Intestinal Research Articles

Gastrointestinal (GI) malignancies represent a significant global health burden, characterized by high mortality rates and profound resistance to conventional therapies. This necessitates the exploration of novel therapeutic vulnerabilities, and two recently discovered forms of regulated cell death, ferroptosis and cuproptosis, offer promising metabolism-centered strategies. Ferroptosis is a non-apoptotic pathway driven by iron-dependent lipid peroxidation, canonically suppressed by the glutathione peroxidase 4 (GPX4) axis. In contrast, cuproptosis is a distinct process wherein excess copper induces lethal proteotoxic stress through direct binding to lipoylated components of the tricarboxylic acid (TCA) cycle. Critically, these pathways are not mutually exclusive; instead, they are intricately connected through shared molecular nodes and metabolic dependencies, including redox homeostasis, key signaling proteins, and mitochondrial integrity. This review systematically examines the molecular crosstalk between ferroptosis and cuproptosis, highlighting the synergistic potential of their co-activation as a powerful anti-cancer strategy in GI tumors. We systematically evaluate both preclinical evidence and clinical studies for therapeutic interventions, ranging from small-molecule inducers to advanced nanoplatforms and immunotherapy combinations. Furthermore, we discuss the pressing challenges of identifying predictive biomarkers for patient stratification and overcoming adaptive resistance. Ultimately, deciphering the ferroptosis-cuproptosis nexus holds immense potential to unlock a new paradigm of synergistic therapies, paving the way for more effective clinical management of GI malignancies.

Employment and insurance disruptions are common among working-age individuals diagnosed with gastrointestinal (GI) cancers, yet underlying mechanisms and consequences associated with insurance instability remain poorly defined. We sought to characterize the incidence and identify predictors of post-diagnosis insurance instability among patients with GI cancer and assess the mediating role of employment disruption. The IBM MarketScan Commercial Claims (2013-2020) database was used to identify adults with newly diagnosed GI cancer who were employed and continuously insured for 12 months before diagnosis. Insurance instability was defined as any change in healthcare coverage within 12 months post-diagnosis. Generalized structural equation modeling estimated direct and indirect effects mediated by early (1-4 months), mid (5-8 months), and late (9-12 months) employment disruption. Within 12 months following GI cancer diagnosis, 1,163 (9.8%) patients experienced a change in insurance type versus 3,547 (8.8%) controls (aHR 1.18, 95%CI 1.10-1.26). Insurance instability was associated with delayed surgery (ARR 1.15, 95%CI 1.04-1.26), earlier chemotherapy (ARR 0.91, 95%CI 0.85-0.98), higher out-of-pocket costs ($3,675 vs. $3,206, p≤0.001) and total spending ($128,514 vs. $116,939, p=0.016). Insurance instability risk was highest among individuals with HMO (HR 2.60, 95%CI 2.32-2.91), EPO (HR 1.82, 95%CI 1.52-2.17), and comprehensive plans (HR 2.66, 95%CI 2.13-3.32) versus PPOs (p<0.001). Employment disruption mediated 97.2% (95%CI 93.8 100%) of the total effect of insurance instability, with 19.9%, 43.4%, and 34.0% attributed to early-phase, mid-phase, and late-phase employment disruption. Insurance instability after GI cancer diagnosis was largely mediated by mid- and late-phase employment disruption, highlighting the need for policies that protect employment and guarantee insurance continuity during cancer care.

Gastrointestinal (GI) cancers remain a significant global health burden with high mortality rates. Chinese herbal medicine (CHM) has emerged as a complementary therapy, yet limited real-world evidence regarding its use and effectiveness in GI cancers. This scoping review evaluated findings on CHM usage patterns and survival outcomes in GI cancer patients from studies using the Taiwan National Health Insurance Research Database, a uniquely data source covering 99.99% of the Taiwanese population. Five databases were searched for studies from January 1, 1997, to November 30, 2024. Information on exposures and outcomes were extracted, alongside study designs, patient characteristics, methodologies, and results. We identified seven studies focusing on liver (n = 3), gastric (n = 2), pancreatic (n = 1) and colon (n = 1) cancers. Of the 6 studies that evaluated usage patterns, Bai-Hua-She-She-Cao (Oldenlandia Diffusae Herba) and Dan-Shen (Salviae Miltiorrhizae Radix et Rhizoma) were the most frequently used herbs among Taiwanese GI cancer patients. Of the 6 studies that investigated survival, complementary CHM use was associated with lower mortality (adjusted HRs = 0.41-0.68) compared to conventional treatment only. Subgroup analyses showed longer durations of CHM use were associated with greater survival benefits. However, potential for confounding and bias tempers any conclusions. This review underscores the potential role of CHM as a complementary treatment for improving survival in GI cancers in real-world settings. These findings will require future rigorously-designed multinational observational studies and trials to further identify the role of specific herbal treatment in contemporary oncological care to improve outcomes for people with GI cancer.

