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Background: The inhibition of PCSK9 lowered LDL cholesterol levels, reducing the risk of cardiovascular events. However, the effect on patients who have undergone surgical myocardial revascularization has not yet been evaluated. Methods: From January 2017 to December 2022, 180 dyslipidemic patients who underwent coronary artery bypass were included in the study. Until December 2019, 100 patients optimized therapy with statin ± ezetimibe (SG). Since January 2020, 80 matched patients added treatment with Evolocumab every 2 weeks (EG). All 180 patients were followed-up at 3 and 12 months, comparing outcomes. Results: The two groups are homogenous. At 3 months and 1 year, a significant decrease in the parameter mean levels of LDL cholesterol and total cholesterol is detected in the Evolocumab group compared to the standard group. No mortality was detected in either group. No complications or drug discontinuation were recorded. In the SG group, five patients (5%) suffered a myocardial infarction during the 1-year follow-up. In the EG group, two patients (2.5%) underwent PTCA due to myocardial infarction. There is no significant difference in overall survival according to the new treatment ( p -value = 0.9), and the hazard ratio is equal to 0.94 (95% C.I.: [0.16-5.43]; p -value = 0.9397). Conclusions: The use of Evolocumab, which was started immediately after coronary artery bypass graft surgery, significantly reduced LDL cholesterol and total cholesterol levels compared to statin treatment alone and is completely safe. However, at one year of follow-up, this result did not have impact on the reduction in major clinical events.

Background . The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods . From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022-January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023-July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results . The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group ( p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise ( p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant ( p = 0.26). Conclusions . Evolocumab initiated "as soon as possible" in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

Obesity is a risk factor for the onset of chronic diseases. One of the most promising approaches to treating obesity consists of reducing dietary fat absorption using extracts from plants because they contain phenolic compounds, especially flavonoids. Paliurus spina-christi , belonging to the Rhamnaceae family, is one of the five species belonging to the Paliurus genus. Herein, the aerial parts of the plant were extracted with methanol through the pressurized cyclic solid-liquid extraction using the Naviglio extractor ® . The extracts were analyzed with High Performance Thin Layer Chromatography and investigated for their in vitro biological potential. The phytochemical analysis revealed that rutin has been shown to be the most abundant flavonoid component. The best antiradical activity was observed for the fruit extract with an IC 50 value of 53.41 ± 1.24 µg/mL. This extract also has a better inhibitory capacity on lipid peroxidation evaluated at a different time of incubation. Potent lipase inhibitor activity of the extract from fruits was also demonstrated with in vitro experiments. This property can be attributed to a direct interaction of main components of P. spina-christi extract with the human pancreatic enzyme as demonstrated by the results of molecular docking experiments conducted on the crystallographic structures of lipase., Competing Interests: The authors declare no conflicts of interest.

Background: Vasoplegic syndrome is a form of vasodilatory shock that can occur before, during or after cardiopulmonary bypass (CPB). We introduce a strategy to reduce the incidence of early hypotension phenomena during Coronary Artery Bypass Graft (CABG) procedures., Materials and Methods: In this prospective cohort study, 100 patients underwent elective CABG with two perioperative CPB settings. The study group (50 patients) was managed with retrograde autologous priming (RAP), 3-minute stepwise for the institution of CPB, and pulsatile flow (PP). The control group (50 patients) was managed without RAP, with the rapid initiation of CPB, and non-pulsatile (NP) flow. The primary endpoints were MAP (mmHg), number of hypotensive phenomena (MAP < 50 mmHg for > 30 sec), the venous return volume on CPB (ml), the cardiac index (L/min/m2), hemoglobin (g/dL), indexed oxygen delivery (DO2i, ml/min/m2), the systemic vascular resistance index (SVRI, dynes s m2/cm5), number of 1-ml boluses of a vasoactive substance (norepinephrine), the positive fluid balance (ml), and the number of red blood cell units for transfusion., Results: During CPB, the mean values in the study and control groups were as follows: MAP, 68± 7 vs 56 ± 7 (p-value, 0.0019); hypotensive phenomena, 3 ± 1 vs 8 ±2 (p-value, 0.019); venous return volume, 840±79 vs 1129 ±123 (p-value, 0.0017); cardiac index, 2.4 ± 0.4 vs 2.7 ±0.2 (p-value, 0.0023); hemoglobin, 9.13 ± 0.29 vs 7.8± 0.23 (p-value, 0.0001); DO2i, 301± 12 vs 276±23 (p-value, 0.0011); SVRI, 1879 ±280 vs 2210 ±140 (p-value, 0.0017); norepinephrine, 1±2 vs 8 ±3 (p-value, 0.0023); positive fluid balance, 750 ±212 vs 1450 ±220 (p-value, 0.005); and total number of red blood cell units for transfusion, 16 ±4.2 vs 27 ± 5.3 (p-value, 0.008)., Conclusions: In this prospective cohort study, during CPB, the study group showed a better preservation of MAP, SVRI, and DO2i, and a reduction of vasoconstrictor use in a CPB setting with the RAP technique, 3-minute stepwise for the initiation of CPB and pulsatile pump flow, compared to the control group. Further studies are needed to validate this perioperative approach to CPB.

