Search Results (126)

Elastography is an ultrasound-based technique that enables the non-invasive assessment of tissue stiffness. In endoscopic ultrasound (EUS), elastography was initially introduced as a strain-based method, providing qualitative or semi-quantitative information on tissue deformation. More recent technological developments have enabled the integration of shear-wave-based elastography into EUS platforms, including shear-wave measurement (SWM), point shear-wave elastography (pSWE), and two-dimensional shear-wave elastography (2D-SWE). Unlike strain elastography, shear-wave techniques provide quantitative estimates of tissue stiffness by measuring shear-wave velocity or a derived elastic modulus. This invited narrative review summarizes the technical principles, terminology, quality-control requirements, and current clinical evidence for EUS-guided shear-wave-based elastography in pancreatic and hepatobiliary diseases. Because much of the available EUS literature derives from EUS-SWM or point SWE rather than true 2D-SWE, acquisition mode is a central determinant when interpreting clinical evidence and clinical readiness. Current data suggest that EUS-guided shear-wave-based elastography is technically feasible and biologically plausible, but its clinical maturity remains indication-specific. Evidence is most encouraging in chronic pancreatitis, early chronic pancreatitis, autoimmune pancreatitis activity monitoring, and selected endo-hepatology settings, particularly liver fibrosis assessment in patients in whom transabdominal techniques may be suboptimal. In contrast, available evidence does not support EUS-guided shear-wave-based elastography as a standalone diagnostic test for differentiating solid pancreatic lesions, including pancreatic ductal adenocarcinoma, because absolute stiffness values often overlap among malignant lesions, inflammatory masses, and background parenchyma. Before routine clinical implementation, standardized acquisition protocols, disease-specific cut-offs, multicenter reproducibility data, and evidence of incremental clinical value beyond established diagnostic pathways are required. Full article

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Rotavirus infection is a major cause of acute gastroenteritis in children, which is characterized by fever, emesis, and diarrhea. In some children, rotaviral infection can spread beyond the gastrointestinal tract and affect the nervous system, kidneys, liver, or pancreas. There are relatively few longitudinal studies of such long-term sequalae. One area of interest has been damage to pancreatic beta islet cells, the lack of which causes type 1 diabetes mellitus. This chronic disease can be life threatening, especially in young children, and is associated with lifelong elevated risks of cardiovascular disease, neuropathy, nephropathy, and retinopathy. This narrative review summarizes the scientific evidence relevant to rotavirus infection and early-onset type 1 diabetes. The results of epidemiologic, animal, and laboratory research indicate that rotavirus infection increases the risk of type 1 diabetes in young children (<5 years of age). Rotavirus vaccination is associated with lower incidence rates; the data suggest a somewhat stronger effect with the pentavalent vaccine than the monovalent vaccine. Continued surveillance of both rotavirus infection and type 1 diabetes are necessary, considering the increases in vaccine hesitancy. The benefits of rotavirus vaccination should be discussed with parents and individuals planning to have children. Full article

Type 2 diabetes mellitus (T2DM) is a highly prevalent and devastating chronic metabolic disease worldwide, with pathogenesis centrally characterized by insulin resistance and pancreatic β-cell dysfunction. Accumulating evidence has demonstrated that glucose metabolic reprogramming represents an adaptive metabolic shift from oxidative phosphorylation to aerobic glycolysis in cells in response to a hyperglycemic microenvironment. This shift acts as an upstream important event driving the initiation and progression of T2DM. This review summarizes the characteristics of glucose metabolic reprogramming in insulin-sensitive target organs under T2DM conditions, including the liver, skeletal muscle, adipose tissue and pancreatic β-cells. It also discusses four major downstream effector mechanisms: mitochondrial energy metabolism disturbance, augmented oxidative stress, disruption of mitochondria-associated endoplasmic reticulum membranes (MAMs) coupled with calcium homeostasis imbalance, and systemic inflammatory response. On this basis, we summarize the intervention strategies targeting the above signaling pathways, including antioxidant therapy, restoration of MAMs integrity and calcium homeostasis, systemic anti-inflammatory intervention, and multi-target regulatory effects of traditional Chinese medicine. Current studies indicate that early intervention in downstream stress events is induced by glucose metabolic reprogramming. This is particularly true for the preservation of MAMs’ integrity; restoration of calcium homeostasis; and inhibition of NLRP3 inflammasome activation, the latter of which is expected to block or delay the progression from prediabetes to clinical T2DM. Nevertheless, substantial gaps still remain in the understanding of the dynamic regulatory mechanisms of MAMs, tissue-specific therapeutic targets, and relevant clinical translational research. Future integration of multi-omics technologies will provide novel therapeutic strategies and theoretical foundations for the early prevention and treatment of T2DM. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