Tobacco smoking is a major global health threat. Pharmacological aids, including nicotine-replacement therapy (NRT), varenicline, and bupropion, improve quit rates but are associated with gastrointestinal (GI) adverse events (AEs) that can compromise adherence. The real-world reporting profiles of these GI AEs, particularly the differences between sexes, have not been comprehensively characterized. We analyzed the FDA Adverse Event Reporting System (FAERS) database from 2004 Q1 to 2024 Q2. After deduplication, reports designating NRT, varenicline, or bupropion as the primary suspect drug were extracted. Disproportionality analyses, including the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were conducted to quantify drug-event associations. The Breslow-Day test was used to assess the homogeneity of RORs between male and female strata. Varenicline was associated with the highest proportion of GI reports (36.0% of its total reports). The disproportionality signal was significantly stronger in women than in men (ROR 6.41 vs. 5.10 for nausea, p < 0.001). NRT was linked to 24.3% of GI reports, with hiccups (PRR = 60.1) being the most prominent signal. In contrast to varenicline, several key GI AE signals for NRT were significantly stronger in men (e.g., nausea, ROR 3.09 in men vs. 2.45 in women, p < 0.001). Bupropion had the lowest proportion of GI reports (2.1%) but still generated significant disproportionality signals (overall ROR 4.50), particularly for anorexia (PRR = 4.80) and dry mouth (PRR = 4.42), with most signals being stronger in women. NRT, varenicline, and bupropion exhibit distinct and statistically significant sex-specific GI AE reporting profiles in a real-world setting. These hypothesis-generating findings underscore the importance of considering sex as a variable in pharmacovigilance studies and may inform future research aimed at personalizing smoking cessation therapy.

Osteoarthritis (OA) is associated with joint pain and disability, with increasing prevalence and economic burden. This study explored non-steroidal anti-inflammatory drugs (NSAID) treatment patterns, gastrointestinal (GI) complications and burden of disease in patients with OA based on Nordic registry data, with emphasis on individuals aged 60 or younger. This non-interventional observational study analysed registry data from Norway, Finland, and Sweden. Adults with primary OA diagnosis in specialty care were matched 1:1 by age and sex with individuals of the general population. The primary outcome was NSAID treatment patterns, assessed by dispensations and daily defined doses (DDD) 1year before and after diagnosis. Secondary outcomes included prevalence of comorbidities, the incidence of GI complications, sick leave, and joint replacements. The study included 189,553 patients with OA from Norway, 341,548 from Sweden, and 218,253 from Finland, 34.1% to 40.4% aged ≤ 60. About half of patients had NSAIDs dispensed before and after diagnosis, (Norway 56.6% and 48.6%; Sweden 50.1% and 44.0%; Finland 58.8% and 58.2%), compared to about one-fifth of the matches (Norway 19.1% and 18.5%; Sweden 12.7% and 12.2%; Finland 22.5% and 21.7%). NSAID use increased with age until approximately 55years, then declined. After diagnosis, fewer patients had NSAID dispensations, but mean DDDs per prescription were generally higher. Secondary analyses showed a higher comorbidity burden, higher rates of GI complications, more sick leave days, and more joint replacements in patients with OA than in matched individuals. Across Nordic countries, patients with OA had more NSAID dispensations, and GI complications were more prevalent compared to matched individuals. Notably, this was already evident in younger patients under the age of 60, underscoring the need for comprehensive GI risk assessment for every patient with OA. The substantial burden of OA was also evidenced by considerable numbers of sick leave days and joint replacements.

