut axis is related to several extraintestinal inflammatory diseases, including endometriosis. This study aims to assess the microbial landscape and pathogenic potential of distinct biological niches during endometriosis. Materials and Methods: A microbiome meta-analysis was conducted on 182 metagenomic sequences (79 of fecal and 103 of vaginal origin) from women with and without endometriosis. Fecal and vaginal microbial diversity, differential abundance, and functional analysis based on disease status were assessed. Random forest, gradient boosting, and generalized linear modeling were used to predict endometriosis based on differentially enriched bacteria. Results: Only intestinal microbes displayed distinctive taxonomic and functional characteristics in women with endometriosis compared to control women. Taxonomic differences were quantified using the microbial endometriosis index (MEI), which effectively distinguished between individuals with and without the disease. The observed functional enrichment pointed to proinflammatory pathways previously related to endometriosis development. Conclusions: Dysbiosis in the oral–gut microbial community appears to play a prevalent role in endometriosis. Our findings pave the ground for future studies exploring the potential mechanistic involvement of the oral–gut axis in disease pathogenesis. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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10 pages, 5313 KiB  
Article
Accuracy of Imaging Scoring Indexes in Pediatric Crohn’s Disease Patients
by Goran Hauser, Goran Palčevski, Barbara Čandrlić, Pero Hrabač and Damir Miletić
Biomedicines 2025, 13(5), 1157; https://doi.org/10.3390/biomedicines13051157 - 9 May 2025
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Abstract
Background: Crohn’s disease (CD) is a chronic inflammatory condition that can affect the gastrointestinal tract and cause significant extraintestinal manifestations. Diagnosing and monitoring disease activity, especially in pediatric patients, remains a challenge due to the variable clinical presentations and limitations of traditional imaging [...] Read more.
Background: Crohn’s disease (CD) is a chronic inflammatory condition that can affect the gastrointestinal tract and cause significant extraintestinal manifestations. Diagnosing and monitoring disease activity, especially in pediatric patients, remains a challenge due to the variable clinical presentations and limitations of traditional imaging methods. Objective: This study aimed to evaluate and compare the diagnostic accuracy and clinical utility of small bowel capsule endoscopy (SBCE) versus magnetic resonance enterography (MRE) for assessing disease activity and extent in pediatric Crohn’s disease using the Pediatric Crohn’s Disease Activity Index (PCDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD) as reference standards. Methods: In this prospective study, 52 pediatric patients with newly diagnosed CD underwent upper and lower endoscopy, MRE, and SBCE. The SBCE images were analyzed using the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI), while the MRE images were scored using the Crohn’s Disease MRI Index (CDMI). Correlations of these findings with PCDAI and SES-CD were statistically analyzed. Results: CECDAI and CDMI demonstrated strong correlations with PCDAI (r = 0.517 and r = 0.525, respectively; p < 0.001). The correlations between CECDAI and SES-CD were less pronounced but significant. SBCE and MRE showed comparable efficacy in detecting small bowel lesions, with both methods offering valuable insights into the disease status. Conclusions: SBCE is a reliable, non-invasive tool for diagnosing and monitoring pediatric CD, comparable to MRE. While SBCE offers higher resolution for mucosal evaluation, it requires additional expertise for optimal interpretation. The adoption of SBCE alongside MRE could enhance diagnostic accuracy and early therapeutic interventions for pediatric CD. Full article
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