Glucagon-like-peptide-1 receptor (GLP-1R) agonists are under development as new drugs to treat type 2 diabetes, liver disease, obesity and cardiovascular diseases. Some of these drugs are solely agonists of the GLP-1R. It turned out that their benefit could be improved when they also stimulated the glucagon receptor (GCGR) and/or the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR). Stimulation of GLP-1R in cell cultures but also in neonatal atrial and/or ventricular cardiomyocytes and adult atrial cardiomyocytes raised the activity of adenylyl cyclase and thus augmented the 3',5'cyclic adenosine monophosphate (cAMP) levels. We discuss here the acute contractile effects of such agonists on isolated human atrial and ventricular cardiac preparations from failing and non-failing hearts. We address the receptors involved, GLP-1R expression in various cardiac regions of the human heart, single and multiple receptor agonists and the post-receptor signal transduction system of the GLP-1R in the human heart. Some of the new drugs addressed are still in the early phases of clinical development. We critically discuss the experimental and clinical data available and we also define research needs for experimental and clinical studies.

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood-brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries-including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury-as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis-Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial-neuronal communication and cognitive-emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood-brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx-particularly Cx43-occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation.

Oxidative stress and inflammation are interconnected pathological processes involved in the progression of neurodegenerative, cardiovascular, and metabolic diseases, highlighting the need for multifunctional therapeutic agents targeting multiple pathways. In this study, two novel hybrid compounds were designed and synthesized in three steps by conjugating butylated phenolic moieties derived from butylated hydroxytoluene and p-coumaric acid with proline and γ-aminobutyric acid (GABA). The aim was the combination of antioxidant, anti-inflammatory, and cytoprotective properties within a single molecular framework. The compounds were evaluated using a comprehensive panel of in vitro and in vivo assays to assess antioxidant, metal-reducing, iron-chelating, antiglycation, anti-inflammatory, and acetylcholinesterase inhibitory activities. Both compounds exhibited significant antioxidant activity, with compound 2 demonstrating superior radical scavenging ability against DPPH, ABTS·⁺ and hydrogen peroxide (IC₅₀ 86 μM, 25 μM and 104 μM, respectively), enhanced ferric-reducing capacity (up to 91% of trolox activity), and strong iron-chelating activity (61.3%). Compound 2 also showed potent inhibition of lipid peroxidation (IC₅₀ 17.5 μM) and moderate antiglycation effects (44%), indicating substantial cytoprotective potential. Furthermore, both compounds selectively inhibited COX-2 over COX-1 and demonstrated moderate lipoxygenase inhibition, while compound 2 exhibited significant in vivo anti-inflammatory activity (53%), exceeding that of ibuprofen. Moderate acetylcholinesterase inhibition was also observed. In summary, the results confirm the design rationale, indicating that compound 2 could be further optimized as a multi-targeting molecule directed against oxidative stress- and inflammation-mediated conditions.

Cardiovascular emergencies most frequently arise from the sudden destabilization of atherosclerotic plaques. Conventional diagnostic strategies predominantly focus on luminal stenosis, despite the fact that most acute coronary events originate from non-obstructive lesions with high inflammatory activity. Recent advances in cardiac computed tomography (CCT) enable visualization of plaque morphology and surrounding perivascular fat, offering a unique window into coronary inflammation. The fat attenuation index (FAI), derived from pericoronary adipose tissue (PCAT) radiodensity, has emerged as a dynamic imaging biomarker capable of detecting vascular inflammation before clinical events occur. This review summarizes current evidence on the role of PCAT inflammation in plaque vulnerability, its implications for acute cardiovascular presentations, and recent technological innovations-including AI-enhanced analysis and photon-counting CT-that advance risk prediction. Inflammation-based imaging derived from CCT, including PCAT-FAI, has emerged as a promising research tool that may enhance risk stratification in patients presenting with chest pain. These developments signify a shift from purely anatomical assessment toward biological characterization of CAD, potentially transforming prevention and acute care.

Klebsiella species, particularly Klebsiella pneumoniae, are among the most frequently isolated Gram-negative pathogens in surgical departments, associated with a growing trend in multidrug resistance. To identify the types of infections caused by Klebsiella spp. in a general surgery department and to analyze their antimicrobial susceptibility patterns. This retrospective observational study includes bacteriological cultures collected from surgical inpatients between October 2016 and December 2024. Only cases with confirmed Klebsiella spp. isolation were included. Specimen types, infection categories, and antibiotic susceptibility profiles were extracted and analyzed. A total of 138 Klebsiella-positive cultures were identified. Clinical characteristics were analyzed in 38 patients with complete records. The most common infection types included surgical site infections (SSIs), intra-abdominal infections, and biliary tract infections. Sensitivity was highest to carbapenems, while marked resistance was observed to ampicillin-sulbactam and third-generation cephalosporins. Some isolates exhibited ESBL or carbapenemase-producing phenotypes. Reported colistin non-susceptibility was elevated in our cohort; however, these results should be interpreted cautiously because the reference broth microdilution method was not systematically documented. The findings underscore the importance of local surveillance of Klebsiella spp. in surgical settings to info rm empirical treatment and control the spread of multidrug-resistant organisms.

Background: Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is increasingly recognized as a thromboinflammatory disorder involving coagulation, innate immunity, endothelial dysfunction, and vascular homeostasis. Emerging evidence suggests that gut microbiome-related inflammatory and metabolic signals may influence pathways potentially relevant to VTE through intestinal barrier dysfunction, microbial translocation, and microbiome-derived metabolites. This review critically examines the direct and indirect evidence relating gut dysbiosis to mechanisms potentially relevant to venous thrombogenesis. Methods: A structured literature search of PubMed, Scopus, and Web of Science was conducted from database inception to February 2026. Observational, translational, experimental, preclinical, and selected genetic studies were narratively synthesized across heterogeneous evidence types. Results: Available evidence suggests that intestinal barrier dysfunction and microbial translocation may increase systemic exposure to lipopolysaccharide and other microbial products, potentially contributing to inflammatory signaling and procoagulant responses. Proposed downstream effects include tissue factor (TF) activation, platelet reactivity, neutrophil extracellular traps (NETs) formation, complement signaling, endothelial perturbation, and impaired balance of anticoagulant and fibrinolytic pathways. Microbiome-derived metabolites, including trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAGln), bile acids, and short-chain fatty acids (SCFAs), have been linked, mainly in experimental or non-VTE settings, to thrombosis-related biology. However, most evidence remains indirect, associative, or experimental, whereas direct human VTE-specific evidence is limited and heterogeneous. Conclusions: The gut microbiome-VTE axis is biologically plausible and supported mainly by mechanistic and indirect evidence, but current data are insufficient to support strong causal conclusions. Further longitudinal, well-phenotyped, mechanistically informed studies are needed to determine whether microbiome-related pathways have measurable clinical relevance in human VTE.

Postprandial triglyceride (TG) metabolism represents a dynamic dimension of lipid physiology that complements conventional fasting lipid assessment. Although low-density lipoprotein cholesterol (LDL-C) remains the primary therapeutic target in cardiovascular prevention, residual cardiovascular risk persists in many individuals despite apparently adequate fasting lipid control. Because most individuals spend the majority of their waking hours in a fed state, postprandial TG responses may provide clinically relevant insight into metabolic flexibility, dietary exposure, and the efficiency of TG-rich lipoprotein clearance.

This narrative review was conducted using a literature search guided by predefined themes, keywords, and databases, without following a formal systematic review protocol. Randomized controlled trials, observational studies, meta-analyses, and major reviews addressing postprandial lipid metabolism, dietary determinants, and cardiometabolic risk were included, with priority given to human studies.

Postprandial TG responses are strongly influenced by dietary composition, eating patterns, and metabolic health. Individuals with insulin resistance, type 2 diabetes, obesity, and metabolic-associated steatotic liver disease (MASLD) frequently demonstrate exaggerated or prolonged postprandial lipemia even when fasting TG concentrations appear acceptable. While circulating TGs serve as practical clinical markers of postprandial lipid handling, cholesterol-enriched remnant lipoproteins more closely reflect atherogenic burden. Nutritional interventions, weight management, and physical activity consistently improve postprandial TG dynamics, whereas pharmacologic therapy provides additional benefit in selected high-risk patients. Non-fasting TG measurements may provide additional insight into postprandial lipid metabolism and residual cardiovascular risk, although standardized protocols and validated clinical thresholds remain to be established.

Postprandial TG metabolism provides clinically meaningful information beyond fasting lipid measurements and represents a useful adjunct for refining residual cardiovascular risk assessment. Although standardized protocols remain limited, integrating nutritional and clinical perspectives may support a more comprehensive and individualized approach to cardiometabolic prevention.

Background/Objectives: Pulmonary embolism (PE) represents a major thrombotic complication in hospitalized patients with coronavirus disease 2019 (COVID-19), yet data on its incidence, clinical predictors, and short-term outcomes in actual cohorts remain heterogeneous. Methods: We conducted a retrospective observational cohort study including 395 consecutive adults hospitalized with RT-PCR-confirmed COVID-19 at a tertiary infectious diseases center between March 2020 and December 2024. Clinical, laboratory, imaging, and treatment data were extracted from electronic records, and PE was defined by computed tomography pulmonary angiography. Univariable and multivariable logistic regression analyses were used to identify independent predictors of PE in the subset of patients who underwent CTPA (n = 120), in whom PE status was definitively ascertained (47 with PE and 73 without PE). Results: Pulmonary embolism was diagnosed in 47 patients (11.9%). Patients with PE more frequently had prior venous thromboembolism (19.1% vs. 8.3%) and prolonged immobilization (61.7% vs. 23.0%), and were more often admitted to the intensive care unit (12.8% vs. 4.3%) than those without PE. Peak D-dimer levels were almost ten-fold higher in the PE group (median 5322 vs. 529.5 µg/L). In multivariable logistic regression, peak D-dimer was independently associated with PE (per log-unit increase, adjusted OR 3.9, 95% CI 2.1-7.1), and prolonged immobilization conferred a substantially higher risk of PE (adjusted OR 5.1, 95% CI 2.4-10.9). Patients with PE experienced more complex hospital courses and more frequent need for advanced therapies, although in-hospital mortality did not differ significantly between groups. Conclusions: In hospitalized COVID-19 patients, PE is frequent and closely linked to marked D-dimer elevation and acquired in-hospital risk factors, particularly prolonged immobilization. This evidence supports the use of dynamic D-dimer assessment and careful evaluation of immobilization status to improve risk stratification, guide decisions on diagnostic imaging and anticoagulation intensity, and identify patients who may benefit from closer post-discharge cardiovascular follow-up (this hypothesis requires confirmation in future prospective studies).

Background: Artificial intelligence (AI) and deep learning (DL) are rapidly changing the field of diagnostics and imaging in cardiology, offering tools for automatic segmentation, quantification of changes, and risk stratification. These technologies have the potential to increase diagnostic accuracy, work efficiency, and individualization of patient care. Methods: This structured narrative review critically evaluates clinically validated applications of artificial intelligence (AI) and deep learning (DL) in cardiovascular medicine, focusing on imaging (echocardiography, coronary CT angiography, cardiac MRI, and ECG), risk stratification, and biomarker integration. A systematic literature search was conducted in PubMed for studies published between January 2015 and December 2026, supplemented by references from key articles. Original English-language studies reporting quantitative clinical outcomes were included, with 78 studies ultimately analyzed. Results: AI and DL models, including convolutional neural networks and transformers, achieved performance comparable to experts in cardiac imaging, myocardial perfusion assessment, valve defect detection, and coronary event prediction. Multimodal approaches improved diagnostic accuracy and reproducibility, while explainable AI enhanced transparency and clinical confidence. Deep learning also enabled faster image acquisition and processing without compromising precision. Conclusions: AI and DL have transformative potential in cardiology, offering fast, accurate, and scalable diagnostic tools. The integration of multimodal data, the validation of algorithms in prospective studies, and ensuring the transparency of models are key. Future research should focus on prospective, multicenter validations and the ethical and safe implementation of AI in everyday clinical practice.

Transcatheter aortic valve implantation (TAVI) has become the preferred treatment for patients with symptomatic severe aortic valve stenosis. Newer-generation devices, increased operator experience, and improved patient selection have contributed to a reduction in complication rates. However, the occurrence of new-onset left bundle branch block (LBBB) after TAVI remains high, and currently it is the most common complication associated with the procedure. This review discusses the current understanding of new-onset LBBB, including its causes, incidence, clinical outcomes, and management strategies.