Background/objectives Oral ivermectin and topical benzyl benzoate are two common treatment options for scabies, but there is ongoing discussion regarding their relative safety and efficacy. A thorough synthesis of the available evidence is required to inform treatment decisions because of the clinical debate caused by the contradictory findings from current randomized controlled trials (RCTs). Methods A systematic review and meta-analysis were conducted on evidence retrieved from PubMed, Scopus, Web of Science, and CENTRAL for RCTs up to August 2025. The primary outcome was the cure rate. Secondary outcomes included pruritus improvement and the incidence of adverse events. Stata MP v. 18 was used to pool outcomes. Results Ten RCTs involving 1,105 patients were included. Cure rates showed no significant difference between ivermectin and benzyl benzoate at 1 week (RR: 1.07, 95% CI [0.88, 1.30], p = 0.51), 2–4 weeks (RR: 0.99, 95% CI [0.88, 1.12], p = 0.91), or after more than 4 weeks (RR: 1.16, 95% CI [0.95, 1.43], p = 0.15). The overall pooled result confirmed no difference (RR: 1.04, 95% CI [0.95, 1.14], p = 0.37). For pruritus, no significant differences were observed at 1 week (RR: 1.07, 95% CI [0.80, 1.43], p = 0.66), 2–4 weeks (RR: 1.19, 95% CI [0.97, 1.46], p = 0.09), or beyond 4 weeks (RR: 1.10, 95% CI [0.89, 1.37], p = 0.38); overall RR: 1.13, 95% CI [0.99, 1.29], p = 0.07. Ivermectin showed significantly fewer adverse events (RR: 0.27, 95% CI [0.16, 0.46], p &amp;lt; 0.001), particularly less burning/stinging (RR: 0.07, 95% CI [0.02, 0.20], p &amp;lt; 0.001). Gastrointestinal (GI) events were not significantly different (RR: 1.47, 95% CI [0.67, 3.22], p = 0.34). Conclusion Oral ivermectin and topical benzyl benzoate exhibit comparable efficacy for the treatment of scabies. However, ivermectin’s significantly better safety and tolerability, combined with the practical advantage of oral administration, establish it as a valuable and often preferable therapeutic choice. Systematic review registration CRD420251143937.

Immunoglobulin A vasculitis (IgAV) is a common immune complex-mediated systemic small vessel vasculitis in children. Gastrointestinal (GI) involvement significantly impacts early prognosis and may precede the appearance of purpura, complicating timely diagnosis. We retrospectively analyzed 195 cases of children diagnosed with IgAV from June 2019 to April 2024, among whom 62 cases had GI involvement. Clinical and laboratory data were collected. Children in the IgAV GI involvement group exhibited lower rates of arthritis/arthralgia and significantly higher levels of neutrophil-to-lymphocyte ratio (NLR) (P = .002, OR = 1.455), platelet count (P = .020, OR = 1.005), and uric acid (P = .017, OR = 1.005), with lower immunoglobulin G (IgG) (P = .004, OR = .818) levels. Multivariate analysis identified NLR, platelet count, uric acid, and IgG as independent predictors. The combined model showed good discrimination (area under the curve [AUC] = 0.753) and high specificity (93.2%). Elevated NLR, platelet count, uric acid, and reduced IgG are independent risk factors for GI involvement in pediatric IgAV and may facilitate early risk stratification.

Introduction: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders, causing progressive cognitive and motor decline. High rates of new diagnoses, coupled with increasing evidence linking gastrointestinal (GI) dysfunction to neurodegeneration, highlight the significance of understanding the gut-brain axis (GBA). Changes in gut microbiota composition are associated with amyloid-beta accumulation in AD and α-synuclein aggregation in PD, suggesting that gut dysbiosis and inflammation may worsen disease pathology. Methods: A systematic literature review was conducted using peer-reviewed primary research articles published between 2014 and 2025. Articles were selected based on their relevance to GI inflammation, gut microbiota dysbiosis, and neurodegenerative diseases. Studies involving human participants and relevant animal models were prioritized. Databases searched included PubMed, Google Scholar, ScienceDirect, JSTOR, and SpringerLink. Results: Gut dysbiosis was consistently associated with increased intestinal permeability, systemic inflammation, and neuroinflammatory responses in AD and PD. Specific microbial imbalances correlated with accelerated disease progression and cognitive decline. Animal studies demonstrated that fecal microbiota transplantation from diseased individuals worsened motor and mental symptoms, while interventions targeting gut health, such as probiotics and dietary modifications, reduced neuroinflammation and improved outcomes. Discussion: Findings support the GBA’s critical role in mediating neurodegeneration through immune activation and inflammatory pathways. Dysbiosis-induced changes in microbial metabolite production, including short-chain fatty acids (SCFAs) and tryptophan derivatives, further contribute to neuroinflammatory processes. Despite promising preclinical results, challenges remain in translating gut-targeted therapies to clinical use due to variability in individual microbiomes and limited longitudinal human data. Conclusion: This review emphasizes the gut microbiota as a modifiable factor in the pathogenesis of AD and PD. Targeting GI inflammation and restoring microbial balance may offer novel therapeutic strategies for slowing disease progression. Future research should focus on validating gut-derived biomarkers, personalizing microbiome-based treatments, and conducting longitudinal clinical trials to optimize gut-brain interventions in neurodegenerative diseases.

Secretin is a gastrointestinal (GI) hormone that slows intestinal motility, an effect thought to be mediated through vagal afferent pathways. In this study we show evidence for a novel function of secretin involving a non-neural mechanism mediated by interstitial cells of Cajal (ICC). Transcripts of secretin receptors (Sctr) are expressed abundantly by ICC in the deep muscular plexus (ICC-DMP). Secretin inhibits small intestinal contractions in the presence of the neurotoxin, tetrodotoxin (TTX) and suppresses excitatory enteric neurotransmission. The inhibitory effects of secretin occur through inhibition of Ca2+ transients in ICC-DMP, likely via Gαs-coupled cAMP production and PKA activation that leads to inhibition of IP3 receptors. Our results provide a novel concept for the role of ICC-DMP in small intestinal motility. ICC-DMP serve as integration hubs in which signaling from the enteric nervous system and hormones converge and integrate regulatory responses controlling intestinal motility. In the case of secretin, integrated responses may serve to slow intestinal transit to enhance digestion and absorption of nutrients.

Background: With rising obesity rates, pharmacological interventions are increasingly used in non-diabetic adults. While being effective in managing weight, these agents frequently cause gastrointestinal (GI) side effects, affecting adherence and long-term outcomes. Objective: To systematically evaluate the frequency, severity, and types of GI adverse effects (AEs) associated with anti-obesity medications in obese adults without diabetes. Methods: Following PRISMA 2020 guidelines, PubMed, Google Scholar, BMJ, and Web of Science were searched (last search July 2025). Eligible studies included randomized controlled trials, non-randomized trials, cohort studies, cross-sectional, and case–control studies. Only reports of GI AEs in non-diabetic adults were included. Risk of bias was assessed using Cochrane RoB 2 and Newcastle–Ottawa scales. Results: Out of 733 articles screened, 12 studies met predefined inclusion criteria, including one large cohort of 18,386 participants, along with randomized and observational trials of smaller size. The most frequently reported GI symptoms were nausea, vomiting, diarrhea, and constipation, predominantly with GLP-1 receptor agonists such as semaglutide and tirzepatide, especially during dose escalation. Orlistat commonly linked to steatorrhea and flatulence, while phentermine was associated with reduced GI motility. Newer agents, including retatrutide and orforglipron, also demonstrated notable GI side effect profiles. Natural products and investigational agents reported fewer adverse events but lacked long-term data and standardized reporting. Limitations: Evidence was limited by heterogeneity in study design and inconsistent reporting of GI outcomes. Conclusion: GI side effects are common across anti-obesity medications, particularly GLP-1 receptor agonists. Although generally mild to moderate, these symptoms can impact adherence and lead to treatment discontinuation. Tailored titration schedules, proactive patient counseling, and standardized adverse event reporting may improve tolerability. Further research is warranted to evaluate long-term GI outcomes and compare safety across emerging pharmacologic agents.

The rising incidence of early-onset gastrointestinal (GI) cancer has made the impact of treatments on fertility of high significance. While there is abundant evidence on oncofertility outcomes in breast cancer and hematological malignancies, data regarding these perspectives in GI cancers is lacking. We sought to evaluate current practices of fertility preservation (FP) among GI oncologists across Europe. A cross-sectional survey was distributed through the Gastrointestinal Tract Cancer Group (GITCG) of the EORTC network and affiliated cooperative groups and cancer centers using a 10-item electronic survey regarding oncofertility practices. The target population was oncologists who routinely treat GI cancers. A statistical analysis was performed based on country, patient volume and tumor type. Two hundred and twenty-six GI oncologists from 27 countries completed the survey, the majority from high volume cancer centers. Fifty seven percent of the participating oncologists routinely discuss the impact of treatment on fertility in any patient <40 years, while 36% discuss this only in the curative setting. Fifty-nine percent refer female patients to standard FP options (embryo/oocyte preservation), while 24% chose to refer to ovarian cryopreservation. Of note, 17% indicated they would not refer a curative patient for FP at all due to time or resource issues. Sixty five percent routinely refer male patients to sperm preservation. Use of Gonadotropin Releasing Hormone analogues (GnRHa) in CRC patients is recommended by 34% of oncologists. In the setting of pelvic radiation, 65% refer a female patient for ovarian transposition before pelvic irradiation; 32% would consider uterine transposition. Sixty one percent would consider a non-radiation protocol as perioperative chemotherapy as a valid option for young female patients. We observed heterogeneity upon country but not upon physician gender. Our study indicates a substantial diversity in current practices in Europe with regard to FP in young cancer patients with GI malignancies, which is not always aligned with current guidelines. There is a need to disseminate and educate GI oncologists on oncofertility perspectives and contemporary data. Additionally, there is a need to establish evidence on the utility of fertility preservation options for patients with GI cancers.

Background - Gastrointestinal (GI) endoscopy is a significant contributor to healthcare-related climate change due to high procedure volumes, intensive decontamination processes, and reliance on single-use products. This systematic review aims to synthesize the current evidence on the environmental impact of GI endoscopy. Methods - MEDLINE, Embase and Web of Science were systematically searched up to May 2025 for studies assessing the environmental impact of GI endoscopy. Two reviewers independently performed study selection, data extraction, and quality assessment. The PRISMA guidelines were followed. Results - A total of 28 studies were included. Most studies assessed carbon emissions; only five studies (18%) examined environmental impacts beyond greenhouse gas emissions. The largest contributors to emissions were patient travel, energy use, and procedure-related products, while waste had limited impact. Overall, scope 3 emissions accounted for the majority of total emissions, though reporting across different emission scopes was inconsistent. In line with heterogeneity in methodology, per-procedure emissions ranged from 5.4 to 73.2 kg CO2 equivalent. Twenty-one studies (75%) were judged to have a high risk of bias. Discussion - Current evidence on the environmental impact of GI endoscopy services is fragmented, methodologically inconsistent, and often limited in coverage. Emissions were dominated by patient travel, energy use and procedure-related products. Broader and more standardized environmental assessments are needed to guide the transition to low-carbon, sustainable GI endoscopy. .

Guava fruit is widely consumed in tropical countries and beyond. The phenolic fraction of guava pulp and processing waste (a single fraction containing seeds, skins, and pulp residues) have been reported to carry in vitro biological activities, acting on biomarkers of metabolic diseases such as type 2 diabetes and obesity (enzymatic inhibition of α-glucosidase and pancreatic lipase), atherosclerosis (mitigation of LDL-cholesterol oxidation), and mutagenesis (suppression of DNA strand scission). However, such bioactivities may be compromised by the exposure of guava phenolics to the harsh conditions found along the human gastrointestinal (GI) tract. To overcome this limitation, guava phenolic extracts were microencapsulated with maltodextrin through freeze-drying. The effect of crude and microencapsulated extracts on biomarkers of metabolic diseases was compared before and after in vitro simulated GI digestion. Moreover, guava waste extracts were tested for their ability to interfere with the intracellular redox status of Caco-2 and HeLa cells incubated with free radicals. Microencapsulation considerably improved the bioaccessibility of guava phenolics across digestion stages, which reflected on the enhancement of most bioactivities measured, with the exception of pancreatic lipase inhibition (both pulp and waste extracts) and LDL oxidative protection (pulp extract). Meanwhile, microencapsulation accentuated intracellular antioxidant activity in Caco-2 cells induced by guava waste extract whereas a prooxidant effect in HeLa cells was intensified. This highlights the selectivity of the same extract toward different cell lines. Overall, microencapsulation was demonstrated as a promising tool for protecting and even enhancing the nutraceutical power of guava phenolics, reinforcing their relevance in the development of functional foods and nutraceutical products.

