Abstract:

Background: Gastroscopy remains a cornerstone in diagnosing upper gastrointestinal tract diseases. However, intragastric foam impairs mucosal visualization, potentially reducing early lesion detection rate. Simethicone is widely used as a defoaming agent in clinical practice, yet its efficacy may be influenced by administration methods and timing. Aims: To investigate the effects of body position changes and waiting time after simethicone administration on defoaming efficacy during gastroscopy. Methods: A prospective study was conducted at the Endoscopy center, Hospitol, Macau, Jul–Aug 2024. Patients scheduled for gastroscopy were divided into a control group (supine position) and an experimental group (body position changes). The experimental group was further subdivided into Group A (traditional sequence: right lateral, supine, left lateral positions, each maintained for 5 min) and Group B (modified sequence: right lateral position for 5 min, followed by alternating head-down/head-up positions for 1 min each, then left lateral position for 3–5 min). The control group was additionally stratified by waiting time post-simethicone administration (≤15 min, 16–30 min, ≥31 min). The primary outcome was mucosal clarity score assessed with the KUO score; secondary outcomes included examination time and polyp detection rate. Results: Group B demonstrated significantly better mucosal clarity compared with both the control group and Group A (P<0.001). Among control patients, those examined within 15 minutes post-medication showed superior defoaming efficacy compared with those examined after 31 minutes (P<0.05). Examination times were comparable across groups. No significant association was observed between mucosal clarity and polyp detection rates. Conclusions: Combining optimized body position changes with appropriate timing post-simethicone administration significantly improves mucosal visualization during gastroscopy. This strategy provides a simple, cost-effective approach to enhance diagnostic performance and is recommended for broader clinical application.

Abstract: Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, with more than 275,000 hospital admissions annually in the United States [2]. While most cases are mild, 15–20% progress to moderately severe or severe disease characterized by systemic inflammation, organ failure, and local complications [1,3]. Overall mortality remains 3–5%, but increases to 20–35% in patients with persistent organ failure requiring intensive care [7].Early assessment remains challenging. Traditional scoring systems (APACHE II, BISAP, Ranson, mCTSI) demonstrate modest accuracy within the first 24 hours [4,11]. Consequently, emerging biomarkers—including IL-6, IL-8, IL-10 [16–17], pentraxin-3 [8], sCD163 [7], NGAL [10], and presepsin—are critical for identifying early severity. Endothelial dysfunction markers including angiopoietin-2 [19], proADM, endocan, and VEGF provide additional predictive value by reflecting microcirculatory failure and shock. Oxidative stress markers such as MDA and GSH depletion correlate with necrosis and multi-organ dysfunction. ICU physiological predictors—vasopressor requirement, rising lactate, Horowitz-index deterioration, and early AKI—remain the strongest bedside indicators of poor outcome [18]. Modern management emphasizes goal-directed fluid therapy, controlled resuscitation with balanced crystalloids, and selective use of CRRT, although no multicenter RCT has yet confirmed its mortality benefit [20]. This review synthesizes classical and novel biomarkers, endothelial and oxidative markers, and ICU predictors to support a modern, precision-based approach to early risk assessment and managementin acute pancreatitis.

Abstract: Metastases to the pancreas (PM), although rare, have been increasingly identified in recent years, especially among high-volume pancreatic centers. They are often asymptomatic and incidentally detected during follow-up examinations, even several years after the treatment of the primary tumor. In this scenario, endoscopic ultrasound (EUS) has emerged as a crucial diagnostic tool for PM, being capable of providing a detailed morphological characterization and safe and effective tissue acquisition for cytohistological examination. The aim of our study was to extensively review the current evidence concerning the role of EUS in the diagnosis of PM, specifically focusing on their morphological features, contrast-enhancement patterns, and tissue acquisition techniques.

Abstract: Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child-Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC pa-tients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP nega-tively correlated with free (ρ = -0.606, p < 0.001) and bioavailable 25(OH)D (ρ = -0.541, p < 0.001). Child-Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = -0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer.

