Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal.

Diabetes is associated with vascular injury and the onset of macrovascular complications. Advanced glycation endproducts (AGEs) and the AGE precursor methylglyoxal (MGO) have been identified as key players in establishing the relationship between diabetes and vascular injury. While most research has focused on the link between AGEs and vascular injury, less is known about the effects of MGO on vasculature. In this review, we focus on the mechanisms linking AGEs and MGO to the development of atherosclerosis. AGEs and MGO are involved in many stages of atherosclerosis progression. However, more research is needed to determine the exact mechanisms underlying these effects. Nevertheless, AGEs and MGO could represent valid therapeutic targets for the macrovascular complications of diabetes.

Superiority of Direct Oral Anticoagulants over Vitamin K Antagonists in Oncological Patients with Atrial Fibrillation: Analysis of Efficacy and Safety Outcomes.

Background and aim. Cancer and atrial fibrillation (AF) may be associated, and anticoagulation, either with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), is necessary to prevent thromboembolic events by reducing the risk of bleeding. The log incidence rate ratio (IRR) and 95% confidence interval were used as index statistics. Higgin's I2 test was adopted to assess statistical inconsistencies by considering interstudy variations, defined by values ranging from 0 to 100%. I2 values of less than 40% are associated with very low heterogeneity among the studies; values between 40% and 75% indicate moderate heterogeneity, and those greater than 75% suggest severe heterogeneity. The aim of this meta-analysis was to compare the safety and efficacy of VKAs and DOACs in oncologic patients with AF. Methods. A meta-analysis was conducted comparing VKAs to DOACs in terms of thromboembolic events and bleeding. A meta-regression was conducted to investigate the differences in efficacy and safety between four different DOACs. Moreover, a sub-analysis on active-cancer-only patients was conducted. Results. A total of eight papers were included. The log incidence rate ratio (IRR) for thromboembolic events between the two groups was −0.69 (p < 0.005). The meta-regression did not reveal significant differences between the types of DOACs (p > 0.9). The Log IRR was −0.38 (p = 0.008) for ischemic stroke, −0.43 (p = 0.02) for myocardial infarction, −0.39 (p = 0.45) for arterial embolism, and −1.04 (p = 0.003) for venous thromboembolism. The log IRR for bleeding events was −0.43 (p < 0.005), and the meta-regression revealed no statistical difference (p = 0.7). The log IRR of hemorrhagic stroke, major bleeding, and clinically relevant non-major bleeding between the VKA and DOAC groups was −0.51 (p < 0.0001), −0.45 (p = 0.03), and 0.0045 (p = 0.97), respectively. Similar results were found in active-cancer patients for all the endpoints except for clinically-relevant non-major bleedings. Conclusions. DOACs showed better efficacy and safety outcomes than VKAs. No difference was found between types of DOACs.

Breast Cancer and Atrial Fibrillation.

This study aims to establish the incidence of atrial fibrillation (AF) in breast cancer (BC) patients, focusing on staging and anti-cancer treatment. A meta-analysis was conducted to investigate the incidence of AF in BC patients and compare this incidence to other cancers. Furthermore, we evaluated the occurrence of AF as an adverse effect of biological therapies vs. non-biological therapies vs. biological therapies + non-biological therapies in BC. Finally, we compared the incidence of AF in early BC and metastatic BC. Thirty studies were included. Twenty-two studies focused on BC, encompassing 166,271 patients. In the BC group, 2.7% of patients developed AF, while in the "all cancer" group, 5.8% of patients developed AF. In addition, there was no difference between different types of therapies (p = 0.61) and between early and metastatic BC (p = 0.57). The type of anti-cancer therapy and the staging of BC does not influence AF's occurrence in this neoplastic disease.

Aortic flow below and visceral circulation during aortic counterpulsation: Evaluation of an in vitro model.

INTRODUCTION: This study aimed to test a computer-driven cardiovascular model for the evaluation of the visceral flow during intra-aortic balloon pump (IABP) assistance. METHODS: The model includes a systemic and pulmonary circulation as well as a heart contraction model. The straight polyurethane tube aorta had a single visceral while four windkessel components mimicked resistance compliance of the brachiocephalic, renal and sub-mesenteric, pulmonary, and systemic circulation. Twelve flow probes were placed in the circuit to measure pressures and flows with the IABP on and off. RESULTS: With the balloon off, the meantime to reach the steady state was 48 ± 16 s; with the balloon on, this figure was 178 ± 20 s. The stability of pressure and flow signals was obtained after 72 ± 11 min. The number of cycles of stability of the system was 93 [86-103]. Measurements were reliable either with samples of 10 or 20 beats. Bland Altman method demonstrated the reliability of measurements. Finally, all measurements were comparable to published in vivo data. CONCLUSION: The presented mock circulation was reliable and gave values with high accuracy both at baseline and during mechanical assistance. This system allows evaluation of the mesenteric flow during IABP, under different clinical/hemodynamic conditions. Nonetheless, its translational potential needs to be further evaluated.

Surgical Risk Factors for Ischemic Stroke Following Coronary Artery Bypass Grafting. A Multi-Factor Multimodel Analysis.

Background: Ischemic stroke after coronary artery bypass (CABG) has been often linked to aortic manipulation during surgery. Objectives: The objective of the study was to estimate the rate of postoperative ischemic stroke within 30 days from CABG by surgical risk factors alone or in combination. Methods: The multinomial propensity score for multiple treatments was used to create six models with a total of 16,255 consecutive patients undergoing isolated CABG. For each model, a different classification variable was used to stratify patients. Results: Balance achieved in all models was substantial, enabling unbiased estimation of the treatment estimand. Both off-pump techniques with (0.009; 95% CI 0.006-0.011) or without proximal anastomoses (0.005; 0.005-0.003), and surgery performed on the beating heart using cardiopulmonary bypass with (0.009; 0.006-0.011) or without proximal anastomoses (0.024; 0.021-0.029) showed a mean stroke estimate significantly lower than the other techniques. Off-pump surgery and on-pump surgery without an aortic cross-clamp yielded nearly equal incidences of stroke (0.012; 0.008-0.015 and 0.018; 0.012-0.023, respectively). Using an aortic cross-clamp significantly increased the stroke estimate (0.075; 0.061-0.088), whereas using a side-biting clamp did not (0.039; 0.033-0.044). The number of aortic touches (0.029; 0.026-0.031) and the number of proximal anastomoses (0.044; 0.035-0.047) did not significantly increase the incidence of stroke. Conclusions: Aortic cross-clamping was found to be the primary cause of post-CABG ischemic stroke. Instead, additional aortic manipulation from a side-biting clamp, on-pump surgery, multiple aortic touches, number of proximal anastomoses, and aortic cannulation were found not to increase the estimate of stroke significantly. Further research on this topic is warranted.

Off-Pump Coronary Artery Bypass Reduces Cardiac Death in Patients with Peripheral Arteriopathy.

OBJECTIVE: The aim of this study was to investigate whether the use of off-pump coronary artery bypass (OPCAB) may enhance early outcomes in subjects with peripheral artery disease (PAD) undergoing coronary artery bypass grafting (CABG). METHODS: We employed a propensity-score (PS) method to compare early postoperative results of OPCAB and on-pump CABG patients with associated PAD. The study population consisted of 1,961 patients: 284 in the OPCAB and 1,677 in the on-pump CABG group. The inverse probability of treatment weighting was used as PS method. RESULTS: The incidence of death (1.2% [95% confidence interval, CI: -0.9 to 3.3%], p = 0.262), stroke (2.2% [95% CI: -1.4 to 5.7%], p = 0.235), acute kidney disease (1.5% [95% CI: -3.8 to 6.8%], p = 0.586), limb ischemia (3.2% [95% CI: -0.6 to 7.0%], p = 0.315), and low output syndrome (1.2% [95% CI: -0.9 to 3.3%], p = 0.262) did not differ between the two groups. On the other hand, the rate of cardiac death (1.2% [95% CI: -0.1 to 2.3%], p = 0.038) was significantly higher in on-pump CABG group. CONCLUSIONS: The OPCAB procedure considerably reduced the occurrence of cardiac death after coronary revascularization. This finding might suggest that the OPCAB procedure should be considered as the first option in patients with higher cardiovascular risk scores. Further research is warranted.

New Biparietal Bipolar Catheter Prototype for Hybrid Atrial Fibrillation Ablation.

OBJECTIVE: To evaluate the size and depth of linear lesions by in vitro testing with a custom-made radio frequency biparietal bipolar ablation catheter in a single-stage setting. METHODS: A custom-made catheter was created to generate linear lesions around the left atrium and pulmonary veins of an ex vivo pig. Two frames were made, 1 epicardial and 1 endocardial. A continuous copper braid electrode and an alignment system consisting of 2 parallel rows of neodymium magnets were embedded in a flexible plastic support. After 24 hours of formalin conservation, samples of the left atrium of a freshly slaughtered pig were sliced in a cryotome, thus obtaining a sequence of 100-µm thick layers extending from the endocardial to the epicardial side. After being digitized through a scanner, these layers were evaluated using morphometric computer software. For each slice, we evaluated the maximum length of the lesions, the maximum epicardial length, the maximum endocardial length, the total area of the lesion, and the total volume. RESULTS: Forty transmural lesions from 40 specimens were obtained. The results were the following (the number in parenthesis is the interquartile range in mm): lesion maximum length (L MAX) was 7.297 mm (0.006), epicardial maximum length (L EPI) was 7.291 mm (0.014), and endocardial maximum length was 7.291 mm (0.018). The total area and total volume were 1018.50 ± 36.51 mm2 and 101.85 ± 3.65 mm3, respectively. CONCLUSIONS: Our prototype showed very promising results. The next step will be to enhance the design for clinical application.

The Impact of Preoperative Inflammatory Markers on the Prognosis of Patients Undergoing Surgical Resection of Pulmonary Oligometastases.

The aim of this study was to assess the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels in patients undergoing resection of pulmonary oligometastases. A retrospective analysis on 141 patients undergoing a first pulmonary metastasectomy in a single center was carried out. Two distinct analysis were performed subdividing patients according to their NLR ratio and CRP level. The main outcomes were survival and time to recurrence. At completion of follow-up 74 patients were still alive (52.5%). Subdividing patients according to their NLR yielded a significant difference in five-year progression-free survival (PFS, NLR < 4:32% vs. NLR ≥ 4:18%, p = 0.01). When subdivided by their CRP levels, patients with preoperative CRP < 5 mg/L demonstrated higher values of five-year overall survival (OS, 57% vs. 34%, p = 0.006) and five-year PFS (35% vs. 22%, p = 0.04). At multivariate analysis, level of neutrophils (p = 0.009) and lung comorbidities (p = 0.021) were independent predictors of death, whereas preoperative CRP (p = 0.002), multiple metastases (p = 0.003) and presence of lung comorbidities (p = 0.001) were independent predictors of recurrence. NLR and CRP are important predictors of prognostic outcome in patients undergoing pulmonary metastasectomy.

The use of both internal thoracic arteries for coronary revascularization increases the estimate of post-operative lower limb ischemia in patients with peripheral artery disease.

BACKGROUND: Patients with a history of peripheral arterial disease (PAD) undergoing coronary artery bypass grafting (CABG) exhibit higher rates of complications. There are conflicting data on the survival benefits for bilateral thoracic artery (BITA) grafting compared with left internal thoracic artery (LITA) CABG in patients with PAD. The aim of the study was to explore the influence of the use of BITA grafts vs. LITA for CABG on post-operative acute lower limb ischemia (ALLI) and main post-operative complications in patients with concomitant PAD. METHODS: We used a propensity-score (PS) based analysis to compare outcomes between the two surgical procedures, BITA and LITA. The inverse probability of treatment weighting PS technique was applied to adjust for pre- and intra-operative confounders, and to get optimal balancing of the pre-operative data. The primary outcome was the estimate of postoperative ALLI. Secondary outcomes included overall death and death of cardiac causes within 30 days of surgery, stroke and acute kidney disease (AKD). RESULTS: The study population consisted of 1961 patients. The LITA procedure was performed in 1768 patients whereas 193 patients underwent a BITA technique. The estimate of ALLI was 14% higher in the BITA compared to the LITA (p < 0.001) group. Thirty-day mortality, cardiac death, occurrence of stroke and AKI did not differ significantly between the groups. CONCLUSIONS: The use of both ITAs led to a significant increase in ALLI. This result was most likely caused by the complete disruption of the ITA collateral providing additional blood supply to the lower extremities. Based on our data, BITA should be used with extreme caution in PAD patients. Further research on this topic is necessary to confirm our findings.

Quantification of Death Risk in Relation to Sex, Pre-Existing Cardiovascular Diseases and Risk Factors in COVID-19 Patients: Let's Take Stock and See Where We Are.

Patients with pre-existing cardiovascular disease (CVD) might be more susceptible to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have higher mortality rates. Nevertheless, the risk of mortality has not been previously quantified. The aim of this meta-analysis is to quantify the risk of mortality in coronavirus disease 2019 (COVID-19) patients. A meta-analysis was conducted analyzing the impact of (1) sex, (2) age, (3) CVD with coronary artery disease (CAD), (4) CAD alone, (5) CVD without CAD, (6) hypertension, (7) cerebrovascular diseases, and (8) diabetes on mortality. Relative risk was assessed for dichotomous variables, mean difference for continuous variables. Twenty-six studies were included, encompassing 8497 patients. Males had 16% higher risk of mortality than females (p < 0.05) and elderly patients had higher chance of dying than younger patients (p < 0.0001). Patients with overall CVD have a 1.96-fold higher mortality risk (p < 0.0001). CAD increases risk of mortality by 1.90-fold (p < 0.05). CVD-CAD were found to increase risk up to 2.03-fold (p < 0.05). Hypertension, cerebrovascular disease and diabetes increase the risk of death up to 1.73-fold, 1.76-fold and 1.59-fold, respectively (p < 0.0001, p < 0.0001, p < 0.05, respectively). Sex, age, presence of CAD and/or other types of CVD, hypertension, cerebrovascular diseases and diabetes mellitus increase mortality in patients with COVID-19.

Clinical and Radiologic Features Together Better Predict Lung Nodule Malignancy in Patients with Soft-Tissue Sarcoma.

We test the hypothesis that a model including clinical and computed tomography (CT) features may allow discrimination between benign and malignant lung nodules in patients with soft-tissue sarcoma (STS). Seventy-one patients with STS undergoing their first lung metastasectomy were examined. The performance of multiple logistic regression models including CT features alone, clinical features alone, and combined features, was tested to evaluate the best model in discriminating malignant from benign nodules. The likelihood of malignancy increased by more than 11, 2, 6 and 7 fold, respectively, when histological synovial sarcoma sub-type was associated with the following CT nodule features: size ≥ 5.6 mm, well defined margins, increased size from baseline CT, and new onset at preoperative CT. Likewise, in the case of grade III primary tumor, the odds ratio (OR) increased by more than 17 times when the diameter of pulmonary nodules (PNs) was >5.6 mm, more than 13 times with well-defined margins, more than 7 times with PNs increased from baseline CT, and more than 20 times when there were new-onset nodules. Finally, when CT nodule was ≥5.6 in size, it had well-defined margins, it increased in size from baseline CT, and when new onset nodules at preoperative CT were concomitant to residual primary tumor R2, the risk of malignancy increased by more than 10, 6, 25 and 28 times, respectively. The combination of clinical and CT features has the highest predictive value for detecting the malignancy of pulmonary nodules in patients with soft tissue sarcoma, allowing early detection of nodule malignancy and treatment options.

Is Peripheral Artery Disease an Independent Predictor of Isolated Coronary Artery Bypass Outcome?

AIM: The aim was to use a propensity score-based analysis to determine the impact of peripheral artery disease (PAD) on early outcomes after coronary artery bypass surgery grafting (CABG) in patients with PAD. METHOD: We conducted a multicentre retrospective analysis of 11,311 consecutive patients who underwent CABG between 1997 and 2017. Patients with previous or concomitant vascular surgery were excluded. The main endpoints were death, stroke, and limb ischaemia requiring percutaneous or surgical revascularisation. Subgroup analyses were performed to test the interaction of PAD with concomitant factors. RESULTS: There was no difference in mortality in patients with and without PAD (p=0.06 and p=0.179, respectively). Patients with PAD had a greater incidence of stroke (p=0.04), acute kidney disease (p=0.003), and limb ischaemia requiring interventions (p<0.001) than those without PAD. The use of off-pump or no-touch aortic techniques did not influence the effect of PAD on the outcomes. Early mortality rate increased in patients with PAD when associated with long cardiopulmonary bypass, cross-clamp times (both p<0.001), and postoperative low cardiac output (p=0.01). CONCLUSIONS: The presence of PAD is associated, independently of other factors, with greater incidence of stroke, acute kidney disease, and limb ischaemia following CABG, irrespective of the technique employed. Operative mortality was greater in patients with PAD only when associated with long cardiopulmonary bypass and aortic cross-clamp times, and low cardiac output.

Are recurrence of ischemic mitral regurgitation and left ventricular reverse remodeling after restrictive annuloplasty ring dependent?

OBJECTIVE: This meta-analysis investigates MR recurrence and degree of left ventricular reverse remodeling (LVRR) in CIMR patients in mitral annuloplasty employing different ring designs. BACKGROUND: The deeper understanding of complex changes caused by chronic ischemic mitral regurgitation (CIMR) have led to new generations of rings that, by maintaining normal 3D annular geometry are supposed to enhance long-term repair durability. METHODS: A meta-analysis of all available reports in literature of MV repair through different ring design was conducted. Meta-regression was performed to investigate the impact of mitral ring characteristics related to flexibility, planarity, symmetry and single type utilized. Twenty studies encompassing a total of 1876 patients were included at the end of the selection process. RESULTS: At meta-regression recurrence of MR was not influenced by the ring employed. Nonetheless, the event rate of MR recurrence in planar rings was 19%. Vs. 11% observed with non-planar rings. Recurrence rate in patients implanted with symmetric rings was 14% whereas it was 7% in asymmetric rings. The non-planar asymmetric IMR-ETlogix showed the lowest recurrence rate (6%). Furthermore, in planar group the reduction of pre- and post-operative LVEDD was - 4%. In the non-planar group, the LVEDD was reduced by 8.6%. In patients implanted with symmetric rings LVEDD reduction was 10.8%. LVRR in the asymmetric group was -5.8%. CONCLUSION: MR recurrence occurred the least with asymmetric rings with less disproportionate asymmetry. In contrast, LVRR occurred at a greater extent in symmetric rings.

Early outcomes following isolated coronary artery bypass surgery: Influence of peripheral artery disease.

BACKGROUND: We carried out a propensity score-based analysis on early outcomes after coronary artery bypass grafting (CABG) in patients with and without peripheral artery disease (PAD). MATERIALS AND METHODS: A total of 11 311 patients undergoing isolated CABG between 1997 and 2017 were included in the study. Patients were divided into two groups based on whether they were affected (n = 1961) or not affected (n = 9350) by PAD. Inverse probability of treatment weighting was employed to reduce confounding preoperative and operative variables. The main endpoints were death, cardiac death, stroke, and limb ischemia requiring percutaneous or surgical revascularization. RESULTS: The excellent balance was obtained, and the groups were very similar. For death and cardiac death, there were no differences between patients with and without PAD (P = .06 and P = .179, respectively). In contrast, PAD patients showed a higher incidence of stroke (P = .04), acute kidney disease (AKD) (P = .003) and limb ischemia requiring intervention (P < .001) than patients without PAD. CONCLUSIONS: The presence of peripheral arterial disease increases the incidence of postoperative stroke, AKD and limb ischemia requiring intervention, independent of patient characteristics, concomitant risk factors, surgical approaches, and techniques. Further larger studies are necessary to confirm our findings.

Clinical outcomes of automated anastomotic devices: A metanalysis.

BACKGROUND AND AIMS: We investigated neurological events, graft patency, major adverse cardiovascular events (MACEs), and mortality at 1 year following coronary artery bypass grafting (CABG) surgery using automated proximal anastomotic devices (APADs) and compared the overall rates with the current literature. METHODS: A systematic review of all available reports of APADs use in the literature was conducted. Cumulative incidence and 95% confidence interval (CI) were the main statistical indexes. Nine observational studies encompassing a total of 718 patients were included at the end of the selection process. RESULTS: The cumulative event rate of neurological complications was 4.8% (lower-upper limits: 2.8-8.0, P < .001; I2 = 72.907%, P = .002; Egger's test: intercept = -2.47, P = 0.16; Begg and Mazumdar test: τ = -0.20, p = 0.57). Graft patency was 90.5% (80.4 to 95.7, P < .001; I2 = 76.823%, P = .005; Egger's test: intercept = -3.04, P = .10; Begg and Mazumdar test: τ = -0.67, P = .17). Furthermore, the overall incidence of MACEs was 3.7% (1.3-10.4, P < .001; I2 = 51.556%, P = .103; Egger's test: intercept = -1.98, P = < .11; Begg and Mazumdar test: τ = -0.67, P = .17). Finally, mortality within 1 year was 5% (3.5-7, P < .001; I2 = 29.675%, P = .202; Egger's test: intercept = -0.91, P = .62; Begg and Mazumdar test: τ = -0.04, P = .88). CONCLUSIONS: APADs do not seem to be correlated with a reduction of either neurological events or mortality. By contrast, these tools showed satisfactory one-year graft patency and a low incidence of MACEs. Further research on this topic is warranted.