Search Results (1,287)

Background: Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic valve stenosis (AS). Balloon post-dilatation (PD) remains an important procedural step to optimize valve function by resolving incomplete valve expansion, which may lead to paravalvular regurgitation and other potentially adverse effects. There are only limited data on the predictors, incidence, and clinical impact of PD during TAVI. Methods: This retrospective, single-center study analyzed 585 patients who underwent TAVI (2016–2022). Pre-procedural evaluations included transthoracic echocardiography and CT angiography to assess key parameters, including the aortic valve calcium score (AVCS); aortic valve calcium density (AVCd); aortic valve maximal systolic transvalvular flow velocity (AV Vmax); and aortic valve mean systolic pressure gradient (AV MPG). We identified imaging predictors of PD and evaluated associated clinical outcomes by analyzing procedural endpoints (according to VARC-3 criteria) and long-term survival. Results: PD was performed on 67 out of 585 patients, with elevated AV Vmax (OR: 1.424, 95% CI: 1.039–1.950; p = 0.028) and AVCd (OR: 1.618, 95% CI: 1.227–2.132; p = 0.001) emerging as a significant independent predictor for PD in TAVI. Kaplan–Meier survival analysis revealed no significant differences in short- and mid-term survival between patients who underwent PD and those who did not. Interestingly, patients requiring PD exhibited a lower incidence of adverse events regarding major vascular complications, permanent pacemaker implantations and stroke. Conclusions: The study highlights AV Vmax and AVCd as key predictors of PD. Importantly, PD was not associated with increased procedural adverse events and did not predict adverse events in this contemporary cohort. Full article

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

Objectives: To assess the clinical and inflammatory outcomes of patients with calcified coronary arteries treated with rotational atherectomy (RA), compared to those with other intervention procedures. Methods: We conducted a systematic search of PubMed (Medline) and Embase. This review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and applied the PICO criteria. Results: A total of 110 articles were analyzed, comprising 2,328,417 patients with moderate to severe coronary calcified lesions treated with RA, conventional percutaneous coronary intervention (PCI), or other advanced interventions. The pooled incidence of short- to mid-term major adverse cardiovascular events (MACEs) was 6% (95% CI 4–7%), increasing to 17% (95% CI 15–21%) at 6 months. Mortality was 2% (95% CI 1–3%) within 6 months, rising to 7% (95% CI 6–9%) thereafter. RA significantly increased the risk of long-term MACEs, mortality, total lesion revascularization (TLR), bleeding, and fluoroscopy time, and was borderline associated with an increased risk of short-term myocardial infarction and a reduced risk of coronary dissection. RA and other invasive procedures showed similar risks for short-term MACEs, mortality, total vascular revascularization (TVR), stent thrombosis, heart failure, stroke, and inflammation. Conclusions: RA is linked to higher long-term risks of MACEs, mortality, TLR, bleeding, and fluoroscopy time compared to other interventions. While RA shows comparable outcomes for short-term MACEs and mortality with other procedures, it may slightly reduce the risk of coronary dissection. These findings underscore the importance of careful patient selection and weighing long-term risks when considering RA for calcified coronary lesions. Full article

Post-craniotomy pain is common yet often sub-optimally managed because systemic opioids can obscure postoperative neurologic examinations. The superficial cervical plexus block (SCPB) has, therefore, emerged as a targeted regional anesthesia option for occipital craniotomies. The SCPB targets the C2–C4 nerves to anesthetize the occipital scalp region, covering the lesser occipital nerve territory that lies within typical posterior scalp incisions. Clinical evidence shows the block is effective in reducing acute postoperative pain after occipital craniotomy and diminishes opioid requirements. Studies have demonstrated successful and long-lasting analgesia, reductions in 24-h opioid consumption, and a lower incidence of severe pain. Moreover, the technique exhibits a low complication rate and is safer than a deep cervical plexus block because the injection remains superficial and avoids critical vascular and neural structures. When delivered under ultrasound guidance, major adverse events are exceedingly rare. By reducing opioid use, the SCPB can help reduce postoperative complications, allowing earlier neurological assessments and fewer opioid-related side effects. Incorporation of the SCPB into multimodal analgesia regimens can, therefore, accelerate postoperative recovery by providing regionally focused, opioid-sparing pain control without clinically significant sedation. Overall, current data support the SCPB as a dependable, well-tolerated, and clinically practical approach for managing post-craniotomy pain in patients undergoing occipital approaches. In this narrative review, we will discuss the mechanism of action and anatomy, the clinical application, safety and tolerability, patient outcomes, and emerging future directions of the superficial cervical plexus block and how it mitigates post-occipital craniotomy pain. Full article

Background: Several epidemiological studies have indicated that metabolic syndrome (MetS) after renal transplantation is caused by an accumulation of non-immunological risks of renal transplantation, and affects the prognosis of the kidney and the patient by increasing the risk of arteriosclerosis and cardiovascular complications. The incidence of MetS in Japanese renal transplant recipients is 14.9 to 23.8%, but its effects on cardiovascular events and kidney prognosis are not clear. Here, we report the results of a longitudinal study on MetS in renal transplant recipients. Methods: A retrospective cohort study was conducted in 104 stable renal transplant recipients who attended our outpatient department from January 2006 to June 2007 and were diagnosed with MetS at least 6 months after renal transplantation until 31 December 2020, or did not have MetS. The impact of MetS on composite vascular events was examined using multivariate Cox proportional hazards analysis. Results: The hazard ratios for the impact of MetS on composite vascular events diagnosed by NCEP Japan, NCEP Original, NCEP Asia, and IDF criteria on composite vascular events were 2.78 (95% CI: 1.15 to 6.75, p = 0.024), 2.65 (95% CI: 1.04 to 6.80, p = 0.042), 2.37 (95% CI: 0.93 to 6.01, p = 0.070), and 1.91 (95% CI: 0.77 to 4.75, p = 0.164), respectively. P for interaction was used to test the influence of each indicator, but was not statistically significant. Conclusions: MetS is a robust risk factor for graft loss and development of cardiovascular events in Japanese renal transplant recipients, even during long-term follow-up. This finding emphasizes the importance of monitoring and managing MetS in this population to improve long-term outcomes. Full article

Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article

Background: Venous thromboembolism (VTE) is conventionally treated with anticoagulant therapy. In contrast, the core treatment for peripheral artery disease (PAD) is antiplatelet therapy. VTE and PAD share common risk factors and may occur in the same patient. Nonetheless, there is little evidence of the best antithrombotic regimen to use when the two conditions coexist, especially in terms of the extended prevention of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and VTE recurrences. Methods: We conducted an online survey of members of the Italian Society of Angiology and Vascular Medicine (SIAPAV) to explore current prescribing habits for extended antithrombotic therapy in patients with PAD and unprovoked VTE. The survey included four clinical scenarios with variations in age, gender, bleeding risk, index VTE event, and severity of PAD. In all cases, patients had received anticoagulation for 6 months, and the key question was how to continue treatment beyond 6 months from the index VTE event. Results: A total of 174 clinicians participated to the survey. The most common choice was combining antiplatelet therapy with a direct oral anticoagulant (DOAC) at a low dose. Full-dose DOAC alone or antiplatelet therapy alone were less frequently chosen. Older age and high bleeding risk increased the preference for antiplatelet therapy alone. Conclusions: This survey highlights the marked variability in antithrombotic prescribing patterns among specialists in vascular medicine for patients with unprovoked VTE and concomitant PAD, reflecting the lack of evidence on optimal management in this specific setting. More research is needed to define the safest and most effective treatment strategies for patients with concurrent PAD and VTE. 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

Background: People with post-stroke cognitive impairment (PSCI) are at increased risk of recurrent stroke, dementia, and accelerated cognitive decline. Objective: To examine the feasibility, safety, acceptability, and suitability of a virtually-delivered vascular risk reduction intervention that integrates tailored cognitive strategy training for people with executive function (EF) impairments post-stroke. Methods: This case series included eight participants who completed up to ten virtual sessions focused on vascular risk reduction and metacognitive strategy training. Sessions averaged 40 min over a 4–5-week period. Results: The intervention was found to be feasible, safe, and acceptable. The recruitment rate was 66.7%, and the retention rate was 87.5% (7 of 8 completed the training). No serious adverse events were reported. Most participants demonstrated improvements on the Canadian Occupational Performance Measure (COPM), with mean performance and satisfaction change scores of 1.22 ± 0.87 and 1.18 ± 0.83, respectively. Conclusions: This technology-enabled intervention was feasible and acceptable for individuals with post-stroke EF impairments. Virtual delivery was a key factor in its accessibility and success. The results are promising for improving self-management of vascular risk factors, warranting further study in larger trials. Full article

Cutaneous wound healing is a complex process involving multiple cellular and molecular events, and current treatments often face limitations in efficacy and safety. Stem-cell therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a promising approach to enhance wound repair through both direct cell replacement and paracrine signaling. This study investigates the therapeutic potential of human chorionic villus mesenchymal stem cells (hCV-MSCs) and their secretory factors in enhancing cutaneous wound healing. Utilizing a rat model, we combined the local administration of hCV-MSC-laden PEGDA/SA/Col-I hydrogel with the systemic delivery of their secretome, aiming to leverage the complementary mechanisms of cellular and cell-free therapies. Our findings demonstrate that hCV-MSCs delivered via PEGDA/SA/Col-I hydrogel significantly accelerated wound closure compared to controls, with near-complete closure observed by day 20. Histological analysis revealed enhanced keratinocyte maturation (increased KRT10/KRT14 ratio) and a higher density of CD31⁺ blood vessels, indicating improved re-epithelialization and angiogenesis. A mass spectrometry analysis of the hCV-MSC secretome identified 849 proteins, with enrichment in pathways related to ECM organization, cell adhesion, and immune regulation. Key proteins such as ANXA1, SERPINE1, and WNT5A were implicated in wound-healing processes. Combination therapy with systemic secretome administration further accelerated wound closure and enhanced collagen deposition, keratinocyte maturation, and vascularization compared to hCV-MSCs alone. Our results highlight the promising application of hCV-MSCs and their secretome in cutaneous wound healing, paving the way for innovative therapeutic strategies that integrate both local and systemic regenerative approaches. Full article

The study of metabolic abnormalities regarding mitochondrial respiration and energy production has significantly advanced our understanding of cell biology and molecular mechanisms underlying cardiovascular diseases (CVDs). Mitochondria provide 90% of the energy required for maintaining normal cardiac function and are central to heart bioenergetics. During the initial phase of heart failure, mitochondrial number and function progressively decline, causing a decrease in oxidative metabolism and increased glucose uptake and glycolysis, leading to ATP depletion and bioenergetic starvation, finally contributing to overt heart failure. Compromised mitochondrial bioenergetics is associated with vascular damage in hypertension, vascular remodeling in pulmonary hypertension and acute cardiovascular events. Thus, mitochondrial dysfunction, leading to impaired ATP production, excessive ROS generation, the opening of mitochondrial permeability transition pores and the activation of apoptotic and necrotic pathways, is revealed as a typical feature of common CVDs. Molecules able to positively modulate cellular metabolism by improving mitochondrial bioenergetics and energy metabolism and inhibiting oxidative stress production are expected to exert beneficial protective effects in the heart and vasculature. This review discusses recent advances in cardiovascular research through the study of cellular bioenergetics in both chronic and acute CVDs. Emerging therapeutic strategies, specifically targeting metabolic modulators, mitochondrial function and quality control, are discussed. Full article

Cardiovascular diseases (CVDs) are the leading cause of global mortality, with type 2 diabetes mellitus (T2DM) and obesity significantly increasing the risk of CVD. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4is) have gained attention for their potential cardioprotective effects. Therefore, this review aims to explore the molecular mechanisms underlying the cardiovascular benefits of these agents. A literature review was conducted searching PubMed databases from 1990 to January 2025, including research on the effects of GLP-1 RA and DPP-4i on cardiovascular health, specifically concerning atherosclerosis, coronary artery disease, vascular health, cardiac arrhythmias, myocardial infarction (MI), and heart failure, with a focus on the biochemical and molecular effects of these drugs. We analyzed 131 scientific publications, which indicate that GLP-1 RA and DPP-4i significantly reduce cardiovascular risk and major adverse cardiovascular events (MACEs), including atherosclerosis, myocardial infarction, and cardiac arrhythmias. These clinical outcomes are attributed to the mitigation of oxidative stress, inflammation, and endothelial dysfunction as well as improvement in mitochondrial function and lipid metabolism. GLP-1 RAs offer substantial cardiovascular benefits, making them valuable in managing T2DM and reducing CVD risk. Their integration into treatment regimens for CVD can reduce hospitalization rates, improve quality of life, and extend life expectancy. DPP-4is, while beneficial, are less effective in cardiovascular protection. Further research is needed to optimize therapeutic strategies and broaden the clinical application of these agents in cardiometabolic care. Full article

Background: Intracerebral hemorrhage management presents clinicians with a significant therapeutic challenge. Maintaining antiplatelet therapy potentially increases the risk of recurrent bleeding, while discontinuation heightens susceptibility to ischemic stroke, particularly during the critical first month after hemorrhage. In contemporary practice, physicians demonstrate considerable hesitancy regarding early antiplatelet reinitiation, complicated by the absence of clear evidence-based treatment guidelines. Aim: This meta-analysis assesses the safety of early antiplatelet resumption following ICH. Methods: We conducted a systematic review by searching Web of Science, Scopus, PubMed, and Cochrane Library from inception to April 2025. Articles were independently screened and data extracted by two reviewers who also assessed study quality. The inclusion criteria are enrollment of adults (≥18 years) with imaging-confirmed intracerebral hemorrhage surviving >24 h, comparing early vs. delayed or withheld antiplatelet therapy. Randomized trials underwent separate evaluation using Cochrane’s Risk of Bias. Statistical analysis was performed using R software (version 4.4.2), with categorical outcomes pooled as risk ratios (RRs) with 95% confidence intervals. Statistical significance was established at p < 0.05. The evidence is limited by the availability of few RCTs, variable antiplatelet regiments, male predominance, and other confounding factors. The review was registered in SFO. Results: Our meta-analysis included 10 studies (8 observational, 2 RCTs) with 5554 patients. Early antiplatelet therapy significantly reduced recurrent intracerebral hemorrhage by 46% (RR 0.54, 95% CI 0.37–0.78, p = 0.001). All-cause mortality showed a non-significant difference (RR 0.81, 95% CI 0.65–1.01, p = 0.06). No significant differences were found for ischemic stroke (RR 0.99, 95% CI 0.60–1.63, p = 0.96), major hemorrhagic events (RR 0.75, 95% CI 0.49–1.13, p = 0.17), or ischemic vascular outcomes (RR 0.71, 95% CI 0.49–1.02, p = 0.60). Conclusions: Our meta-analysis reveals that early antiplatelet therapy following intracerebral hemorrhage significantly reduces recurrent hemorrhagic events (46% reduction) without increasing major ischemic or hemorrhagic complications. Full article

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by excessive proliferation of one or more myeloid lineages, frequently accompanied by an elevated risk of thrombotic events. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are implicated in numerous inflammatory and vascular pathophysiological processes. In this study, we analyzed the association between selected MMP polymorphisms, rs1799750, rs243865, rs3025058, rs3918242, and rs17576, and thrombotic risk as well as clinical characteristics in patients with MPNs. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Among the polymorphisms analyzed, a statistically significant association was identified between the MMP-9 rs3918242 CT genotype and an increased risk of arterial thrombosis (OR = 4.206, CI 1.337–13.234, p = 0.014). Moreover, rs3918242 CT was associated with thrombotic events (both arterial and venous thrombosis combined), suggesting a potential contributory role in the prothrombotic phenotype observed in MPNs (OR = 3.200, CI 1.110–9.258, p = 0.031). These findings indicate that genetic variation in MMP-9, particularly rs3918242, may serve as a predictive marker for vascular complications in MPN patients. Further studies with larger cohorts are warranted to confirm these associations and to elucidate the molecular mechanisms underlying the contribution of MMP polymorphisms to thrombosis in MPNs. Full article

This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1–27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden. Full article