Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability

An Alternative Technique to Achieve Haemostasis During PEVAR Using Perclose ProGlide

Introduction: Percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) using the Perclose ProGlide suture mediated closure device is currently performed on a global scale. A safe, effective, and cheap technique for achieving haemostasis during PEVAR is described that allows the reversible downsizing of the arteriotomy, without using any other devices. Technique: The procedure consists of pulling the blue thread of the pre-implanted ProGlide, advancing the knot close to the arterial wall by pushing it with the dilator of a small introducer sheath, and maintaining the system under tension by grasping the end of the blue thread with a haemostat until bleeding control is achieved. Discussion: Seventeen PEVAR femoral access downsizing procedures have been performed between February and June 2018 and no complications were observed. The technique could be useful in everyday practice and has now become the author's standard practice. Keywords: PEVAR, Femoral artery access downsizin

Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability

Intra-QT Spectral Coherence as a Possible Noninvasive Marker of Sustained Ventricular Tachycardia

Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the q wave to the T wave peak (QTp) and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the QTp-Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without (0.508±0.150 versus 0.607±0.150, P<0.05). Although the responsible mechanism remains conjectural, the QTp-Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias

One-year experience in carotid endarterectomy combining general anaesthesia with preserved consciousness and sequential carotid cross-clamping

Background and aim of the work: We report 1-year single-centre experience in carotid endarterectomy (CEA) combining general anaesthesia with preserved consciousness (GAPC) and standardized carotid sequential cross-clamping, for our protocol effectiveness evaluation in reduction of perioperative stroke, death or cardiologic complications. Methods: We considered all patients who underwent CEA in 2016. All patients underwent superficial cervical plexus block and GAPC with Remifentanil. The surgical technique consisted of common carotid artery (CCA) cross-clamping, carotid bifurcation isolation, external (ECA) and internal carotid artery (ICA) cross-clamping. After CCA cross-clamping, we performed a neurological tolerance test (NTT); this allowed selective shunting only for positive NTT. Primary end-points were: transient ischemic attack (TIA)/stroke, myocardial infarction, death in perioperative period. Secondary end-points were: carotid shunting, peripheral cranial nerves injuries (PCNI), GAPC intolerance, other complications, reintervention in perioperative period, length of hospital stay. Results: 104 consecutive patients underwent CEA with this protocol in the considered period. Twenty-seven (25.9%) patients were symptomatic. Mean clamping time was 48±13.5 minutes. Five cases (4.8%) requested internal carotid artery shunting. No TIA/stroke, myocardial infarction or death were recorded in the perioperative period. PCNI were observed in 19 cases (18.2%) in the immediate post-operative period; 16 of them (84.2%) showed complete or partial resolution at discharge. Only one patient (0.9%) showed GAPC intolerance. No other complication occurred. Three patients (2.9%) underwent reintervention for neck haematoma drainage. Mean hospital stay were 3±0.9 days. Conclusions: GAPC associated with sequential carotid cross-clamping appeared to be safe and effective in prevention of major neurological and cardiologic complications during CEA

Accumulation and erosion of Mars' south polar layered deposits

International audienceMars' polar regions are covered with ice-rich layered deposits that potentially contain a record of climate variations. The sounding radar SHARAD on the Mars Reconnaissance Orbiter mapped detailed subsurface stratigraphy in the Promethei Lingula region of the south polar plateau, Planum Australe. Radar reflections interpreted as layers are correlated across adjacent orbits and are continuous for up to 150 kilometers along spacecraft orbital tracks. The reflectors are often separated into discrete reflector sequences, and strong echoes are seen as deep as 1 kilometer. In some cases, the sequences are dipping with respect to each other, suggesting an interdepositional period of erosion. In Australe Sulci, layers are exhumed, indicating recent erosion

Secondary endovascular procedures improve overall patency and limb salvage in patients undergoing in situ saphenous vein infragenicular bypass