Diabetes mellitus (DM), particularly Type 2 DM (T2DM), is increasingly recognized as both a risk factor and an early manifestation of pancreatic ductal adenocarcinoma (PDAC), yet the molecular mechanisms bridging these conditions remain poorly understood. There is growing evidence that chronic metabolic stress in diabetes induces persistent cellular reprogramming and metabolic memory through stable post-translational and epigenetic alterations, independent of conventional insulin resistance, obesity, and inflammatory pathways. We aim to elucidate how hyperglycaemia and metabolic overload contribute to the accumulation of major intermediates, such as acetyl-CoA, Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), and reactive oxygen species, which induce broad changes in post-translational modifications in diabetes-induced PDAC. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Web of Science databases, to retrieve studies published between 2005 and 2025. This review synthesizes current understanding of post-translational modifications (PTM) dynamics in diabetes-associated PDAC, with emphasis on their role in modulating oncogenic pathways such as KRAS-MAPK and PI3K-AKT. We introduce the concept of PTM remodeling, wherein transient metabolic perturbations become persistently stabilized, contributing to metabolic memory and tumor initiation. In addition, we examine how PTM-driven alterations influence the pancreatic tumor microenvironment, including stromal activation, immune evasion, and metabolic crosstalk, reinforcing a bidirectional link between tumor progression and systemic metabolic dysfunction. Furthermore, emerging therapeutic strategies targeting PTM-regulating enzymes, metabolic substrates, and signaling nodes are discussed as potential approaches to disrupt this axis. Collectively, precision targeting of PTM-mediated metabolic reprogramming represents a promising framework for early intervention and therapeutic development in PDAC associated with diabetes. Full article

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The most common types—type 1 and type 2 diabetes—have different etiologies and pathophysiological mechanisms. Type 1 diabetes (T1DM) results from autoimmune destruction of the insulin-producing pancreatic β-cells, leading to the development of absolute insulin deficiency, whereas in type 2 diabetes (T2DM), impaired carbohydrate metabolism is primarily caused by insulin resistance and relative insulin deficiency. Current diagnostic criteria do not allow for the detection of the disease at the preclinical stage. MicroRNA (miRNA) influences post-translational regulation of gene expression by inhibiting mRNA translation and also promotes mRNA degradation. The aim of this review is to summarize current evidence on the role of microRNAs in the pathogenesis of T1DM and T2DM and to evaluate their potential as early diagnostic biomarkers and therapeutic targets. It is demonstrated that T1DM and T2DM exhibit altered expression of specific microRNAs involved in β-cell apoptosis, autoimmune inflammation, and insulin signaling. In T1DM, key miRNAs include miR-21, miR-25, miR-146a, and miR-375, which reflect β-cell destruction and the autoimmune process. In T2DM, critical roles are played by miR-9, miR-29, miR-34a, miR-103/107, miR-126, miR-143, and miR-375, which regulate insulin secretion, lipid metabolism, and tissue insulin sensitivity. Particular attention is given to microRNAs whose expression changes several years before clinical disease onset (miR-15a, miR-126, miR-375), offering opportunities for early diagnosis. Data are presented on circulating miRNAs in stable biological fluids (blood, urine). It should be emphasized, however, that the proposed microRNA panel currently represents only a potential diagnostic tool. This panel requires further validation and confirmation by clinicians in large-scale prospective studies and does not yet claim to be ready for routine clinical use. Nevertheless, the development of such a universal microRNA panel, followed by thorough clinical evaluation, has promising biomedical potential, which will not only allow for the diagnosis of diabetes at an early stage but also identify new therapeutic targets for personalized medicine. Full article