We evaluated the effects of carbohydrate (CHO) ingestion at rates of 60 (maltodextrin:fructose ratio 1:0), 90 (2:1), and 120 (1:1) g·h⁻¹ on whole body substrate metabolism, exogenous CHO oxidation (via U-13C enriched glucose-fructose drinks) and gastrointestinal (GI) symptoms in elite male marathon runners (n=8; marathon PB, 02:22:54 ± 00:05:37). After 24 h of a high-CHO (8 g·kg-1) diet and pre-exercise meal (2 g·kg-1), participants completed 120-minute running trials comprising 15 mins at 95% lactate threshold (LT), 90 mins at 94% lactate turnpoint and a final 15 mins at 95% LT. Mean whole body CHO oxidation (120 g·h⁻1, 3.06 ± 0.19; 90 g·h⁻1, 2.46 ± 0.12; 60 g·h⁻1, 2.08 ± 0.03 g·min⁻1) and hour 2 mean exogenous CHO oxidation (120 g·h⁻1, 1.68 ± 0.16; 90 g·h⁻1, 1.31 ± 0.18; 60 g·h⁻1, 0.89 ± 0.11 g·min⁻1) were different between all trials (P<0.01 for all pairwise comparisons), such that 120 g·h⁻1 > 90 g·h⁻1 > 60 g·h⁻1. Running economy was improved in the 120 g·h⁻¹ condition, with a 2.6% lower O₂ cost compared to 60 g·h⁻¹ (P = 0.021). The incidence of moderate or severe (≥4) GI symptoms was high in all trials, though peak symptoms of nausea, stomach fullness and abdominal cramps were greatest for 120 g·h⁻1. We report for the first time that CHO ingestion at 120 g·h⁻1 confers a metabolic advantage to male marathoners by better maintaining whole-body rates of CHO oxidation, increasing exogenous CHO oxidation and improving running economy. However, gut training strategies, preceding practical application, are warranted.

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation, driven by alloreactive donor T cells in the gut. However, the roles of additional donor and host cells in this process are not fully understood. We conducted multiplexed imaging to generate comprehensive spatial maps of healthy and GVHD-afflicted duodena at single-cell resolution. We profiled 59 biopsies from patients with varying gastrointestinal (GI) aGVHD manifestations and 18 healthy controls and measured the spatial expression of 40 proteins, designated to delineate distinct epithelial cell populations of the gut, stromal cells, and immune cells. Normal duodenum was stereotypical across individuals, showing organization and zonation of epithelial, stromal, and immune cells. Patients with aGVHD exhibited increased fibrosis, alterations in crypt morphology, loss of Paneth cells, and accumulation of endocrine cells in the crypts. Homeostatic immune organization was disrupted, with a prominent reduction in immunoglobulin A-secreting plasma cells. CD8 T cells were enriched only in a subset of patients, whereas others exhibited noncanonical enrichments of macrophages and neutrophils. Immune composition was correlated with the time after transplantation, with shared dynamics observed across individuals. Host cells dominated the plasma and T cell compartments in the gut for extended periods of time after transplantation, suggesting that additional players may drive aGVHD across individuals in addition to donor-derived T cells. This spatial atlas of healthy and GI aGVHD uncovers epithelial and immune dynamics across individuals, offering insights into disease pathophysiology and potential clinical applications.

Postoperative delirium (POD) is a serious complication in elderly patients undergoing gastrointestinal (GI) cancer surgery. This study aimed to identify the perioperative risk factors for POD, focusing on domain-specific cognitive function. We retrospectively analyzed patients ≥ 65years old who underwent GI cancer surgery and preoperative geriatric screening. POD was assessed using the Delirium Symptomatology Test. Cognitive domains were evaluated using the Japanese Montreal Cognitive Assessment (MoCA-J). A receiver operating characteristic (ROC) analysis identified the most predictive domain combination and compared its discriminative performance with that of conventional tools. Independent associations with POD were examined using Firth's logistic regression. Of 167 patients, 13 (7.8%) developed POD. The MoCA-J Memory + Orientation composite score showed the highest predictive accuracy. In the multivariable analysis, a composite score < 7 (odds ratio [OR] = 12.81, 95% confidence interval [CI]: 1.95-84.0), older age (per year, OR = 1.10, 95% CI: 1.01-1.21), preexisting respiratory disease (OR = 7.82, 95% CI: 1.40-43.9), and intraoperative blood loss (per 100ml increment, OR = 1.53, 95% CI: 1.05-2.25) were independently associated with POD. The MoCA-J domain-specific composite score for memory and orientation was the strongest predictor of POD, alongside established factors, such as older age, preexisting respiratory disease, and intraoperative blood loss.

