RSAD2 is abundant in atherosclerotic plaques and promotes interferon-induced CXCR3-chemokines in human smooth muscle cells.

In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs). Silencing RSAD2 in IFN-γ-stimulated hAoSMCs resulted in reduced expression and secretion of key CXCR3-chemokines, CXCL9, CXCL10, and CXCL11. Conditioned medium from RSAD2-deficient hAoSMCs exhibited diminished monocyte attraction in vitro compared to conditioned medium from control cells. Furthermore, RSAD2 transcript was elevated in carotid lesions where it was expressed by several different cell types, including endothelial cells, macrophages and smooth muscle cells. Interestingly, RSAD2 displayed significant correlations with CXCL10 (r = 0.45, p = 0.010) and CXCL11 (r = 0.53, p = 0.002) in human carotid lesions. Combining our findings, we uncover a novel role for RSAD2 in hAoSMCs, which could potentially contribute to monocyte recruitment in the context of atherosclerosis.

Health-related quality of life after Nuss procedure for pectus excavatum: a cross-sectional study.

OBJECTIVES: Pectus excavatum (PE) can cause both physical and psychosocial symptoms and affect patients' health-related quality of life. Previous international studies have shown that the Nuss procedure increases both self-esteem and body image. The aim of the study was to evaluate the health-related quality of life in patients who have undergone the Nuss procedure for PE. METHODS: The study had a cross-sectional multicentre design. All patients (N = 420) who underwent the Nuss procedure for PE in 3 cardiothoracic departments in Sweden from 2000 to 2019 were invited to answer the RAND-36 and Nuss Questionnaire modified for adults. Genders were compared using the Mann-Whitney U-test. Patients were divided into groups based on age at time of surgery (<20, 20-30 or >30 years) and analysed by the Kruskal-Wallis H-test with post-hoc analyses. RESULTS: A total of 236 patients returned the questionnaires; 82.2% were males. Men scored significantly better on the modified Nuss Questionnaire total (P = 0.01) and psychosocial (P = 0.02) subscales. Patients who had surgery at <20 years of age had significantly better scores on the same scales (P = 0.007 and 0.006, respectively) compared to patients aged 20-30 years at the time of surgery. However, no significant difference was seen in comparison with patients >30 years. Patients who had their bar removed had significantly better values on both scales. CONCLUSIONS: Male gender, young age at surgery and bar removal seem to be associated with better health-related quality of life after the Nuss procedure for PE.

Translation and psychometric evaluation of the Swedish versions of the Nuss Questionnaire modified for Adults and the Single Step Questionnaire.

BACKGROUND: Pectus excavatum (PE) is the most common congenital chest wall deformity. Most individuals with PE suffer from psychosocial problems, with low self-esteem and poor body image. Correctional surgery for PE is available, the most widely used is the Nuss procedure. The Nuss procedure has previously been reported to improve self-esteem, body image and health-related quality of life (HRQoL). To assess HRQoL among individuals with PE, the Nuss Questionnaire modified for Adults (NQ-mA) and Single Step Questionnaire (SSQ) has been developed. The aim of the current study was to translate and culturally adapt NQ-mA and SSQ to fit a Swedish context, and to evaluate the psychometric properties, and validate the culturally adapted versions. METHODS: Individuals who had undergone the Nuss procedure for pectus excavatum were invited to participate in a multicentre study with cross-sectional design. HRQoL was assessed by NQ-mA, SSQ and RAND-36. Psychometric properties for NQ-mA and SSQ were evaluated by content validity index and construct validity (exploratory factor analysis, confirmatory factor analysis, and inter-scale correlations). Known-groups validity, as well as floor and ceiling effects, were evaluated. Internal consistency reliability was examined using Cronbach's alpha. RESULTS: In total 236 individuals participated in the study. Content validity index for NQ-mA showed satisfactory results, except for two items. Factor analysis for NQ-mA suggested a two-factor model, with exclusion of two items. Subscales correlated adequately with RAND-36's domains. Known-groups validity for NQ-mA demonstrated high sensitivity for between-group differences. Ceiling effects were present in several items. Cronbach's alpha for NQ-mA was .89. Confirmatory factor analysis for SSQ resulted in a three-factor model, with exclusion of five items. However, this model was shown to be unstable through further exploratory factor analysis testing, and no further psychometric tests were conducted for SSQ. CONCLUSION: The 10-item Swedish version of NQ-mA was shown to be valid for research and clinical assessment of HRQoL in individuals with pectus excavatum. The Swedish version of SSQ requires revision of items before further validation can be performed.

The no-touch saphenous vein is an excellent alternative conduit to the radial artery 8 years after coronary artery bypass grafting: A randomized trial.

BACKGROUND: In 2004, a prospective randomized trial demonstrated that after 3 years, saphenous veins (SVs) harvested with a no touch (NT) technique had a greater patency than radial grafts for coronary bypass surgery. Here we report the 8-year follow-up data of this trial. METHODS: The trial included 108 patients undergoing coronary artery bypass grafting (CABG). Each patient was assigned to receive 1 NT SV and 1 radial artery (RA) graft to either the left or right coronary territory to complement the left internal thoracic artery (LITA). Sequential grafting was common, so overall graft patency as well as the patency of each anastomosis were assessed. RESULTS: Angiography was performed in 84 patients (78%) at mean of 97 months postoperatively. Graft patency were high and similar for both NT and RA: 86% for NT versus 79% for RA (P = .22). The patency of coronary anastomoses was significantly higher with the NT SV grafts (91% vs 81%; P = .046). The NT grafts also had excellent patency in coronary arteries with <90% stenosis (93% patency) and in coronary arteries of small diameter (87% patency) or with mild calcification (88% patency). Patency for the LITA was 92%. CONCLUSIONS: NT SV grafts have excellent patency similar to that of RA grafts after 8 years. In addition, NT SV grafts can be used in situations that are not ideal for RA grafts.

Pedicled versus skeletonized internal thoracic artery grafts: a randomized trial.

OBJECTIVE: Concerns have been raised regarding whether skeletonization of the internal thoracic artery could damage the graft and thereby reduces its patency. The objective of this study was to compare patency rates at mid- and long-term follow-up between pedicled and skeletonized left internal thoracic artery grafts. METHODS: This randomized controlled trial included 109 patients undergoing coronary artery bypass surgery. The patients were assigned to receive either one pedicled or one skeletonized left internal thoracic artery graft to the left anterior descending artery. Follow-up was performed at 3 years with conventional angiography, and at 8 years with computed tomography angiography. Differences between patency rates were analyzed with Fisher's exact test and a generalized linear model. RESULTS: The patency rates for pedicled and skeletonized left internal thoracic artery grafts were 46/48 (95.8%) versus 47/52 (90.4%), p = 0.44 at 3 years, and 40/43 (93.0%) versus 37/41 (90.2%), p = 0.71 at 8 years, respectively. The difference in patency rates for pedicled and skeletonized grafts was 5.4% (95% confidence interval: -4.2-14.5) at 3 years and 2.8% (95% confidence interval: -9.9-14.1) at 8 years. All failed grafts, except for one with a localized stenosis, were anastomosed to native coronary arteries with a stenosis less than 70%. Three patients suffered sternal wound infections (two in the pedicled group, one in the skeletonized group). CONCLUSIONS: The skeletonization technique can be used without jeopardizing the patency of the left internal thoracic artery. The most important factor in graft failure was target artery stenosis below 70%.

No-touch saphenous vein grafts in coronary artery surgery (SWEDEGRAFT): Rationale and design of a multicenter, prospective, registry-based randomized clinical trial.

The SWEDEGRAFT study (ClinicalTrials.gov Identifier: NCT03501303) tests the hypothesis that saphenous vein grafts (SVGs) harvested with the "no-touch" technique improves patency of coronary artery bypass grafts compared with the conventional open skeletonized technique. This article describes the rationale and design of the randomized trial and baseline characteristics of the population enrolled during the first 9 months of enrollment. The SWEDEGRAFT study is a prospective, binational multicenter, open-label, registry-based trial in patients undergoing first isolated nonemergent coronary artery bypass grafting (CABG), randomized 1:1 to no-touch or conventional open skeletonized vein harvesting technique, with a planned enrollment of 900 patients. The primary end point is the proportion of patients with graft failure defined as SVGs occluded or stenosed >50% on coronary computed tomography angiography at 2 years after CABG, earlier clinically driven coronary angiography demonstrating an occluded or stenosed >50% vein graft, or death within 2 years. High-quality health registries and coronary computed tomography angiography are used to assess the primary end point. The secondary end points include wound healing in the vein graft sites and the composite outcome of major adverse cardiac events during the first 2 years based on registry data. Demographics of the first 200 patients enrolled in the trial and other CABG patients operated in Sweden during the same time period are comparable when the exclusion criteria are taken into consideration. RCT# NCT03501303.

Dacron Graft Intussusception Technique for Treatment of Type A Aortic Dissections: Technical Notes and Preliminary Results.

INTRODUCTION: Optimal surgical management for acute type A aortic dissection (AAAD) remains unclear. The in-hospital mortality rate is still high (15%), and the intraoperative bleeding is an independent risk factor for hospital mortality. OBJECTIVE: The aim of our study was describe a new method for aortic anastomosis in the repair of AAAD and report the hospital mortality and bleeding complications. METHODS: Between January 2008 and November 2014, 24 patients, 16 male, median age 62 years, underwent surgical treatment of AAAD. The surgical technique consisted of intussusception of a Dacron tube in the dissected aorta, which is anastomosed with a first line of 2-0 polyester everting mattress suture and a second line of 3-0 polypropylene running suture placed at the outermost side. Open distal anastomosis was performed with bilateral selective antegrade cerebral perfusion in 13 (54.1%) patients. RESULTS: Cardiopulmonary bypass and aortic clamping time ranged from 75 to 135 min (mean=85 min) and 60 to 100 min (mean=67 min), respectively. The systemic circulatory arrest ranged from 29 to 60 min (mean=44.5 min). One (4.1%) patient required reoperation for bleeding, due to the use of preoperative clopidogrel. The postoperative bleeding was 382-1270 ml (mean=654 ml). We used an average of 4.2 units of red blood cells/patient. There were two (8.3%) hospital deaths, one due to intraoperative bleeding and another due to mesenteric ischemia. The average length of stay in the intensive care unit and hospital was 44 hours and 6.7 days, respectively. CONCLUSION: This new method for surgical correction of AAAD was reproducible and resulted in satisfactory clinical outcomes.

Dacron graft intussusception technique for treatment of type a aortic dissections: technical notes and preliminary results

Abstract Introduction: Optimal surgical management for acute type A aortic dissection (AAAD) remains unclear. The in-hospital mortality rate is still high (15%), and the intraoperative bleeding is an independent risk factor for hospital mortality. Objective: The aim of our study was describe a new method for aortic anastomosis in the repair of AAAD and report the hospital mortality and bleeding complications. Methods: Between January 2008 and November 2014, 24 patients, 16 male, median age 62 years, underwent surgical treatment of AAAD. The surgical technique consisted of intussusception of a Dacron tube in the dissected aorta, which is anastomosed with a first line of 2-0 polyester everting mattress suture and a second line of 3-0 polypropylene running suture placed at the outermost side. Open distal anastomosis was performed with bilateral selective antegrade cerebral perfusion in 13 (54.1%) patients. Results: Cardiopulmonary bypass and aortic clamping time ranged from 75 to 135 min (mean=85 min) and 60 to 100 min (mean=67 min), respectively. The systemic circulatory arrest ranged from 29 to 60 min (mean=44.5 min). One (4.1%) patient required reoperation for bleeding, due to the use of preoperative clopidogrel. The postoperative bleeding was 382-1270 ml (mean=654 ml). We used an average of 4.2 units of red blood cells/patient. There were two (8.3%) hospital deaths, one due to intraoperative bleeding and another due to mesenteric ischemia. The average length of stay in the intensive care unit and hospital was 44 hours and 6.7 days, respectively. Conclusion: This new method for surgical correction of AAAD was reproducible and resulted in satisfactory clinical outcomes.

Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel: a nationwide study.

AIMS: Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients. METHODS AND RESULTS: All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012-13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72-120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53-1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72-120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04-2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56-0.92), P = 0.012]. CONCLUSION: The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.

Adiponectin: An Endothelium-Derived Vasoprotective Factor?

Adipose tissue (AT) is now widely accepted as a key secretary organ, as well as an energy storage depot. It secretes a series of cytokines, hormones and bioactive molecules: adipokines. Adiponectin is an abundant systemic adipokine that uniquely is reduced in obesity and increases on weight loss, is anti-inflammatory, promotes insulin sensitivity and affords cardiometabolic protection. It was considered a true adipokine, in that it is exclusively generated by the adipocytes of the adipose tissue. However, recent evidence points to it being secreted by a range of other organs. This review summarizes the non-adipose sources of adiponectin especially that derived from the endothelium, its vasoprotective role and intracellular signalling pathways. Endothelium derived adiponectin may potentially be a new target for clinical intervention in cardiovascular disease.

"No-touch" versus "endo" vein harvest: early patency on symptom-directed catheterization and harvest site complications.

OBJECTIVE: "No-touch" (NT) saphenous vein harvesting preserves the adventitial vasa vasorum, prevents medial ischemia, and is associated with an improved short-term and long-term vein graft patency. It may also be associated with a higher rate of harvest site complications. Endovascular vein harvesting (endo-vein) has a low rate of harvest site complications but also a tendency toward a lower patency rate. METHODS: During a 2-year period (2011-2012), we compared the vein graft patency at symptom-directed cardiac catheterization as well as wound complication rates in 210 patients who received either NT (87 patients) or endo-vein (123 patients). RESULTS: The recatheterization rate for the two groups was similar: 9 (10.3%) of 87 of the NT patients versus 11 (9.0%) of 123 of the endo-vein patients. There was a significant difference in vein graft patency between the groups: 15 (94%) of 16 NT vein grafts were patent versus 6 (27%) of 22 of endo-veins (P < 0.02). The endo-vein graft patency during this 2-year period was similar to the total endo-vein patency (37%) during a 4-year period. A comparison between a more experienced and a less experienced harvester revealed no difference in patency rate. Harvest site complications were significantly higher with the NT harvest: 18% of the NT patients requiring vacuum-assisted wound closure or intravenous antibiotics versus 2% of the endo-vein patients (P < 0.0001). The application of platelet-rich plasma did not significantly lower wound complication rates (P = 0.27). CONCLUSIONS: These results suggest that NT vein harvesting may be associated with improved graft patency, but methods should be developed to lower wound complication rates.

The no-touch saphenous vein as the preferred second conduit for coronary artery bypass grafting.

BACKGROUND: Injury incurred while saphenous veins are being obtained results in poor graft patency and impairs the results of coronary artery bypass grafting. A novel method of obtaining veins, the no-touch technique, has shown improved long-term saphenous vein graft patency. METHODS: This randomized trial included 108 patients undergoing coronary artery bypass grafting and compared the patency of no-touch saphenous vein with that of radial artery grafts. Each patient was assigned to receive one no-touch saphenous vein and one radial artery graft to either the left or the right coronary territory to complement the left internal thoracic artery. RESULTS: Angiography was performed in 99 patients (92%) at a mean of 36 months postoperatively. Graft and grafted coronary artery patency was evaluated. The patency of grafts for no-touch saphenous vein and radial artery was 94% versus 82% (p = 0.01), respectively. The patency of coronary arteries grafted with no-touch saphenous vein and radial artery grafts was 95% versus 84% (p = 0.005), respectively. Eighty-nine of 96 (93%) left internal thoracic artery grafts were patent. CONCLUSIONS: No-touch saphenous vein grafts showed a significantly higher patency rate than the radial artery grafts and the patency was comparable to the patency for left internal thoracic artery grafts. This highlights the improvement in saphenous vein graft quality with the no-touch technique and increases the number of situations in which saphenous veins may be preferable to radial artery grafts as conduits in coronary artery bypass grafting.

The vasa vasorum and associated endothelial nitric oxide synthase is more important for saphenous vein than arterial bypass grafts.

No-touch (NT) saphenous vein (SV) grafts are superior to SVs harvested by the conventional technique (CT), with a patency comparable with the internal thoracic artery (ITA). Preservation of the vasa vasorum is implicated in the success of NT harvesting. We compared the vasa vasorum and endothelial nitric oxide synthase (eNOS) in NT SV with ITA and radial artery (RA) grafts. Skeletonized SV (SSV) was also analyzed. The NT SV had a higher number and larger vasa vasorum compared with ITA (P = .0001) and RA (P = .0004) that correlated with eNOS protein. Activity of eNOS in SSV grafts was significantly lower than NT SV grafts (P = 004). Since a high proportion of the vasa vasorum are removed in SSV using the CT, we suggest that preservation of the vasa vasorum and eNOS-derived NO contributes to the high patency for NT as compared with SSV grafts.

The "no-touch" harvesting technique for vein grafts in coronary artery bypass surgery preserves an intact vasa vasorum.

OBJECTIVES: Our objective was to evaluate the impact of vein graft harvesting technique on structure and function of vasa vasorum. METHODS: Paired segments of great saphenous veins harvested either with conventional harvesting technique or no-touch technique were obtained from 9 consecutive patients undergoing coronary artery bypass grafting. Quantitative measurements, using immunohistochemistry and morphometry, were performed. Ultrastructural analyses of vasa vasorum were performed with electron microscopy. Video footage of superficial vasa vasorum in an implanted saphenous vein graft harvested with the no-touch technique was captured during a coronary bypass operation and is presented for online viewing. RESULTS: The total area of vasa vasorum in vein grafts harvested with the conventional technique was significantly reduced both in the media (P = .007) and in the adventitia (P = .014) compared with vein grafts harvested with the no-touch technique. Ultrastructural findings indicated that the no-touch technique preserved an intact vasa vasorum whereas the conventional technique did not. Video footage showed retrograde flow in the vasa vasorum in vein graft harvested with the no-touch technique. CONCLUSIONS: These findings show that the no-touch technique for saphenous vein graft harvesting for coronary bypass grafting preserves an intact vasa vasorum. This could represent one of the mechanisms underlying the improved patency of saphenous vein grafts harvested with this technique.

Perivascular fat-derived leptin: a potential role in improved vein graft performance in coronary artery bypass surgery.

Perivascular tissue (PVT) surrounding many blood vessels, including those used as bypass conduits, is the source of adipocyte-derived relaxing factors, one of which is leptin. Here, we assessed leptin levels and identified leptin localization in the cushion of fat surrounding 'no-touch-harvested' saphenous veins (SVs) used as grafts in 15 patients undergoing coronary artery bypass surgery (CABG). Leptin protein was identified in perivascular fat (PVF) extracts by Western blot analysis and leptin levels were 2.2 (0.5-4.2) ng/mg protein [mean (range), n=10] as assessed by ELISA. There was dense leptin immunostaining of fat and adipocyte membranes surrounding these no-touch SV grafts. PVT-derived factors are suggested to play an important role in the superior patency rate of the internal thoracic artery used as a bypass graft. Our findings suggest that, as a potent vasodilator, PVF-derived leptin may also play an important role both at harvesting and in the improved long-term performance of no-touch SVs in patients undergoing CABG.