Search Results (4,990)

Background: Cholinesterase inhibitors (ChEIs) are commonly prescribed for the treatment of Alzheimer’s disease (AD) and achieve long-term benefits for cognition and survival in real-world settings. However, the discontinuation rate is high due to their side effects, with gastrointestinal (GI) symptoms hampering long-term prescriptions. The risk of side effects associated with rivastigmine was previously shown to be lower with transdermal delivery than with oral capsules; however, this has yet to be examined in detail for donepezil, the most widely used ChEI. The daily application of a donepezil transdermal patch was officially approved in Japan in 2023. The incidence of side effects was lower with the donepezil transdermal patch than with oral donepezil in healthy volunteers, but has not yet been assessed in clinical settings. Results: We herein report three AD patients in two different memory clinics who developed GI symptoms with oral ChEIs that were attenuated by switching to the donepezil transdermal patch. Conclusions: The donepezil transdermal patch may improve tolerability and adherence in patients who develop gastrointestinal adverse effects with oral donepezil. Full article

Abdominal radiography is commonly used as an initial diagnostic tool in dogs and cats with gastrointestinal (GI) signs. Historically, abdominal radiographs were considered unreliable for detecting GI masses, with detection rates below 50%. The purpose of this retrospective, case–control study was to determine the accuracy of abdominal radiographs in identifying the presence and location of GI masses and to assess the influence of the reviewer experience. Radiographs from 114 dogs and 111 cats were reviewed by two board-certified radiologists, one first year radiology resident, and one rotating intern. Patients were categorized into three groups: animals with a GI mass greater than 2 cm (dogs n = 44; cats n = 41), animals with a normal abdomen (both n = 50), and animals with abdominal disease but no GI mass (both n = 20). Reviewers demonstrated high specificity but low sensitivity for both detection and localization of GI masses. Sensitivity for detecting a mass ranged from 34 to 64% in dogs and 36 to 71% in cats; specificity exceeded 87% in dogs and 92% in cats. Sensitivity for location identification ranged from 9 to 58% in dogs and 21 to 68% in cats; specificity exceeded 76% in dogs and 81% in cats. No statistically significant differences in detection rates were found among reviewers. The accuracy of plain digital radiography for the detection of gastrointestinal masses in dogs (75%) and cats (81%) is better than previously reported film radiography but remains inferior to other imaging modalities. However, its high specificity supports its clinical utility in ruling out gastrointestinal masses. Full article

Background: Neurogenic bowel dysfunction (NBD) is a major chronic sequela of spinal cord injury (SCI) with substantial implications for rehabilitation and long-term management. However, population-level evidence describing how gastrointestinal (GI) diagnostic codes are used following SCI, particularly within administrative healthcare systems, remains limited. Methods: We conducted a nationwide retrospective cohort study using administrative claims data from the Korean National Health Insurance Service (NHIS). A total of 584,266 adults with trauma-related SCI encounters between 2009 and 2019 were identified. GI diagnostic codes—paralytic ileus (K56), irritable bowel syndrome (K58), and functional bowel disorders (K59)—were evaluated as administrative proxies for bowel dysfunction. Demographic characteristics, disability status, regional factors, and health behaviors were analyzed using multivariable logistic regression. Results: GI diagnostic codes were frequently recorded after SCI, most commonly irritable bowel syndrome (approximately 30%) and functional bowel disorders (approximately 37%), whereas paralytic ileus was uncommon. Greater disability severity, female sex, older age, and rural residence were consistently associated with higher odds of GI diagnostic coding. Physical activity showed robust inverse associations across all models. Inverse associations observed with smoking and alcohol consumption were interpreted as reflecting residual confounding or health-related selection, rather than biological protective effects. Conclusions: Patterns of GI diagnostic coding after SCI likely reflect the clinical burden and management needs of neurogenic bowel dysfunction within healthcare systems, rather than the development of new gastrointestinal diseases. These findings underscore the importance of individualized bowel management, incorporation of structured physical activity into rehabilitation programs, and equitable access to SCI rehabilitation services, particularly for individuals with greater disability or those living in rural areas. Full article

