To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction.Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation.CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups.Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.
Despite advancements in managing atherosclerotic cardiovascular disease (ASCVD), mortality and morbidity rates remain high. This is partially attributed to systemic inflammation (SI) which leads to increased cardiovascular risk in people with both ASCVD and CKD. An early understanding of the clinical perception towards SI and usage of high sensitivity C-reactive protein (hsCRP) could help improve identification and management in people with ASCVD and CKD. The FLAME-ASCVD (systemic inFLAMmation and rolE of hsCRP as a biomarker in AtheroSclerotic CardioVascular Disease) study aimed to assess cardiologists' awareness of SI and hsCRP in this population across ten countries.
Methods
The FLAME-ASCVD study employed a real-world, cross-sectional, survey involving cardiologists from ten countries, including the United Kingdom. Participants included cardiologists with at least three years of clinical practice experience, seeing a minimum of 15 people with both ASCVD and CKD per month. Responses from 602 cardiologists were evaluated, with this analysis focussing on the subset of 60 UK cardiologists.
Results
While SI was acknowledged as a CV risk factor by 65% of UK cardiologists, with 77% of UK cardiologists acknowledging the role of SI in recurrent CV events, 54% of UK cardiologists reported not considering SI in decision-making, due to the lack of available treatments. Despite acknowledging CRP (87%) and hsCRP (32%) as valid biomarkers, UK cardiologists reported lower utilization of SI in patient management, with only 23% intending to test for SI in this patient population (compared to 64% globally), highlighting a discrepancy in clinical practice. Similarly, discussions with patients about SI were less common among UK cardiologists (30%) compared to the global average (43%). However, UK cardiologists were more likely to identify the lack of effective SI treatments as the most common unmet need for people with both ASCVD and CKD (58%), compared to cardiologists globally (41%).
Conclusions
The UK subgroup analysis of the FLAME-ASCVD study provides valuable insights into UK cardiologists' perceptions of SI and hsCRP in people with ASCVD and CKD. Addressing the identified gaps requires increased efforts towards education, guideline development, and further research targeting the residual inflammatory risk in patients with ASCVD and CKD. This study was fully funded by Novo Nordisk. Novo Nordisk employees were involved in all aspects of study conduct and are coauthors of this abstract.
Conflict of Interest
This study was fully funded by Novo Nordisk. Novo Nordisk employees were involved in all aspects of study conduct and are coauthors of this abstract.
We aimed to assess and compare the morphological characteristics of ostial and non-ostial left main coronary artery (LMCA) lesion without heavy calcification using intravascular ultrasound (IVUS) imaging.Between Oct. 2004 and Oct. 2007, 153 patients with confirmed or suspected coronary artery narrowing in coronary angiography with satisfactory IVUS images and non-heavy calcification were included in the study (ostial lesions, n = 47; non-ostial lesion, n = 106). IVUS analysis included plaque composition, external elastic membrane (EEM), lumen, plaque cross-sectional area (CSA), plaque burden (plaque CSA/EEM CSA) at the lesion, proximal and/or distal reference site, and remodeling index (RI, lesion EEM CSA/reference EEM CSA). Negative remodeling was defined as RI < 0.95.LMCA mean reference lumen and vessel diameter was 4.1 +/- 0.8 mm and 5.3 +/- 0.8 mm respectively. Incidence of patients with minimum lumen area (MLA < 6.0 mm(2)) was similar between the two groups (29.5% for ostial lesions and 31.9% for non-ostial lesions, P = 0.87). There were significantly more fibrous (70.2% vs. 35.8%) and soft (8.5% vs. 3.8%) plaques while significantly less calcified plaque (19.2% vs. 43.4%) in patients with hostile lesions compared those with non-ostial lesions (all P < 0.05). Compared to non-ostial lesions, ostial lesion had significant smaller plaque area [(10.8 +/- 4.5) mm(2) vs. (13.3 +/- 5.4) mm(2), P = 0.007], less plaque burden (54.8% +/- 15.9% vs. 61.9% +/- 14.5%, P = 0.020), smaller RI (0.9 +/- 0.2 vs. 1.0 +/- 0.2, P = 0.000) and higher incidence of negative remodeling (74.5% vs. 34.9%, P = 0.000). Multivariant Logistic regression analysis showed that the site of lesion (ostial or non-ostial lesion, OR = 4.9, P = 0.004), plaque area (OR = 1.2, P = 0.01) and plaque burden (OR = 0.003, P = 0.000) were the independent predictors of LMCA remodeling.Negative remodeling might be responsible for the development of LMCA ostial narrowing.
Heart failure is a worldwide pandemic with an unacceptable high level of morbidity and mortality. Understanding the different pathophysiological mechanisms will contribute to prevention and individualized therapy of heart failure. We established mouse models for ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) by inducing myocardial infarction and Coxsackievirus B3 infection respectively. Isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry technology was used to identify the protein expression profiles in control and failing hearts. A total of 1638 proteins were identified and compared in this proteomics analysis. Among them, 286 proteins were differently expressed. Gene ontology, KEGG pathway and ingenuity pathway analysis was performed to systematically assess the potential connections of the differentially expressed proteins to biological functions. Compared with control group, the differentially expressed proteins derived from the hearts of ICM and DCM mice were partially similar and mainly modulated in oxidative phosphorylation, metabolism and protein folding pathways. Moreover, difference still existed, the differentially expressed proteins between DCM and ICM hearts were significantly modulated in oxidative phosphorylation, metabolic and AMPK signaling pathways. Confirmatory western bolt analysis demonstrated that SDHB was down-regulated in both ICM and DCM hearts, while UQCRQ, GLUT4 and adiponectin were up-regulated in ICM hearts. ATP concentration significantly decreased in both DCM and ICM hearts. The protein expression of phospho-AMPKα decreased significantly in DCM hearts, but increased in ICM. In summary, oxidative phosphorylation, cardiac metabolism and protein folding play critical roles in the pathogenesis of heart failure. The diverse changes in protein expression profiles between failing hearts induced by either myocardial infarction or CVB3 infection demonstrated the heterogeneity of heart failure. Understanding the differences in proteome profiles could offer more precise therapeutic options for heart failure.
This article focuses on the application of materialist dialectics in the probation teaching of eight-year medical program. Conclusion drawn from questionnaires indicates that it has a positive influence on improving students' interests, meanwhile cultivating their abilities on self-education and development, forging them a correct diagnostic thinking and habits for their clinical work in the future.
Key words:
Eight-year medical program; Medical student; Clinical probation; Materialist dialectics
Abstract Background Elevated serum lactic acid level is associated with poor outcomes in patients with critical diseases like shock. However, the clinical implication of this biomarker in patients with acute myocardial infarction remains unclear. Purpose We aimed to explore the predictive power of serum lactic acid level on admission for in-hospital outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Methods Consecutive patients undergoing pPCI with available data on serum lactid acid level were evaluated for eligbility in this retrospective cohort study. The primary outcome was all-cause death during hospitalization. Enzymatic infarct size and major adverse cardiovascular events (MACE, defined as a combination of all-cause death, recurrent myocardial infarction, and unplanned repeated revascularization) were considered secondary outcomes. Independent preditors of in-hospital death were determined by multiple logisic regression analysis. Odds ratio (OR) with 95% confidence interval (CI) was used to demonstrate the association. The predictive power of serum latictic acid level for in-hospital death was evaluated through receiver operator characteristic curve, which generated C-statictic. A combination model was further constructed by adding serum latictic acid level to the Global Registry of Acute Coronary Events (GRACE) risk score (LA-GRACE risk score). The linear dependence between serum lactic acids level and othe clinical variables was analysed using Spearman rank correlation. Results Of the 302 patients enrolled in the current analysis, 15 (5.0%) died during hospitalization. Serum lactic acid level (OR=1.657, 95% CI: 1.115 to 2.463, p=0.012)and left ventricular ejection fraction (OR=0.858, 95% CI: 0.767 to 0.959, p=0.007) were the only two independent predictors of in-hospital death. The C-statistic of serum lactic acid level for predicting in-hospital death was 0.886 (95% CI: 0.793 to 0.979). The LA-GRACE risk score improved the C-statistic of the GRACE score from 0.898 to 0.911 (p=0.294), with continuous net reclassification improvement of 0.567 (p=0.023) and integrated discrimination improvement of 0.206 (p=0.003). High serum lactic acid level was also asscoiated with larger enzymatic infarct size (p=0.002) and MACE (p=0.004). Further, it significantly correlated with white blood cell counts (r=0.264, p<0.001), serum creatinine level (r=0.189, p=0.001), and systolic blood pressure (r=−0.122, p=0.034). Conclusion Serum lactic acid level on admission is asscoiated with poor myocardial perfusion and in-hospital outcomes in patients with acute myocardial infarction undergoing pPCI. It may contribute to better risk stratification in these populations. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the National Program on Key Basic Research Project of China (Grant No: 2019YFC0840601 and 2014CBA02003), National Natural Science Foundation of China (Grant No: 81870267, 81970295, 81521001, 81670318 and 81570314), Grant of Shanghai Shenkang on Key Clinical Research Project (Grant No: SHDC2020CR2015A and SHDC12019104), Grant of Shanghai Science and Technology Committee (Grant No: 19MC1910300, 18411950200 and 20JC1410800), Key Medical and Health Projects of Xiamen Province (No: 3502Z20204004), Grant of Shanghai Municipal Commission of Health and Family Planning (Grant No: 2017YQ057), Grant of Zhongshan Hospital Affiliated to Fudan University (Grant No: 2018ZSLC01), VG Funding of Clinical Trials (2017-CCA-VG-036) and Merck Funding (Xinxin-merck-fund-051). ROC of lactic acid and GRACE score
The stiffness of the myocardial extracellular matrix (ECM) and the transplanted cell type are vitally important in promoting angiogenesis. However, the combined effect of the two factors remains uncertain. The purpose of this study is to investigate in vitro the combined effect of myocardial ECM stiffness postinfarction with a bone marrow-derived cell subset expressing or not expressing CD34 on endothelial lineage commitment. Myocardial stiffness of the infarct zone was determined in mice at 1 h, 24 h, 7 days, 14 days, and 28 days after coronary artery ligation. Polyacrylamide (PA) gel substrates of different stiffnesses were prepared to mechanically mimic the myocardial ECM after infarction. Mouse bone marrow-derived CD34+ and CD34– cells were seeded on the flexible PA gels. The double-positive expression for DiI-acetylated low-density lipoprotein (acLDL) uptake and fluorescein isothiocyanate-Ulex europaeus agglutinin-1 (FITC-UEA-1) binding, the endothelial lineage antigens CD31, von Willebrand factor (vWF), Flk-1, and VE-cadherin, as well as cytoskeleton were measured by immunofluorescent staining on day 7. Cell apoptosis was evaluated by both immunofluorescent staining and flow cytometry at 24 h after culture. We found that the numbers of the CD34+ cell subset adherent to the flexible substrates (4–72 kPa) was much larger than that of the CD34– subset. More double-positive cells for DiI-acLDL uptake/FITC-UEA-1 binding were seen on the 42-kPa (moderately stiff) substrate, corresponding to the stiffness of myocardial ECM at 7–14 days postinfarction, compared with those on substrates of other stiffnesses. Similarly, the moderately stiff substrate showed benefits in promoting the positive expressions of the endothelial lineage markers CD31, vWF, Flk-1, and VE-cadherin. In addition, the cytoskeleton F-actin network within CD34+ cells was organized more significantly at the leading edge of the adherent cells on the moderately stiff (42 kPa) or stiff (72 kPa) substrates as compared with those on the soft (4 kPa and 15 kPa) substrates. Moreover, the moderately stiff or stiff substrates showed a lower percentage of cell apoptosis than the soft substrates. Infarcted myocardium-like ECM of moderate stiffness (42 kPa) more beneficially regulated the endothelial lineage commitment of a bone marrow-derived CD34+ subset. Thus, the combination of a CD34+ subset with a "suitable" ECM stiffness might be an optimized strategy for cell-based cardiac repair.
Abstract CD47‐SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47‐SIRPα axis is associated with on‐target off‐tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano‐degrader is developed to inhibit CD47‐SIRPα axis in a site‐specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano‐degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high‐affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor‐mediated endocytosis. To enhance its tissue specificity, Ly6G antibody conjugation (aRLP) is applied, enabling its attachment to neutrophils and accumulation within inflammatory sites. In the myocardial infarction model, aRLP accumulated in the infarcted myocardium blocks CD47‐SIRPα axis and subsequently promoted the efferocytosis of apoptotic cardiomyocytes by macrophage, improved heart repair. This nano‐degrader efficiently degraded SIRPα in lysosomes, providing a new strategy for immunotherapy with great clinical transformation potential.
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