Search Results (789)

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

Diabetes-related pathophysiological processes contribute to endothelial dysfunction, arterial stiffening (AS), hypertension, vascular remodeling, and impaired myocardial perfusion. This study aimed to assess the relationship between arterial wall parameters and sST2 concentration as potential risk factors in type 2 diabetes (T2DM) and investigate sex-related differences. To achieve this, we enrolled 100 patients with suspected or exacerbated coronary artery disease (CAD) and divided them into a T2DM group (n = 58) and a control group (n = 42). Endothelial reactivity (lnRHI), ABI, sST2 levels, and carotid–femoral (cfPWV) and carotid–radial pulse wave velocity (crPWV) were assessed. Coronary angiography was performed in every patient, and epicardial flow and myocardial perfusion were evaluated using QuBE and FLASH. Our results showed that the coronary angiographic findings were similar in both groups. However, T2DM patients had a significantly higher central AS (cfPWV 10.8 ± 2 vs. 9.9 ± 2.7 m/s, p < 0.05) and vascular age (70.0 ± 12.3 vs. 61.3 ± 15.4 years, p < 0.05), while peripheral AS, RHI, and ABI showed no differences. CfPWV correlated with renal function; higher HbA1c and sST2 levels were additionally associated with advanced vascular age. Notably, central AS and vascular age were higher in men with T2DM but not in women. These findings indicate that T2DM patients exhibit increased central AS and vascular aging, influenced by sST2 levels, suggesting fibrosis as a target for precision medicine in T2DM. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

Coronary artery disease (CAD) is the main cause of morbidity and death worldwide, and atherosclerosis represents the leading pathophysiological pathway responsible for CAD. Atherosclerotic process is a complex interplay of mechanisms and mediators resulting in plaque formation, progression and destabilization, the latter being the most frequent cause of acute cardiovascular events. Considering the systemic nature of atherosclerosis, polyvascular disease involvement is possible and has been described since 1960s. Accordingly, epidemiologic studies reported that concomitant CAD and atherosclerosis in other arterial beds like carotid arteries, lower limb arteries, mesenteric and renal circulation, and aorta, is frequent and related to increased chance of future cardiovascular events. Although risk factors, atherosclerotic plaque features and mechanisms of plaque destabilization are largely shared across different sites, many studies have reported some disparities among districts. Moreover, simultaneous polyvascular disease has been associated with increased likelihood of having particular plaque characteristics depending on the affected arterial level. In this comprehensive narrative review, we aim to discuss about epidemiology of concomitant CAD and atherosclerosis in other arterial beds, and to examine differences in risk factors, plaque features and mechanisms of plaque instability between CAD and other atherosclerotic locations. Finally, we review the studies observing differences on plaque features according to involved atherosclerotic sites, focusing on CAD. Full article

Background and Objectives: The causes and clinical outcomes of renal perfusion abnormalities occurring after para-aortic lymphadenectomy (PANDx) for gynecologic malignancies are unknown. We investigated the potential involvement of accessory renal artery (ARA) obstruction in their development by reassessing perioperative contrast-enhanced computed tomography (CECT). Materials and Methods: This retrospective study investigated a clinical database to identify urinary contrast defects using CECT in all patients who had undergone PANDx between January 2020 and December 2024. The perfusion defects in the kidney detected by CECT were extracted by a gynecologic oncologist and evaluated by a radiologist and urologist for suspected obstruction of ARAs. Results: Postoperative renal contrast defects were observed in 3.8% (6/157) of patients. Renal parenchymal fibrosis, cortical atrophy, and parenchymal thinning were observed as universal findings in all patients showing renal contrast defects. In five of the six cases, ARAs supplying the infarcted renal segments were identified on preoperative CECT, and arterial obstruction was confirmed on postoperative imaging. The remaining case was considered to be latent pyelonephritis. All five patients underwent laparotomy, and preoperative CECT failed to detect ARAs. The median resected para-aortic lymph node was 23 nodes (range: 15–33) in five patients, showing no statistically significant difference compared to patients without perfusion abnormalities (p = 0.19). Postoperative serum creatinine levels remained stable. Conclusions: ARA obstruction appears to be a risk factor for segmental renal infarction after para-aortic lymphadenectomy in gynecological malignancies; however, the clinical impact on urinary function may be limited. Awareness of this potential complication is essential for gynecologic oncologists performing PANDx. Full article

Objectives: Patients with acute heart failure (AHF) often receive initial non-invasive ventilation (NIV). This study aimed to evaluate the prognostic role of NIV in patients hospitalized for AHF. Methods: This was a retrospective cohort study. We enrolled patients admitted to our cardiac intensive care unit with a diagnosis of AHF. Anthropometric, clinical, pharmacological, and instrumental assessments were collected. Both in-hospital and 180-day post-discharge mortality were evaluated. Results: Among 200 patients (mean age 81 ± 9 years; 52% male), NIV was applied in 80 cases (40%). These patients had more severe NYHA functional class, a higher prevalence of de novo AHF, required higher diuretic doses, and had longer hospital stays. In multivariate analysis, NIV remained significantly associated with length of stay (LOS) (r = 0.26; p = 0.0004). In-hospital mortality was 5% overall and significantly higher in the NIV group compared to non-NIV patients (10% vs. 1.6%, p < 0.001). At 180 days, mortality was also significantly higher in the NIV group [hazard ratio (HR) 1.84; 95% confidence interval (CI): 1.18–2.85; p = 0.006]. After adjusting for age, BNP, CRP, arterial blood gas parameters, renal function, and LVEF, NIV remained an independent predictor of 180-day mortality (HR 1.61; 95% CI: 1.01–2.54; p = 0.04). Conclusions: Patients with AHF who required NIV exhibited more severe disease and longer hospital stays. NIV use was independently associated with both in-hospital and post-discharge mortality, suggesting its potential role as a prognostic marker in AHF. Full article

Advanced glycation end-products (AGEs) are formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids due to the consumption of high-carbohydrate diets; their production is also promoted by a sedentary lifestyle as well as cigarette smoking. Elevated levels of AGEs in the circulatory system and internal organs of the body are commonly observed in a number of cardiovascular diseases such as hypertension, diabetes, atherosclerosis, coronary artery disease, aortic aneurysm, atrial fibrillation, myocardial infarction, and heart failure, which are associated with the development of oxidative stress and myocardial inflammation. The adverse effects of AGEs on the cardiovascular system are elicited by both non-receptor mechanisms involving the cross-linking of extracellular and intracellular proteins, and by receptor-mediated mechanisms involving the binding of AGEs with advanced glycation end-product receptors (RAGEs) on the cell membrane. AGE–RAGE interactions along with the cross-linking of proteins promote the generation of oxidative stress, the production of inflammation, the occurrence of intracellular Ca²⁺-overload, and alterations in the extracellular matrix leading to the development of cardiovascular dysfunction. AGEs also bind with two other protein receptors in the circulatory system: soluble RAGEs (sRAGEs) are released upon the proteolysis of RAGEs due to the activation of matrix metalloproteinase, and endogenous secretory RAGEs (esRAGEs) are secreted as a spliced variant of endogenous RAGEs. While the AGE–RAGE signal transduction axis serves as a pathogenic mechanism, both sRAGEs and esRAGEs serve as cytoprotective interventions. The serum levels of sRAGEs are decreased in ischemic heart disease, vascular disease, and heart failure, as well as in other cardiovascular diseases, but are increased in chronic diabetes and renal disease. Several interventions which can reduce the formation of AGEs, block the AGE–RAGE axis, or increase the levels of circulating sRAGEs have been shown to exert beneficial effects in diverse cardiovascular diseases. These observations support the view that the AGE–RAGE axis not only plays a critical role in pathogenesis, but is also an excellent target for the treatment of cardiovascular disease. Full article

Background and Objectives: Severe sepsis complicated by refractory shock is associated with high mortality. Adding continuous hemofiltration to venovenous extracorporeal membrane oxygenation (ECMO) may accelerate clearance of inflammatory mediators and improve haemodynamic stability, but evidence remains limited. We analysed 44 consecutive septic-shock patients treated with combined ECMO-hemofiltration (ECMO group) and compared them with 92 septic-shock patients managed without ECMO or renal replacement therapy (non-ECMO group). Methods: This retrospective single-centre study reviewed adults admitted between January 2018 and March 2025. Demographic, haemodynamic, laboratory and outcome data were extracted from electronic records. Primary outcome was 28-day mortality; secondary outcomes included intensive-care-unit (ICU) length-of-stay, vasopressor-free days, and change in Sequential Organ Failure Assessment (SOFA) score at 72 h. Results: Baseline age (49.2 ± 15.3 vs. 52.6 ± 16.1 years; p = 0.28) and APACHE II (27.8 ± 5.7 vs. 26.9 ± 6.0; p = 0.41) were comparable. At 24 h, mean arterial pressure rose from 52.3 ± 7.4 mmHg to 67.8 ± 9.1 mmHg in the ECMO group (mean change [∆] + 15.5 mmHg, p < 0.001). Controls exhibited a modest 4.9 mmHg rise that did not reach statistical significance (p = 0.07). Inflammatory markers decreased more sharply with ECMO (IL-6 ∆ −778 pg mL⁻¹ vs. −248 pg mL⁻¹, p < 0.001). SOFA fell by 3.6 ± 2.2 points with ECMO versus 1.6 ± 2.4 in controls (p = 0.01). Twenty-eight-day mortality did not differ (40.9% vs. 48.9%, p = 0.43), but ICU stay was longer with ECMO (median 12.5 vs. 9.3 days, p = 0.002). ΔIL-6 correlated with ΔSOFA (ρ = 0.46, p = 0.004). Conclusions: ECMO-assisted hemofiltration improved early haemodynamics and organ-failure scores and accelerated cytokine clearance, although crude mortality remained unchanged. Larger prospective trials are warranted to clarify survival benefit and optimal patient selection. Full article

Background/Objectives: To evaluate the diagnostic performance of non-enhanced MRA in detecting intratumoral aneurysms in renal AML, using digital subtraction angiography (DSA) as the reference standard. Methods: Fourteen female patients (mean age, 39 years; range, 21–57 years) who received prophylactic transcatheter arterial embolization (TAE) for non-hemorrhagic renal AML(s) between July 2010 and September 2018 were included in this study. All received a non-enhanced MRA scan prior to TAE. Non-enhanced MRA images were obtained using the flow-in technique with three-dimensional balanced steady-state free precession (SSFP). The MRA and DSA images were jointly evaluated by three radiologists. In this study, significant aneurysms were defined as aneurysms with a diameter of 3 mm or more within the renal AML. The MRA images assessed the number and location of significant aneurysms. The DSA images were used as the reference standard. Results: DSA identified 30 significant aneurysms in eight kidneys; MRA identified 26, giving a sensitivity of 87%. There were no false positives, resulting in a specificity of 100%. Conclusions: Flow-balanced SSFP MRA is effective in detecting significant aneurysms in renal AML and could be a viable alternative for patient follow-up. Full article

Background: High plasma levels of Galectin-3 (Gal-3) and uric acid (UA) are associated with a decline in renal function in different populations. However, this association has not yet been studied in patients with coronary artery disease (CAD). Methods: We included 556 patients with stable CAD. Plasma levels of Gal-3, UA, N-Terminal probrain natriuretic peptide (NT-proBNP), calcidiol, fibroblast growth factor 23, phosphate, parathormone, and klotho were assessed at baseline. The primary outcome was the percentage decrease in eGFR; the secondary outcomes were the absolute decrease in eGFR and achieving a reduction of ≥20% in this parameter. Results: Age was 63.1 ± 12.2 years, and 73.9% of patients were male. The median eGFR was 86.77 (72.27, 97.85) mL/min/1.73 m². After 3.47 (2.10–5.72) years of follow-up, eGFR declined by 3.62% [−2.07–13.82]. Baseline UA (0.012 [CI95% 0.003, 0.020]; p = 0.008), Gal-3 (0.0153 [CI95% 0.001, 0.029]; p = 0.037), and NT-proBNP (0.017 [CI95% 0.000–0.025]; p = 0.027) were independent positive predictors of the percentage decrease in eGFR, while calcidiol (−0.005 [CI95% −0.009, −0.002]; p = 0.005) was an inverse predictor of this outcome. Similarly, UA and Gal-3 were positive independent predictors of the absolute decline in eGFR (0.009 [0.003, 0.017]; p = 0.004 and 0.012 [0.001, 0.023]; p = 0.031, respectively), while calcidiol was inversely associated (−0.003 [−0.005]–[−0.001]; p = 0.020). Uric acid (1.237 [1.046–1.463]; p = 0.013) and NT-proBNP (1.000 [1.000–1.001]; p = 0.049) levels were positive independent predictors of a ≥20% decrease in eGFR. In patients with eGFR ≥ 60 mL/min/1.73 m², UA was the only biomarker independently associated with renal function decline. Conclusions: In patients with CAD and normal or mildly reduced renal function, UA and Gal-3 plasma levels are independent positive predictors of a future decrease in eGFR. These findings could lead to a change in the approach to patients with CAD in the future. Full article

Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare, often fatal congenital disorder characterized by severe neonatal respiratory distress and associated with complex multisystem malformations. In approximately 90% of cases, the condition is linked to deletions or mutations affecting the FOXF1 gene or its upstream enhancer region on chromosome 16q24.1. This review analyzes reported prenatal cases with 16q24.1 deletion involving FOXF1, aiming to identify recurrent sonographic features and elucidate the underlying genomic and epigenetic mechanisms. We reviewed prenatal cases reported in the literature involving deletions of the 16q24.1 region, including the FOXF1 gene. Here, we expand the case series by reporting a fetus with increased nuchal translucency measuring 8 mm and a de novo 16q24.1 deletion. We identified nine prenatal cases with a 16q24.1 deletion, all involving the FOXF1 gene or its enhancer region. The main ultrasound findings included increased nuchal translucency and cystic hygroma during the first trimester, and cardiac, renal, and intestinal malformations from 20 weeks of gestation onward. Prenatal diagnosis of ACDMPV based solely on ultrasound findings is challenging. In most reported cases, the pregnancy was carried to term, with the diagnosis being confirmed by post-mortem histopathological examination. In the only case in which the pregnancy was terminated at 14 weeks’ gestation, histological examination of the fetal lungs, despite them being in the early stages of development, revealed misaligned pulmonary veins in close proximity to the pulmonary arteries and bronchioles. Evidence highlights the significance of non-coding regulatory regions in the regulation of FOXF1 expression. Differential methylation patterns, and possible contributions of parental imprinting, highlight the complexity of FOXF1 regulation. Early detection through array comparative genomic hybridization (array CGH) or next-generation sequencing to identify point mutations in the FOXF1 gene, combined with increased awareness of ultrasound markers suggestive of the condition, could improve the accuracy of prenatal diagnosis and genetic counseling. Further research into the epigenetic regulation of FOXF1 is crucial for refining recurrence risk estimates and improving genetic counseling practices. Full article

Background/Objective: Bridging stent optimal choice in fenestrated and branched endovascular aortic repair (f/bEVAR) is under investigation. This systematic review and meta-analysis studied the outcomes of the BeGraft peripheral and peripheral PLUS as bridging stents in f/bEVAR. Methods: The methodology was pre-registered to the PROSPERO (CRD420251007695). Following the PRISMA guidelines and PICO model, the PubMed, Cochrane and Embase databases were searched for observational studies and randomized control trials, in English, from 2015 to 2025, reporting on f/bEVAR patients using the second-generation BeGraft peripheral or the BeGraft peripheral PLUS balloon expandable covered stent (BECS; Bentley InnoMed, Hechingen, Germany) for bridging. The ROBINS-I assessed the risk of bias and GRADE the quality of evidence. Target vessel technical success, occlusion/stenosis, endoleak Ic/IIIc, reintervention and instability during follow-up were primary outcomes, assessed using proportional meta-analysis. Results: Among 1266 studies, eight were included (1986 target vessels; 1791 bridged via BeGraft); all retrospective, except one. The ROBINS-I showed that seven were at serious risk of bias. According to GRADE, the quality of evidence was “very low” for primary outcomes. Target vessel technical success was 99% (95% CI 98–100%; I² = 12%). The mean follow-up was 20.2 months. Target-vessel instability was 3% (95% CI 2–5%; I² = 44%), occlusion/stenosis was 1% (95% CI 1–4%; I² = 8%) and endoleak Ic/IIIc was 1% (95% CI 0–3%; I² = 0%). The estimated target-vessel reintervention was 2% (95% CI 2–4%; I² = 12%). Celiac trunk, superior mesenteric and renal artery instability were 1% (95% CI 0–16%; I² = 0%;), 1% (95% CI 0–5%; I² = 14%) and 4% (95% CI 2–7%; I² = 40%), respectively. Conclusions: The BeGraft peripheral and peripheral PLUS BECS performed with high technical success and low instability when used for bridging in f/bEVAR. Cautious interpretation is required due to the very low quality of evidence. Full article

Systemic sclerosis (SSc) is a heterogeneous disease characterized by vascular alterations, immune dysregulation, and fibrosis. Solid evidence supports the hypothesis that endothelial dysfunction is the key player in SSc vascular injury and a critical factor concurring to the initiation of SSc pathogenesis. This narrative review reports on persistent endothelial dysfunction, resulting from oxidative stress, autoimmunity, and impaired vascular repair, in the course of SSc, and how it can trigger and sustain fibrotic remodeling of various organs. In this paper, we also analyze the impact on SSc of impaired angiogenesis and vasculogenesis, diminished endothelial progenitor cell function, and endothelial-to-mesenchymal transition, which can collectively disrupt vascular homeostasis and promote myofibroblast activation. These pathologic events underlie the hallmark clinical manifestations, i.e., Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. The review highlights how recognizing SSc as a paradigm of systemic endothelial dysfunction may reframe our understanding of its physiopathology, modify current therapeutic strategies, and unveil new therapeutic targets. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article