Acute pancreatitis is a common inflammatory digestive disease with an unpredictable clinical course, ranging from self-limited forms to severe forms, associated with complications and increased mortality. Early identification of patients at risk of severe disease is particularly important from a surgical perspective, as it has a significant impact on subsequent management. Traditional severity scores, such as APACHE (Acute Physiology And Chronic Health Evaluation) II and BISAP (Bedside Index for Severity in Acute Pancreatitis), remain widely used, but their rigid structure and delayed applicability may limit initial risk assessment. In this review we highlight the evolving role of artificial intelligence in predicting the severity of acute pancreatitis and supporting clinical decision-making, with a focus on surgical management. Recent advances show that data-driven models could improve early risk assessment compared to traditional methods. Although their potential clinical benefits are becoming increasingly clear, real-world implementation remains limited. Initial results are encouraging, but important questions regarding reliability, safety, and integration into clinical practice still need to be addressed. Full article

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

Background: Patients with severe acute pancreatitis (SAP) are at high risk for developing chronic critical illness (CCI) and persistent inflammation, immunosuppression, and catabolism syndrome (PICS). However, the specific risk factors and prognostic implications of these conditions remain unclear. Methods: This single-center retrospective cohort study enrolled adult patients with SAP requiring ICU stay > 14 days. Least absolute shrinkage and selection operator (LASSO) regression was used to select risk factors, followed by multivariable logistic regression to identify independent predictors for CCI and PICS. Discriminative ability of early severity scores was assessed using the area under the curve (AUC) and compared via the DeLong’s test. Kaplan–Meier and Cox regression evaluated in-hospital and 90-day mortality differences. Results: Among 156 SAP patients, 60 (38.5%) developed CCI, 38 (24.4%) progressed to PICS, and 32 (20.5%) met both criteria. After multivariable adjustment and sensitivity analyses, the computed tomography severity index (CTSI) emerged as an independent risk factor for both CCI (odds ratio [OR]: 1.40, 95% confidence interval [CI] 1.18–1.66) and PICS (OR: 1.56, 95% CI 1.29–1.89), with AUC values of 0.747 and 0.804, respectively. Significant differences in both the in-hospital and 90-day mortality rates were observed among the three groups (p < 0.001). The patients meeting both CCI and PICS criteria exhibited markedly increased risks of in-hospital (hazard ratio [HR]: 7.80, 95% CI 1.53–39.77; p = 0.013) and 90-day mortality (HR: 3.11, 95% CI 1.08–8.95; p = 0.035) after the multivariable adjustment. Conclusions: CTSI is an independent risk factor for CCI and PICS in patients with SAP. Both CCI and PICS were associated with a heightened risk of adverse outcomes. Future studies are warranted to explore the clinical characteristics and targeted interventions for this high-risk subgroup. Full article