Background: Behçet-like syndrome (BLS) refers to the presence of Behçet’s disease (BD) features occurring in association with distinct clinical–pathological conditions such as inborn errors of immunity, myeloproliferative disorders, infections, or drug exposure. BLS may differ clinically from BD and is increasingly recognized as a separate entity. Distinguishing BLS from primary BD is essential for appropriate management, and studying BLS may provide insights into BD pathogenesis. Objectives: To summarize clinical features, treatments, and genetic abnormalities reported in BLS, we reviewed all published cases up to January 2024. Methods: A systematic search of PubMed, Scopus, and Embase was performed using the terms “Behçet-like syndrome”, “Behçet-like disease”, and “Pseudo-Behçet disease”. We included English-language reports of patients > 12 years old with a defined underlying etiology and Behçet-like manifestations, defined by ≥2 ICBD criteria and/or gastrointestinal involvement, mucosal ulcers, thrombosis, or non-recurrent disease. Epidemiological, clinical, laboratory, histological, and treatment data were extracted and analyzed descriptively. Results: Of 679 publications, 53 met inclusion criteria, comprising 100 patients with BLS. The median age was 44 years (IQR 22–52), with a female predominance (1:2). Fifty-three percent were from non-European countries. A genetic disorder was identified in 70% of cases, while HLA-B51 was present in 10%. Frequent manifestations included skin lesions (68%), fever (56%), intestinal involvement (43%), and joint symptoms (43%). Treatments included glucocorticoids (65%), conventional DMARDs (32%), and biologics (22%), mainly anti-TNF agents. Antiviral/antibiotic therapy was used in 9% and chemotherapy in 15%. Two patients with trisomy-8 MDS underwent allogeneic stem cell transplantation. Conclusions: Diverse conditions—including monogenic diseases, immune defects, myeloproliferative disorders, infections, and drug-related reactions—can produce Behçet-like features. Our findings highlight differences in clinical expression and treatment response across BLS etiologies. Recognizing BLS is essential for appropriate management and may contribute to a deeper understanding of BD pathogenesis and future targeted therapies. Full article

Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers for PO, achieving efficient encapsulation (η > 69%) and a high adsorption capacity (27.64 g/g). A pH-sensitive calcium alginate shell was subsequently applied to construct colon-targeted microspheres (Ca-Alg@PO-SECs). The resulting system improved the thermal and photostability of PO. In vitro dissolution assays confirmed the system’s pH-responsiveness, maintaining integrity under simulated gastric conditions while enabling localized release at intestinal pH. In a DSS-induced acute UC mouse model, Ca-Alg@PO-SECs effectively alleviated clinical symptoms, as evidenced by improved body weight, colon length, and disease activity index. At the inflammatory level, the formulation modulated key cytokines (IL-1β, IL-6, and IL-10). Overall, Ca-Alg@PO-SECs provides a biocompatible, colon-targeted delivery strategy that preserves the bioactivity of essential oils and offers a promising preclinical approach for localized UC therapy. Full article

