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- Anttila, V., et al.
(författare)
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Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
- 2023
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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- Barbu, Mikael, et al.
(författare)
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Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial
- 2022
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:4, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery. Methods: Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood–brain barrier injury marker β-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients’ age, operation time, and degree of hemolysis. Results: No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th–75th percentile 327%−702%), NfL +57% (28%−87%), S100B +1145% (783%−2158%), GFAP +17% (−3%−43%), NSE +168% (106%−228%), while β-trace protein was reduced (−11% (−17−3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis. Conclusion: Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood–brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome. © 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.
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- Bengmark, S., et al.
(författare)
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NEUESTER STAND DER LEBERCHIRURGIE
- 1982
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Ingår i: Zentralblatt fur Chirurgie. - 0044-409X. ; 107:12, s. 689-696
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Tidskriftsartikel (refereegranskat)
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- Deb, S., et al.
(författare)
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SUPERIOR SVG: no touch saphenous harvesting to improve patency following coronary bypass grafting (a multi-Centre randomized control trial, NCT01047449)
- 2019
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSingle centre studies support No Touch (NT) saphenous vein graft (SVG) harvesting technique. The primary objective of the SUPERIOR SVG study was to determine whether NT versus conventional (CON) SVG harvesting was associated with improved SVG patency 1year after coronary artery bypass grafting surgery (CABG).MethodsAdults undergoing isolated CABG with at least 1 SVG were eligible. CT angiography was performed 1-year post CABG. Leg adverse events were assessed with a questionnaire. A systematic review was performed for published NT graft patency studies and results aggregated including the SUPERIOR study results.ResultsTwo hundred and-fifty patients were randomized across 12-centres (NT 127 versus CON 123 patients). The primary outcome (study SVG occlusion or cardiovascular (CV) death) was not significantly different in NT versus CON (NT: 7/127 (5.5%), CON 13/123 (10.6%), p=0.15). Similarly, the proportion of study SVGs with significant stenosis or total occlusion was not significantly different between groups (NT: 8/102 (7.8%), CON: 16/107 (15.0%), p=0.11). Vein harvest site infection was more common in the NT patients 1month postoperatively (23.3% vs 9.5%, p<0.01). Including this study's results, in a meta-analysis, NT was associated with a significant reduction in SVG occlusion, Odds Ratio 0.49, 95% Confidence Interval 0.29-0.82, p=0.007 in 3 randomized and 1 observational study at 1year postoperatively.ConclusionsThe NT technique was not associated with improved patency of SVGs at 1-year following CABG while early vein harvest infection was increased. The aggregated data is supportive of an important reduction of SVG occlusion at 1year with NT harvesting.Trial registrationNCT01047449.
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