Search Results (404)

Introduction: Chronic intestinal failure (CIF) and the resulting dependence on home parenteral nutrition (HPN) often occur abruptly, profoundly disrupting the daily lives of patients and their caregivers. Both groups face persistent psychological and relational challenges, yet evidence on their long-term mental-health trajectories remains scarce. This study aimed to assess the progression of anxiety symptoms over 12 months in CIF patient–caregiver pairs, and to explore whether participation in a systemic–relational psychotherapy program could influence these outcomes. Methods: The Hamilton Anxiety Rating Scale (HAM-A) was administered to all participating patient–caregiver pairs, who were also invited to attend free biweekly psychotherapy sessions for one year. Pairs who accepted (Group Y) were compared with those who declined (Group N). Results: At baseline, both patients and caregivers in both groups exhibited high anxiety levels. Group Y (n = 10) patients had significantly higher total HAM-A scores than Group N (n = 40) patients (p = 0.048); a similar, non-significant trend was observed among caregivers. Emotional and somatic component scores remained largely unchanged at 6 and 12 months, regardless of group allocation. Conclusions: CIF imposes a substantial and persistent anxiety burden on both patients and caregivers. In this cohort, a brief systemic–relational psychotherapy program, offered quarterly, did not significantly modify anxiety levels over 12 months. These findings highlight the need for more intensive, sustained, and possibly earlier psychological interventions tailored to the dyadic experience of living with CIF and HPN. Full article

Cardiac hypertrophy is a critical contributor to cardiac dysfunction and the development of heart failure, yet effective therapeutic strategies remain limited. Propylene glycol alginate sulfate sodium (PSS) is a marine sulfated polysaccharide drug used in the treatment of cardiovascular diseases and has shown cardiac function benefits. Here, we designed a pH-responsive PSS-loaded nanoparticle drug delivery system. It was self-assembled by negatively charged PSS with positively charged trimethyl chitosan glycocholic acid (TMC-GA) via electrostatic interaction, and further stabilized the nanoparticles with Hydroxypropyl methylcellulose phthalate (HP55) excipients. The prepared TMC-GA/HP55@PSS nanoparticles were spherical, with a mean particle size of 361.5 ± 1.26 nm, zeta potential of −30.3 ± 0.9 mV, and encapsulation efficiency of 92.52 ± 2.4%. In vitro release study demonstrated the pH-responsive property of TMC-GA/HP55@PSS under intestinal conditions and facilitated nanoparticles absorption in the intestinal epithelium. In vitro experiments confirmed the biocompatibility of PSS and its ability to improve myocardial cell hypertrophy. In vivo, both PSS and its nanoparticles significantly ameliorated pressure overload–induced cardiac hypertrophy in mice, with TMC-GA/HP55@PSS exhibiting better cardioprotective efficacy. This study is the first to integrate pH-responsiveness and bile acid transport-mediated uptake into PSS nanocarrier systems. The findings provide valuable data and enlightenment for designing novel formulations and expanding the clinical applications of PSS. Full article