Abstract:

Advances in single-cell and spatial multi-omics technologies have transformed the understanding of neutrophils from short-lived effector cells to highly heterogeneous and transcriptionally plastic immune populations. Within the inflamed intestinal microenvironment, gradients of cytokines, oxygen tension, and microbial metabolites such as short-chain fatty acids dynamically modulate neutrophil differentiation and function, shaping either tissue-protective or tissue-destructive phenotypes. Recent studies highlight the de novo expression of the NADPH oxidase enzyme DUOX2 in intestinal neutrophils as a pivotal mediator of redox signaling. DUOX2-derived reactive oxygen species activate epithelial and immune signaling cascades through NF-κB and p38 MAPK pathways, thereby amplifying inflammation, promoting barrier disruption, and sustaining microbial dysbiosis. Although this oxidative response enhances antimicrobial defense, it concurrently contributes to neutrophil extracellular trap (NET)-driven thrombo-inflammation and chronic tissue injury. Experimental evidence indicates that selective ablation of myeloid DUOX2 attenuates colitis, underscoring its potential as a therapeutic target. Emerging interventions that modulate this axis, including JAK/STAT inhibitors, CXCR2 antagonists, p38/MK2 inhibitors, and butyrate-based metabolic regulators, offer promising avenues to restore neutrophil homeostasis while maintaining host defense. Integrating single-cell transcriptomics, redox proteomics, and advanced imaging approaches will be essential for translating neutrophil plasticity into biomarker-guided and precision-based therapeutic strategies for durable mucosal healing in IBD.

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LD) dysregulation as key drivers of disease progression, although their interaction remains poorly characterized. This review synthe-sizes current mechanistic insights into how CS and LD regulation affect the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, includ-ing upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can ac-tivate peroxisome-proliferator receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent cellular senescence (CS) under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid ox-idation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor – kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. A comprehensive understanding of this dynamic crosstalk between CS and lipid metabo-lism could identify novel therapeutic targets to modulate the MASLD progression.

Abstract:

Background and Objectives: With more than 1.9 million new cases and 0.9 million deaths in 2020, colorectal cancer (CRC) was the third most common cancer and the second most common cause of cancer mortality worldwide. The adenoma detection rate as a precursor to the formation of CRC is directly related to the degree of bowel preparation for colonoscopy.Materials and Methods: This is a retrospective single-center study on a total number of 4835 colonoscopies performed in a period of 34 months during the global COVID-19 pandemic.The main goal of the research was related to the emergence of differences in cleaning in relation to gender, age, days of preparation, the type of cleaning agent.Results: There is no signification difference between gender. Compared to younger respondents, older respondents had a lower likelihood of having adequate bowel preparation. Compared to PEG, other solutions had a lower probability of adequate bowel preparation.Conclusions: Better cooperation between patients and medical staff is needed, as well as public health campaigns that raise awareness of the importance of good preparation for colonoscopy.

Abstract: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal discomfort, pain, and altered bowel habits, as well as extraintestinal manifestations such as fatigue, musculoskeletal pain, gastroesophageal reflux, depression, and anxiety. Despite prevalences of approximately 10% in the general population, its fundamental etiopathogenesis remains unclear. Current theories mainly point toward a multifactorial aetiology crediting psychological stress with a prominent role. The paradigms currently embraced for IBS are mainly based on, and emphasize, the gut-brain axis, visceral hypersensitivity, central sensitization, neuroendocrinology, dysbiosis, motility abnormalities, and post-infectious persistent low-grade mucosal inflammation. Yet, they don’t fully explain its diverse clinical presentations nor IBS’s symptomatic overlap with conditions such as fibrositis/fibromyalgia syndrome. Available treatments are mostly symptomatic and provide limited relief, indicating a still major gap in our mechanistic understanding. This paper proposes a hypothesis for IBS etiopathogenesis as an organic disease of the extracellular matrix driven by myofibroblast overactivity in the gut wall and abdominal soft tissue, along with downstream consequences stemming from tissue stiffness. This process is theorized to mechanically compress visceral structures and nerves, impair synchronized organ motility, and induce substrate stiffness-mediated visceral hypersensitivity. In this theoretical framework the extraintestinal manifestations reflect mechanistic overlap with fibromyalgia, which helps unify functional-psychosomatic syndromes as a medical entity with a shared organic mechanism. This mechanism, along with known mechanisms of gut dysbiosis and the gut-brain axis, helps explain “medically unexplained symptoms” of fibromyalgia-type syndromes and offers testable predictions for future research and suggests new avenues for IBS diagnosis and treatment.