Background: The introduction of tyrosine kinase inhibitors has revolutionised the treatment of gastrointestinal stromal tumours (GISTs), yet the role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal GISTosis remains controversial. Methods: A retrospective analysis was conducted on patients with peritoneal GISTosis who underwent CRS plus HIPEC in an 18-year period. We analysed the clinicopathological characteristics and evaluated the perioperative and long-term outcomes based on the extent of disease (peritoneal cancer index, PCI), the resection (completeness of cytoreduction score) and the IM-administration. The survival factors were also analysed and the Kaplan–Meier estimator to model and estimate overall (OS) and progression-free survival (PFS). The median follow-up period was 72 months (range, 12–146). Results: A total of 25 patients (M:F = 15:10) with a median age of 57 years (range, 32–69) underwent CRS with HIPEC for peritoneal GIST metastases, detected either synchronously (n = 11) or metachronously (n = 14). The media PCI score was 9 (range, 4–20) and complete cytoreduction was achieved in 80%. Grade III complications were observed in two patients, whereas there was no postoperative mortality. Neoadjuvant imatinib-mesylate (IM) therapy was administered in 60% of patients who detected with metachronous metastases (n = 8/14), whereas adjuvant IM therapy was administered in 19 of 25 patients. Median OS was 62 months (95% CI = 22.8–101.2). Median OS and DFS for patients with PCI scores ≤ 10 were significantly longer compared to those with PCI scores > 10 (p = 0.009 and p = 0.024, respectively). Patients with CC scores of 0–1 had a significantly longer OS compared to those with CC scores of 2 (p = 0.005) and 3 (p = 0.002) and longer PFS compared to those with CC scores of 3 (p = 0.005). The need for imatinib did not significantly impact OS (p = 0.240) or PFS (p = 0.243). Conclusions: CRS combined with HIPEC shows promising results in peritoneal GISTosis, especially in patients with lower PCI and CC scores. Until larger studies validate its safety and efficacy, it should be primarily performed in expert hands in specialised peritoneal surface oncology centres. Full article

Astroviruses are non-enveloped, positive-sense single-stranded RNA viruses known to infect various mammals and birds, including humans, often causing gastrointestinal disorders. In recent years, astroviruses have also been linked to neurological and respiratory diseases across several species, including ruminants, mink, deer, and other mammals. Notably, astrovirus infections in goats have been documented in countries such as Switzerland and China, where novel genotypes have been identified in fecal samples. However, their role in the context of disease remains unclear, and reports focusing solely on goat astrovirus in the United States have not been published. A necropsy case of a Boer goat kid with a history of diarrhea was submitted for investigation following death in January 2025. Fresh tissues were received and used for histopathology and enteric pathogen testing, including parasitic, bacterial, and viral workups. Metagenomic-based next-generation sequencing (mNGS) was also applied for this case. Histological examination revealed severe necrotizing enterocolitis. The small intestine exhibited epithelial ulcerations, villus atrophy, hyperplastic and dilated crypts with necrotic debris, few intraenterocytic coccidian parasites, and increased inflammatory cells in the lamina propria. The large intestine showed similar findings with pleomorphic crypt enterocytes. Standard enteric pathogen tests were negative except for aerobic culture that identified Escherichia.coli and Enterococcus hirae. mNGS and bioinformatic analysis identified a novel astrovirus in the intestinal content that showed the highest nucleotide identity (86%) to the sheep strain Mamastrovirus 13 sheep/HA3 from China based on BLAST analysis. Phylogenetic analysis indicated that the newly identified caprine astrovirus IL90175 clustered with astrovirus strains from small ruminants in Asia and Europe. This research reports the discovery, histopathologic features, and genetic characteristics of a gastrointestinal disease-causing astrovirus in a goat kid, which had not been previously described in the United States. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Objective: This umbrella review aimed to synthesize evidence from meta-analyses on the efficacy of rebamipide in major gastrointestinal disorders and dyspeptic symptoms. Methods: This umbrella review followed Joanna Briggs Institute standards and was registered in PROSPERO (CRD420251185686). A comprehensive search of MEDLINE, EMBASE, Cochrane, and Scopus (1 January 1985, to 10 September 2025) was conducted to identify systematic reviews and meta-analyses assessing rebamipide therapy. Methodological quality was appraised using AMSTAR-2, ROBIS, and GRADE tools. Pooled data were analyzed using fixed- or random-effects models according to heterogeneity, as assessed using the I² statistic. Results: Eleven meta-analyses (88 primary studies) were included. Rebamipide significantly improved H. pylori eradication (OR = 1.76; 95% CI: 1.44–2.16), reduced NSAID-induced mucosal injury (OR = 2.72; 95% CI: 1.89–5.14), enhanced ulcer healing after endoscopic submucosal dissection (OR = 2.28; 95% CI: 1.42–3.65), and alleviated dyspeptic symptoms (OR = 2.95; 95% CI: 1.04–8.37). Overall evidence quality was moderate to high, with low to moderate risk of bias. Conclusions: Rebamipide demonstrates consistent therapeutic benefits across diverse gastrointestinal disorders, improving H. pylori eradication rates, mucosal protection, ulcer healing, and symptom relief. These findings support rebamipide as an effective and well-tolerated adjunctive agent for the prevention and management of upper gastrointestinal diseases. Full article