Acute mesenteric ischemia (AMI) is a life-threatening condition characterised by oxidative stress, inflammation, apoptosis, and necrosis of intestinal epithelial cells. Different drugs with vasoactive, antioxidant, and anti-inflammatory properties have been used to treat AMI. Levosimendan is a drug with proven anti-ischemic effects used in the management of acute congestive heart failure. This study evaluated the protective effects of levosimendan pretreatment on intestinal, as well as lung, heart, and kidney tissue in a rat model of mesenteric artery ischemia/reperfusion (I/R) injury. Male Wistar rats (N = 24) were divided into four groups: control, I/R, levosimendan (LS) 1 mg/kg i.p, and LS + I/R (1 mg/kg i.p. 30 min before injury). I/R by itself caused elevation of oxidative markers (thyobarbituric acid reactive species (TBARS), hydrogen peroxide (H₂O₂), super oxide anjon radical (O₂⁻), and nitrogen dioxide (NO₂⁻)), induced inflammation (macrophage infiltration and Interleukin-6 (IL-6) production), and apoptosis (nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), cleaved caspase-3 (CC3), and terminal deoxy-nucleotidyl transferase (TdT)-mediated dUTP nick end labelling (TUNEL)). Levosimendan pretreatment significantly reduced oxidative stress markers and enhanced antioxidant defences (catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)). Histological analysis revealed reduced mucosal damage and preserved goblet cells in intestinal tissue. Similar protective effects of levosimendan were observed in other organs such as lung, heart, and kidney. Immunohistochemistry showed reduced epithelial apoptosis and upregulation of antioxidant and anti-inflammatory proteins. These findings highlight levosimendan’s ability to protect mesenteric I/R tissue injury and multi-organ damage by suppressing oxidative stress, inflammation, and apoptosis, emphasising its therapeutic potential in clinical settings. Full article

Background/Objectives: Crohn’s disease (CD) is one of the most frequent causes of short bowel syndrome (SBS), a severe clinical condition with huge morbidity and social costs. SBS occurs when, following intestinal resections, the remaining small bowel in continuity is less than 200 cm in length. Intestinal failure (IF) can complicate SBS when intravenous nutritional or electrolyte supplementation is required to maintain dietary needs. The primary aim of this study was to identify clinical predictive factors of SBS in a cohort of outpatients with CD. Methods: We conducted a prospective, single-center, cohort study enrolling consecutive CD outpatients at a tertiary-level inflammatory bowel disease center. Detailed demographic and clinical features were collected. Significant factors associated with the onset of SBS in the univariate analysis were input into a multivariate logistic regression model to identify independent predictors of SBS. Results: In total, 232 CD patients (52.6% male, median age 49 years [IQR 37–60]) were included: 24.6% of them were smokers; extraintestinal manifestations (EIMs) were present in 21.6% of patients; and 67.7% of patients had at least one intestinal resection (27% of them with more than one surgical intervention). At enrollment, 96.1% of patients were on advanced therapies, and considering the course of the disease, 24.6% of patients were exposed to ≥3 different advanced therapies. A total of 18 patients had SBS and 9 had IF. In univariate analysis, the following variables were statistically associated with the risk of developing SBS: disease duration (p < 0.001), upper gastrointestinal disease localization (L4) (p < 0.001), penetrating behavior (p = 0.023), perianal disease (p = 0.036), length of first intestinal resection (p < 0.001), shorter time elapsing from CD diagnosis to start the first advanced therapy (p < 0.001), and treatment with advanced therapy after first intestinal resection (p < 0.001). In multivariate analysis, disease duration (OR 1.083, 95% C.I. 1.025–1.145, p = 0.005) and L4 (OR 20.079, 95% C.I. 2.473–163.06, p = 0.005) were independently associated with the development of SBS. Conversely, the number of different advanced therapies before the onset of SBS was independently associated with a reduced risk of developing SBS (OR 0.247, 95% C.I. 0.107–0.58, p = 0.001). Conclusions: Our data identifies several clinical features that could possibly predict the development of SBS in CD. Further studies with a larger sample size are needed to confirm our findings. Full article

Patients undergoing immunosuppressive therapy are at risk of adverse gastrointestinal symptoms such as diarrhea, nausea, intestinal barrier leakage, and nutrient malabsorption. One mechanism underlying these complications may be increased levels of oxidative stress in the cell, and thus an increased predisposition of enterocytes to programmed death. We examined the effects of triple immunosuppressive regimens on the concentration of glutathione, the SLC1A5 receptor, caspase-3, caspase-9, Bcl-2, Bax, and apoptosis in the rat intestine. For this purpose, we used Western blot analysis, ELISA, and the TUNEL method. The study began with 36 rats divided into six groups, which were administered the drugs for a period of six months. Our results suggest that chronic use of standard immunosuppressive regimens increases the risk of oxidative stress in the rat intestine, as manifested by increased expression of glutathione or the SLC1A5 transporter. The use of rapamycin in combination with cyclosporine A or mycophenolate mofetil leads to increased cellular apoptosis in the rat intestine, which is associated with a failure of compensatory mechanisms for elevated oxidative stress. The combination of tacrolimus with rapamycin results in the highest percentage of TUNEL positivity, and the apoptotic pathway is not a result of increased oxidative stress in the tissue. Full article

