Search Results (814)

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral arterial disease and is associated with high rates of major amputation and mortality. The angiosome concept has become an important tool for planning targeted revascularization. However, its clinical value may be limited in patients with complex arterial disease, impaired collateral circulation, and microvascular dysfunction. This review explores the relationship between angiosome-guided revascularization and the emerging woundosome concept, which focuses on functional wound perfusion. Methods: A narrative review with a structured literature search was performed using PubMed/MEDLINE, Scopus, and Web of Science. Studies evaluating angiosome-guided revascularization, direct versus indirect revascularization, collateral circulation, pedal arch integrity, and perfusion-related outcomes in CLTI and diabetic foot disease were included. Results: Most observational studies and meta-analyses suggest that direct angiosome-targeted revascularization may improve wound healing and limb salvage in selected patients. However, clinical outcomes are also influenced by collateral circulation, anatomical variability, infra-malleolar perfusion, pedal arch integrity, and microvascular function. The woundosome concept expands the traditional angiosome model by emphasizing effective perfusion of the wound bed through direct arterial inflow, collateral pathways, and functional perfusion assessment. Conclusions: Combining the angiosome and woundosome concepts may provide a more practical and individualized approach to revascularization planning in CLTI by integrating anatomical vascular mapping with functional wound perfusion assessment. Full article

Background: Complex EVAR is a well-established option for treating complex aortic pathologies. However, depending on the type of it, long-term effectiveness is often compromised. For example, chimney EVAR is related to type IA endoleaks related to the gutter and proximal neck degeneration, late failures after fenestrated or branched EVAR are rare. Although redo-endovascular procedures are recommended for failed repairs, the use of branched endoprostheses (BEVAR) to address failed Complex EVAR (C-EVAR) cases is rarely documented. This study aims to evaluate the technical feasibility and 30-day outcomes of using BEVAR as a definitive rescue strategy for these patients. Methods: A retrospective single-center analysis was conducted on a series of twelve patients who had previously undergone failed C-EVAR. Clinical and procedure-related variables were collected. Statistical analysis was performed using Stata v18.0 software. Results: The reasons for reintervention were type Ia endoleak (ten patients), type Ib (one patient), and type III + Ia (one patient). Branched devices were used: eleven patients received the Zenith t-Branch (Cook Medical, Bloomington, IN, USA), and one received the G-Branch device (Lifetech Scientific, Shenzhen, China). Technical and clinical success was achieved in 11 out of 12 patients (91.7%). One perioperative death (due to haemothorax and sepsis) and three major complications were recorded in the first 30 days following repair. No patient of this cohort was deemed fit enough for open conversion. Imaging follow-up at 30 days revealed two type I leaks and seven type II leaks, with no type III leaks recorded. Patency was maintained in all treated visceral vessels (the celiac trunk, the superior mesenteric artery, and the renal arteries) in survivors. Conclusions: Repairing failed C-EVAR using branched endovascular aneurysm repair is a feasible and effective technique. This approach can resolve complex issues such as proximal sealing and component integrity failures, successfully excluding the aneurysmal sac while avoiding the morbidity and mortality associated with open surgery in high-risk patients. Full article

Heart failure with reduced ejection fraction (HFrEF) is increasingly recognized as a systemic metabolic disorder. The aim of this study was to characterize amino acid-related metabolic differences between heart failure with moderately reduced ejection fraction (HFmrEF) (LVEF 40–49%) and HFrEF (LVEF < 40%) and to derive a biologically interpretable composite metabolomic index capable of discriminating between these two stages of systolic dysfunction. We conducted a cross-sectional metabolomic analysis of 42 patients stratified by left ventricular ejection fraction (LVEF < 40% vs. 40–49%). The reference group comprised patients with mildly reduced ejection fraction (LVEF 40–49%), without inclusion of individuals with preserved or normal cardiac function. Targeted amino acid profiling was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Metabolites were standardized and analyzed individually and in combination. A composite index (Heart Failure Amino Acid-Derived Systolic Index: HASI-40), integrating markers of proteolysis and metabolic resilience, was derived to distinguish patients with HFrEF from those with HFmrEF. Discrimination was assessed using receiver operator curve (ROC) analysis with internal validation and multivariable adjustment. Patients with LVEF < 40% exhibited a coordinated metabolic phenotype characterized by reduced methionine, sarcosine, serine, and taurine. While individual metabolites did not retain significance after multiple-testing correction, the composite HASI-40 index remained strongly associated with HFrEF (OR 5.56, 95% CI: 1.70–18.14; p = 0.004), although the wide confidence interval indicates limited precision due to sample size. The index demonstrated good discrimination with an area under the curve (AUC) of 0.862, which improved when combined with age (AUC 0.932). The index represents a standardized composite measure and does not define a diagnostic cutoff for individual patients. These findings suggest that HFmrEF and HFrEF exhibit partially distinct metabolic phenotypes despite overlapping clinical characteristics. These findings suggest that HASI-40 captures metabolic differences between patients with HFmrEF (LVEF 40–49%) and those with HFrEF (LVEF < 40%), reflecting progression toward more advanced systolic dysfunction. However, due to the absence of a control group with preserved ejection fraction, small sample size, and lack of external validation, the index should be considered exploratory and hypothesis-generating rather than clinically applicable. Full article

Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease traditionally defined and assessed by sinonasal symptoms such as nasal obstruction, rhinorrhea, facial pressure, and olfactory dysfunction. However, the burden of CRS extends beyond the sinonasal compartment, including a range of systemic and functional complaints that are not routinely addressed in standard rhinologic practice. Among these, vestibular symptoms, including dizziness, imbalance, and nonspecific disequilibrium, are frequently reported by patients with CRS, yet remain underrecognized and poorly integrated into current diagnostic frameworks and clinical guidelines, despite being captured as a single, psychometrically limited item within the 22-item Sinonasal Outcome Test (SNOT-22). Clinical observations and limited published data, mostly small observational studies and case reports, suggest that vestibular symptoms may fluctuate in parallel with CRS disease activity and may improve following effective medical or surgical control of sinonasal inflammation. Proposed mechanisms include Eustachian tube dysfunction, immune-mediated and neurogenic pathways, trigemino-vestibular interactions, and altered multisensory integration, although current evidence does not establish a causal relationship between CRS disease activity and measurable peripheral vestibular dysfunction. Comparative observations in allergic rhinitis and post-viral upper-airway inflammation situate CRS within a broader inflammatory upper-airway–vestibular interface. This Commentary highlights vestibular dysfunction as an underappreciated extra-sinonasal dimension of CRS with potential clinical and functional relevance. By drawing attention to this clinical blind spot, we aim to encourage more systematic symptom inquiry, interdisciplinary dialogue, and prospective research into the functional consequences of chronic upper-airway inflammation. Full article

Objective: Peripheral arterial occlusive disease (PAOD) is characterized by impaired tissue perfusion, chronic ischemia, and increased platelet reactivity. Hyperbaric oxygen therapy (HBOT) is used as adjunctive treatment in advanced PAOD, but its effect on platelet function remains insufficiently studied. This study examined the association between HBOT and platelet aggregation. Methods: This prospective observational study included 90 patients with Fontaine stage IV PAOD and chronic ulceration, assigned to an HBOT group (n = 60) or waiting-list control group (n = 30). Patients were predominantly male; mean age was 66.82 ± 9.42 years in the study group and 63.00 ± 8.31 years in controls, and diabetes mellitus was present in 55.0% and 63.3%, respectively. Prior revascularization included open surgery in 33.3% and 30.0%, endovascular treatment in 36.7% and 43.3%, and no option for revascularization in 30.0% and 26.7%, respectively. HBOT was administered over 4 weeks (20 sessions, 2.0–2.5 ATA). Platelet aggregation was measured by impedance aggregometry using arachidonic-acid-induced aggregation (ASPI), adenosine-diphosphate-induced aggregation (ADP), and thrombin-receptor-activating peptide-induced aggregation (TRAP) agonists. Changes were analyzed using generalized estimating equation models adjusted for antiplatelet therapy, diabetes mellitus, smoking, and C-reactive protein (CRP). Results: Significant group × time interactions were observed for all platelet activation pathways, indicating greater reductions in the HBOT group than controls: ASPI (β = −290.5; p < 0.001), ADP (β = −243.6; p < 0.001), and TRAP (β = −330.9; p < 0.001). No significant change was observed in controls. HBOT was associated with reduced pain intensity, while CRP and platelet-to-lymphocyte ratio (PLR) remained stable. Ulcer size showed no significant change after 4 weeks. Conclusions: In patients with PAOD, HBOT was associated with reduced platelet reactivity independent of antiplatelet therapy. Further randomized studies are needed to determine its clinical significance. Full article

Hemoptysis is a potentially life-threatening phenomenon with a wide range of underlying causes. While most episodes are linked to common conditions such as infections, malignancy, or pulmonary embolism, a proportion of cases are due to unusual and often unexpected etiologies. This narrative review summarizes published case reports, series, and observational studies describing rare causes of hemoptysis, including vascular malformations, congenital anomalies, benign tumors, systemic diseases, and unusual infections. These conditions are frequently overlooked, which may delay recognition and appropriate management. The reviewed examples highlight the variety of diagnostic challenges and the broad spectrum of therapeutic strategies that may be required, ranging from endovascular procedures and surgery to targeted medical therapy. Despite advances in diagnostic methods, a subset of patients remain classified as having idiopathic or cryptogenic hemoptysis. For this reason, clinicians should keep a broad differential diagnosis in mind and remain aware of rare but clinically important entities. Awareness of these uncommon presentations and individualized patient management are essential for improving outcomes and avoiding missed critical diagnoses. Full article

Background: Objective performance assessment is essential in surgical skill training, yet current methods are labor-intensive and focus on observing the trainee rather than the end-product of the procedure. Machine learning (ML) methods offer reproducible feedback but have mainly relied on kinematic or video data, often reducing assessment to binary or ternary classification. Our objective was to compare ML regression models predicting expert-assigned scores of vascular anastomoses from computational fluid dynamics (CFD) features of the final product. Additionally, we aimed to assess biomechanical plausibility of predictions. Methods: A total of 146 participants performed 419 end-to-side anastomoses on case-specific three-dimensional (3D) printed simulators. Anastomoses were digitized via 3D scanning, ranked by experts, and characterized using CFD-derived hemodynamic features. These served as input for linear models (Ridge, Partial Least Squares), support vector machines, and tree-based ensembles (Random Forest, Extremely Randomized Trees, and Extreme Gradient Boosting [XGBoost]), evaluated using 10-fold nested cross-validation with genetic hyperparameter optimization. Results: Inter-rater reliability of expert indicated strong agreement (intraclass correlation coefficient ICC3k = 0.846). XGBoost achieved the lowest mean root mean squared error of 0.758 (95% bootstrap CI: 0.722–0.799) and a coefficient of determination (R²) of 0.673 (0.617–0.725), with the most stable performance across folds. Shapley additive explanations (SHAP) identified the wall shear stress gradient, transverse wall shear stress, and maximum pressure as the most influential features—variables associated with intimal hyperplasia and atherosclerotic remodeling. Conclusions: Tree-based ensemble methods, particularly XGBoost, effectively modeled biomechanical properties against expert scores. Combining CFD and ML can provide reproducible, mechanistically relevant feedback in vascular surgical skill training. Full article

Bicuspid aortic valve (BAV) is one of the most common congenital heart defects, introducing significant hemodynamic disturbances to the circulatory system. This narrative review analyzed articles published between 2012 and 2025 and indexed in PubMed. The aim was to synthesize key information on the etiopathogenesis of BAV, its potential complications and associated risks, as well as available pharmacological and surgical treatment strategies, with emphasis on indications and contraindications for specific surgical techniques. Analyses demonstrate that isolated BAV with typical valvular aortopathy is associated with a more favorable prognosis compared to valvular aortopathy syndromes. Valve phenotype shows important sex-related relationships in its presentation and progression. From a hemodynamic perspective, BAV alters blood flow angles, which may contribute to weakening of the aortic wall and secondary valve changes. BAV is also frequently associated with genetic disorders such as Marfan syndrome. The heterogeneity of aortopathies linked to BAV creates significant challenges for echocardiographers, cardiologists and cardiac surgeons, particularly in determining the optimal timing and strategy for surgical intervention. Full article

Background/Objectives: The composition of atherosclerotic plaques is increasingly recognized as a key factor determining cardiovascular risk. Features such as intraplaque hemorrhage, a necrotic lipid core, and the integrity of the fibrous cap are strongly associated with plaque instability and the occurrence of adverse clinical events. Magnetic resonance imaging (MRI) allows for non-invasive characterization of plaque microstructure through quantitative mapping of T1 and T2 relaxation times; however, image noise may limit the accuracy of these measurements. Methods: In this experimental study, a total of 15 ex vivo atherosclerotic plaque samples were imaged using a 1.5T scanner with a fast spin-echo sequence featuring variable repetition times (TR: 200–12,000 ms) and echo times (TE: 21–240 ms) to obtain T1 and T2 maps. An Attention–Residual–Dense U-Net neural network was trained on pairs of noisy and reference images to reduce Rician noise while preserving structural details. Results: The 15 samples examined exhibited T1 values ranging from 1768 to 3294 ms and T2 values ranging from 138 to 202 ms, which were shorter than those for water (T1: 3323 ms; T2: 114 ms), which is consistent with the presence of collagen, lipids, and mineral deposits. Variability among samples reflected differences in composition, with the shortest relaxation times suggesting advanced calcifications. The application of deep learning methods allowed for a threefold improvement in the signal-to-noise ratio (SNR) while preserving the microarchitecture of the lamina. Conclusions: Quantitative T1/T2 mapping combined with deep learning-based image enhancement methods constitutes a robust tool for high-resolution characterization of atherosclerotic plaque composition under ex vivo conditions. The results obtained indicate the potential for translating this method to in vivo studies to better detect tissue heterogeneity and features associated with plaque instability. Full article

Background: Lower limb arterial calcification (LLAC) is a robust imaging biomarker of peripheral artery disease (PAD) severity. Vitamin K antagonists are presumed to accelerate cardiovascular calcification. Direct oral anticoagulants (DOACs) may influence vascular calcification differently, but lower limb data are limited. Methods: We performed a single-center retrospective cross-sectional study comparing LLAC on clinically acquired non-contrast CT between DOAC users and controls without anticoagulation. Patients were propensity score-matched 1:1 (48 DOAC vs. 48 control; n = 96) using baseline clinical covariates. Associations between LLAC scores and perioperative or cardiovascular events were assessed. Segment-specific LLAC was quantified on non-contrast CT and normalized for arterial segment length. A prespecified exposure–duration sensitivity analysis compared the outcomes in patients with ≥5 years of continuous DOAC therapy (n = 22) versus matched controls. Results: In the matched cohort, total LLAC scores did not differ significantly between DOAC and control groups (infrarenal aorta: median 7596.0 vs. 8637.0 (p = 0.487), iliac segment: median 5689.5 vs. 5193.5 (p = 0.602). However, in patients with ≥5 years of DOAC use, LLAC scores were significantly lower in proximal segments: infrarenal aorta median 5593.5 vs. 11,185.0 (p = 0.001997) and iliac arteries 5624.5 vs. 11,501.0 (p = 0.001867)). Higher LLAC was associated with major adverse cardiovascular events (such as myocardial infarction, stroke, or significant bleeding) in controls (p = 0.0023) but not in DOAC-treated patients. Conclusions: In this propensity-matched, cross-sectional CT study, long-term DOAC exposure was associated with lower proximal LLAC scores in a small duration-defined subgroup, while the primary matched analysis showed no overall difference in total LLAC scores. Because baseline (pre-DOAC) imaging was unavailable and residual confounding/survivor bias is possible, these findings should be considered hypothesis-generating and require prospective validation. The cohort reflected a mixed lower-extremity vascular population rather than exclusively classic chronic atherosclerotic PAD, which may limit biological interpretation and generalizability. Full article

Background/Objectives: RNA interference (RNAi) is a promising strategy for mitigating diseases at the molecular level. However, RNAi is limited by its instability in biological fluids and impermeability to cellular membranes. In response, our lab has previously patented a non-ionizable lipid nanoparticle (LNP) platform (R8-PLP) for RNAi therapeutic delivery. This formulation incorporates 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve particle stability and drug retention. However, long-anchored PEGylated lipids like DSPE-PEG may impair internalization and stimulate immune responses. The literature suggests substituting short-anchored PEGylated-lipids like 1,2-dimyristoyl-rac-glycero-3-[methoxy(polyethylene glycol)-2000] (DMG-PEG) to attenuate these effects. Here, we evaluated whether substituting DMG-PEG for DSPE-PEG in our R8-PLP would improve in vitro cellular delivery and gene transfection without compromising in vitro critical quality attributes (CQAs) or increasing cytotoxicity. Methods: CQAs [encapsulation efficiency (EE%), particle size (nm), homogeneity (polydispersity index; PDI), and membrane zeta-potential] were assessed at assembly and after storage for up to 28 days at 4 °C. Additionally, in-serum stability at 4 °C and serum release kinetics at 37 °C were assessed. Human aortic smooth muscle cells (HASMCs) were treated with R8-PLPs and analyzed for cellular uptake (fluorometry), cytotoxicity (LIVE/DEAD stain), and gene modulation (qPCR). Results: DMG-PEG incorporation at variable mol% did not alter R8-PLP size, homogeneity, or siRNA EE% at assembly or after long-term storage, but did accelerate siRNA release kinetic profiles compared to DSPE-PEG controls. DMG-PEG substitution enhanced cellular uptake compared to DSPE-PEG R8-PLPs without increasing cytotoxicity. DMG-PEG incorporation also achieved significant silencing versus non-treated controls but did not improve gene silencing compared to DSPE-PEG R8-PLPs. Conclusions: Thus, DMG-PEG substitution did not enhance R8-PLP in vitro gene modulation efficacy despite improving cellular uptake and maintaining CQAs. Full article

The superior mesenteric artery (SMA) is the second unpaired ventral branch of the abdominal aorta. The SMA supplies the abdominal organs that develop from the midgut. This study investigated the morphological characteristics of the SMA by (i) measuring its diameter in different sexes; (ii) assessing the vertical distance between the SMA and inferior mesenteric artery (IMA) origins in males and females, and (iii) observing if the hepatic artery arose from the SMA instead of the celiac trunk. This retrospective cross-sectional study included the contrast-enhanced CT angiograms of 260 patients (n = 205 males and 55 females) who attended the Radiology department at Sultan Qaboos University Hospital from 1 January 2021 to 31 December 2023. All included patients were aged 19–50 years and had no history of vascular pathology that altered the vascular dimensions, nor had any history of major abdominal trauma or abdominal surgeries. The mean diameter of the SMA in the study population was 7.51 ± 1.11 mm. The mean diameter of the SMA was found to be wider in males (7.73 ± 1.05 mm) compared to females (6.71 ± 0.96 mm, p < 0.001). The mean distance between the SMA and IMA was 62.67 ± 10.91 mm. The average distance between SMA and IMA in males and females was found to be 63.36 ± 10.67 mm and 60.09 ± 11.48 mm (p = 0.048), respectively. Incidence of the right hepatic artery originating from SMA, accessory right hepatic artery, and common hepatic artery originating from SMA was 7.7%, 0.38%, and 2.3%, respectively. Prior anatomical knowledge of arteries is important for occlusion, bypass grafting, and endovascular surgeries involving SMA. Full article

Background/Objectives: Fenestrated and branched endovascular aortic repair (F/BEVAR) is increasingly used for the treatment of complex aortic aneurysms, and is traditionally performed under general anesthesia (GA). Data on the use of local anesthesia (LA) for F/BEVAR remain limited. This study aimed to report early outcomes of F/BEVAR performed under LA versus GA, with a focus on feasibility and perioperative complications in a high-risk patient population. Methods: This single-center retrospective analysis included patients undergoing F/BEVAR under LA or GA. Primary outcomes were in-hospital mortality and in-hospital complications. Secondary outcomes included early reintervention, intensive care unit and hospital length of stay, blood transfusion requirements, and technical success. Results: A total of 359 patients were included, of whom 25 (7.0%) were treated under LA and 334 (93.0%) under GA. Conversion from LA to GA occurred in 6 patients (24%). Patients in the LA group represented a higher-risk cohort, with advanced age, higher ASA class, larger aneurysm diameters, and a greater proportion of emergency and ruptured repairs. Technical success was high, and procedural metrics were within expected ranges. In-hospital mortality was numerically higher in the LA group (12.0% vs. 2.9%, p = 0.05). Overall, in-hospital complications were more frequent in the LA group (68.0% vs. 41.3%, p = 0.009), including a higher rate of spinal cord ischemia (24.0% vs. 8.5%, p = 0.02). Blood transfusion requirements were also greater in patients treated under LA (p = 0.004), while blood loss, ICU stay, and hospital length of stay were comparable. Early reintervention occurred more frequently in the LA group (31.8% vs. 10.4%, p = 0.009). Conclusions: LA appears feasible in selected high-risk patients undergoing complex F/BEVAR. However, given substantial baseline differences between groups, no conclusions can be drawn regarding comparative safety or efficacy relative to GA. These findings should be considered preliminary. Full article

Background: Trace elements function as essential micronutrients involved in oxidative balance, mitochondrial activity, and cardiovascular metabolism. Cigarette smoking represents a significant source of toxic metals and may disrupt systemic trace element homeostasis. Alterations in micronutrient and metal balance may contribute to oxidative stress, endothelial dysfunction, and myocardial remodeling, which are central mechanisms in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). This study aimed to investigate whether smokers with HFpEF exhibit distinct hair trace element profiles compared with smokers without HFpEF. Methods: In this prospective pilot study, scalp hair samples were collected from adults undergoing clinical evaluation for suspected cardiovascular disease. Trace element concentrations were determined using inductively coupled plasma mass spectrometry (ICP-MS). Participants were first stratified according to smoking status and subsequently, within the smoker subgroup, according to HFpEF diagnosis based on the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide score (HFA-PEFF) algorithm. Differences in trace element concentrations were analyzed using appropriate statistical tests, with multiple-comparison correction using the Benjamini–Hochberg false discovery rate (FDR). Active smoking was defined as ≥10 cigarettes per day for at least 1 year, and cumulative exposure was quantified in pack-years. Results: Fifty-eight participants were included, including 27 active smokers. In unadjusted analyses, several trace elements differed between smokers with HFpEF and those without HFpEF, including vanadium, lithium, aluminum, and copper. However, after FDR correction, only copper remained significantly elevated in smokers with HFpEF (q = 0.004). Hair copper concentrations were markedly higher in the HFpEF group compared with smokers without HFpEF. These differences were observed alongside echocardiographic features consistent with diastolic dysfunction and structural cardiac remodeling. Conclusions: In this hypothesis-generating pilot study, smokers with HFpEF demonstrated elevated hair copper concentrations, suggesting disturbances in trace element and micronutrient homeostasis. Altered copper metabolism may reflect oxidative stress-related cardiometabolic remodeling associated with HFpEF. These findings raise the hypothesis that cardiometabolic phenotype, rather than smoking exposure alone, may modulate trace element homeostasis in HFpEF; however, causal relationships cannot be established. Full article