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Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins of lower limbs causing a wide range of symptoms and signs with a high prevalence in the general population and with disabling consequences in the most severe forms. The etiology and pathophysiology of CVD is complex and multifactorial, involving genetic, proteomic, and cellular mechanisms that result in changes to the venous structure and functions. Expressions of several genes associated with angiogenesis, vascular development, and the regulation of veins are responsible for the susceptibility to CVD. Current evidence shows that several extracellular matrix alterations (ECM) could be identified and in some cases pharmacologically targeted. This review shows the most up to date information on molecular determinants of CVD in order to provide a complete overview of the current knowledge on this topic. In particular, the article explores the genetic influence, the hormonal influence, ECM imbalance, and histopathology of CVD and the role of endothelial dysfunction in CVD.

Objective: This review aims to analyze biomolecular and cellular events responsible for arterial aneurysm formation with particular attention to vascular remodeling that determines the initiation and the progression of arterial aneurysm, till rupture. Methods: This review was conducted searching libraries such as Web of Science, Scopus, ScienceDirect and Medline. Used keywords with various combinations were: "arterial aneurysms", "biology", "genetics", "proteomics", "molecular", "pathophysiology" and extracellular matrix" RESULTS: There are several genetic alterations responsible of syndromic and non-syndromic disease that predispose to aneurysm formation. ECM imbalance, mainly due to the alteration of vascular smooth muscle cells (VSMCs) homeostasis, overexpression of metalloproteinases (MPs) and cytokines activation, determines weakness of the arterial wall that dilates thus causing aneurysmal disease. Altered mechanotransduction in the ECM may also trigger and sustain anomalous cellular and biochemical signaling. Different cell population such as VSMCs, macrophages, perivascular adipose tissue (PVAT) cells, vascular wall resident stem cells (VWRSCs) are all involved at different levels CONCLUSIONS: Improving knowledge in vascular biology may help researchers and physicians in better targeting aneurysmal disease in order to better prevent and better treat such important disease.

Background The endovascular aneurysm repair (EVAR) is a successful treatment for aorto-iliac aneurysms. The success of EVAR is enhanced by the use of devices that maintain the patency of targeted arteries namely the iliac branch device (IBD) With this study we aimed to evaluate the association between the use of Jotec E-ventus during EVAR with IBD and prognosis in patients with aorto-iliac aneurysms. Methods This is a retrospective, multicentric study enrolling patients referred to our Vascular Surgery Units from January 2015 to January 2020. All patients underwent EVAR with IBD using Jotec E-ventus as bridging stent. Primary endpoint was the development of types I and III endoleaks. Secondary endpoint was the onset of device occlusion with loss of vascular patency. Results We studied 32 patients (mean age 71.7±4.5y). Of these, 25 patients were treated with standard EVAR procedure whereas 7 were treated with isolated IBD due to extension of disease involving iliac bifurcation. Median follow-up lasted 15[IQR11-27] months. During follow-up, incidence rates for endoleaks and occlusion were 3.98(95%CI 0.48-14.41) and 1.99(95%CI 0.05-11.12) per 100 pts/year. Conclusions Jotec E-ventus during EVAR is associated with a low rate of severe complications in a small cohort of patients with aorto-iliac aneurysms.

Several studies showed the association between non-traditional risk factors [proteinuria and estimated Glomerular Filtration Rate (eGFR)] and cardiovascular (CV) and renal outcomes. Nevertheless, the etiologic role of traditional CV risk factors in referred CKD patients is less defined. Herein, we examined the association between smoking habit and CV events, mortality and CKD progression. We undertook an observational analysis of 1306 stage III–V CKD patients. Smoking habit was modeled as a categorical (never, current or former smokers) and continuous (number of cigarettes/day) variable. Mean eGFR was 35.8 ± 12.5 mL/min/1.73 m2. Never, current and former smokers were 61.1%, 10.8% and 28.1%. During a median follow-up of 2.87 years, current and former smokers were at significant risk for CV events (HRs of 1.93 [95% CI, 1.18–3.16] and 1.44 [95% CI, 1.01–2.05]) versus never smokers. Current smokers were at increased mortality risk (HR 2.13 [95% CI, 1.10–4.11]). Interactions were found between former smokers and proteinuria (p = 0.007) and diabetes (p = 0.041) for renal risk, and between current smokers and male gender (p = 0.044) and CKD stage V (p = 0.039) for renal and mortality risk. In referred CKD patients, smoking habit is independently associated with CV events and mortality. It acts as a risk “amplifier” for the association between other risk factors and renal outcomes.

The use of sutureless prostheses has expanded due to their ability to reduce surgical times, thus favoring their implantation in high-risk patients. It is not uncommon that these patients have an ascending aortic aneurysm requiring treatment with a vascular prosthesis; therefore, using a sutureless aortic valve may be associated. To date, however, little is known about the time sequence of this intervention, that is, if sutureless implantation should precede or follow that of the vascular prosthesis.

Diabetes mellitus (DM) affects the biology of multipotent cardiac stem/progenitor cells (CSCs) and adult myocardial regeneration. We assessed the hypothesis that senescence and senescence-associated secretory phenotype (SASP) are main mechanisms of cardiac degenerative defect in DM. Accordingly, we tested whether ablation of senescent CSCs would rescue the cardiac regenerative/reparative defect imposed by DM. We obtained cardiac tissue from nonaged (50- to 64-year-old) patients with type 2 diabetes mellitus (T2DM) and without DM (NDM) and postinfarct cardiomyopathy undergoing cardiac surgery. A higher reactive oxygen species production in T2DM was associated with an increased number of senescent/dysfunctional T2DM-human CSCs (hCSCs) with reduced proliferation, clonogenesis/spherogenesis, and myogenic differentiation versus NDM-hCSCs in vitro. T2DM-hCSCs showed a defined pathologic SASP. A combination of two senolytics, dasatinib (D) and quercetin (Q), cleared senescent T2DM-hCSCs in vitro, restoring their expansion and myogenic differentiation capacities. In a T2DM model in young mice, diabetic status per se (independently of ischemia and age) caused CSC senescence coupled with myocardial pathologic remodeling and cardiac dysfunction. D + Q treatment efficiently eliminated senescent cells, rescuing CSC function, which resulted in functional myocardial repair/regeneration, improving cardiac function in murine DM. In conclusion, DM hampers CSC biology, inhibiting CSCs' regenerative potential through the induction of cellular senescence and SASP independently from aging. Senolytics clear senescence, abrogating the SASP and restoring a fully proliferative/differentiation-competent hCSC pool in T2DM with normalization of cardiac function. ispartof: DIABETES vol:71 issue:5 pages:1081-1098 ispartof: location:United States status: published

BACKGROUND AND AIMS Acute kidney injury (AKI) often occurs in patients undergoing major cardiac surgery with cardiopulmonary bypass (CPB). Despite renal ischemia remains the key trigger, sustained oxidative stress is now acknowledged as a significant contributor. Selenium-binding protein 1 (SEPP1) is an intracellular protein whose blood levels increase in response to systemic cardiovascular and oxidative stress, as well as in the course of chronic kidney injury. METHOD In this pilot prospective study, we measured circulating SEPP1 levels in a cohort of 45 patients undergoing cardiac surgery with CPB in order to test its possible role in predicting the following occurrence of AKI. Serum samples of SEPP1 were collected before CPB (baseline) and at 4, 8 and 12 h after the end of the procedure and measured with a commercially available ELISA kit. RESULTS In the whole cohort, there was a significant statistical trend in SEPP1 levels from baseline to 12 h after CPB [39 (10–45) versus 3263 (1886–5042) ng/mL; P 0.3 mg/dL or an absolute 1.5-fold increase from baseline and/or a reduced urine output ( CONCLUSION Increased SEPP1 levels in patients undergoing CPB may reflect a sustained response to systemic oxidative stress. Such a response becomes more prominent when renal damage is also occurring. Studies on larger and more heterogeneous cohorts are needed to confirm whether SEPP1 may be a candidate as an early and specific biomarker of AKI in this high-risk setting.

Despite increasing improvement in extracorporeal membrane oxygenation (ECMO) technology and knowledge, thrombocytopenia and impaired platelet function are usual findings in ECMO patients and the underlying mechanisms are only partially elucidated. The purpose of this meta-analysis and systematic review was to thoroughly summarize and discuss the existing knowledge of platelet profile in adult ECMO population. All studies meeting the inclusion criteria (detailed data about platelet count and function) were selected, after screening literature from July 1975 to August 2019. Twenty-one studies from 1.742 abstracts were selected. The pooled prevalence of thrombocytopenia in ECMO patients was 21% (95% CI 12.9–29.0; 14 studies). Thrombocytopenia prevalence was 25.4% (95% CI 10.6–61.4; 4 studies) in veno-venous ECMO, whereas it was 23.2% (95% CI 11.8–34.5; 6 studies) in veno-arterial ECMO. Heparin-induced thrombocytopenia prevalence was 3.7% (95% CI 1.8–5.5; 12 studies). Meta-regression revealed no significant association between ECMO duration and thrombocytopenia. Platelet function impairment was described in 7 studies. Impaired aggregation was shown in 5 studies, whereas loss of platelet receptors was found in one trial, and platelet activation was described in 2 studies. Platelet transfusions were needed in up to 50% of the patients. Red blood cell transfusions were administered from 46 to 100% of the ECMO patients. Bleeding events varied from 16.6 to 50.7%, although the cause and type of haemorrhage was not consistently reported. Thrombocytopenia and platelet dysfunction are common in ECMO patients, regardless the type of ECMO mode. The underlying mechanisms are multifactorial, and understanding and management are still limited. Further research to design appropriate strategies and protocols for its monitoring, management, or prevention should be matter of thorough investigations. Electronic supplementary material The online version of this article (10.1007/s00134-020-06031-4) contains supplementary material, which is available to authorized users.

Background Chronic Venous Disease (CVD) has a high prevalence in the western world. Varicose veins (VVs) are the main signs of this disease that is characterized by important pathological vessel wall changes. The aim of this study is to correlate the main histopathological abnormalities with related clinical issues of CVD. Methods A cohort of patients with VVs scheduled for open surgical treatment namely stab avulsion of VVs was recruited. Subsequently, venous tissue from stab avulsion was collected in order to evaluate the following biomarkers: Vascular-Endothelial Growth Factor (VEGF), Protein Gene Product 9.5 (PGP 9.5), Fibronectin (FN), and Matrix Metalloproteinase-9 (MMP-9). The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) criteria were used to classify CVD. Results Fourteen tissue fragments were processed for histological and immunohistochemical studies. Of these, 43% were from CEAP C2 patients, 36% from CEAP C3 patients, and 21% from CEAP C4 patients. CEAP Class C2 had few to moderate structures positive to VEGF; occasional structures positive to Fibronectin, numerous structures positive to MMP9, few to moderate structures positive to PGP 9.5. CEAP Class C3 had moderate structures positive to VEGF; few to moderate structures positive to Fibronectin; many structures positive to MMP9; few to moderate structures positive to PGP 9.5. CEAP Class C4 had numerous structures positive to VEGF; numerous structures positive to Fibronectin; abundant structures positive to MMP-9; few structures positive to PGP 9.5. Conclusions In this study, positive VEGF, FN, and MMP-9 structures were found with increasing trends in relation to the disease staging. VEGF and FN are associated with a progressive increase from C2 to C4. The MMP-9 marker has an important positivity even at early stage of the disease, being higher in CEAP C4 patients. PGP 9.5 decreases in CEAP C4 patients and this is concordant to decreased vein wall innervation.

BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR) should be considered as the preferred treatment modality for infrarenal abdominal aortic aneurysm for patients with suitable anatomy and reasonable life expectancy. Surgical cut-down of both femoral arteries during EVAR procedure is associated with an increased risk of local complications. Therefore, nowadays most EVAR procedures are performed with a totally percutaneous approach. METHODS: Based on the evaluation of the Ankle Brachial Index (ABI) variation, the purpose of this study was to evaluate possible hemodynamic alterations on arterial perfusion of the lower limbs in two different types of access for EVAR procedures: totally percutaneous (p-EVAR) and EVAR with surgical access (s-EVAR). RESULTS: Our study considered 38 patients (36 men, mean age of 70.6±8.3 years) subjected to EVAR procedure between January 1, 2019 and December 31, 2020. The variation in pre- and postoperative ABI values (∆ ABI) and procedure-related complications rate were considered as primary outcomes. The p-EVAR group consisted of 27 patients (92.6% males, mean age of 72.3±8.6) while the s-EVAR group was composed by 11 patients (100% males, mean age of 69±8.1). The follow-up period was ranged from a minimum of 6 to a maximum of 12.3 months. In particular, the pre- and postoperative Δ ABI and the procedure-related complications rate, both considered as primary outcomes, did not show any significant difference between two groups, and in both groups, the technical success rate was 100%. CONCLUSIONS: Pre- and postoperative Δ ABI and the procedure-related complications rate, did not show any significant difference between two groups. We can confirm that percutaneous access is safe, and its use should be encouraged when any contraindication on his employment does not exist.

Background: The efficacy of novel nonvitamin K antagonist oral anticoagulants (NOACs) in nonvalvular atrial fibrillation (AF) to prevent stroke is well assessed, but NOACs use in AF that occurs after bioprosthetic aortic valve replacement (AVR) is not endorsed. This retrospective real-world study evaluated the efficacy and safety of NOACs prescribed no earlier than 4 months after AVR as an alternative to warfarin in patients with AF. Methods: We pooled 1032 patients from the databases of 5 centers. Ischemic/embolic events and major bleeding rates were compared between 340 patients assuming NOACs and 692 prescribed warfarin. Propensity score matching was performed to avoid the bias between groups. Results: The NOACs vs warfarin embolic/ischemic rate was 13.5% (46 of 340) vs 22.7% (157 of 692), respectively, (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.37-0.75; P < .001), and the incidence rate was 3.7% vs 6.9% patients/year, respectively (log-rank test P = .009). The major bleeding rate was 7.3% (25 of 340) vs 13% (90 of 692) (HR, 0.5; 95% CI, 0.33-0.84; P = .007), and the incidence rate was 2% vs 4% patients/year (log-rank test P = .002.) After propensity score matching, the NOACs vs warfarin embolic/ischemic rate was 13.1% (42 of 321) vs 21.8% (70 of 321) (HR, 0.6; 95% CI, 0.4-0.9; P = .02), and the incidence rate was 4.1% vs 6.7% patients/year (log rank test P = .01). The major bleeding rate was 7.8% (25 of /321) vs 13.7% (44 of 321) (HR, 0.5; 95% CI, 0.31-0.86; P = .01), and the incidence rate was 2.4% vs 4.2% patients/year (log-rank P = .01). Conclusions: In a real-word study, NOACs use overcomes the indications provided by guidelines. This study evidenced that NOACs use in patients who developed AF after bioprosthetic AVR was more effective in prevention of thromboembolism and safe in reduction of major bleeding events compared with warfarin.

Nicola Ielapi,1,2,&ast; Michele Andreucci,3,&ast; Umberto Marcello Bracale,4 Davide Costa,1,5 Egidio Bevacqua,6 Nicola Giannotta,1,6 Maria Grazia Bevacqua,7 Giuseppe Filiberto Serraino,7 Pasquale Mastroroberto,7 Michele Provenzano,6 Raffaele Serra1,6 1Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology” at the Department of Surgical and Medical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Department of Public Health and Infectious Disease, Sapienza University of Rome, Rome, Italy; 3Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 4Department of Public Health, Vascular Surgery Unit, University Federico II of Naples, Naples, Italy; 5Department of Law, Economics and Sociology, University Magna Graecia of Catanzaro, Catanzaro, Italy; 6Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Italy; 7Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy&ast;These authors contributed equally to this workCorrespondence: Raffaele SerraDepartment of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy, Email rserra@unicz.itBackground: Venous return in the circulatory system of lower limbs results from the interaction of several mechanisms and reflects the balance between blood inflow and outflow. Blood outflow improves during the lying position especially with leg elevation both in patients with chronic venous disease (CVD) and in healthy subjects in sedentary settings with short-term immobilization. This study evaluated the level of comfort of hospital inpatients, without CVD, lying with a moderate leg elevation during hospital stay.Methods: This was a clinical trial examining 60 consecutive patients referred to vascular surgery, cardiac surgery, and nephrology units. After inclusion, patients were randomly assigned to two groups: A (leg elevation) in which patients were made to lie in the hospital bed with moderate elevation of the legs, and B (no leg elevation) in which patients were made to lie in the hospital bed without leg elevation.Results: The whole population consisted of 40 patients undergoing leg elevation (group A) and 20 without leg elevation (group B). During each day of hospitalization, measurements such as ankle and calf circumference, heart rate, blood pressure, and body temperature were collected. Subjective data such as perceived heaviness in the lower limbs, comfort perception and hours of sleep were also collected. In this study, patients of group A recorded a decrease in calf and ankle circumference (delta in ankle and calf circumference (difference between end of study visit and baseline visit) were significantly decreased in group A vs group B (p< 0.001 for both sides), and patients perceived less leg heaviness and even reported more leg comfort compared to patients of Group B (p< 0.001)). Among patients of group A, the bigger advantage in terms of comfort perception was recorded in patients with 15° leg elevation.Conclusion: Moderate leg elevation during hospital stay seems to effectively improve leg comfort in hospitalized patients.Keywords: venous system, lower limb, circulation, leg elevation, hospital stay, vein symptoms, leg discomfort