Background/Objectives: Fecal peritonitis following penetrating abdominal trauma is a serious condition that often results in sepsis and organ failure. The aim of our study was to develop a novel conscious porcine model of sepsis and organ dysfunction caused by multiple penetrating injuries to the small and large intestines. Methods: Twelve female Yorkshire pigs (average weight 50.6 ± 6.5 kg) were divided into two groups: Penetrating Abdominal Trauma (PAT) (n = 8) and Control (n = 4). All surgical procedures were performed under anesthesia with adequate analgesia. In the PAT group, the small and large intestines were punctured, and feces mixed with saline were introduced into the abdominal cavity to induce peritonitis. The Control group received sham surgery with only saline solution. The animals were observed in a conscious state over a period of 72 h, vital parameters were recorded, and blood samples were taken regularly. We adapted a pig-specific SOFA score and developed pig-specific SIRS criteria and NEWS2 score to assess organ function. The model was validated by independent investigators. Results: The survival rate in the PAT group was 75%, with an average survival time of 58.5 h, while all animals in the Control group survived to euthanasia. Monitoring showed pathophysiological changes, such as tachycardia, leucopenia, and thrombocytopenia, indicative of sepsis and organ dysfunction. Blinded investigators independently confirmed the model’s validity. Conclusions: A new swine model of penetrating abdominal trauma and sepsis has been successfully developed that demonstrates significant physiological and immunologic changes comparable to human sepsis. This new model provides a realistic platform for future research into sepsis, its diagnostics, and the evaluation of therapeutic strategies. Full article

Background: The catecholamine-induced hypertensive crisis is a rare, life-threatening condition caused by excessive catecholamine release, often resulting in cardiogenic shock and multiorgan failure. Management is challenging, especially when hemodynamic instability persists despite standard medical therapy. Methods: We conducted a narrative review of published articles between 2013 and 2025. The search was conducted in MEDLINE (PubMed, Scholar and Embase). We also presented a case managed at our reference center. Results: Overall, 42 studies including 69 patients were included. ECMO was the most commonly used modality, often serving as a bridge to surgery. The overall hospital mortality rate was 17.4%. Timing of adrenalectomy varied, with no clear consensus on the optimal approach. We report also a case of a 43-year-old woman with neurofibromatosis type 1 who developed acute cardiogenic shock due to an adrenal paraganglioma. She was supported with ECMO and underwent emergency bowel resection for intestinal ischemia, followed by adrenalectomy. Despite aggressive treatment, the patient died from progressive multiorgan failure. Conclusions: This case highlights the complexity of managing paraganglioma crisis, the potential role of ECMO as a bridge to surgery, and the importance of individualized, multidisciplinary care. Early recognition and referral to specialized centers are essential, though further studies are needed to guide optimal management strategies. Full article

Type 2 diabetes mellitus (T2DM) is a multifactorial disorder defined by insulin resistance, β-cell dysfunction, and chronic hyperglycemia. Although peripheral mechanisms have been extensively studied, increasing evidence implicates the gastrointestinal tract in disease onset. Insights from bariatric surgery, gut hormone signaling, and incretin-based therapies suggest that the gut contributes actively beyond nutrient absorption. Yet, a cohesive framework integrating these observations remains absent, leaving a critical gap in our understanding of T2DM’s upstream pathophysiology. This work builds upon the anti-incretin theory, which posits that nutrient-stimulated neurohormonal signals—termed “anti-incretins”—arise from the proximal intestine to counteract incretin effects and regulate glycemic homeostasis. The excess of anti-incretin signals, perhaps stimulated by macronutrient composition or chemical additives of modern diets, disrupts this balance and may cause insulin resistance and β-cell depletion, leading to T2D. We hypothesize that the neuroendocrine signals produced by cholecystokinin (CCK)-I and secretin-S cells, both located in the proximal intestine, function as endogenous anti-incretins. In this context, we hypothesize a novel model centered on the chronic overstimulation of I and S cells by high-fat, high glycemic index modern diets. This drives what we term “amplified digestion”—a state marked by heightened vagal and hormonal stimulation of biliary and pancreatic secretions, increased enzymatic and bile acid activity, and alterations in bile acid composition. This condition leads to an extended breakdown of carbohydrates, lipids, and proteins into absorbable units, thereby promoting excessive nutrient absorption and ultimately contributing to insulin resistance and progressive β-cell failure. Multiple lines of clinical, surgical, and experimental evidence converge to support our model, rooted in the physiology of digestion and absorption. Western dietary patterns appear to induce an over-digestive adaptation—marked by excessive vagal and hormonal stimulation of biliary and pancreatic secretion—which amplifies digestive signaling. This heightened state correlates with increased nutrient absorption, insulin resistance, and β-cell dysfunction. Interventions that disrupt this maladaptive signaling—such as truncal vagotomy combined with duodenal bypass—may offer novel, physiology-based strategies for T2DM treatment. This hypothesis outlines a potential upstream contributor to insulin resistance and T2DM, grounded in digestive tract-derived neurohormonal dysregulation. This gut-centered model may provide insight into early, potentially reversible stages of the disease and identify a conceptual therapeutic target. Nonetheless, both the hypothesis and the accompanying surgical strategy—truncal vagotomy combined with proximal intestinal bypass—remain highly exploratory and require systematic validation through mechanistic and clinical studies. Further investigation is warranted to clarify the molecular regulation of I and S enteroendocrine cells, including the genetic and epigenetic factors that may drive hypersecretion. While speculative, interventions—surgical or pharmacologic—designed to modulate these digestive signals could represent a future avenue for research into T2DM prevention or remission, pending rigorous evidence. Full article

Background/Objectives: Infants with high-output enterostomies often require prolonged parenteral nutrition (PN), increasing risks of infections, liver dysfunction, and impaired growth. Mucous fistula refeeding (MFR) is proposed to enhance intestinal adaptation, weight gain, and distal bowel maturation. This systematic review and meta-analysis assessed its effectiveness, safety, and technical aspects. Methods: Following PRISMA guidelines, studies reporting MFR-related outcomes were included without data or language restrictions. Data sources included PubMed, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Library, and UpToDate. Bias risk was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis employed random- and fixed-effects models, with outcomes reported as odds ratios (ORs) and 95% confidence interval (CI). Primary outcomes assessed were weight gain, PN duration, and complications and statistical comparisons were made between MFR and non-MFR groups. Results: Seventeen studies involving 631 infants were included; 482 received MFR and 149 did not. MFR started at 31 postoperative days and lasted for 50 days on average, using varied reinfusion methods, catheter types, and fixation strategies. MFR significantly improved weight gain (4.7 vs. 24.2 g/day, p < 0.05) and reduced PN duration (60.3 vs. 95 days, p < 0.05). Hospital and NICU stays were also shorter (160 vs. 263 days, p < 0.05; 122 vs. 200 days, p < 0.05). Cholestasis risk was lower (OR 0.151, 95% CI 0.071–0.319, p < 0.0001), while effects on bilirubin levels were inconsistent. Complications included sepsis (3.5%), intestinal perforation (0.83%), hemorrhage (0.62%), with one MFR-related death (0.22%). Conclusions: Despite MFR benefits neonatal care, its practices remain heterogeneous. Standardized protocols are required to ensure MFR safety and efficacy. Full article

Background/Objectives: Short bowel syndrome (SBS) is the leading cause of pediatric intestinal failure. Plasma citrulline is considered a marker indicating an enterocyte volume and may help evaluate the response to teduglutide; however, this interpretation may vary depending on the remnant bowel anatomy. Methods: We conducted a retrospective case series of four pediatric patients with SBS (aged < 15 years) who received teduglutide for 12 months at our hospital between 2018 and 2023. Changes in plasma citrulline levels and parenteral nutrition requirements were assessed in addition to bowel anatomy classification. Results: This study included two males and two females. All patients showed an increase in plasma citrulline levels and a reduction in the requirement for parenteral nutrition (PN) after 12 months of teduglutide treatment. In SBS type 2 (jejunocolic anastomosis), citrulline levels increased by 114% and 52%, with PN reduction rates of 100% and 30%, respectively. In SBS type 3 (jejunoileal anastomosis), citrulline levels increased by 13.6% and 34%, with PN reductions of 33% and 73%, respectively. Conclusions: Teduglutide treatment increased plasma citrulline levels and reduced PN levels in all cases. However, the magnitude of the citrulline change varied across bowel anatomy types, suggesting that the anatomical difference in the remnant bowel may influence the biomarker response. Further detailed pediatric cases are required to clarify the role of citrulline in evaluating GLP-2 analogue treatment outcomes. Full article

Background/Objectives: Patients with stage IV gastric cancer who develop chronic intestinal failure require home parenteral nutrition (HPN). This study aimed to evaluate the prognostic relevance of nutritional and immune–inflammatory biomarkers and to construct an individualised survival prediction model using machine learning techniques. Methods: A secondary analysis was performed on a cohort of 410 patients with TNM stage IV gastric adenocarcinoma who initiated HPN between 2015 and 2023. Nutritional and inflammatory indices, including the Controlling Nutritional Status (CONUT) score and lymphocyte-to-monocyte ratio (LMR), were assessed. Independent prognostic factors were identified using Cox proportional hazards models. A Random Survival Forest (RSF) model was constructed to estimate survival probabilities and quantify variable importance. Results: Both the CONUT score and LMR were independently associated with overall survival. In multivariate analysis, higher CONUT scores were linked to increased mortality risk (HR = 1.656, 95% CI: 1.306–2.101, p < 0.001), whereas higher LMR values were protective (HR = 0.632, 95% CI: 0.514–0.777, p < 0.001). The RSF model demonstrated strong predictive accuracy (C-index: 0.985–0.986) and effectively stratified patients by survival risk. The CONUT score exerted the greatest prognostic influence, with the LMR providing additional discriminatory value. A gradual decline in survival probability was observed with an increasing CONUT score and a decreasing LMR. Conclusions: The application of machine learning to immune–nutritional data offers a robust tool for predicting survival in patients with advanced gastric cancer requiring HPN. This approach may enhance risk stratification, support individualised clinical decision-making regarding nutritional interventions, and inform treatment intensity adjustment. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is increasingly recognized as a systemic condition with cardiovascular implications. Among these, heart failure has emerged as a significant complication. The aim of this narrative review was to explore the cellular and molecular pathways that link IBD and heart failure. Drawing upon findings from epidemiologic studies, experimental models, and clinical research, we examined the pathways through which IBD may promote cardiac dysfunction. Chronic systemic inflammation in IBD, driven by cytokines such as TNF-α and IL-1β, can impair myocardial structure and function. Furthermore, intestinal barrier dysfunction and gut dysbiosis can facilitate the translocation of proinflammatory microbial metabolites, including lipopolysaccharide and phenylacetylglutamine, and deplete cardioprotective metabolites like short-chain fatty acids, thereby exacerbating heart failure risk. Additional contributing factors include endothelial and microvascular dysfunction, autonomic dysregulation, nutritional deficiencies, shared genetic susceptibility, and adverse pharmacologic effects. IBD contributes to heart failure pathogenesis through multifactorial and interrelated mechanisms. Recognizing the role of the gut–heart axis in IBD is crucial for the early identification of cardiovascular risk, providing guidance for integrating care and developing targeted therapies to reduce the risk of heart failure in this vulnerable population. Full article

Crohn’s disease (CD), characterized by chronic gastrointestinal inflammation, is complicated by intestinal stenosis resulting from dysregulated fibrogenesis and is marked by excessive extracellular matrix (ECM) deposition, fibroblast activation, and luminal obstruction. While biologics control inflammation, their failure to halt fibrosis underscores a critical therapeutic void. Emerging evidence highlights the multifactorial nature of stenosis-associated fibrosis, driven by profibrotic mediators and dysregulated crosstalk among immune, epithelial, and mesenchymal cells. Key pathways, including transforming growth factor (TGF-β), drosophila mothers against decapentaplegic protein (Smad) signaling, Wnt/β-catenin activation, epithelial–mesenchymal transition (EMT), and matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP)-mediated ECM remodeling, orchestrate fibrotic progression. Despite the current pharmacological, endoscopic, and surgical interventions for fibrostenotic CD, their palliative nature and inability to reverse fibrosis highlight an unmet need for disease-modifying therapies. This review synthesizes mechanistic insights, critiques therapeutic limitations with original perspectives, and proposes a translational roadmap prioritizing biomarker-driven stratification, combinatorial biologics, and mechanistically targeted antifibrotics. Full article

Introduction: This study aims to elucidate the impact of AQP1 on cardiac function and the intestinal microbiota in mice with chronic heart failure and to further investigate the broad effects of AQP1 on the gut microbiota composition in these mice. Methods: AQP1 knockout mice were used as the experimental group, with wild-type mice serving as the control group. The study evaluated the effects of AQP1 on various physiological parameters, including blood pressure, heart rate, cardiac function, cardiac color Doppler ultrasound, and 24 h urine collection. Additionally, the high-throughput sequencing of gut microbiota was performed to identify key microbial communities. Results: The deletion of the AQP1 gene did not significantly alter key cardiovascular metrics such as systolic blood pressure (SBP), mean blood pressure (MBP), or left ventricular mass (LV mass). However, we found that AQP1 knockout affected 24 h urine output in mice. Echocardiography results showed that AQP1 expression influenced LV mass, LVAW; d, and LVPW; s. Moreover, substantial differences were observed in the intestinal microbiota profiles between AQP1 knockout mice with heart failure and their wild-type counterparts. These findings suggest that AQP1 may contribute to cardiac dysfunction in mice with chronic heart failure through the regulation of gut microbiota. Conclusion: Our investigation provides initial insights into the role of AQP1 in modulating the intestinal microbiota in a murine model of heart failure. However, the precise mechanisms underlying this association require further exploration and detailed analysis. Full article

Wilson’s disease is a rare autosomal recessive disorder of copper metabolism characterized by excessive copper accumulation in the liver, brain, and other tissues. This paper provides an overview of the primary pharmacological agents used in its treatment, including penicillamine, trientine, tetrathiomolybdate, and zinc. Their mechanisms of action, therapeutic applications, and side-effect profiles are examined, emphasizing how each agent helps reduce copper overload. Additionally, brief information is given on novel therapies such as gene therapy and artificial intelligence applications. Furthermore, information about the structural and chemical properties of these compounds is provided, highlighting the molecular features that enable them to chelate copper or reduce its intestinal absorption. By integrating pathophysiological insights with chemical and mechanistic perspectives, this paper offers a comprehensive review of existing treatment strategies for Wilson’s disease and stresses the importance of careful, patient-specific management to optimize long-term outcomes. Full article