Animal venoms are complex biochemical systems composed of proteins, peptides, and small molecules with bioactivity. Traditionally regarded as toxic agents, venom components are increasingly recognized as valuable molecular libraries that can modulate cellular processes in human disease pathophysiology. This review highlights the translational potential of venom-derived molecules, with emphasis on clinically approved venom-derived drugs such as captopril, while also discussing their therapeutic potential for diseases such as cancer, autoimmunity, cardiovascular diseases, chronic pain, neuropsychiatric disorders, and infectious diseases. Special emphasis is given to the mechanisms by which these toxins modulate ion channels, enzymes, and receptor systems. Recent advances in venomics, harnessing proteomics, transcriptomics, and high-throughput screening, are also discussed, which can accelerate the clinical translation of venom-derived therapeutics. Key challenges related to assessing the immunogenicity of the venom-derived compounds, bioavailability, and safety have also been addressed alongside emerging strategies to overcome them. Collectively, these advances can provide a logical framework for developing novel therapeutics, bridging the gap between toxinology and drug discovery.

Lipoproteins are molecules composed of phospholipids and apolipoproteins that transport triacylglycerol and cholesterol in blood and are implicated in the development of many diseases.

In this study, we fill a knowledge gap by precisely characterizing the apolipoprotein profile (with Bio-Plex Human Apolipoprotein Assay) in three metabolically separate groups of individuals (lean individuals and obese individuals without and with metabolic syndrome) and at four distinct time points (0, 3, 6, and 12 months post bariatric surgery).

Obese patients had a higher baseline ApoB/ApoA1 ratio, which returned to the reference level over the follow-up period. The above is of clinical importance, as the ratio is a predictor of adverse cardiovascular events common in obese subjects. Interestingly, plasma concentrations of most of the investigated apolipoproteins appeared to be relatively stable at the onset of the experiment, with changes observed later in time. We detected significant drops in the levels of ApoC3, ApoD, and ApoH that occurred as early as three months post intervention. On the other hand, the levels of ApoA2, ApoE, and ApoJ increased with time. Of the above, ApoE is known to be involved in the removal of TAGs and cholesterol from the blood. Conversely, ApoJ appears to be one of the determinants of the tissues' responsiveness to insulin. Thus, it may be an indicator of the reduced insulin resistance observed a few months after the surgery.

Overall, the investigated proteins have a documented role in the development and progression of vascular pathologies. Hence, our results may be interpreted as a sign of improved cardiovascular fitness of our patients.

Background/Objectives: Anthracycline-induced cardiotoxicity remains a major challenge in cancer treatment, and researchers are showing interest in artificial intelligence (AI) to improve the prediction and detection of cancer therapy-related cardiac dysfunction (CTRCD). Current surveillance strategies rely mainly on left ventricular ejection fraction and, more recently, global longitudinal strain. Methods: The present study was designed to evaluate cardiac performance in a rat model of doxorubicin-induced cardiotoxicity and empagliflozin-mediated cardioprotection using a machine learning-based analytical framework. Eighteen adult male Sprague-Dawley rats were assigned to five experimental groups. We aimed to quantify ventricular wall dynamics and contractility using an advanced image-processing and object-detection model that has not been previously used to distinguish normal from impaired cardiac kinetics. During real-time recording, simultaneous electrocardiogram monitoring was performed, enabling direct correlation between deep learning-based ventricular wall motion metrics and cardiac electrical activity. The cardioprotective effects of empagliflozin were further validated by immunofluorescence staining (cTnI, vimentin, α-SMA, and Cx43) of rat cardiomyocytes and paraffin-embedded cardiac tissue, demonstrating attenuation of cellular injury and structural remodeling. Results: The integrated analysis of cardiac kinetic patterns derived via machine learning distinguishes not only extreme cardiotoxicity, but also tracks a graded pattern consistent with ECG-derived severity and treatment-related functional preservation. These findings indicate that the algorithm captures the gradient of empagliflozin's cardioprotective effect within this internally validated preclinical setting. Additionally, immunofluorescence results validated the benefits of SGLT2 inhibition on myocardial integrity. Conclusions: The novelty of the present work lies at the intersection of advanced cardiac kinetic analysis using AI, preclinical modeling, and SGLT2-mediated cardioprotection in cardio-oncology.

Spinal dural arteriovenous fistulas (sDAVFs) are the most common spinal vascular malformation and a treatable cause of progressive myelopathy, yet diagnosis and optimal management remain challenging. This study presents a nine-year institutional experience using a multidisciplinary treatment algorithm that prioritizes endovascular embolization, with surgery reserved for unsuccessful or contraindicated cases.

We retrospectively analyzed 15 patients treated between 2015 and 2023, all diagnosed by MRI and confirmed by digital subtraction angiography. Endovascular embolization was attempted as the initial treatment modality in all patients using contemporary liquid embolic agents.

Three patients (20%) subsequently required surgical disconnection following unsuccessful or incomplete embolization. Lesions ranged from Th5 to L5, and most patients presented with varying degrees of motor deficits, gait disturbance, paresthesias, or sphincter dysfunction. Neurological improvement occurred in all but one patient, and no treatment-related complications were observed. Prior embolization attempts aided intraoperative localization in surgically treated cases, facilitating precise fistula identification.

These findings demonstrate the feasibility and favorable outcomes of a multidisciplinary, stepwise treatment strategy in this single-center experience. Endovascular embolization served as the initial treatment modality, while surgical disconnection provided an effective complementary option in selected cases where embolization was unsuccessful or incomplete.

Background/Objectives: Self-management intervention strategies are recommended to address the needs of breast cancer survivors (BCSs) who have cardiovascular diseases (CVDs). Despite the benefits, these strategies are often suboptimally implemented, resulting in inadequate cardiovascular management among BCS with CVDs. The project aims to develop a nurse-led and GP-supported self-management (NGPS) intervention to reduce cardiovascular risks in BCS with CVDs and evaluate its feasibility and potential effects in primary care settings using the double diamond co-design process and the Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions. Methods: The study will be conducted in two phases. In phase I, an evidence-based and co-designed NGPS protocol with end-users will be preliminarily developed based on the identified research evidence, relevant theories, practice guidelines and the current practice standards in Australia. The co-design workshop(s) will involve healthcare professionals and BCSs with CVDs to further refine and validate the developed preliminary protocol. In phase II, a one-group pre-post pilot study will evaluate the feasibility of the intervention and study procedures, such as recruitment, retention, adherence, acceptability, and safety as primary outcomes. The study will also preliminarily explore the effectiveness of the intervention such as physiological measures as secondary outcomes to inform a future large-scale trial. Phase II also involves follow-up qualitative interviews to explore participants' experiences of the pre-post pilot study. The participants will be recruited from primary medical centres in Victoria. Conclusions: The findings will provide a co-designed evidence-based intervention for primary care nurses and General Practitioners (GPs) to promote long-term health outcomes for patients with both breast cancer (BC) and CVDs. Clinical registration: ClinicalTrial.gov (registration No. NCTO7313397).

Pulmonary arterial hypertension (PAH) is a progressive disease leading to right ventricular (RV) hypertrophy and failure. This study aims to evaluate the prognostic value of combining the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with right ventricular myocardial work (RVMW) parameters in patients with PAH, to improve early risk stratification.

A total of 43 PAH patients diagnosed via right heart catheterization were enrolled. Echocardiography-derived TAPSE/sPAP ratio and RVMW parameters, including right ventricular global work efficiency (RVGWE), global work index (RVGWI), global constructive work (RVGCW), and global wasted work (RVGWW), were measured. Clinical worsening events were recorded during a median 515-day follow-up. Statistical analyses included correlation tests, Firth penalized logistic regression, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis.

The TAPSE/sPAP ratio correlated negatively with RVGCW (r = -0.346, p = 0.023) and RVGWW (r = -0.417, p = 0.005), but not with RVGWE or RVGWI. Clinical worsening events occurred in 25.6% of patients, with significantly lower TAPSE/sPAP ratio (0.16 vs. 0.24 mm/mmHg), RVGWE (72.0% vs. 88.5%), and RVGWI (431.0 vs. 641.0 mmHg%) in the Event group (all p < 0.05). Multivariate Firth penalized logistic regression was used for combining TAPSE/sPAP ratio with RVGWE. ROC analysis demonstrated that the combination of TAPSE/sPAP and RVGWE yielded superior predictive power (AUC = 0.949, p < 0.001) compared to individual parameters.

Non-invasive assessment of TAPSE/sPAP ratio and RVGWE provides significant prognostic value in PAH. Their combination enhances early risk prediction, offering a practical tool for clinical management.

Background: Lipoprotein(a) [Lp(a)] is a genetically determined, atherogenic, and prothrombotic lipoprotein. However, its prognostic value in patients who undergo successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains undefined. Methods: This single-center retrospective cohort study included 1509 patients who underwent successful CTO PCI. The primary outcome was cardiovascular death; secondary outcome was major adverse cardiovascular events (MACEs, cardiovascular death or nonfatal myocardial infarction). Multivariable Cox regression and restricted cubic splines (RCS) assessed the association between Lp(a) and outcomes. Results: Over median follow-up of 810 days, 53 (3.5%) cardiovascular deaths and 62 (4.1%) MACEs occurred. Each 1-SD increase in log-transformed Lp(a) was associated with a 51% higher risk of cardiovascular death (aHR 1.51, 95% CI 1.11-2.05, p = 0.008) and a 44% higher risk of MACEs (aHR 1.44, 95% CI 1.09-1.91, p = 0.011). Compared with Lp(a) < 30 mg/dL, Lp(a) ≥ 50 mg/dL conferred a 2.07-fold higher risk of cardiovascular death (95% CI 1.07-4.00, p = 0.029) and a 1.94-fold higher risk of MACEs (95% CI 1.07-3.53, p = 0.030). RCS analysis demonstrated a linear dose-response relationship between log-transformed Lp(a) and both cardiovascular death (p for nonlinearity = 0.653) and MACEs (p for nonlinearity = 0.562). The association was modified by age, hypertension, and left ventricular ejection fraction and remained robust in sensitivity analyses. Conclusions: In patients undergoing successful CTO PCI, elevated Lp(a) was independently and linearly associated with higher risks of cardiovascular death and MACEs. These findings suggest that Lp(a) may serve as a useful prognostic marker to enhance risk stratification in this high-risk population. Large-scale prospective cohorts are needed to validate these findings before clinical translation can be considered.

Chronic right heart failure (RHF) is a complex, progressive syndrome that remains underrecognized and inadequately defined in current clinical guidelines, where it is often relegated to a secondary complication of left-sided heart disease. Because the thin-walled right ventricle (RV) is well adapted to maintain pressures within the highly distensible venous system well below plasma oncotic pressure but poorly equipped to sustain pressure overload, when myocardial failure supervenes, conventional RV systolic indices frequently fail to capture the very essence of the syndrome. This review clarifies the distinct pathophysiological and haemodynamic foundations of chronic RHF, framing it fundamentally as the heart's inability to decongest the systemic venous circulation. We highlight how backward failure, rather than isolated RV systolic dysfunction, drives systemic and multi-organ congestion. To bridge existing diagnostic gaps, we propose a pragmatic, diagnostic algorithm. Under this framework, a Definite Diagnosis of chronic RHF requires evidence of elevated right atrial/central venous pressures-defined as clinically raised jugular venous pressure plus an echocardiographic dilated inferior vena cava (>21 mm with <50% collapse)-alongside at least one of four minor criteria: (1) systemic or visceral congestion (e.g., persistent oedema, congestive hepatomegaly); (2) echocardiographic RV systolic dysfunction (TAPSE < 17 mm, FAC < 35%, S' < 9.5 m/s; RV free-wall strain > -20%); (3) non-invasive signs of pulmonary hypertension (TRV > 2.8 m/s); or (4) impaired RV-pulmonary arterial coupling (TAPSE/PASP ratio < 0.35). By centering diagnosis on systemic venous hypertension as a result of right heart backward failure rather than isolated RV metrics, this framework offers a coherent, readily applicable tool for diagnosing chronic RHF in routine clinical practice.

Acute aortic syndrome (AAS) comprises acute aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer, and limited intimal tear, conditions that require rapid recognition because mortality and resource use are strongly influenced by time to diagnosis, anatomical extent, malperfusion, and the need for emergency surgical or endovascular intervention. This revised narrative review synthesizes contemporary evidence on clinical, genetic, environmental, and health-system determinants of prolonged hospitalisation, intensive care unit (ICU) utilisation, bed occupancy, and costs in patients with AAS. Beyond summarising established risk factors, the review adds a resource-oriented framework that links hypertension, advanced age, female sex, smoking-related comorbidity, hereditary aortopathies, haemodynamic instability, malperfusion, delayed diagnosis, operative complexity, and postoperative complications to measurable downstream outcomes such as ICU length of stay, total hospital length of stay, reoperation, readmission, and longitudinal imaging surveillance. We searched PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for relevant studies, registries, guideline documents, and cost analyses published between January 2000 and May 2026, with particular emphasis on studies from the last five years. The review was not designed as a meta-analysis; therefore, effect estimates are interpreted according to study design and generalisability. AAS imposes a disproportionate burden on hospital systems because high-risk patients often require advanced imaging, prolonged haemodynamic monitoring, complex open or endovascular repair, ICU care, and lifelong follow-up. Earlier diagnosis, structured risk stratification, targeted genetic evaluation, aggressive control of modifiable risk factors, and system-level pathways such as dedicated aortic networks may shorten hospital stay and reduce avoidable costs.

Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended.