Search Results (285)

Type 2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance, progressive β-cell dysfunction, and persistent hyperglycemia. While GLP-1 receptor agonists have revolutionized the management of T2D by improving glycemic control and reducing body weight, their insulinotropic effects increase the workload on pancreatic β-cells, which may hasten β-cell decline in certain individuals. Peptide YY (PYY), a gut-derived hormone secreted alongside glucagon-like peptide-1 (GLP-1) from L-cells, presents a unique and complementary therapeutic approach. In contrast to GLP-1, PYY does not directly induce insulin release but confers metabolic advantages by suppressing appetite through Y2 receptor pathways, enhancing insulin sensitivity via peripheral Y1/Y4 receptors, and slowing gastric emptying to minimize postprandial glucose surges. Notably, recent research suggests PYY supports the preservation and restoration of pancreatic islets by improving their structure and function without increasing the secretory demand. PYY levels are substantially increased after bariatric surgery, where it plays a pivotal role in weight-loss-independent improvements in glycemic regulation and islet hormone dynamics. These attributes position PYY as a strong candidate for use in combination with GLP-1 analogs, especially in individuals with advanced β-cell impairment or those who respond inadequately to GLP-1 monotherapy. This review discusses PYY’s physiological functions, mechanistic actions, and therapeutic opportunities in T2D, highlighting its potential as a valuable adjunct or alternative in gut-hormone-oriented treatment strategies. Full article

Motility disorders, particularly gastroparesis, are prevalent complications following solid organ transplantation, significantly impacting quality of life, nutritional status, graft survival, and mortality. This comprehensive review synthesises evidence from PubMed, Scopus, and Embase databases on pathophysiology, clinical manifestations, diagnosis, management, and prognostic factors across transplant types. Mechanisms include vagal nerve injury (highest in lung transplants, prevalence 40–91%), immunosuppressive effects (e.g., tacrolimus accelerates motility; mycophenolate impairs it), surgical trauma, microbiome dysbiosis (reduced Firmicutes/Bacteroidetes ratio), and metabolic factors like post-transplant diabetes (OR 5.17 in kidney recipients). Pediatric and thoracic recipients face the highest risks, with lung transplant gastroparesis conferring a 2.7-fold increased mortality/retransplantation hazard (p < 0.05). Diagnosis relies on gastric emptying scintigraphy (gold standard, sensitivity 85–95%) and wireless motility capsules (100% sensitivity for delay), while management encompasses prokinetics (60–80% response), endoscopic G-POEM (85% success), gastric electrical stimulation (100% quality-of-life improvement in series), and nutritional support. Prognostic factors include younger age (better intervention response), aetiology (anatomical worse than metabolic), and early therapy success. Outcomes vary: lung recipients experience severe impacts on chronic allograft dysfunction (83% oesophageal motility abnormalities correlate with 66–67% rejection). Future directions emphasise microbiome therapies, AI predictive models (AUC 0.85), and wearables for continuous monitoring. Multidisciplinary approaches are essential to balance immunosuppression with GI management, addressing ethical dilemmas like drug interactions and access disparities. Ultimately, early screening and personalised interventions can mitigate complications, enhancing long-term transplant success. Full article

TAAR1 agonists have emerged as promising therapeutic agents capable of modulating glucose homeostasis, enhancing insulin secretion and suppressing appetite, making them attractive candidates for the treatment of obesity and related metabolic disorders. Despite their potential, the number of TAAR1-targeting compounds with well-defined pharmacological profiles remains limited. In this study, we identified and characterized JP-14, a novel aminoguanidine-based TAAR1 agonist, in a comprehensive panel of pharmacological assays. JP-14 promoted glucose uptake in HepG2 cells and reduced lipid deposition during 3T3-L1 adipocyte differentiation, with both actions dependent on TAAR1 signaling. In differentiated 3T3-L1 adipocytes, JP-14 reduced intracellular levels of both neutral lipids and phospholipids, indicating dual anti-steatotic and anti-phospholipidotic activity. In zebrafish larvae, toxicity profiling confirmed 10 µg/mL as a safe concentration for further in vivo studies. These assays showed that JP-14 promoted lipid mobilization and partially prevented fructose-induced lipid accumulation, demonstrating systemic metabolic benefits in vivo. Moreover, JP-14 markedly delayed gastric emptying in mice, an effect similar to loperamide and reversed by TAAR1 antagonism, supporting its role in regulating satiety and energy balance. Collectively, our findings establish JP-14 as a safe and metabolically active TAAR1 agonist with multifaceted effects on glucose and lipid metabolism. JP-14 represents a valuable pharmacological tool for probing TAAR1-mediated mechanisms in metabolic regulation. Full article

Background: Pancreatic and hepatobiliary tumors continue to rank among the deadliest cancers worldwide. Due to a low response rate to treatment, these tumors continue to have a high death rate, a poor prognosis and survival rate, and an overall poor patient outcome. The multimodal strategy used in current treatment includes systemic therapy, radiation therapy, and surgery. However, surgery remains the only treatment with curative intent. Preoperative biliary drainage has a direct impact on the perioperative prognosis of patients with obstructive jaundice and significantly compromised liver function due to hepato-bilio-pancreatic malignancies. Our study’s goal was to determine the safest and most efficient preoperative biliary drainage technique by conducting a systematic review and meta-analysis of resectable periampullary cancers. Methods: Our approach consisted of searching PubMed, BMC Medicine, and Scopus databases using keywords with a result of 1104 articles from 2010 to 2023. The remaining 24 articles that met our inclusion criteria were subjected to meta-analysis using R Commander 4.3.2. Results: Endoscopic retrograde biliary drainage (ERBD) demonstrated a higher rate of postprocedural pancreatitis (RR = 2.22, p < 0.01), intra-abdominal abscess (RR = 1.64, p < 0.01), and delayed gastric emptying (DGE) (RR = 2.07, p < 0.01) than percutaneous transhepatic biliary drainage (PTBD) or endoscopic nasobiliary drainage (ENBD). Plastic stent (PS) had higher rates of catheter occlusion (RR = 2.20, p < 0.01) and POPF (RR = 1.66, p < 0.01) compared to self-expandable metallic stent (SEMS), which could explain a longer hospital stay (MD = 2.41 days, p < 0.01). However, PS had lower rates of grade 1–2 complications (RR = 0.79, p = 0.017) and wound infection rates (RR = 0.66, p = 0.017) than self-expandable metallic stent (SEMS). Conclusions: The choice of a preoperative drainage method can influence postprocedural and postoperative complications rates. ERBD appears to be associated with higher procedure-related and postoperative complication rates and may be linked to a prolonged hospital stay compared to ENBD or PTBD. Moreover, the type of stent placed through ERBD procedure had an important impact on prognosis, as PS had a higher rate of catheter occlusion and POPF, with a prolonged hospital stay compared to SEMS, while mild complications and wound infections were less common in PS group. Full article

Background/Objectives: Lipid-based formulations are widely used to enhance the oral bioavailability of poorly water-soluble drugs. However, for weakly basic drugs with higher solubility under acidic conditions, precipitation and recrystallisation after gastric emptying can compromise a formulation’s ability to maintain the drug in a solubilised, absorbable state. To address this, we evaluated an enteric coating strategy to preserve the biopharmaceutical performance of a silica-solidified lipid-based formulation. Methods and Results: The model weakly basic BCS Class IV drug, abiraterone acetate, was loaded into a lipid-based formulation and solidified using mesoporous silica nanoparticles. In an in vitro lipolysis model, introducing the formulation only after the onset of the intestinal phase led to lower precipitation and over 50% greater drug presence in the aqueous phase compared to a two-stage gastric–intestinal digestion. In an in vivo pharmacokinetic study in Sprague Dawley rats, the silica–lipid formulation (6 mg/kg), delivered in gelatine minicapsules enteric-coated with Eudragit L100-55, resulted in a 2.6-fold higher systemic exposure compared to the non-coated formulation (p < 0.0001). Conclusions: These findings support the use of enteric coating for lipid-based formulations and silica nanoparticles containing weakly basic drugs as a strategy to maintain formulation integrity until reaching the small intestine. Full article

Background: Despite advances in surgical techniques and perioperative care, pancreatic resections such as pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) remain high-risk procedures. Postoperative complications significantly impact morbidity, mortality, and patient quality of life. Methods: This narrative review summarizes recent literature on major complications following pancreatic surgery, including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and post-pancreatectomy hemorrhage (PPH), with an emphasis on incidence, risk factors, outcomes, and current preventive strategies. Results: POPF is a leading complication, occurring in 5–22% of cases and often linked with sepsis and hemorrhage. Key risk factors include high BMI, soft pancreatic texture, and small duct size. Preventive measures like Pasireotide, modified anastomosis techniques, and neoadjuvant therapy show variable success. DGE affects up to 57% of PD patients and is associated with prolonged recovery; antecolic reconstruction and erythromycin may reduce incidence. PPH, though less frequent (3–13%), can be life-threatening, particularly when secondary to POPF. Endovascular approaches are now favored for late arterial bleeding. Other complications include wound infections, abscesses, bile leaks, and pulmonary issues, all contributing to extended hospital stays and diminished quality of life. Conclusions: Pancreatic surgery continues to carry significant risks, with POPF, DGE, and PPH being the most impactful complications. While multiple interventions have shown promise, standardized protocols and predictive tools are still needed. Surgery should be performed in high-volume centers with experienced multidisciplinary teams to optimize outcomes. Full article

Dumping Syndrome (DS) is a significant complication following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). This condition is characterised by gastrointestinal and vasomotor symptoms resulting from altered anatomy and hormonal dysregulation, notably accelerated gastric emptying and an exaggerated release of gut peptides. Based on the timing of symptom onset after food ingestion, DS is classified as early (EDS) or late (LDS). The critical roles of peptides such as GLP-1, GIP, insulin, and YY peptide are highlighted, along with the involvement of neuroendocrine pathways in symptom manifestation. Diagnosis relies on a combination of clinical evaluation and dynamic testing, with the oral glucose tolerance test (OGTT) often considered a key reference standard for diagnosis. Initial management involves dietary modifications, emphasising the glycaemic index of foods and meal distribution. In cases where nutritional interventions are insufficient, pharmacotherapy with agents such as acarbose, somatostatin analogues (octreotide and pasireotide), GLP-1 receptor agonists (liraglutide), calcium channel blockers (verapamil), and emerging therapies, including herbal medicine, may be considered. For refractory cases, surgical options like bypass reversal or partial pancreatectomy are reserved, although their efficacy can be variable. Despite advancements in understanding and treating DS, further large-scale, randomised controlled trials are essential to validate novel strategies and optimise long-term management. This review provides an updated and comprehensive overview of the aetiology, pathophysiological mechanisms, diagnostic approaches, and current management strategies for DS. Full article

Background: Bariatric surgery (BS) is the most effective long-term treatment for severe obesity, but many patients develop food intolerances that either reduce protein and micronutrient intake or shift consumption toward easily tolerated, calorie-dense “safe” foods (e.g., sweets, ice cream, sugar-sweetened beverages, refined-flour snacks), compromising nutrient adequacy and weight-loss maintenance. This narrative review summarizes evidence on the prevalence, mechanisms, and clinical impact of food intolerances after BS, focusing on red meat, dairy, water, cereal, and vegetables, and offers practical nutritional management strategies. Methods: A targeted literature search of PubMed and Cochrane Library from the past 10 years was conducted. Studies were selected based on relevance and quality. Results: Intolerance patterns vary by food type and surgical method. Red meat is the most frequently problematic food, with some patients symptomatic for years despite gradual improvement. Dairy products cause gastrointestinal discomfort in some cases, partly due to lactose intolerance. Cereal products may initially cause swallowing difficulties but are generally well tolerated two years postoperatively. Water intolerance mainly occurs shortly after sleeve gastrectomy (SG), linked to sleeve aperistalsis and edema, resolving within weeks. Cooked vegetables are overall well tolerated across procedures. Mechanisms behind intolerance include mechanical restriction, altered gastric emptying, exaggerated entero-hormonal responses, and new taste aversions. Conclusions: Food intolerances are a common, procedure-specific consequence of BS, requiring systematic assessment and personalized dietary management. Early management—modification of consistency, portion control, and supplementation—can improve product tolerance, prevent nutritional deficiencies, and support sustainable weight loss. However, further prospective studies on the mechanisms of food intolerances are needed. Full article

Delayed gastric emptying (DGE) is a significant complication following pancreaticoduodenectomy, affecting 20–40% of patients and impacting hospital stay, healthcare costs, and adjuvant therapy initiation. Different gastrojejunostomy configurations have been investigated to reduce DGE rates, with conflicting results presented in the literature. This retrospective study analyzed 65 consecutive patients who underwent pylorus-preserving pancreaticoduodenectomy at Bnai-Zion Medical Center between August 2018 and December 2023. All procedures were performed by a single experienced surgeon using either antecolic (AC, n = 25) or transmesocolic (TMC, n = 40) reconstruction. DGE was classified according to International Study Group of Pancreatic Surgery criteria. The statistical analysis included logistic regression to identify risk factors. The overall DGE incidence was 23.1% (15/65 patients). The AC group demonstrated significantly higher DGE rates compared to the TMC group (40% vs. 12.5%, p = 0.01). Logistic regression analysis revealed a 5.91-fold increased risk of DGE with AC reconstruction (OR: 5.91; 95% CI: [1.44, 24.25]; p = 0.014). All severe DGE cases (grades B and C) occurred exclusively in the AC group. Hospital stay was significantly longer in DGE patients (median: 26 vs. 13 days, p < 0.001). Other variables, including age, gender, smoking, diabetes, BMI, and surgical approach, showed no significant association with DGE. In this single-surgeon study, antecolic reconstruction was associated with significantly higher rates and severities of delayed gastric emptying compared to transmesocolic reconstruction. These findings suggest that reconstruction technique represents a modifiable risk factor for DGE prevention, though larger prospective studies are needed to confirm these results. Full article

The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments. Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis. Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy. Full article

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

Background/Objectives: Incretin-based therapies have demonstrated benefits in glycemic control and the prevention of long-term complications of diabetes. In addition to glucose-dependent insulin secretion stimulation, glucagon-like peptide-1 (GLP-1) also inhibits gastric acid secretion, delays gastric emptying, inhibits gut motility and induces satiety. We aimed to understand the modulation of gastric fundus motility by GLP-1 receptor agonists (GLP-1RA). Methods: We have studied the relaxation to sodium nitroprusside (SNP) and noradrenaline (NA) of gastric fundus isolated from Wistar rats and Goto-Kakizaki (GK) rats, an animal model of spontaneous non-obese type 2 diabetes, after Liraglutide treatment (200 μg/kg s.c., b.i.d., 14 days). Results: Decreased relaxation induced by SNP and NA (0.01–889 μM) was observed in treated groups, with no significant changes in SNP maximum relaxation or in nNOS/p-nNOS levels between treated and non-treated rats of both animal models. Accordingly, in rat gastric fundus pre-contracted with 5 µM of carbachol, GLP-1RA (0.05–111.1 nM) induced contractile responses that were GLP-1R-dependent and -independent. Exenatide showed more intrinsic activity, while Liraglutide showed more potency than GLP-1 in Wistar rats. Moreover, GLP-1 showed more intrinsic activity in diabetic rats compared to control ones. Conclusions: Liraglutide-induced increased gastric muscle tone may contribute to the significant decrease in caloric intake and body weight in all treated rats, causing a reduction in gastric accommodation during food intake. Thus, the increased gastric fundus tone induced by GLP-1RA may constitute a peripheral mechanism by which they can reduce food intake and induce satiety. Full article

Background and Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying, raising concerns about periprocedural safety in elective endoscopy. We aimed to evaluate the association between pre-procedural GLP-1 RA use and post-procedural complications such as aspiration pneumonia. Methods: In this retrospective cohort study, adults (18–89 years) undergoing outpatient esophagogastroduodenoscopy or colonoscopy within the HCA Healthcare network from 1 July 2021 to 31 March 2024 were identified. Patients were classified as GLP-1 RA users (n = 953) or non-users (n = 3289) based on home medication records. Primary outcomes included aspiration, post-procedural oxygen requirement, hypotension, hospitalization, ICU admission, length of stay, and all-cause inpatient mortality. Multivariable logistic and negative-binomial regression models, incorporating an interaction term for anesthesia type, were adjusted for age, sex, body mass index, ASA class, and key comorbidities. Results: No aspiration events were reported in either group. GLP-1 RA use was associated with lower odds of post-procedural oxygen requirement (OR 0.43, 95% CI 0.25–0.76), hospitalization (OR 0.73, 95% CI 0.39–1.36), and mortality (0.1 vs. 0.9%, p = 0.014), and a shorter hospital stay (IRR 0.54, 95% CI 0.40–0.71). Rates of hypotension and ICU admission were similar between both groups. In anesthesia-stratified analysis among GLP-1 RA users, those receiving MAC/MS had higher odds of hospitalization compared with GA (OR 1.87, 95% CI 1.23–2.85, p = 0.003), whereas other outcomes were not significant. Conclusions: Pre-procedural GLP-1 RA therapy was not associated with increased peri-procedural complications. Although hospitalization was more frequent with MAC/MS, this difference did not extend to other clinically significant outcomes. Further prospective studies are needed to clarify the clinical implications of anesthesia choice. Full article

Post-operative pancreatic fistula (POPF) is a serious yet far too common complication following distal pancreatectomy (DP), as it affects 20–30% of patients after DP. POPF raises the risk of other complications and causes delays to a patient’s oncologic care. In this review, we present the latest data on patient risk factors for developing POPF, such as obesity, smoking, young age, thick pancreas, lack of epidural anesthesia, hypoalbuminemia, and elevated drain amylase levels. Other risk factors that have been identified with irregular consistency include open surgical approach, non-malignant or neuroendocrine tumor pathology, simultaneous splenectomy, simultaneous vascular resection, and long operative time. We also review the consequences of POPF, which include hemorrhage, infection, delayed gastric emptying, re-operation, re-admission, delays in adjuvant chemotherapy initiation, reduced progression-free survival, and reduced overall survival. Finally, we present strategies that have been studied for avoiding POPF after DP, including reducing pressure at the sphincter of Oddi, the use of sealants and patches, optimizing pancreatic transection, strategies for post-operative drain placement, the use of post-operative somatostatin analogues, and pre-clinical studies of experimental devices and techniques that may inform future trials. This review informs readers on the current state of the art with regard to POPF after DP and sets the stage for future studies to improve patient outcomes. Full article

Autonomic dysfunction of the stomach typically manifests as delayed gastric emptying or gastroparesis and is seen in individuals with both type 1 and 2 diabetes. However, impaired gastric motility is only modestly associated with the presence of upper gastrointestinal symptoms, and the diagnosis of gastroparesis essentially requires a formal measurement of gastric emptying, ideally employing a sensitive and precise technique such as scintigraphy. There is a bidirectional relationship between gastric emptying and glycemia: insulin-induced hypoglycemia accelerates, while acute elevations in blood glucose may delay gastric emptying. On the other hand, relatively more rapid emptying is associated with a higher initial rise in postprandial glucose. The management of gastroparesis requires an individualized approach, integrating dietary modifications, nutritional supplementation, pharmacological therapies, and, in severe cases, advanced interventions including gastrojejunostomy and gastric electrical stimulation. This review provides an overview of the pathophysiology and diagnosis of autonomic neuropathy of the diabetic stomach and discusses current clinical management strategies. Full article