Abstract: A key, but frequently underappreciated parallel between alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), now also termed metabolic dysfunction-associated steatotic liver disease (MASLD), is the delivery of excessive amounts of calories to the liver via the portal circulation: ethanol in the case of ALD, and nutrient-derived substrates in NAFLD/MASLD. A second, equally salient point is the liver’s distinctive dual blood supply. The portal vein provides approximately 80% of hepatic blood flow, delivering deoxygenated but nutrient-rich blood from the gut, while the hepatic artery supplies the remaining 20% yet contributes about half of the organ’s total oxygen requirements. Notably, only the hepatic artery possesses myogenic regulatory capacity that allows it to dynamically adjust flow and thus modulate hepatic oxygenation. A third consideration is that the liver receives approximately 25% of total cardiac output, which means that maintaining a stable hepatic blood supply is essential for cardiovascular homeostasis and survival. To this end, the liver has developed a unique and specialized mechanism, the hepatic artery buffer response (HABR), that stabilizes total hepatic blood flow independently of metabolic fluctuations or needs. However, this prioritization of constant flow means that the hepatic arterial blood supply, even with maximal vasodilatation, cannot always ensure that oxygen delivery matches nutrient demand, especially under conditions of caloric excess. An imbalance between oxygen delivery and nutrient availability— “oxygen-nutrient mismatch”—can lead to tissue hypoxia and liver cell damage. Over four decades ago, Lautt postulated that this kind of imbalance might play a role in the pathogenesis of alcohol-related liver disease (ALD). We have extended this paradigm to non-alcoholic fatty liver disease (NAFLD), now also called MASLD, theorizing that analogous mechanisms may be involved. Comorbidities such as obstructive sleep apnea (OSA) are associated with recurrent episodes of nocturnal hypoxemia. The concomitant presence of intermittent hypoxia and increased nutrient flux may synergistically exacerbate hepatocellular injury, providing a plausible mechanistic explanation for the more rapid progression of MASLD observed in patients with OSA and other conditions associated with hypoxemic episodes. The attenuated association between ALD and metabolic syndrome, compared with MASLD, likely stems from inherent differences in substrate metabolism. Carbohydrates, lipids, and proteins are subject to multiple complex cytosolic metabolic pathways that permit alternative, often non-oxidative, fates in states of metabolic dysfunction. In contrast, hepatic ethanol metabolism proceeds via a more linear, obligate oxidative route, offering limited flexibility. Therapeutic strategies that reduce hepatic caloric overload, increase basal hepatic metabolic rate (for example, with Resmiritom), or enhance hepatic oxygenation (such as through hyperbaric oxygen therapy) represent promising approaches for disease modification.

Abstract: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts. Autoantibodies, particularly anti-mitochondrial antibodies (AMA) and antinuclear antibodies (ANA), are central to diagnosis, prognosis, and pathogenesis. This review provides a comprehensive overview of classical and emerging autoantibodies associated with PBC, including AMA-M2, anti-gp210, anti-sp100, anti-KLHL12, and anti-RPL30. We discuss their diagnostic significance, pathogenic implications, and potential utility in patient stratification and therapeutic monitoring. Furthermore, we explore the role of microbial factors and environmental triggers in autoantibody generation, highlighting molecular mimicry and gut–liver axis interactions. Advances in autoantibody profiling may pave the way for personalized medicine and improved outcomes in PBC.

Abstract: Background/Objectives: Microbial dysbiosis is implicated with a pathogenic role in both irritable bowel syndrome (IBS) and several dermatological conditions. Yet, few studies have assessed a potential overlapping epidemiologic association. We aimed to assess the 1-year prevalence of common dermatologic conditions following an initial IBS diagnosis and to evaluate the reverse association using reciprocal analyses; Methods: We conducted a retrospective study using TriNetX. Patients aged 18-50 with no history of inflammatory bowel disease, celiac disease or infectious intestinal disease were matched 1:1 to healthy controls by demographics and comorbidities. The primary outcome was the prevalence of acne vulgaris, psoriasis, atopic dermatitis, hidradenitis suppurativa, rosacea, vitiligo, alopecia areata, urticaria, 1-year after IBS diagnosis, measured using Odds Ratios (OR) and 95% confidence intervals. To confirm bidirectionality, reciprocal analyses were performed; Results: Over a 1-year period, IBS patients were less likely to have acne vulgaris (OR: 0.78, CIs: 0.75-0.80) and vitiligo (OR: 0.78, CIs: 0.64-0.95) compared to those without. IBS patients were more likely to have psoriasis (OR: 1.14, CIs: 1.08-1.21), hidradenitis suppurativa (OR: 1.11, CIs: 1.03-1.20), rosacea (OR: 1.10, CIs: 1.03-1.18), and urticaria (OR: 1.27, CIs: 1.21-1.34) compared to healthy controls. No association was found for atopic dermatitis or alopecia areata. In the reciprocal analysis, alopecia areata patients (OR: 0.76, CIs: 0.64-0.90) had a lower prevalence of IBS compared to healthy controls. IBS was shown to occur more frequently in patients with psoriasis (OR: 1.15, CIs: 1.07-1.23), rosacea (OR: 1.23, CIs: 1.15-1.31), and urticaria (OR: 1.06, CIs: 1.01-1.12) compared to healthy controls. No association was seen in patients with acne, atopic dermatitis, hidradenitis suppurativa, and vitiligo; Conclusions: IBS shows a bilateral positive overlapping association with psoriasis, rosacea and urticaria. Hidradenitis suppurativa showed a positive association only among IBS patients, with no reciprocal relationship. Moreover, our findings suggest that acne and vitiligo were inversely associated with IBS, however this was not supported in our reciprocal analysis. Although no association was initially found between IBS and alopecia areata, the reciprocal analysis suggests a potential inverse association. No association was seen with atopic dermatitis bilaterally. Clinicians who treat these disorders should be aware of the potential bidirectional association.

Abstract: Inflammatory bowel diseases include Crohn's disease (CD) and ulcerative colitis (UC). These diseases are characterised by periods of exacerbated inflammation of the gastrointestinal mucosa, interspersed with periods of remission. Current pharmacological interventions are only partially effective. There is a need for effective dietary therapies and interventions involving plant substances that can alleviate the course of this dis-ease. This study aimed to determine the effects of a 28-day dietary intervention involving a 3% solution of chemically pure, low-molar-mass oat beta-glucan (OBG) in patients diagnosed with de novo UC. Similar-aged men and women were compared. The OBG was isolated and prepared for consumption as a sterile aqueous suspension. This solution had previously been evaluated for in vitro toxicity using 3D intestinal co-cultures comprising Caco-2, HT29-MTX and THP-1 cells. Before and after the dietary intervention, endoscopic colon examinations were performed, and blood haematological, biochemical and immunological parameters, as well as stool calprotectin concentrations, were analysed. The Disease Activity Index (DAI), endoscopic Mayo score, the Lichtiger Colitis Activity Index (LCAI) and the neutrophil-to-lymphocyte ratio (NLR) were also determined. Following dietary intervention, the Mayo score, DAI index, faecal calprotectin levels, and indices of peripheral blood white cells, CRP, and proinflammatory cytokine concentrations were decreased. The obtained results demonstrated the beneficial effect of dietary intervention with OBG in accelerating the achievement of clinical remission in patients with UC.

Abstract:

Background: In pediatric celiac disease (CD), intestinal malabsorption and the restrictive nature of a gluten-free diet (GFD) frequently result in persistent macro- and micronutrient imbalances, despite histological remission. The present review evaluates the evidence on nutritional adequacy of the GFD, identifies common deficiencies, and considers biomarker strategies and dietary recommendations to optimize growth and metabolic health. Methods: A narrative review of the literature was conducted, focusing on studies of nutrient intake, product composition of gluten-free foods, biomarker assessment, and clinical outcomes in children with CD. Both macronutrient (protein, fat, carbohydrate, fiber) and micronutrient (iron, vitamin D, calcium, B-vitamins, zinc, magnesium) domains were included. Results: Children with CD on long-term GFD demonstrate higher intake of lipids (especially saturated fat) and simple carbohydrates, alongside consistently low intake of dietary fiber and key micronutrients. Gluten-free products often exhibit lower protein content, higher glycemic index, and reduced fortification compared to gluten-containing equivalents. Biomarkers including prealbumin, ferritin, 25-hydroxyvitamin D, and inflammatory mediators aid in early detection of malnutrition. Nutritional deficits contribute to impaired linear growth, delayed puberty and increased metabolic risk. Conclusions: Nutritional adequacy of the GFD cannot be assumed in children with CD. Routine monitoring using standardized biomarker panels, combined with personalized dietary counselling and improved formulation and fortification of gluten-free products, is essential to mitigate long-term adverse outcomes. Future work should advance precision nutrition approaches and public-health initiatives to optimize dietary quality in this vulnerable population.

Abstract: Background/Objectives: High-quality bowel preparation is essential for the diagnostic accuracy of colonoscopy, which remains the gold standard for colorectal cancer screening. Aims: In our study, we aimed to compare the efficacy and tolerability of three bowel preparation regimens—Moviprep with Donat Mg, Plenvu, and Plenvu with Donat Mg—commonly used in clinical practice in Slovenia. Methods: We conducted a randomized, multicenter, prospective study across three Slovenian gastroenterology centers. A total of 300 patients undergoing elective colonoscopy were randomly assigned to one of the three bowel preparation groups. Bowel cleanliness was evaluated using the Boston Bowel Preparation Scale, and lesion detection was assessed using polyp detection rate (PDR) and adenoma detection rate (ADR). Patients also completed a questionnaire assessing adverse effects, overall tolerability, and willingness to repeat the same regimen. Statistical analyses included ANOVA, chi-square, Kruskal-Wallis, and t-tests. Results: All three regimens achieved high bowel preparation adequacy (≥95%), with no statistically significant differences in total BBPS scores, PDR, or ADR. Adverse effects were mild and comparable between groups, with thirst and bloating being the most frequently reported symptoms. Patient satisfaction and willingness to repeat the preparation were high across all regimens, with no significant differences. Conclusions: Moviprep with Donat Mg, Plenvu, and Plenvu with Donat Mg are all effective, safe, and well-tolerated bowel preparation regimens. Each achieved a high level of bowel cleanliness and lesion detection, exceeding ESGE minimum standards. Their comparable efficacy and tolerability support their interchangeable use in routine colonoscopy practice.

Abstract: Background/Objectives: Microbial dysbiosis is implicated with a pathogenic role in both irritable bowel syndrome (IBS) and several dermatological conditions. Yet, few studies have assessed a potential overlapping epidemiologic association. We aimed to assess the 1-year prevalence of common dermatologic conditions following an initial IBS diagnosis and to evaluate the reverse association using reciprocal analyses; Methods: We conducted a retrospective study using TriNetX. Patients aged 18-50 with no history of inflammatory bowel disease, celiac disease or infectious intestinal disease were matched 1:1 to healthy controls by demographics and comorbidities. The primary outcome was the prevalence of acne vulgaris, psoriasis, atopic dermatitis, hidradenitis suppurativa, rosacea, vitiligo, alopecia areata, urticaria, 1-year after IBS diagnosis, measured using Odds Ratios (OR) and 95% confidence intervals. To confirm bidirectionality, reciprocal analyses were performed; Results: Over a 1-year period, IBS patients were less likely to have acne vulgaris (OR: 0.78, CIs: 0.75-0.80) and vitiligo (OR: 0.78, CIs: 0.64-0.95) compared to those without. IBS pa-tients were more likely to have psoriasis (OR: 1.14, CIs: 1.08-1.21), hidradenitis suppurativa (OR: 1.11, CIs: 1.03-1.20), rosacea (OR: 1.10, CIs: 1.03-1.18), and urticaria (OR: 1.27, CIs: 1.21-1.34) com-pared to healthy controls. No association was found for atopic dermatitis or alopecia areata. In the reciprocal analysis, alopecia areata patients (OR: 0.76, CIs: 0.64-0.90) had a lower prevalence of IBS compared to healthy controls. IBS was shown to occur more frequently in patients with psoriasis (OR: 1.15, CIs: 1.07-1.23), rosacea (OR: 1.23, CIs: 1.15-1.31), and urticaria (OR: 1.06, CIs: 1.01-1.12) compared to healthy controls. No association was seen in patients with acne, atopic dermatitis, hidradenitis suppurativa, and vitiligo; Conclusions: IBS shows a bilateral positive overlapping association with psoriasis, rosacea and urticaria. Hidradenitis suppurativa showed a positive association only among IBS patients, with no reciprocal relationship. Moreover, our findings suggest that acne and vitiligo were inversely associated with IBS, however this was not supported in our reciprocal analysis. Although no association was initially found between IBS and alopecia areata, the reciprocal analysis suggests a potential inverse association. No association was seen with atopic dermatitis bilaterally. Clinicians who treat these disorders should be aware of the potential bidirectional association.