Intraoperative temperature regimen usually is planned preoperatively by a "team." Selecting and understanding the impact of the temperature regimen (normothermia, or mild, moderate, or severe hypothermia) usually are related to the type of cardiac surgery (eg, using circulatory arrest or open-heart surgery). Cardiopulmonary bypass constitutes a challenging situation for monitoring temperature because of the rapid and extraordinary degree of heat transferred through the bypass circuit during heating and cooling. The core compartment undergoes the fastest temperature changes because of the rapid rate of blood reinfused into the organs. In modern cardiac surgery, different types and technologies of heater-cooler devices can be used in clinical practice, thanks to the development process that took its cue from past experiences. In this context, the authors review the role of thermal exchange in cardiac surgery and the progress achieved from first-to-second-generation heater-cooler devices.

Background: Aging and Diabetes Mellitus (DM) independently and additively increase cardiovascular risk and a pathophysiological basis for this epidemiological link is currently the subject of intense investigations. Both aging and DM affect the biology and regenerative potential of tissue specific cardiac adult stem/progenitor cells (CSCs). In aged subjects over half of the CSCs are senescent with a senescence-associated secretory phenotype (SASP) that renders otherwise healthy CSCs to senescence, impairing their proliferative and differentiation potential. Although a link to organismal aging is clear, cells can undergo senescence, regardless of age. Yet, it is unclear whether the SASP is induced by Diabetes per se in CSCs and whether targeting senescent cells within the diabetic CSC compartment rescues their regenerative biology. Methods: In order to investigate the effects of DM on CSC senescence and to try separate those of aging from Diabetes on senescence events, we obtained peri-infarct/border zone biopsies from non-aged patients (50-64 years old) with DM type 2 (T2DM) and non-diabetic (NDM) patients with post-infarct cardiomyopathy undergoing surgical coronary revascularization. Results: Ischemic injury in DM is associated with a higher ROS production, as revealed by the exacerbated expression of 8-OH-deoxyguanosine, nitrotyrosine, and 4-hydroxinonenal targeting both cardiomyocytes as well as CSCs. The latter associated with an increased number of senescent and dysfunctional T2DM-hCSCs (isolated from atrial samples of T2DM and NDM patients with ischemic cardiomyopathy) identified by increased p16INK4a positive cells, reduced telomerase activity and telomere length, reduced proliferation, clonogenesis/spherogenesis and myogenic differentiation when compared to NDM-hCSCs in vitro. Importantly, T2DM-hCSCs show a defined SASP, as demonstrated by the increased secretion of MMP-3, PAI1, IL-6, IL-8, IL-1β and GM-CSF. A combination of two senolytics, Dasatinib and Quercetin, clears senescent T2DM-hCSCs in vitro restoring expansion and myogenic differentiation capacities of the diabetic hCSC pool. Conclusions: DM hampers human CSC biology, inducing a variety of hallmarks of senescence in non-aged subjects that contribute to the deficit of their regenerative potential. Clearance of senescent cells by senolytics abrogates the SASP and restores a fully proliferative- and differentiation- competent hCSC pool in T2DM.

