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To investigate the impact of minor perioperative bleeding requiring transfusion of 1–2 red blood cell (RBC) units on the outcome after coronary artery bypass grafting (CABG). Sixteen cardiac surgical centers contributed to the prospective European CABG registry (E-CABG). 1014 patients receiving 1–2 RBC units during or after isolated CABG were compared to 2264 patients not receiving RBCs. In 827 propensity score matched pairs, transfusion of 1–2 RBC units did not affect the risk of in-hospital/30-day death (p=0.523) or stroke (p=0.804). However, RBC transfusion was associated with an increased risk of acute kidney injury (p=0.008), sternal wound infection (p=0.001), postoperative use of antibiotics (p=0.001), prolonged use of inotropes (p<0.0001), use of intra-aortic balloon pump (p=0.012), length of intensive care unit stay (p<0.0001) and length of in-hospital stay (p<0.0001). Matched paired analysis excluding pre- and postoperative critical hemodynamic conditions showed that RBC transfusion was associated with an increased risk of major complications except in-hospital/30-day death. Minor perioperative bleeding and subsequent transfusion of 1–2 RBC units did not affect the risk of early death, but increased the risk of other major adverse events. Minimizing perioperative bleeding and prevention of even low-volume RBC transfusion may improve the outcome after CABG. •1–2 red cell units did not affect the risk of early death after coronary surgery.•Transfusion was associated with an increased risk of other major adverse events.•-The results persisted after excluding patients with critical hemodynamic conditions.

No data exists on inter-institutional differences in terms of adherence to international guidelines regarding the discontinuation of antithrombotics and rates of severe bleeding in coronary artery bypass grafting (CABG). This is an analysis of 7118 patients from the prospective multicentre European CABG (E-CABG) registry who underwent isolated CABG in 15 European centres. Preoperative pause of P2Y12 receptor antagonists shorter than that suggested by the 2017 ESC guidelines (overall 11.6%) ranged from 0.7% to 24.8% between centres (adjusted P < 0.0001) and increased the rate of severe-massive bleeding [E-CABG bleeding grades 2-3, OR 1.66, 95% confidence interval (CI) 1.27-2.17; Universal Definition of Perioperative Bleeding (UDPB) bleeding grades 3-4, OR 1.50, 95% CI 1.16-1.93]. The incidence of resternotomy for bleeding (overall 2.6%) ranged from 0% to 6.9% (adjusted P < 0.0001), and surgical site bleeding (overall 59.6%) ranged from 0% to 84.6% (adjusted P = 0.003). The rate of the UDPB bleeding grades 3-4 (overall 8.4%) ranged from 3.7% to 22.3% (P < 0.0001), and of the E-CABG bleeding grades 2-3 (overall 6.5%) ranged from 0.4% to 16.4% between centres (P < 0.0001). Resternotomy for bleeding (adjusted OR 5.04, 95% CI 2.85-8.92), UDPB bleeding grades 3-4 (adjusted OR 6.61, 95% CI 4.42-9.88), and E-CABG bleeding grades 2-3 (adjusted OR 8.71, 95% CI 5.76-13.15) were associated with an increased risk of hospital/30-day mortality. Adherence to the current guidelines on the early discontinuation of P2Y12 receptor antagonists is of utmost importance to reduce excessive bleeding and early mortality after CABG. Inter-institutional variation should be considered for a correct interpretation of the results in multicentre studies evaluating perioperative bleeding and use of blood products.

It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and 5 specific risk scores for early mortality after surgery for IE—(1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intracardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intracardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l’Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa)—was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley–McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. A total of 1,012 patients from 5 European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs 0.693 or less, P = .01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than 5 established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration. [Display omitted]

Abstract Objectives We aimed to assess the long-term survival following surgical repair because of acute type A aortic dissection (ATAAD) and the correlation with the preoperative GERAADA (German Registry for Acute Type A Aortic Dissection)-score value. Methods We enrolled patients who underwent emergent aortic surgery because of ATAAD from 2010 to 2022 from 9 hospitals. Follow-up information was obtained by matching the clinical patient data with a national administrative database. Discrimination and calibration of GERAADA were tested at 1, 2, 5, and 10 years. The relationship between long-term outcome and score was also tested through time-to-event methods. Results A total of 1110 patients were analysed: Median age was 67 years [IQR 57-75], and 30.8% of subjects were female. Median GERAADA score was 14.3% [10.2-22]. Mean length of follow-up was 4.19 years. The Kaplan-Meier estimates of survival at 5 and 10 years were, respectively, 62.5% ± 1.5%, and 48.5% ± 2.1%. Discrimination was poor but remained stable over the time (area under the curve [AUC] at 1-year follow-up: 0.66; 95% CI 0.63-0.70. AUC at 10-year follow-up: 0.64; 95% CI 0.61-0.68). Calibration plots showed underprediction until 50%-predicted probability and progressive overprediction afterward. There is a steep mortality in the first couple of months after surgery while afterward the mortality rate is constantly lower. GERAADA score was found to be a predictor of long-term mortality with a nonlinear association. Conclusions GERAADA score showed a poor performance in predicting long-term survival. Acute type A aortic dissection (ATAAD) is a life-threatening condition and emergency surgical treatment is still the gold standard, also if burdened by a high perioperative mortality risk. Graphical abstract

Objectives: The aim of the present study was to evaluate the risk of late mortality and major adverse cardiovascular and cerebral events after coronary artery bypass grafting (CABG) in patients with prior percutaneous coronary intervention (PCI). Methods: A total of 2948 patients undergoing isolated CABGs were included in a prospective multicenter registry. Outcomes were adjusted for multiple covariates in logistic regression, Cox proportional hazards analysis and competing risk analysis. Results: In all, 2619 patients fulfilled the inclusion criteria of this analysis. Of them, 2199 (79.1%) had no history of PCI and 420 (20.9%) had a prior PCI. An adjusted analysis showed that a single prior PCI and multiple prior PCIs did not increase the risk of 30-day and 5-year mortality. Patients with multiple prior PCIs had a significantly higher risk of 5-year myocardial infarction (SHR 2.566, 95%CI 1.379–4.312) and repeat revascularization (SHR 1.774, 95%CI 1.140–2.763). Similarly, 30-day and 5-year mortality were not significantly increased in patients with prior PCI treatment of single or multiple vessels. Patients with multiple vessels treated with PCI had a significantly higher risk of 5-year myocardial infarction (SHR 2.640, 95%CI 1.497–4.658), repeat revascularization (SHR 1.648, 95%CI 1.029–2.638) and stroke (SHR 2.215, 95%CI 1.056–4.646) at 5-year. The risk for repeat revascularization was also increased with a prior single vessel PCI, but not for other outcomes. Conclusions: Among patients undergoing CABGs, multiple prior PCIs seem to increase the risk of late myocardial infarction and the need for repeat revascularization, but not the risk of mortality.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in industrialized countries. Coronary artery disease (CAD) represents the most prevalent form of cardiovascular disease and remains a leading cause of morbidity, mortality, and long-term disability worldwide. Therefore, the identification of early biomarkers and clarification of the mechanism of action of pharmacological adjuvants is urgently needed. Nutraceuticals such as Arthrospira platensis (commonly known as spirulina) have emerged as promising modulators for their notable vascular anti-inflammatory properties. In this study, we provide novel evidence of the anti-inflammatory and anti-atherosclerotic potential of Arthrospira platensis toward endothelial cells and immune interactions, combining in vitro assays with bioinformatic profiling. Spirulina treatment significantly attenuated endothelial and angiogenic activation, reducing pro-inflammatory cytokine and VEGFA/VEGFR2 expression. Additionally, it also decreased the activation and adhesion capabilities of THP-1 monocytic cell lines. Through computational analysis of the complex molecular mixture present in Arthrospira platensis, we have identified a subset of compounds exhibiting high structural similarity to CHEMBL3559503, a well-characterized synthetic molecule with dual activity as a TLR9 agonist and anti-angiogenic agent. This represents a novel insight, suggesting that spirulina may serve as a natural source of analogues capable of modulating both immune and angiogenic pathways. These results highlight Arthrospira platensis as a promising candidate nutraceutical for targeting endothelial/immune crosstalk in the context of atherosclerosis prevention, offering both mechanistic insights and translational potential.

Coronary Artery Disease (CAD), mainly due to the progressive development of atherosclerotic plaques, is one of the world’s leading causes of mortality and morbidity. A significant percentage of initial events (around 30%) remain fatal to this day despite significant advances in the diagnosis and treatment of cardiovascular diseases (CVDs). Early detection and risk stratification are therefore essential. In this study, we adopted a multi-omics approach integrating transcriptomic (RNA-seq) and epigenomic (ATAC-seq) profiling of peripheral blood mononuclear cells (PBMCs) from a cohort of individuals undergoing clinically indicated cardiac computed tomography angiography (CCTA) to uncover potential novel molecular markers of CAD. We identified 39 genes consistently dysregulated across all CAD subtypes. ATAC-seq analysis revealed distinct chromatin accessibility patterns at CAD-associated loci, with a predominance of quiescent and transcriptionally active states. Validation in an independent cohort confirmed the expression patterns of key Differentially Expressed Genes (DEGs), such as Claudin 18 (CLDN18), supporting the robustness of our findings. Consequently, the integration of multi-omics data allowed us to identify a core gene signature and regulatory patterns associated with disease severity, offering potential biomarkers for clinical risk stratification in patients with CAD.