Abstract:

Background/Objectives: Ultrasonography (US) is a non-invasive and repeatable examination for evaluating chronic constipation. However, only few studies have investigated drug therapy decisions based on rectal US results. To date, the efficacy and safety of elobixibat have not been evaluated using rectal US classification in patients with chronic constipation. This study aimed to evaluate the efficacy and safety of elobixibat in patients with chronic constipation classified as “no fecal retention” by rectal US. Methods: We retrospectively analyzed 32 patients with chronic constipation who underwent rectal US and received elobixibat (10 mg/day) between May 2019 and December 2024. Patients were classified into four groups according to rectal US findings: no fecal retention, fecal retention without hard stools, fecal retention with hard stools, and gas retention. The primary endpoint was the response rate of spontaneous bowel movements (SBMs) within 3 days after starting elobixibat in the “no fecal retention” group. Results: Among 18 patients in the “no fecal retention” group, 94.4% achieved SBMs within 3 days after elobixibat administration, indicating a favorable response. Adverse events included abdominal distension and abdominal pain, each observed in one patient (3.1%). Conclusions: Elobixibat was effective and well tolerated in patients with chronic constipation classified by rectal US findings.

Abstract: Background: Fontan-associated liver disease (FALD) is a progressive condition resulting from chronic hepatic venous congestion following the Fontan procedure for univentricular heart defects. As survival improves in these patients, recognition and management of FALD have become increasingly important. Objective: To describe the pathophysiological mechanisms, imaging findings, and diagnostic approach to FALD, with a focus on the role of ultrasonography, including contrast-enhanced ultrasound (CEUS). Methods: This narrative review explores the evolution of FALD through a multidisciplinary lens, integrating cardiovascular and hepatic imaging data. Particular attention is paid to Doppler ultrasound and CEUS, both in early parenchymal changes and in the differential diagnosis of potential complications such as hepatic nodules. Results: FALD is characterized by progressive fibrosis due to long-standing passive congestion, resulting in a wide spectrum of imaging findings. B-mode ultrasound reveals hepatomegaly, heterogeneous parenchyma, and gallbladder wall thickening. Doppler studies show altered hepatic venous flow patterns, while CEUS provides dynamic vascular evaluation, highlighting areas of altered perfusion. In advanced stages, hypovascular areas in the late phase may simulate malignant lesions, emphasizing the need for careful interpretation. The role of liver biopsy, though limited by invasiveness, remains crucial in selected cases. Surveillance strategies are not standardized but require close multidisciplinary follow-up. Conclusion: FALD presents complex diagnostic challenges requiring integrated imaging and clinical assessment. CEUS emerges as a valuable, non-invasive tool in characterizing hepatic congestion and guiding management. Increased awareness and standardized protocols are essential for early detection and tailored care in this growing patient population.

Abstract:

Background: The intestinal microbiota (IM) modulates host physiology, and its alteration (dysbiosis) is associated with several diseases, including obesity. This condition influences the pharmacokinetics of drugs prescribed for related comorbidities, although the underlying mechanisms remain poorly understood. Mrp2, an essential ABC transporter of the intestinal biochemical barrier, regulates the absorption of dietary toxins and orally administered drugs, thereby modulating their bioavailability. However, its regulation in the obesity context is poorly characterized, and the role of IM alteration in this process remains unknown. Objective: To evaluate the role of the IM as a key factor, along with downstream candidate mediators, in the regulation of Mrp2 under obesity conditions. Methods: Male C57BL/6 mice were fed either a control diet or High-Fat Diet (HFD) for 8 weeks, followed by 2 weeks with or without 5% inulin supplementation. Metabolic and biochemical parameters were evaluated. Intestinal barrier integrity, inflammatory cytokines, oxidative stress (OS) markers, and plasma endotoxin levels were assessed. Mrp2 expression was analyzed at mRNA and protein levels, and transporter activity was determined using the everted intestinal sac model. Fecal microbiota composition was characterized by 16S rRNA sequencing. Results: HFD feeding induced obesity, insulin resistance, hyperglycemia, dyslipidemia, intestinal dysbiosis, elevated endotoxemia, barrier dysfunction, inflammation, and OS. These alterations were associated with marked downregulation of Mrp2 expression and activity. Inulin supplementation restored IM composition, improved metabolic and intestinal parameters, and reduced inflammation and OS. These positive changes correlated with normalization of Mrp2. Conclusion: Our findings provide the first evidence that intestinal dysbiosis, inflammation, and OS act as a central regulatory axis of intestinal Mrp2 in obesity, with the IM functioning as a key modulator.

Abstract: Endobiliary radiofrequency ablation (RFA) has emerged as a promising adjunct to biliary stenting in the palliative management of unresectable extrahepatic cholangiocarcinoma. By generating localized thermal injury through a high-frequency alternating current (400–500 kHz) delivered via an intraductal electrode, RFA induces coagulative necrosis of malignant tissue, aiming to delay tumor ingrowth, maintain ductal patency, and improve quality of life. The procedure can be performed during endoscopic retrograde cholangiopancreatography or percutaneously, using bipolar probes advanced over a guidewire under fluoroscopic control. Technical success depends on adequate positioning of the electrodes within the stricture, correct energy settings (7–10 W for 60–120 s), and appropriate stent selection. Preclinical studies demonstrated controlled necrosis extending through the bile-duct wall, while clinical investigations have evaluated its impact on outcomes. Early retrospective series and several randomized controlled trials showed that RFA combined with stenting prolongs stent patency and, in selected subgroups, improves survival compared with stenting alone, without increasing the overall rate of complications. Meta-analyses have confirmed a consistent benefit in stent function and a moderate survival advantage, particularly in distal malignant strictures, although results remain heterogeneous due to differences in technique, patient selection, and stent type. The most frequent adverse events are cholangitis, pancreatitis, and acute cholecystitis. Overall, endobiliary RFA is a safe, technically feasible, and clinically relevant option to enhance biliary drainage in advanced cholangiocarcinoma. Standardization of procedural parameters and prospective trials are still needed to better define its therapeutic role and identify patients most likely to benefit.

Abstract: Background: We investigated the roles and regulation of contractile and sodium ion transporter proteins in the pathogenesis of diarrhea in acute ulcerative colitis. Methods: Acute ulcerative colitis was induced in male Sprague-Dawley rats using dextran sulfate sodium (DSS) in drinking water for seven days. The effects of nobiletin, a citrus flavonoid, were also examined. Results: Increased myeloperoxidase activity, colon mass, and inflammatory cell infiltration associated with damage to goblet cells and the epithelial cell lining indicated the development of acute ulcerative colitis. SERCA-2 calcium pump expression remained unchanged, whereas the phospholamban (PLN) regulatory peptide was reduced and its phosphorylated form (PLN-P) increased, suggesting a post-translational enhancement of SERCA-2 activity in the inflamed colon. Higher levels of IP3 were associated with a decrease in the Gαq protein levels without altering phospholipase C expression, suggesting that IP3 regulation is independent of Gαq protein signaling. In addition, the expression of sodium/hydrogen exchanger isoforms NHE-1, NHE-3 and carbonic anhydrase-1 and sodium pump activity were decreased in the inflamed colon. Nobiletin treatment of colitis selectively reversed the inflammatory and oxidative stress markers, including superoxide dismutase and catalase without restoring the expression of ion transporters. Conclusions: This study highlights alterations in the expression of ion transporters and their regulatory proteins in acute ulcerative colitis. These changes in the ion transporters are likely to reduce NaCl absorption and alter contractility, thereby contributing to the pathogenesis of diarrhea in the present acute model of ulcerative colitis. Nobiletin selectively ameliorates acute colitis in this model.