Background Much debate is still going on about the best ablation strategy—via endocardial or epicardial approach—in patients with atrial fibrillation (AF), and evidence gaps exist in current guidelines in this area. More specifically, there are no clear long-term outcome data after failed surgical AF ablation. Methods Since June 2008, 549 surgical AF ablation procedures through a right minithoracotomy were performed at our institution. From 2008 to 2011, a unipolar radiofrequency device was used (151 patients), whereas from 2011 to 2020 a bipolar radiofrequency device was used (398 patients). Patients were scheduled for surgery on the basis of the following criteria: recurrent episodes of paroxysmal or persistent lone AF refractory to maximally tolerated antiarrhythmic drug dosing and at least one failed cardioversion attempt. Besides the recommended follow-up by the local cardiologist, starting from 2021, surviving patients were asked to undergo assessment of left ventricular function and to complete a questionnaire addressing quality of life and predisposing factors for recurrent AF. Results At a mean follow-up of 77 months, the rate of AF recurrence was 20.7% (n = 114). On multivariate analysis, impaired left ventricular ejection fraction (58 patients, 51%, p = 0.002), worsening of European Heart Rhythm Association (EHRA) symptom class (37 patients, 32%, p = 0.003) and cognitive decline or depression (23 patients, 20%, p = 0.023) during follow-up were found to be significantly associated with AF recurrence. Conclusions Surgical AF ablation through a right minithoracotomy is safe, but a better outcome could be achieved using a hybrid approach. Patients after initial failed surgical AF ablation show worsening of cardiac function, clinical status and quality of life at follow-up compared to patients with successful AF ablation.

Background Elevated plasma free hemoglobin is associated with multi-organ injury. In this context, minimally invasive extracorporeal technologies represent a way to reduce this complication following cardiac surgery. Methods We present a pilot study focused on plasma free hemoglobin levels in 40 patients undergoing isolated coronary artery bypass grafting (CABG). The same circuits for minimally invasive extracorporeal circulation (MiECC) were used in all patients. The ECMOLIFE magnetic levitation pump was used in the study group (n = 20), and the AP40 Affinity CP centrifugal blood pump was used in the control group (n = 20). Results In the immediate postoperative period, plasma free hemoglobin (PFH) and lactate dehydrogenase (LDH) were significantly lower in the study group than in the control group (10.6 ± 0.7 vs 19.9 ± 0.3 mg/dL, p = 0.034; and 99.16 ± 1.7 vs 139.17 ± 1.5 IU/L, p = 0.027, respectively). Moreover, patients treated with the magnetic levitation pump showed lower creatinine and indirect bilirubin (0.92 vs 1.29 mg/dL, p = 0.030 and 0.6 ± 0.4 vs 1.5 ± 0.9 mg/dL, p = 0.022, respectively) at 24 h after the procedure, and received fewer transfusions during the whole postoperative period (3 vs 9 red blood cell units (RBC), p = 0.017). Conclusion Our pilot study suggests that the use of magnetically levitated centrifugal pumps for extracorporeal circulation support is associated with a lower risk of hemolysis, though larger studies are warranted to confirm our results.

Background and Aims Cardiopulmonary bypass (CPB) may trigger organs damage, including kidney injury, due to a massive cytokine release. In this observational, prospective study, we have analyzed the possible impact of chronic treatment with ACE-Inhibitors (ACE-I) on the inflammatory response and renal function after CPB. Method Sixty-nine patients undergoing major cardiac surgery with CPB were enrolled. Patients were stratified according to long-term (>6 mo.) ACE-I use (n=38) or not (n=31). The primary endpoint was to analyze the changes in their IL-1 alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF alpha, EGF and VEGF plasma levels. Secondary (renal) endpoints were: postoperative acute kidney injury (AKI), recovery of baseline GFR values and the absolute changes in renal function indexes. Results After CPB, IL-1alpha, IL-1beta, IL-4 and TNF-alpha remained stable overtime, while a significant decrease in IL-2 plasma levels was noticed in the ACE-I group (p=0.01). IL-6 and IL-8 plasma levels increased after surgery and tended to decrease after 48h. IL-10 plasma levels showed a similar variation, but both their rise and decrease were more pronounced in patients under ACE-I treatment (p=0.007). Finally, VEGF and EGF showed a marked initial decrease with a tendency to normalization 10 days after surgery (p for trend ranging from 0.01 to 0.001) (Figure 1-2). The occurrence of AKI within 2 days after surgery, the rate of GFR recovery and the absolute changes in renal function indexes were not statistically different between groups (Figure 3). Conclusion Chronic, long-term ACE-I treatment may influence the inflammatory response following CPB. On the other hand, this drug class apparently has neutral impact on perioperative renal outcomes.