Background Colon cancer and pancreatic ductal adenocarcinoma are among the most aggressive tumors for which therapeutic options are limited. Both cancers share common features, such as some KRAS pathogenic variants and common epidemiology. The integration of multidimensional datasets by combining machine learning and bioinformatics approaches could provide deeper insights into the intricate KRAS‐related networks underlying cancer progression and unveil novel biomarkers and potential therapeutic targets. This study aimed to uncover colon and pancreatic cancers that shared transcriptional changes closely related to KRAS missense mutations. Methods Feature Selection (FS) technique and Qiagen's Ingenuity Pathway Analysis (IPA) were used to combine DNA‐Seq and RNA‐Seq data from mutant and wild‐type (WT) KRAS colon and pancreatic tumor samples. Results From the FS, we prioritized 70 genes (54 protein‐coding genes and 16 ncRNA‐coding genes) that were able to discriminate between WT and mutated KRAS patients. These genes were involved in KRAS signaling and other related processes, such as EMT signaling, glycolysis, apical junction, Wnt/beta‐catenin signaling, and IL‐2/STAT5 signaling. Using IPA, we identified a top‐scoring network of 19 upregulated genes in both tumor types stratified into mutant KRAS and WT KRAS samples. For a set of genes, qRT–PCR performed on colon and pancreatic representative cancer cell lines showed concordant expression trends when comparing colon‐dominant KRAS mutants versus WT KRAS and dominant pancreatic KRAS mutants versus WT KRAS, as expected according to in silico analyses. Conclusions Our findings may provide insight into the common transcriptional signatures potentially underlying colon and pancreatic KRAS‐mutant cancers. However, further studies are needed to elucidate the diagnostic and prognostic value of targets identified as common features in our study.

IntroductionThe use of Stereotactic Body Radiotherapy (SBRT) is controversial in Ultra-Central lung tumors, a subset of central lung tumors characterized by proximity to critical mediastinal structures. This is of interest in oligometastatic (≤3 metastases) patients, who can yield survival benefit from local treatments. The aim of our study is to assess the determinants of efficacy and toxicity in this setting.Materials and methodsClinical and dosimetric parameters were reviewed in a cohort of oligometastatic patients treated with SBRT for ultra-central tumors. Local control rate (LC) and toxicity were assessed. Statistical Analysis was carried out to assess the impact of those predictors on local recurrence and adverse events.ResultsOne-hundred-nine consecutive patients were included. A median Biologic Effective Dose (BED) of 105 (75–132) Gy10 was prescribed. At a median follow-up of 17 (range 3–78) months, 2-year LC was 87%. Improved LC was correlated to Planning Treatment Volume (PTV) covered by 95% of the prescription dose (V95% PTV) > 85% (HR 0.15, 95%CI 0.05–0.49, p = 0.0017) and to Gross Tumor Volume (GTV) < 90 cm3 (HR 0.2, 95%CI 0.07–0.56, p = 0.0021). Overall and grade ≥ 3 toxicity incidence was 20% and 5%, respectively. Patients experiencing acute and late toxicities received significantly higher dose to 1 cm3 (D1cm3) of esophagus and lung volume receiving ≥5 Gy (V5Gy) (p = 0.016 and p = 0.013), and higher dose to 0.1 cm3 (D0.1cm3) of heart (p = 0.036), respectively.Conclusion V95% PTV > 85% and GTV < 90 cm3 are independent predictors of LC. Dose to esophagus, lung and heart should be carefully assessed to minimize treatment-related toxicities.

Posidonia oceanica is an endemic seagrass of the Mediterranean Sea, forming extensive meadows and providing valuable ecosystem services underwater as well as on the shore. P. oceanica constantly generates new leaves while shedding the older ones. The latter may be deposited on the shoreline, forming “banquettes” that exhibit variable thickness, ranging from a few centimeters to several meters. These deposits act as natural barriers against coastal erosion, preventing sand loss and dissipating wave energy. Moreover, the degradation of the washed-up leaves releases large amounts of nutrients, relevant for the coastal food web. However, the presence of banquettes in touristic areas is often perceived as a nuisance, thus leading to their removal by local administrations. This study proposes a multidisciplinary approach for the assessment of P. oceanica banquettes along the coastline of the Campania region (Southern Italy), estimating their biomass and the associated concentrations of nutrients and other chemical elements, with the final aim to assess the potential loss of natural capital and ecosystem services due to their removal. Regional estimates show that approximately 40 tons of C are stored annually in the beached biomass, representing a potential carbon loss associated with their removal. The results highlight the crucial role that P. oceanica banquettes play in the blue carbon cycle and provide valuable insights to support their sustainable management.