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With exercise at pre-randomisation (P2-P1) there was no significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to -0.014, p less then 0.0001; -0.016, 95% CI -0.024 to -0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions. Conclusions Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.Protein C (PC) activity tests are routinely performed in a thrombophilia workup to screen for PC deficiency. Currently used tests combine conversion of PC to activated PC (APC) by the snake venom Protac with subsequent APC detection through hydrolysis of a chromogenic peptide substrate or prolongation of a clotting time. In this prospective cohort study, we analyzed how different modes of PC activation and subsequent APC determination influence the diagnostic accuracy of PC activity testing in a cohort of 31 patients with genetically confirmed PC deficiency. In addition to chromogenic and clot-based measurement, an oligonucleotide-based enzyme capture assay utilizing a basic exosite-targeting aptamer was used for APC detection. To study the influence of the PC activation step on diagnostic sensitivity, PC activation through Protac and through the thrombin-thrombomodulin (TM) complex were compared. Twenty-six (84%) and 24 (77%) PC deficient patients were identified as true-positive using the chromogenic and the clot-based PC activity assay, respectively. True-positive results increased to 27 (87%) when the basic exosite-targeting aptamer approach was used for APC measurement. Additional replacement of the PC activator Protac by thrombin-TM gave true-positive results in all patients. These data indicate that the mode of PC activation is crucial in determining the accuracy of PC activity testing and that diagnostic sensitivity can be significantly improved by replacing the PC activator Protac with thrombin-TM. APC detection using a basic exosite-targeting aptamer achieves high sensitivity toward mutations outside the active center while being less subject to interfering factors than clot-based PC activity assays.Background Postoperative pneumonia (POP) is a frequent complication following cardiac surgery, related to increased morbidity, mortality and healthcare costs. The objectives of this study were to investigate the risk factors associated with POP in adults undergoing elective cardiac surgery and to develop and validate nomogram models. Methods We conducted a multicenter retrospective study in four cardiac centers in China. Adults operated with elective open-heart surgery from 2016 to 2020 were included. Patients were randomly allocated to training and validation sets by 73 ratio. Demographics, comorbidities, laboratory data, surgical factors, and postoperative outcomes were collected and analyzed. Risk factors for POP were identified by univariate and multivariate analysis. Nomograms were constructed based on the multivariate logistic regression models and were evaluated with calibration, discrimination and decision curve analysis. Results A total of 13,380 patients meeting the criteria were included and POP developed in 882 patients (6.6%). The mortality was 2.0%, but it increased significantly in patients with POP (25.1 vs. 0.4%, P less then 0.001). Using preoperative and intraoperative variables, we constructed a full nomogram model based on ten independent risk factors and a preoperative nomogram model based on eight preoperative factors. Both nomograms demonstrated good calibration, discrimination, and were well validated. The decision curves indicated significant clinical usefulness. Finally, four risk intervals were defined for better clinical application. Conclusions We developed and validated two nomogram models for POP following elective cardiac surgery using preoperative and intraoperative factors, which may be helpful for individualized risk evaluation and prevention decisions.Background Type 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases and increase mortality. Clinical outcomes of patients after percutaneous coronary intervention (PCI) were worse in T2DM patients than those without T2DM. New-onset diabetes after PCI (NODAP) is often observed during long-term follow-up and this further aggravates cardiovascular diseases. Several studies had focused on patients after PCI with known T2DM. Previous studies showed that impaired glucose tolerance and aging are risk factors that promote NODAP. Considering the unique characteristics of patients after PCI, we will further study relevant risk factors. We sought to investigate the potential predictors of acute coronary syndrome patients with NODAP by a multicenter retrospective cohort study. Methods This is a multicenter retrospective cohort study including patients after PCI. Clinical medical records of these patients were collected from four hospitals in different areas in China, from 2010 to 2021. Patients' demographic information, medical history, diagnostic testing, PCI-related information, medication situation will be summarized using descriptive statistics, and correlation analysis was performed on the development of new-onset diabetes. Variation will be described and evaluated using χ2 test or Kreskas-Wallis test. The prediction model will be verified by a validation set. Discussion A novel diabetes prediction model for patients after PCI is established, and this study can achieve advanced intervention for the occurrence of NODAP. Owing to its retrospective nature, this study has some limitations, but it will be further studied through supplement data collection or prospective study. The study has been registered for clinical trials by the Chinese Clinical Trial Registry (ChiCTR2100047241).Background Trends in mortality from aortic stenosis across European countries are not well-understood, especially given the significant growth in transcatheter aortic valve implantation (TAVI) in the last 10 years. Methods Age-standardised death rates were extracted from the World Health Organisation Mortality Database, using the International Classification of Diseases 10th edition code for non-rheumatic aortic stenosis for those aged > 45 years between 2000 and 2017. The UK and countries from the European Union with at least 1,000,000 inhabitants and at least 50% available datapoints over the study period were included a total of 23 countries. Trends were described using Joinpoint regression analysis. Results No reductions in mortality were demonstrated across all countries 2000-2017. Large increases in mortality were found for Croatia, Poland and Slovakia for both sexes (>300% change). buy PBIT Mortality plateaued in Germany from 2008 in females and 2012 in males, whilst mortality in the Netherlands declined for both sexes from 2007. Mortality differences between the sexes were observed, with greater mortality for males than females across most countries. Conclusions Mortality from aortic stenosis has increased across Europe from 2000 to 2017. There are, however, sizable differences in mortality trends between Eastern and Western European countries. The need for health resource planning strategies to specifically target AS, particularly given the expected increase with ageing populations, is highlighted.Background Extracorporeal cardiac shock waves (ECSW) have great potential in the treatment of coronary heart disease. Endothelial progenitor cells (EPCs) are a class of pluripotent progenitor cells derived from bone marrow or peripheral blood, which have the capacity to migrate to ischemic myocardium and differentiate into mature endothelial cells and play an important role in neovascularization and endothelial repair. In this study, we investigated whether ECSW therapy can improve EPCs dysfunction and apoptosis induced by hypoxia and explored the underlying mechanisms. Methods EPCs were separated from ApoE gene knockout rat bone marrow and identified using flow cytometry and fluorescence staining. EPCs were used to produce in vitro hypoxia-injury models which were then divided into six groups Control, Hypoxia, Hypoxia + ECSW, Hypoxia + LY294002 + ECSW, Hypoxia + MK-2206 + ECSW, and Hypoxia + L-NAME + ECSW. EPCs from the Control, Hypoxia, and Hypoxia + ECSW groups were used in mRNA sequencing reactions. mRNA CSW were eliminated using inhibitors specific to PI3K (LY294002), Akt (MK-2206), and eNOS (L-NAME). Conclusion ECSW exerted a strong repaired effect on EPCs suffering inhibited hypoxia injury by inhibiting cell apoptosis and promoting angiogenesis, mainly through activating the PI3K/Akt/eNOS signaling pathway, which provide new evidence for ECSW therapy in CHD.Mesenchymal stem cells (MSCs) have been proven capable of differentiating into endothelial cells (ECs) and increasing vascular density in mouse ischemia models. However, the therapeutic potential of MSCs in neointimal hyperplasia after vascular injury is still not fully understood. In this study, we proposed that sustained release of miR-217 inhibitor encapsulated by nanoparticles in MSCs can enhance the therapeutic effects of MSCs on alleviating neointimal hyperplasia in a standard mouse wire injury model. We intravenously administered MSCs to mice with injured arteries and examined neointimal proliferation, endothelial differentiation and senescence. We demonstrated that MSCs localized to the luminal surface of the injured artery within 24 h after injection and subsequently differentiated into endothelial cells, inhibited neointimal proliferation and migration of vascular smooth muscle cells. Transfection of MSCs with poly lactic-co-glycolic acid nanoparticles (PLGA-NP) encapsulating an miR-217 agomir abolished endothelial differentiation as well as the therapeutic effect of MSCs. On the contrary, silencing of endogenous miR-217 improved the therapeutic efficacy of MSCs. Our study provides a new strategy of augmenting the therapeutic potency of MSCs in treatment of vascular injury.Background Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is the rescue treatment proposed to patients with refractory cardiogenic shock. The VA-ECMO implantation promotes inflammation and ischemia-reperfusion injuries through the VA-ECMO flow, causing digestive mucosa barrier disrupture and inducing translocation of bacterial wall components-Lipopolysaccharides (LPS) with further inflammation and circulatory impairment. LPS is a well-studied surrogate indicator of bacterial translocation. Oxiris membrane is a promising and well-tolerated device that can specifically remove LPS. The main study aim is to compare the LPS elimination capacity of Oxiris membrane vs. a non-absorbant classical renal replacement (RRT) membrane in patients with cardiogenic shock requiring VA-ECMO. Methods ECMORIX is a randomized, prospective, single-center, single-blind, parallel-group, controlled study. It compares the treatment with Oxiris membrane vs. the standard continuous renal replacement therapy care in patients with cardiogenic shock support by peripheral VA-ECMO.
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