Introduction: Dual antiplatelet therapy (DAPT), combining aspirin and a P2Y12 inhibitor, is standard care following percutaneous coronary intervention (PCI). However, DAPT increases the risk of gastrointestinal (GI) bleeding, prompting frequent co-prescription of proton pump inhibitors (PPIs). Despite their protective role, concerns exist that PPIs may diminish the efficacy of DAPT and worsen cardiovascular outcomes. This study evaluates the impact of PPI use on clinical outcomes in patients receiving DAPT post-PCI. Research Question: Does PPI use compromise the effectiveness of DAPT in post-PCI patients? Methods: A systematic search of online databases from inception to April 2025 identified eight studies (n = 12,586) assessing the impact of PPIs on aspirin and clopidogrel efficacy after PCI. Both randomized controlled trials and observational studies were included. Primary outcomes were all-cause mortality, recurrent myocardial infarction (MI), and major adverse cardiovascular events (MACE). Secondary outcomes included cardiac death, angina, arrhythmia, heart failure (HF), revascularization, stent thrombosis, and stroke. A random-effects model was used to pool data, with results expressed as risk ratios (RRs) and 95% confidence intervals (CIs). Results: Compared to non-PPI users, PPI use was significantly associated with an increased risk of stent thrombosis (RR 1.58; 95% CI 1.02–2.44; P = 0.04) and revascularization (RR 1.26; 95% CI 1.06–1.51; P = 0.01). No significant differences were observed in MACE (RR 1.30; 95% CI 0.91–1.86; P = 0.15), all-cause mortality (RR 1.24; 95% CI 0.91–1.69; P = 0.18), cardiac death (RR 1.13; 95% CI 0.60–2.14; P = 0.71), recurrent MI (RR 1.21; 95% CI 0.89–1.63; P = 0.22), stroke (RR 0.82; 95% CI 0.34–2.02; P = 0.67), heart failure (RR 1.07; 95% CI 0.65–1.77; P = 0.79), or angina (RR 0.94; 95% CI 0.62–1.41; P = 0.76). Conclusion: PPI use in patients on DAPT post-PCI does not significantly affect MACE, mortality, or recurrent MI risk. However, it is linked to higher risks of stent thrombosis and revascularization. These findings highlight important clinical considerations regarding PPI co-prescription in this population. While PPIs are vital for GI protection, clinicians must balance this benefit against potential cardiovascular risks. Individualized decisions should weigh GI bleeding risk, and further large-scale randomized trials are needed to guide optimal post-PCI management.

Ampullary carcinomas (AC) pose a diagnostic challenge while delineating into their prognostically distinct subtypes, pancreaticobiliary (PB) and intestinal (INT). This study aimed to correlate AC's histomorphological (HE) subtypes with its immunohistochemical (IHC) subtypes and evaluate their prognostic outcome. This study was conducted in the Department of Pathology at a tertiary care cancer hospital. One hundred cases of ACs in pancreatoduodenectomy specimens were selected. Slides were reviewed for HE subtyping of ACs, including Intra-Ampullary papillary-tubular Neoplasms into HE-PB and HE-INT subtypes. IHCs (MUC1, MUC2, MUC5AC, CDX2 and CK20) were performed. ACs were classified into IHC-PB or IHC-INT types using various IHC schemata. IHC and HE subtypes were correlated using Pearson's Chi-square test. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated for the IHCs. Survival status was analyzed using the Kaplan-Meier survival analysis. The PB subtype showed a higher pathological tumor stage than INT. Among the various schemas evaluated, the Harthimmer Integrated Liu Layered Scoring system performed best with a significant correlation between HE and IHC subtypes. INT subtypes had better prognostic outcomes than PB subtypes. We found an essential prognostic role of CDX2 in the stratification of ACs.

BackgroundParkinson’s disease (PD) is a multisystem disorder frequently comorbid with non-motor symptoms like depressive disorder (DD) and gastrointestinal (GI) dysfunction. Chronic neuroinflammation and disruption of the gut-brain axis are implicated as shared pathological drivers, but the precise molecular mechanisms connecting these conditions remain elusive. We hypothesized that a common microRNA (miRNA)-mediated inflammatory profile underlies this clinical triad, representing a point of pathological convergence.MethodsWe analyzed the expression of a panel of inflammatory bowel disease (IBD)-associated miRNAs, key inflammatory markers, and glial response in postmortem brain tissue (dorsolateral prefrontal cortex and caudate nucleus) from patients with PD, DD, and matched healthy controls. To investigate causality and gut-brain axis involvement, two mouse models were used: (i) PD-associated α-synucleinopathy was induced in dorsal raphe serotonin (5-HT) neurons; and (ii) DD-like based on corticosterone (CORT)-induced stress. Mice were assessed for depressive-like behaviors and GI dysmotility, and their brain (medial prefrontal cortex and caudate-putamen) and ileum tissues were analyzed for the same molecular markers.ResultsWe identified a conserved miRNA pattern in the brains of both PD and DD patients, characterized by the significant downregulation of miR-199a-5p and miR-219a-5p and the upregulation of miR-200a-3p. This dysregulation was strongly associated with a pro-inflammatory state, as evidenced by increased expression of TNFα, IFN-γ, and NFκB1, as well as changes in the glial response. Mice with α-synucleinopathy in the 5-HT system exhibited a depression-like phenotype and reduced intestinal motility, accompanied by increased Iba1 and GFAP signal. Comparable effects were observed in mice subjected to CORT-induced stress. Notably, the same pattern of miRNAs and inflammatory cytokines observed in the human brain was replicated in the brain and ileum of DD-PD-like mice, providing direct evidence of a parallel pathological process spanning the gut-brain axis.ConclusionThis study identifies a specific inflammation-miRNA pathway as a common molecular mechanism connecting the pathophysiology of PD, DD, and gut dysfunction. This pattern represents a critical point of convergence that drives a shared, bidirectional inflammatory cascade along the gut-brain axis. Targeting this miRNA triad could provide a new therapeutic approach for addressing the motor, psychiatric, and GI symptoms of these interconnected disorders simultaneously.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12974-025-03608-y.

Background: Mavacamten, a novel cardiac myosin inhibitor, has emerged as a targeted therapy for obstructive hypertrophic cardiomyopathy (HCM). While clinical trials have demonstrated its efficacy, real-world post-marketing surveillance is essential to characterize its safety profile. This study analyzes adverse events (AEs) reported in the FDA Adverse Event Reporting System (FAERS) for adult patients receiving mavacamten. Methods: A retrospective analysis of the FAERS database was conducted to identify AE reports linked to mavacamten use. Events were classified as serious or non-serious. Organ system involvement was categorized into cardiovascular (CVS), gastrointestinal (GI), central nervous system (CNS), respiratory, musculoskeletal, renal/urinaryn (RUS), and general categories. Frequency tables and bar charts summarized the distribution of events. Logistic regression analyses (univariate and multivariate) were performed to assess odds ratios (ORs) for serious AEs within each system. Results: Of 2,192 reports, 823 (37.5%) were classified as serious. Most events occurred in females (60.3%) with a mean age of 66.4 ± 13.4 years. Cardiovascular events were reported in 29.7% of cases, with 70.8% of them being serious coded. General adverse events (40.7%), GI (9.9%), CNS (22.0%), and respiratory (20.7%) events were also prevalent. Multivariate logistic regression identified serious cardiovascular AEs (AOR 8.73), renal/urinary events (AOR 1.93), GI events (AOR 1.53), and general events (AOR 1.34) as significant predictors of SAEs. Notably, falls (AOR 5.37) and hypotension (AOR 3.52) were independently associated with increased odds of SAEs. Death was reported in 2.3% of cases. Conclusion: Post-marketing surveillance of mavacamten reveals a substantial proportion of serious AEs, predominantly cardiovascular and systemic. These findings highlight the importance of careful monitoring, particularly for hypotension, renal dysfunction, and falls, in patients treated with mavacamten. Further longitudinal studies are warranted to define risk profiles better and mitigate adverse outcomes in real-world settings.