Background Acute Kidney Injury (AKI) represents a clinical condition with poor prognosis. The incidence of AKI in hospitalized patients was about 22–57%. Patients undergoing cardiac surgery (CS) are particularly exposed to AKI because of the related oxidative stress, inflammation and ischemia-reperfusion damage. Hence, the risk profile of patients undergoing CS who develop AKI and who are consequently at increased mortality risk deserves further investigation. Methods We designed a retrospective study examining consecutive patients undergoing any type of open-heart surgery from January to December 2018. Patients with a history of AKI were excluded. AKI was diagnosed according to KDIGO criteria. Univariate associations between clinical variables and AKI were tested using logistic regression analysis. Variable thresholds maximizing the association with AKI were measured with the Youden index. Multivariable logistic regression analysis was performed to assess predictors of AKI through backward selection. Mortality risk factors were assessed through the Cox proportional hazard model. Results We studied 158 patients (mean age 51.2±9.7 years) of which 74.7% were males. Types of procedures performed were: isolated coronary artery bypass (CABG, 50.6%), valve (28.5%), aortic (3.2%) and combined (17.7%) surgery. Overall, incidence of AKI was 34.2%. At multivariable analysis, young age (p = 0.016), low blood glucose levels (p = 0.028), estimated Glomerular Filtration Rate (p = 0.007), pH (p = 0.008), type of intervention (p = 0.031), prolonged extracorporeal circulation (ECC, p = 0.028) and cross-clamp (p = 0.021) times were associated with AKI. The threshold for detecting AKI were 91 and 51 minutes for ECC and cross-clamp times, respectively. At survival analysis, the presence of AKI, prolonged ECC and cross-clamp times, and low blood glucose levels forecasted mortality. Conclusions AKI is common among CS patients and associates with shortened life-expectancy. Several pre-operative and intra-operative predictors are associated with AKI and future mortality. Future studies, aiming at improving prognosis in high-risk patients, by a stricter control of these factors, are awaited.

Cardiovascular disease includes health problems related to the heart, arteries and veins and is a significant healthcare problem worldwide. Cardiovascular disease may be acute or chronic and relapses are frequent. Biomarkers involved in this field may help clinicians and surgeons in diagnosis and adequate decision making. Relevant articles searched in the following databases Medline, Scopus, ScienceDirect, were retrieved and analysed. Several biomarkers have been identified and we analyzed those of most importance from a clinical and surgical point of view. Biomarkers can better identify high-risk individuals, facilitate follow-up process, provide information regarding prognosis and better tailor the most appropriate surgical treatment.

Study objective Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO). Design Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020. Setting Patients on ECMO support. Patients Anticoagulation management on ECMO patients. Interventions Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review. Measurements The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcomes were blood-product transfusions, cerebrovascular accidents, mortality on ECMO, ECMO duration, intensive care unit and hospital discharge rates, and in-hospital mortality. Main results Thirty-one trials enrolling 1684 participants were included in the systematic review. Four trials enrolling 547 subjects were included in the meta-analysis. The use of a POC testing device resulted in improved detection of surgical bleeding (RR: 0.68, 95% CI 0.49 to 0.94, I2 = 0%; χ2 test for heterogeneity, P = 0.02). The use of POC-guided algorithms did not affect bleeding (RR:0.78, 95% CI 0.58 to 1.04, I2 = 47%; χ2 test for heterogeneity, P = 0.09), thrombosis events (RR:1.35, 95% CI 0.86 to 2.12, I2 = 37%; χ2 test for heterogeneity, P = 0.19), or ECMO circuit/change (RR:0.90, 95% CI 0.48 to 1.71, I2 = 28%; χ2 test for heterogeneity, P = 0.75). Conclusion Routine use of POC tests did not improve the main clinical outcomes beyond suggesting a diagnosis of surgical bleeding in ECMO patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been studied so far as prognostic factors of cardiovascular diseases. Their role interplayed with endothelial inflammation, has emerged as optimal predictors for major cardiovascular disease events and as prognostic factors for post-procedural outcomes. Methods: A review of the current literature was undertaken to investigate the relationship between NLR and PLR with percutaneous, cardiac surgery, and vascular surgery procedures. Results: Our findings show that perioperative NLR and PLR levels are significantly correlated with patient morbidity and mortality rates. Conclusions: These biomarkers have several attractive characteristics, as they are inexpensive and quickly available, and they can contribute to the early identification of patients at high risk for periprocedural adverse events.

Chronic kidney disease (CKD) is a clinical condition characterized by high morbidity and mortality. Globally, CKD is also increasing in prevalence and incidence. The two principal kidney measures namely estimated glomerular filtration rate (eGFR) and albuminuria have been found to be predictors of renal and cardiovascular (CV) endpoints including peripheral artery disease (PAD). The prevalence of PAD was increased in CKD patients and, particularly, in patients with more severe CKD stages. Despite the fact that revascularization strategies are suitable in CKD patients in similar fashion to non-CKD patients, few CKD patients underwent these procedures. In fact, if it is true that revascularization improves prognosis in PAD patients irrespective of baseline eGFR, it was also demonstrated that CKD patients, who underwent revascularization, were at higher risk for amputations, mortality, re-intervention and perioperative complications. With the present review article, we have examined the association between CKD, PAD and peripheral revascularization highlighting data about epidemiology, pathophysiologic mechanisms, and results from previous observational and intervention studies. We have also examined the future perspectives and challenges of research around the association between CKD and PAD.

Background Shaggy aorta (SA) depicts the severe aortic surface degeneration, extremely friable and likely to cause spontaneous peripheral and visceral embolization or during catheterization, aortic manipulation, surgery or minimally invasive procedures. This study aims to provide the most accurate and up-to-date information on this disease. Methods Potentially eligible studies to be included were identified by searching the following databases: CENTRAL Library, ClinicalTrials.gov , MEDLINE, CINAHL, using a combination of subject headings and text words to identify relevant studies: (Shaggy aorta) OR (aortic embolization) OR (aortic embolism) OR (aortic thrombus) OR (aortic plaque). From a total of 29111 abstracts, and after applying inclusion and exclusion criteria, we considered 60 studies for inclusion in this review. Results Appropriate measurement and assessment of the aortic wall are pivotal in the modern era, in particular when percutaneous procedures are performed, as SA has been identified as an independent risk factor for spinal cord injury, mesenteric embolization, and cerebral infarction after endovascular aortic repair. Furthermore, SA increases the rate of cerebral complications during trans-catheter aortic valve implantation (TAVI). Conclusions In conclusion, prompt diagnosis of SA syndrome and appropriate guidelines on the management of this conditions may help physicians to better assess the patient risk and to minimize the dreadful related complications

Metalloproteinases (MPs) are proteolytic enzymes involved in extracellular matrix deposition, regulation of cellular signals of inflammation, proliferation, and apoptosis. Metalloproteinases are classified into three families: Matrix-MPs (MMPs), A-Disintegrin-and-Metalloprotease (ADAMs), and the A-Disintegrin-and-Metalloproteinase-with-Thrombospondin-1-like-Domains (ADAMTS). Previous studies showed that MPs are involved in the development of aortic aneurysms (AA) and, concomitantly, in the onset of chronic kidney disease (CKD). CKD has been, per se, associated with an increased risk for AA. The aim of this review is to examine the pathways that may associate MPs with CKD and AA. Several MMPs, such as MMP-2, -8, -9, and TIMP-1 have been shown to damage the AA wall and to have a toxic effect on renal tubular cells, leading to fibrosis. Similarly, ADAM10 and 17 have been shown to degrade collagen in the AA wall and to worsen kidney function via pro-inflammatory stimuli, the impairment of the Renin-Angiotensin-Aldosterone System, and the degradation of structural proteins. Moreover, MMP-2 and -9 inhibitors reduced aneurysm growth and albuminuria in experimental and human studies. It would be important, in the future, to expand research on MPs from both a prognostic, namely, to refine risk stratification in CKD patients, and a predictive perspective, likely to improve prognosis in response to targeted treatments.