Diabetes mellitus (DM) is a complex metabolic disorder associated with a heightened risk of cardiovascular events, largely driven by a hypercoagulable and hypofibrinolytic state. The pathophysiological interplay between chronic hyperglycemia, oxidative stress, insulin resistance, and systemic inflammation fosters profound alterations in the coagulation cascade, endothelial function, and platelet activity. This narrative review synthesizes evidence from studies published between 2008 and 2026, focusing on coagulation and platelet-related biomarkers selected based on their biological relevance to thrombosis, endothelial dysfunction, and inflammation, as well as the availability of clinical and interventional data across different forms of DM. Although there are numerous biomarkers involved in the pathogenesis of various forms of diabetes, this narrative review critically examines key coagulation biomarkers—including D-dimer, fibrinogen, prothrombin, tissue thromboplastin or tissue factor, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, plasminogen activator inhibitor-1, von Willebrand factor, and β-thromboglobulin—across distinct diabetes subtypes, including type 1, type 2, gestational, and secondary forms linked to endocrinopathies and pancreatic diseases. The literature reveals substantial subtype-specific heterogeneity in hemostatic alterations. For instance, Type 1 DM is characterized by early endothelial dysfunction and platelet activation, while Type 2 DM presents with elevated coagulation factors, impaired fibrinolysis, and a proinflammatory milieu. Gestational DM exhibits pregnancy-specific changes in coagulation, yet distinguishing them from obesity-related effects remains challenging. Secondary diabetes forms, such as those associated with Cushing’s syndrome or pancreatitis, further underscore the diversity in thrombotic risk profiles. Among the coagulation and platelet activation biomarkers reviewed, fibrinogen, P-selectin, and plasminogen activator inhibitor-1 demonstrate the most consistent associations with glycemic control, vascular dysfunction, and therapeutic modulation, particularly in type 2 diabetes, suggesting greater potential for clinical translation. In contrast, evidence for markers such as D-dimer, tissue factor or tissue thromboplastin, and soluble urokinase plasminogen activator receptor remains heterogeneous and insufficient for routine clinical application. By synthesizing mechanistic insights and clinical data, this review highlights the urgent need for subtype-tailored coagulation assessment in diabetes management. A better understanding of the dynamic alterations in coagulation pathways may facilitate earlier detection of vascular complications and inform personalized antithrombotic strategies. Full article

Leptin receptor-deficient WBN/Kob-Lepr fa/fa (WKF) rats spontaneously developed chronic pancreatitis and severe diabetes with obesity. Here, we evaluated the protective effects of diet restriction and chronic exercise against fatty and inflammation-induced disorders in the vulnerable pancreas of WKF rats. Six-week-old male WKF rats were divided into obese control (Obese), diet restriction (DR), and diet restriction + exercise (DR + Ex) groups. WBN/Kob (WK) rats were used as lean control (Lean). Lean and Obese rats had free access to food, whereas food intake for DR and DR + Ex rats was restricted to 69% and 70% of the Obese level, respectively. The DR + Ex rats exercised voluntarily on a wheel ergometer daily. After six weeks, the rats were euthanized with isoflurane after overnight fasting. Obese rats exhibited diabetes, early stages of pancreatitis, diffuse pancreatic islets, and ultrastructural deteriorations in the pancreatic acinar cells, such as lipid droplet accumulation and swollen mitochondria with destroyed cristae, whereas Lean rats did not. DR rats exhibited improved glucose metabolism and serum triglyceride levels, effectively preventing inflammatory processes in the pancreas. However, DR rats exhibited no amelioration in the serum free fatty acids (FFAs) level, and limited improvements in ultrastructural deterioration in pancreatic cells. Chronic exercise combined with diet restriction (DR + Ex) improved serum FFA levels, the boundary of pancreatic islets, and the ultrastructure of subcellular organelles. These results demonstrate that diet restriction suppresses pancreatic inflammation, and further additional exercise effectively improves fatty pancreas-related deterioration by skeletal muscle activity linked through the circulatory network in WKF rats. Full article

Obesity is increasingly recognized as a disease of dysregulated intercellular communication rather than merely an energy imbalance. Extracellular vesicles (EVs), membrane-bound nanoparticles (30–1000 nm) released by nearly all cell types, act as central mediators of this pathological crosstalk. In obesity, hypertrophic adipocytes, pro-inflammatory macrophages, and dysfunctional endothelial cells secrete EVs carrying altered cargo, including pro-inflammatory miRNAs (e.g., miR-34a, miR-155), bioactive lipids, and stress proteins, which propagate systemic metabolic dysfunction. Adipose tissue-derived EVs impair hepatic fatty acid oxidation, promote steatohepatitis, suppress pancreatic beta-cell insulin secretion, induce skeletal muscle insulin resistance via PPARγ repression, and contribute to endothelial dysfunction and atherosclerosis. EV-mediated adipocyte–macrophage crosstalk reinforces chronic adipose inflammation. Circulating EVs also provide biomarkers: subpopulation ratios, miRNA signatures, and tissue factor-positive EVs reflect disease severity, predict cardiovascular risk, and monitor therapeutic responses, with machine learning enhancing diagnostic precision. Therapeutically, EVs from mesenchymal stem cells, Wharton’s jelly MSCs, adipose progenitors, and M2 macrophages reverse insulin resistance, hepatic steatosis, and adipose inflammation in preclinical models. Engineering strategies improve EV potency and tissue targeting, and Phase I trials confirm safety, though manufacturing and cost remain barriers. Preclinical and early clinical studies of MSC-EVs confirm a favorable safety profile, though manufacturing scalability and cost remain barriers to widespread clinical adoption. Overall, EVs represent both diagnostic tools and therapeutic vehicles in precision obesity medicine, offering a pathway from symptom management toward true disease remission. Full article

Background and Objectives: Serum biomarker discovery in resectable pancreatic ductal adenocarcinoma (PDAC) remains a critical unmet need, as over 80% of patients present with unresectable disease. Serum proteomics offers a promising approach for identifying circulating biomarkers associated with early-stage disease; however, clinical translation has been limited by inconsistent validation and the absence of clinically relevant comparator populations. Materials and Methods: We performed a discovery-phase study using data-independent acquisition mass spectrometry-based serum proteomics in 35 patients with resectable, non-metastatic PDAC and 34 non-cancer controls without hepato-biliary-pancreatic disease. Following quality filtering (≥80% detection threshold), 407 proteins were retained for analysis. Differential abundance was assessed using Welch’s t-test with Benjamini–Hochberg correction (FDR < 0.01, |FC| ≥ 1.5). Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis and logistic regression with repeated stratified 5-fold cross-validation (100 repetitions) and bootstrap resampling (1000 iterations). Functional enrichment analysis was performed using g:Profiler. Results: Ninety proteins were significantly altered in PDAC (50 increased, 40 decreased). Inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) demonstrated the highest individual diagnostic performance (AUC = 0.90), followed by coagulation factor XIII A chain (F13A1; AUC = 0.89) and ferritin light chain (FTL; AUC = 0.86). Functional enrichment revealed significant overrepresentation of secretory granule lumen components (adjusted p = 0.001) and complement/coagulation pathways (adjusted p < 0.001). An enrichment-guided three-protein panel (ITIH3, F13A1, and FTL) achieved an AUC of 0.98 (95% CI: 0.95–1.00), with a cross-validated mean AUC of 0.96, sensitivity of 83% (95% CI: 66.4–93.4%), and specificity of 100% (95% CI: 89.7–100%) within the discovery cohort. Conclusions: This discovery-phase study identifies a biologically coherent serum protein signature enriched for secretory granule lumen components in resectable PDAC. The three-protein panel demonstrates strong internal validation performance; however, these estimates may be optimistic due to feature selection performed prior to cross-validation. External validation in independent cohorts—including chronic pancreatitis controls and parallel CA19-9 assessment—will be essential to determine clinical applicability. Full article

Objectives: This study aimed to evaluate the genetic and clinical characteristics of hereditary pancreatitis (HP) in a cohort of Romanian pediatric patients, with a focus on the correlation between specific gene mutations and disease severity, recurrence patterns, and associated complications. Methods: A retrospective analysis was conducted on pediatric patients diagnosed with HP. Genetic testing was performed to identify mutations in key genes. Clinical data were collected regarding age of onset, recurrence, severity, surgical interventions, and progression to chronic pancreatitis. Exploratory computational analyses were performed to illustrate potential patterns between genetic variants and clinical characteristics. Results: PRSS1 variants were associated with earlier onset and more severe disease. A substantial proportion of patients developed chronic pancreatitis during the study period. Surgical complications were observed in over half of the cohort. The findings are consistent with the role of genetic mutations in influencing the clinical trajectory of HP. Genotype–phenotype correlations may inform hypotheses regarding early risk stratification and tailored management strategies. Conclusions: Genetic testing is essential for the accurate diagnosis and personalized treatment of HP. Integrating genetic diagnostics into clinical practice may improve outcomes and guide early intervention in high-risk pediatric patients. Full article