Background and Objectives: Ultrasound-guided placement of tunneled hemodialysis catheters may be useful when fluoroscopy is unavailable or radiation exposure should be avoided. This study describes a technique based on direct ultrasound visualization of the metallic guidewire within the right atrium and evaluates one-year clinical and functional outcomes. Materials and Methods: We conducted a single-center retrospective observational study of 319 adult hemodialysis patients undergoing tunneled catheter placement. The technique combined intravascular guidewire length measurement with subcostal ultrasound visualization of the guidewire tip in the right atrium. Baseline characteristics, insertion site, immediate complications, blood flow rate, Kt/V, and extracorporeal circuit pressures were analyzed. Results: Mean age was 55.9 ± 14.5 years, and 58.6% were women. The main causes of chronic kidney disease were diabetes mellitus and arterial hypertension. Mean blood flow rate was 349 mL/min at 3 months and 357 mL/min at 12 months. Mean Kt/V at 12 months was 1.57. No catheter malpositions requiring immediate repositioning were documented. Procedure-related complications were infrequent and mainly local. Conclusions: Ultrasound-guided tunneled catheter placement using direct visualization of the guidewire within the right atrium was technically feasible and associated with favorable functional parameters and few immediate complications. Given the retrospective design and lack of a comparative group, these findings should be interpreted with caution. Prospective comparative studies are needed to confirm safety, reproducibility, and clinical utility.

Diabetes self-management (DSM) is essential for optimal glycemic control and prevention of complications. Psychological factors, particularly fear of hypoglycemia (FOH), may be associated with self-management behaviors, yet their relationship with glycemic outcomes remains unclear.

To examine the associations between FOH, DSM, and glycemic control (HbA1c) and to identify demographic and clinical factors associated with DSM among adults with diabetes.

A cross-sectional descriptive correlational study was conducted among 180 adults attending outpatient clinics at Qassim University Medical City between October 2025 and January 2026. Data were collected using a structured questionnaire including demographic and clinical variables, the Diabetes Self-Management Questionnaire (DSMQ), and a validated FOH screening tool. Glycemic control was assessed using the most recent HbA1c value documented in the medical record within the previous three months. Pearson's correlation and multiple linear regression analyses were performed using SPSS version 26.

The mean DSM score was 26.71 ± 3.57, indicating a moderately acceptable level, with physical activity as the lowest-performing domain. The mean HbA1c was 7.95 ± 1.85%, reflecting suboptimal control. FOH was positively associated with DSM (r = 0.49, p < 0.001) but not with HbA1c. DSM was not significantly correlated with HbA1c. In the regression analysis, FOH showed the strongest independent association with DSM (β = 0.44, p < 0.001). The model explained 50.1% of the variance.

FOH was significantly associated with DSM; however, the cross-sectional design does not allow conclusions regarding whether this association reflects adaptive concern, maladaptive fear, or greater self-care awareness. The lack of association between FOH, DSM, and HbA1c highlights the complexity of glycemic control and supports the need for integrated, patient-centered interventions addressing both behavioral and psychological aspects of diabetes care.

Semaglutide and tirzepatide, glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, respectively, have revolutionized the management of type 2 diabetes mellitus and obesity. Beyond their established metabolic indications, emerging preclinical and clinical evidence suggests these incretin-based therapies exert pleiotropic effects across multiple organ systems through mechanisms extending beyond glycemic control and weight reduction. This comprehensive review synthesizes current evidence for unconventional applications of semaglutide and tirzepatide across five distinct therapeutic domains: oncology, psychiatry and addiction medicine, orthopedics, aesthetic medicine, and human reproduction. In oncology, both agents demonstrate antitumor activity primarily through immune and metabolic reprogramming rather than direct cytotoxicity, with promising signals in pancreatic, thyroid, breast, and colorectal cancers. In psychiatry, modulation of mesolimbic dopamine reward pathways and GABAergic neurotransmission underlies robust preclinical and observational evidence for reducing alcohol use disorder, substance use, and binge-eating behaviors. Orthopedic applications include clinically meaningful improvements in knee osteoarthritis pain and function, though bone health signals remain mixed. Aesthetic medicine faces the dual challenge of managing GLP-1 receptor agonist-associated facial volume loss while exploring therapeutic potential in inflammatory dermatoses. In reproductive medicine, metabolic improvements translate to benefits in polycystic ovary syndrome and male fertility, though periconception safety concerns persist. Across all domains, evidence derives predominantly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials remaining limited. This review critically evaluates mechanisms, efficacy signals, safety considerations, and research priorities for each application domain, providing a roadmap for translating unconventional uses of semaglutide and tirzepatide into evidence-based clinical practice.

Background: Gestational diabetes mellitus (GDM) is characterized by pregnancy-induced insulin resistance and β-cell dysfunction and is increasingly recognized as a state of cardiometabolic and endothelial dysregulation. Salusin-β, a bioactive peptide implicated in vascular inflammation and metabolic disorders, may play a role in GDM pathophysiology. However, data regarding its clinical relevance in GDM remain limited. Objective: This study aimed to compare serum salusin-β levels between women with GDM and healthy pregnant controls and to evaluate its diagnostic performance. Methods: This prospective study included 144 pregnant women between 24 and 28 weeks of gestation (70 with GDM and 74 healthy controls). GDM was diagnosed using a 75-g oral glucose tolerance test according to American Diabetes Association criteria. Serum salusin-β levels were measured using ELISA. Between-group comparisons were performed using appropriate parametric or non-parametric tests. Multivariable logistic regression analysis was performed to evaluate the independent association between salusin-β and GDM. Sensitivity analyses using an expanded adjustment model were also conducted. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Salusin-β levels were significantly lower in women with GDM compared to controls (68.53 [53.05-84.27] vs. 128.03 [76.74-261.35] pg/mL; p < 0.001). In the expanded multivariable logistic regression analysis, lower serum salusin-β levels remained independently associated with GDM (OR = 0.990, 95% CI: 0.985-0.996, p = 0.001). ROC analysis demonstrated acceptable discriminatory performance (AUC = 0.754, 95% CI: 0.672-0.833). The optimal cut-off value of 87.1 pg/mL yielded 80.0% sensitivity and 66.2% specificity. Conclusions: Serum salusin-β levels are significantly reduced in women with GDM and independently associated with disease presence. Although not sufficient as a standalone diagnostic marker, salusin-β demonstrates moderate discriminatory ability and may serve as a complementary biomarker reflecting vascular and metabolic dysregulation in GDM.

Background: Anemia is frequently observed in patients undergoing transcatheter aortic valve implantation (TAVI) and may reflect persistent biological vulnerability in the post-procedural period. The relationship between systemic immune-inflammatory burden and anemia at entry into structured cardiac rehabilitation (CR) after TAVI remains insufficiently explored. Methods: This retrospective observational study included 80 consecutive patients referred to CR after successful TAVI. Anemia was defined by World Health Organization (WHO) criteria (hemoglobin <13 g/dL in men; <12 g/dL in women). Systemic inflammatory burden was assessed using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammation index (SII = platelet × neutrophil/lymphocyte). Multivariable logistic regression, adjusted for age, sex, body mass index (BMI), type 2 diabetes mellitus, and estimated glomerular filtration rate (eGFR), was used to evaluate independent associations with anemia. Results: Anemia was present in 67.5% of patients at CR entry. Compared with non-anemic patients, anemic patients exhibited significantly higher CRP (4.25 vs. 2.58 mg/L; p = 0.014), NLR (2.86 vs. 2.34; p = 0.004), PLR (132.33 vs. 102.13; p = 0.003), and SII (566.01 vs. 448.30; p = 0.011). In multivariable models, NLR (OR 4.09; 95% CI 1.50-11.19; p = 0.006), PLR (OR 4.89; 95% CI 1.41-17.02; p = 0.013), SII (OR 4.96; 95% CI 1.35-18.14; p = 0.016), and CRP (OR 2.17; 95% CI 1.07-4.39; p = 0.032) were independently associated with anemia. Area under the ROC curve (AUC) was 0.70 for NLR and PLR, 0.68 for SII, and 0.67 for CRP. Conclusions: Systemic inflammatory burden is independently associated with anemia at the time of entry into CR facility after TAVI. These findings support an integrated approach to patient evaluation and provide a basis for future mechanistic and interventional studies.

Background/Objectives: Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality worldwide. Type 2 diabetes mellitus (T2DM) further increases CAD risk through metabolic disturbances and endothelial dysfunction. Adropin, S100A1, and SERCA2b are important regulators of endothelial function, energy metabolism, and calcium homeostasis. This study aimed to investigate the gene and protein expression levels of these biomarkers in CAD patients with and without T2DM. Methods: Gene and protein expression levels of adropin (ENHO), S100A1, and SERCA2b were evaluated in peripheral blood samples obtained from healthy controls (n = 50), CAD patients (n = 46), and CAD patients with T2DM (CAD+T2DM) (n = 40). Gene expression was determined using real-time PCR, while protein levels were measured with ELISA. Additionally, in silico bioinformatics analyses, such as protein-protein interaction networks and pathway enrichment analyses, were performed to explore potential molecular relationships among these biomarkers. Results: Adropin and ENHO gene expression levels were significantly lower in CAD patients and inversely related to the SYNTAX score. S100A1 levels were also reduced, and SERCA2b gene expression was significantly decreased, especially in the CAD+T2DM group. Bioinformatics analyses revealed that these molecules participate in interconnected pathways related to calcium signaling, cardiac muscle contraction, and metabolic regulation. Conclusions: These findings demonstrate links between altered levels of adropin, S100A1, and SERCA2b and CAD with or without T2DM. However, these observations are preliminary and need validation in larger prospective studies and mechanistic research before drawing definitive conclusions about their clinical utility, disease progression, or prognostic value.

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.

Background/Objectives: Inflammation plays a central role in the pathophysiology and prognosis of non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to investigate the clinical and prognostic significance of the Cumulative Inflammatory Index (IIC) in patients with NSTEMI. Methods: This single-center, retrospective study included 2274 individuals, comprising 1172 patients with NSTEMI and 1102 angiographic controls without acute coronary syndrome or obstructive coronary artery disease. IIC was calculated using mean corpuscular volume, red cell distribution width, neutrophil count, and lymphocyte count. The primary outcome was 360-day all-cause mortality in the NSTEMI cohort. Logistic regression, receiver operating characteristic curve analysis, and DeLong testing were performed. Results: Patients with NSTEMI had significantly higher IIC values than controls [9.08 (4.05-15.03) vs. 1.90 (1.45-2.89), p < 0.001]. Among NSTEMI patients, non-survivors had significantly higher IIC levels than survivors [14.25 (8.56-26.59) vs. 8.57 (3.73-14.06), p < 0.001]. In multivariable logistic regression analysis, IIC remained independently associated with 360-day all-cause mortality after adjustment for age, diabetes mellitus, estimated glomerular filtration rate, hemoglobin, albumin, and C-reactive protein (OR: 1.045, 95% CI: 1.029-1.060; p < 0.001). IIC showed a modestly higher area under the curve among the evaluated indices (AUC: 0.704). Conclusions: IIC was significantly elevated in patients with NSTEMI and was independently associated with 360-day all-cause mortality. IIC may serve as a simple adjunctive marker for risk stratification in patients with NSTEMI.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in the management of type 2 diabetes mellitus and obesity, have recently attracted attention for their potential effects on periodontal tissues. This systematic review aimed to evaluate the current evidence regarding the relationship between GLP-1-based therapies and periodontal health, with particular emphasis on anti-inflammatory, osteogenic, and regenerative mechanisms. A comprehensive literature search of PubMed, Web of Science, and Embase databases identified 22 eligible studies, including in vitro, animal, and human investigations. The available evidence suggests that GLP-1RAs such as liraglutide and exendin-4 may attenuate periodontal inflammation, reduce alveolar bone loss, and enhance osteogenic differentiation of periodontal ligament and dental pulp stem cells through modulation of pathways including MAPK/ERK, Wnt/β-catenin, NF-κB, and PKCβ2. Clinical observations additionally indicate a bidirectional relationship between periodontitis and incretin signalling, with periodontal therapy associated with increased systemic GLP-1 levels. However, the current evidence remains heterogeneous and is largely limited to preclinical and observational studies. Randomised clinical trials are required to determine the clinical efficacy and therapeutic relevance of GLP-1-based therapies in periodontitis management.

Diabetic kidney disease (DKD) remains one of the most severe microvascular complications of type 2 diabetes mellitus (T2DM) and a leading cause of chronic kidney disease (CKD) worldwide. Nevertheless, despite considerable progress in elucidating its molecular background, early diagnosis and accurate stratification of disease progression remain challenging when relying on conventional clinical biomarkers such as albuminuria and estimated glomerular filtration rate (eGFR). Growing evidence indicates that DKD is driven by interconnected pathogenic mechanisms, including chronic hyperglycemia, activation of the protein kinase C (PKC) signaling pathway, renin-angiotensin-aldosterone system (RAAS) dysregulation, oxidative stress, inflammatory cascades, and immune system activation involving Toll-like receptors (TLR) and the NLRP3 inflammasome. These processes collectively contribute to endothelial dysfunction, podocyte injury, extracellular matrix accumulation, and progressive renal fibrosis. Exosomes and their molecular cargo, particularly miRNAs, have emerged as promising regulators and non-invasive biomarkers reflecting ongoing renal injury. Urinary exosomal microRNAs (uEV-miRNAs) are of interest due to their stability in biological fluids and their direct origin from nephron segments, enabling real-time reflection of renal pathophysiology. Accumulating studies suggest that differentially expressed microRNAs (miRNAs), including miR-21-5p, miR-30a-5p, miR-192-5p, and miR-142-3p, are closely associated with key pathways in DN. However, their clinical translation remains limited by methodological heterogeneity, the lack of standardized isolation protocols, and insufficient validation in large longitudinal cohorts. This review navigates the current landscape of knowledge on the molecular mechanisms underlying DKD and examines the emerging role of uEV-miRNAs as diagnostic biomarkers. Altogether, uEV-miRNAs offer a promising avenue for improving early detection, risk stratification, and disease monitoring in DKD.