Gastrointestinal infections are a major cause of morbidity worldwide. Rotavirus (RVA) is the most frequent cause of severe diarrheal disease in children and is associated with high direct and indirect costs. Symptoms of RVA infection are nonspecific, so diagnostic confirmation requires laboratory testing, which is not routinely performed due to its high cost. For this reason, only a small proportion of hospitalizations are correctly classified. In this context, this study was conducted to determine the prevalence of RVA and 19 other potential etiological agents in 642 samples from pediatric patients with gastrointestinal symptoms at the Social Security Mexican Institute (IMSS). The findings revealed a prevalence of RVA of 26.8%. When analyzing the 321 samples that were processed for the full panel, the positivity rate was 94.4% (for any of the etiological agents tested) and a high percentage of coinfections were detected (69.8%), including up to seven different etiological agents in the same child. The RVA was more frequent in children under 1 year of age, with higher circulation in winter and spring, while bacterial infections showed a seasonal trend in summer. The proportion of hospitalizations was higher in coinfections than in monoinfections, and RVA was the pathogen with the highest percentage of hospitalizations. The results emphasize the etiological complexity of gastrointestinal infections in the pediatric population, highlighting the importance of using multiplex diagnostic tests for appropriate clinical care and effective epidemiological control strategies. Full article

Background: Serum C–C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore examined the clinical relevance of seCCL18 in a single-center SSc cohort. Methods: A total of 151 patients with SSc (83 diffuse cutaneous (dcSSc), 68 limited cutaneous SSc (lcSSc); median (IQR) disease duration: 9 (4;16) years) and 47 age- and sex-matched healthy controls (HCs) were enrolled. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay. Elevated seCCL18 was defined as >130 ng/mL (mean + 2 SD of the healthy control group). Organ involvement and disease activity (EUSTAR Activity Index, EUSTAR-AI) were assessed at baseline, while survival was analysed longitudinally. Results: Patients with SSc had significantly higher seCCL18 levels than HCs (mean ± SD: 99.9 ± 43.2 vs. 75.0 ± 27.5 ng/mL, p < 0.01). Elevated seCCL18 was associated with SSc-ILD (81.1% vs. 60.5%, p = 0.022), reduced forced vital capacity (FVC < 70%: 16.2% vs. 3.5%, p = 0.006), and reduced diffusing capacity for carbon monoxide (DLCO < 70%: 80.6% vs. 54.4%, p = 0.005). Higher seCCL18 levels were observed in patients with myocardial disease (104.8 ± 41.8 vs. 83.8 ± 44.2 ng/mL, p = 0.008), left ventricular diastolic dysfunction (107.1 ± 40.5 vs. 84.5 ± 45.0 ng/mL, p < 0.001), and oesophageal involvement (110.7 ± 38.3 vs. 93.3 ± 43.1 ng/mL, p = 0.009). SeCCL18 levels above the cut-off were more frequently associated with tendon friction rubs (51.4% vs. 27.4%, p = 0.007), active disease (EUSTAR-AI ≥ 2.5: 73% vs. 44%, p = 0.002), and elevated inflammatory markers (CRP > 5 mg/L: 51.4% vs. 19.3%, p < 0.001; ESR > 28 mm/h: 37.8% vs. 18.4%, p = 0.015). During a median follow-up of 87 months, 22 patients (15%) died. Elevated baseline seCCL18 predicted poorer survival in univariate analysis (log-rank p = 0.013) and remained an independent predictor of mortality in multivariable Cox regression (HR 1.789; 95% CI 1.133–2.824; p = 0.013), together with declining DLCO and reduced six-minute walk test performance. Conclusions: Elevated seCCL18 may identify patients with systemic sclerosis who exhibit a more severe multisystem phenotype, including cardiopulmonary, gastrointestinal, and musculoskeletal involvement, increased inflammatory activity, and reduced long-term survival. These findings suggest that seCCL18 may have some clinical utility as a prognostic biomarker reflecting widespread disease involvement beyond the lungs, even in patients with long-standing disease; however, the lack of an established cut-off value requires further validation in prospective, multicentre studies. Full article

Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article

Inflammatory Bowel Diseases (IBD), most notably ulcerative colitis (UC) and Crohn’s disease (CD), are long-standing disorders driven by dysregulated immune responses within the gastrointestinal tract and characterized by several metabolic disturbances, which are believed to influence disease progression. We have recently shown that a systemic deficiency of taurine, a semi-essential amino acid with anti-inflammatory properties, marks IBD. To characterize the temporal dynamics and determinants of taurine deficiency in IBD, we conducted a prospective longitudinal study assessing serum taurine levels in a cohort of 47 patients with IBD compared with 33 healthy controls. Serum taurine concentrations were measured at baseline and after a median follow-up period of 45 months using ELISA. Patients were stratified by disease subtype (UC and CD), age group, and clinical activity status at baseline and follow-up. Serum taurine levels were significantly lower in IBD patients at both baseline and the end of follow-up (p < 0.05), and remained stable over time within the CD and UC cohorts. In healthy individuals, but not in IBD patients, taurine concentrations declined with age, suggesting that age-related metabolic regulation of taurine is altered in the context of chronic intestinal inflammation. Stratification by disease activity revealed that taurine deficiency was present in both active and inactive IBD, particularly among younger patients, and differences between active and inactive disease were minimal. These findings indicate that the persistent reduction in serum taurine in IBD is independent of age, disease subtype, or clinical activity, and remains relatively constant over time across most patient subgroups, suggesting an underlying alteration in taurine metabolism or homeostasis associated with IBD pathophysiology. Further investigation is needed to elucidate the mechanisms linking taurine dysregulation to IBD progression. Full article

Background: Site-specific long-term outcomes, including neurofibromatosis type 1 (NF1), Ki-67 prognostic value, and very late recurrences of small bowel gastrointestinal stromal tumors (GISTs), remain inadequately defined. Methods: This retrospective cohort study investigated the clinical characteristics, diagnostic challenges, and long-term outcomes of patients with small bowel GISTs. This retrospective, single-center study (2008–2024) analyzed 27 consecutive patients (average age: 62.2 years) with jejunal/ileal GISTs. Clinicopathologic features, diagnostic yield of balloon-assisted enteroscopy (BAE), treatments, and outcomes were evaluated during a 10.2-year median follow-up period. Recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier with log-rank testing. Ki-67 was assessed using MIB-1; a prespecified 5% cut-off was chosen based on prior evidence. Results: Tumor (mean size, 62.4 mm) sites included the jejunum (74.1%) and ileum (25.9%). NF1 was present in 3/27 (11.1%) patients, all with multiple jejunal tumors. Among the 14 patients who underwent BAE, biopsy was attempted in six and yielded a histological diagnosis in one (16.7%). Six patients had recurrence; two died from disease >10 years postoperatively. Five-year OS and RFS were 91.3% and 68.7%, respectively. Adverse RFS was associated with ileal location (p = 0.03), size ≥ 10 cm (p < 0.001), mitoses > 5/50 high-power fields (p = 0.002), and Ki-67 ≥ 5% (p < 0.001). One patient labeled low risk by conventional models had recurrence with Ki-67 = 10%. Another classified as low risk by conventional models experienced recurrence >10 years after surgery, with a Ki-67 index of 10%. Conclusions: Extended, risk-adapted surveillance may be reasonable for small-bowel GISTs, and it may be beneficial to incorporate Ki-67 (≥5%) into site-based risk stratification. These observations remain hypothesis-generating and require validation in larger, multicenter cohorts and prospective studies. Full article

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article