Infective endocarditis (IE) on atrial septal defect (ASD) closure devices, while extremely rare, has been reported to be more frequent early after the procedure. We describe a case of late IE after percutaneous closure of patent foramen ovale (PFO). We also performed a literature review on this subject. We reviewed a total of 42,365 patients who were treated with percutaneous devices: 13,916 for ostium secundum (OS) (32%), 24,726 for PFO (58%) and 3,723 for OS+PFO (8%). Among these patients, we identified 50 cases of IE after atrial septal defect device closure (0.001%). In contrast to previous reports, nearly 66% of IE in this setting occurred late, after at least 6 months from the procedure (33/50 patients). A statistical analysis clearly showed that the mean time from the procedure to IE increased in the last five years, probably associated with a change in antiplatelet therapy after ASD closure. Management of IE on an ASD occluder should always be discussed in the setting of a multidisciplinary heart team that includes a cardiologist, cardiac surgeon, and anesthetist. While surgical strategies gave excellent results, conservative management might be considered in cases of small IE vegetations and for patients in good general condition. However, in these cases, the patient must be closely observed with repeated blood and instrumental tests.

Glioblastoma is thought to originate from neural stem cells (NSCs) of the subventricular zone that acquire genetic alterations. In the adult brain, NSCs are largely quiescent, suggesting that deregulation of quiescence maintenance may be a prerequisite for tumor initiation. Although inactivation of the tumor suppressor p53 is a frequent event in gliomagenesis, whether or how it affects quiescent NSCs (qNSCs) remains unclear. Here, we show that p53 maintains quiescence by inducing fatty-acid oxidation (FAO) and that acute p53 deletion in qNSCs results in their premature activation to a proliferative state. Mechanistically, this occurs through direct transcriptional induction of PPARGC1a, which in turn activates PPARα to upregulate FAO genes. Dietary supplementation with fish oil containing omega-3 fatty acids, natural PPARα ligands, fully restores quiescence of p53-deficient NSCs and delays tumor initiation in a glioblastoma mouse model. Thus, diet can silence glioblastoma driver mutations, with important implications for cancer prevention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fruits from Buglossoides purpurocaerulea (L.) I. M. Johnst. were extracted with methanol through maceration. The phytochemical composition of obtained raw extract was investigated with gas chromatography-mass spectrometry (GC-MS) and high-performance thin layer chromatography (HPTLC) analyses. The total phenolic and flavonoid contents were also quantified and in vitro antioxidant activity was assessed using the DPPH assay and the β-carotene bleaching test. In order to verify the anti-arthritic potential, the raw extract was evaluated for its anti-denaturation effect on heat-treated bovine serum albumin (BSA), chosen as a protein model. Linoleic and α-linolenic acids were the most abundant identified apolar constituents. HPTLC analyses allowed the identification of rosmarinic acid. The sample showed a concentration-dependent antioxidant activity and it was also proven to be effective in preventing the heat-induced denaturation of BSA, with an IC 50 value equal to 15.7 ± 0.5 µg/mL.

Interesting photobiological properties have been demonstrated for some Cachrys species, including C. libanotis L., C. sicula L., and C. pungens Jan. The present study was designed to assess the photocytotoxic activity of Prangos ferulacea Lindl. (synonym of C. ferulacea (L.) Calest.). This plant was previously considered a Cachrys species but, at present, it is part of the Prangos genus. P. ferulacea is an orophilous plant present in the eastern Mediterranean and in western Asia. Three different extraction techniques were utilized. Obtained extracts were compared both for their phytochemical content and for their photobiological properties on human melanoma cells irradiated with UVA light. The apoptotic responses, together with the antioxidant activity, were also assessed. P. ferulacea extracts were able to affect cell viability in a concentration-dependent manner, with the sample obtained through supercritical CO 2 extraction showing the highest activity (IC 50 = 4.91 μg/mL). This research points out the interesting content in the photoactive compounds of this species, namely furanocoumarins, and could provide a starting point for further studies aimed at finding new photosensitizing agents useful in cancer photochemotherapy.

Objectives: The UEFA 2020 European Football Championship held in multiple cities across Europe from June 11 to July 11, 2021, was won by Italy, providing an opportunity to examine the relationship between emotional stress and the incidence of acute cardiovascular events (ACE)., Methods and Results: Cardiovascular hospitalizations in the Cardiac Care Units of 49 hospital networks in Italy were assessed by emergency physicians during the UEFA Euro 2020 Football Championship. We compared the events that occurred during matches involving Italy with events that occurred during the remaining days of the championship as the control period. ACE was assessed in 1,235 patients. ACE during the UEFA Euro 2020 Football Championship semifinal and final, the most stressful matches ended with penalties and victory of the Italian team, were assessed. A significant increase in the incidence of Takotsubo Syndrome (TTS) by a factor of 11.41 (1.6-495.1, P < 0.003), as compared with the control period, was demonstrated during the semifinal and final, whereas no differences were found in the incidence of ACS [IRR 0.93(0.74-1.18), P = 0.57]. No differences in the incidence of ACS [IRR 0.98 (0.87-1.11; P = 0.80)] or TTS [IRR 1.66(0.80-3.4), P = 0.14] were found in the entire period including all matches of the UEFA Euro 2020 compared to the control period., Conclusions: The data of this national registry demonstrated an association between the semifinal and final of UEFA Euro 2020 and TTS suggesting that it can be triggered by also positive emotions such as the victory in the European Football Championship finals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Polimeni, Spaccarotella, Ielapi, Esposito, Ravera, Martuscelli, Ciconte, Menichelli, Varbella, Imazio, Navazio, Sinagra, Oberhollenzer, Sibilio, Cacciavillani, Meloni, Dominici, Tomai, Amico, Corda, Musumeci, Lupi, Zezza, De Caterina, Cernetti, Metra, Rossi, Calabrò, Murrone, Volpe, Caldarola, Carugo, Cortese, Valenti, Boriani, Fedele, Ventura, Manes, Colavita, Feola, Versaci, Assennato, Arena, Ceravolo, Amodeo, Tortorici, Nassiacos, Antonicelli, Esposito, Favale, Licciardello, Tedesco and Indolfi.)

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.