BACKGROUND: Secondary interventions strongly improves patency and limb salvage rates in patients undergoing infrainguinal vein bypass. The aim of this study was to evaluate the influence of secondary endovascular procedures performed during the follow-up on patency and limb salvage in patients with critical limb-threatening ischemia (CLTI) undergoing in situ saphenous vein infragenicular bypass. METHODS: From January 2018 to December 2019 541 patients in 43 centers have been enrolled into the LIMBSAVE registry (treatment of critical Limb IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique). In all patients a strict surveillance program with Duplex scan was established (1, 3, 6, 9, 12, 18, 24 months). During the follow-up indications for endovascular procedures were anastomotic stenoses, improvement of run-in (iliac stenosis) or run-off (tibial vessels' stenoses or occlusions). Two-year estimated outcomes in terms of overall patency, and limb salvage were analyzed by life-table analysis (Kaplan-Meier test). Outcomes obtained in patients undergoing endovascular procedure (Group-endo) were compared by means of Gehan-Breslow-Wilcoxon Test with those obtained in patients with no secondary RESULTS: Two groups were homogeneous in terms of demographics and intraprocedural details. Overall mean duration of follow-up was 12.1 months (range 1-24). During the follow-up period (&gt;30 days) 55 endovascular procedures were performed in 49 patients (9.1%) (Group-endo). Most of endovascular procedures (37/55, 67.3%) was performed to treat stenoses at proximal or distal anastomosis. Secondary endovascular procedures (40/55, 72.7%) were predominantly performed within 6 months from the index procedure. Estimated 2-year overall patency (97.9% vs. 85.2%, P=0.05), and limb salvage (100% vs. 93.9%, P=0.05) rates were significantly better in Group-endo. CONCLUSIONS: Secondary endovascular procedures in patients with CLTI undergoing in situ saphenous infragenicular bypass significantly improve the rates of overall patency and limb salvage in the mid-term period. improve overall patency and limb salvage in patients undergoing in situ saphenous vein infragenicular bypass. J Cardiovasc Surg 2023;64:430-6. DOI

Factors Affecting Patency of In Situ Saphenous Vein Bypass: Two Year Results from LIMBSAVE (Treatment of critical Limb Ischaemia with infragenicular Bypass adopting in situ SAphenous VEin technique) Registry

objective: the aim was to demonstrate contemporary outcomes of in situ saphenous vein bypass using a valvulotome.methods: analysis of two year outcomes of a multicentre registry based on the treatment of critical limb ischaemia with infragenicular bypass adopting in situ SAphenous VEin technique (LIMBSAVE). Between January 2018 and december 2019, 541 patients in 43 centres were enrolled. In all patients an innovative valvulotome was used. early outcomes were assessed. two year outcomes according to KaplaneMeier curves in terms of patency and limb salvage were evaluated. Associations between patient and procedure variables were analysed with univariable and multivariable analyses.results: In all cases, a valvulotome was able to lyse the valves. vein injury due to the in situ technique was 3.5%. Thirty day mortality and major amputation rates were 3% and 0.9%, respectively. Mean follow up was 12.1 months. Two year estimated primary patency, primary assisted patency, secondary patency, and limb salvage were 69.1%, 81.4%, 86.5%, and 94.5%, respectively. multivariable analysis showed an association between pre-operative vein diameter &lt; 3 mm and lower primary patency (hazard ration [HR] 14.3, p &lt;.001), primary assisted patency (HR 9.4, p = .002), secondary patency (HR 7.2, p =. 07), and limb salvage (HR 7.8, p = .005) rates. distal anastomosis to a tibial or foot vessel was also associated with lower primary patency (HR 4.8, p = .033), and primary assisted patency (HR 6, p = .011) rates. Use of a suprafascial tributary collateral as a graft was associated with lower primary patency (HR 6.7, p = .013), and primary assisted patency (HR 4.2, p = .042) rates.conclusion: vein diameter &lt; 3 mm, distal anastomosis on a tibial or foot vessel, and use of a suprafascial tributary collateral as a graft were significantly associated with loss of patency and limb loss during follow up

Adapted Physical Activity for the Promotion of Health and the Prevention of Multifactorial Chronic Diseases: the Erice Charter

The Erice Charter was unanimously approved at the conclusion of the 47th Residential Course "Adapted Physical Activity in Sport, Wellness and Fitness: New Challenges for Prevention and Health Promotion", held on 20-24 April 2015 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health. After an intense discussion the participants identified the main points associated with the relevance of physical activity for Public Health, claiming the pivotal role of the Department of Prevention in coordinating and managing preventive actions. The participants underlined the importance of the physicians specialized in Hygiene, Preventive Medicine and Public Health. The contribution of other operators such as physicians specialized in Sport Medicine was stressed. Further, the holders of the new degree in Human Movement and Sport Sciences were considered fundamental contributors for the performance of physical activity and their presence was seen as a promising opportunity for the Departments of Prevention. Primary prevention based on recreational physical activities should become easily accessible for the population, avoiding obstacles such as certification steps or complex bureaucracy. The Sport Doctor is recognized as the principal referent for preliminary physical evaluation and clinical monitoring in secondary and tertiary prevention actions based on adapted physical activities. Developing research in the field is essential as well as implementing higher education on physical activity management in Schools of Public Health

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen