A systematic review of guidelines for dual antiplatelet therapy in coronary artery bypass graft.

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. METHODS AND RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.

Long-term tracking of fasting blood glucose variability and peripheral artery disease in people without diabetes.

INTRODUCTION: Long-term changes of fasting blood glucose (FBG) in relation to lower-extremity peripheral artery disease (lower-extremity PAD) in people without diabetes has barely been reported. Our study aimed to investigate the association between FBG variability and the incidence of lower-extremity PAD in people without diabetes. RESEARCH DESIGN AND METHODS: We included 7699 participants without prior lower-extremity PAD and diabetes from the Atherosclerosis Risk in Communities study in the final analysis. At least two measurements of FBG were required during follow-up. Variability of FBG was identified using SD, coefficient of variation (CV), variability independent of the mean (VIM) and average real variability. Lower-extremity PAD was defined as an ankle brachial index <0.9, or hospitalization with a lower-extremity PAD diagnosis. Cox regression model was used to calculate HR for incidence of lower-extremity PAD and FBG variability. RESULTS: During a median follow-up of 19.5 years, 504 (6.5 %) lower-extremity PAD events were observed, 54.4% (n=274) were male, and 17.5% (n=88) were African-American. FBG variability was positively associated with incident lower-extremity PAD, with a linear relationship. HRs for CV and VIM were 1.015 (95% CI: 1.001 to 1.03; p=0.023), and 1.032 (95% CI: 1.004 to 1.06; p=0.022) for lower-extremity PAD, respectively. Participants in the lowest quartile of CV were at lower lower-extremity PAD risk compared with the highest ones (HR: 1.499, 95% CI: 1.16 to 1.938; p=0.002). CONCLUSIONS: Higher FBG variability was independently associated with increased prevalence of lower-extremity PAD in people without diabetes. TRIAL REGISTRATION NUMBER: NCT00005131.

Use of personal protective equipment against coronavirus disease 2019 by healthcare professionals in Wuhan, China: cross sectional study.

OBJECTIVE: To examine the protective effects of appropriate personal protective equipment for frontline healthcare professionals who provided care for patients with coronavirus disease 2019 (covid-19). DESIGN: Cross sectional study. SETTING: Four hospitals in Wuhan, China. PARTICIPANTS: 420 healthcare professionals (116 doctors and 304 nurses) who were deployed to Wuhan by two affiliated hospitals of Sun Yat-sen University and Nanfang Hospital of Southern Medical University for 6-8 weeks from 24 January to 7 April 2020. These study participants were provided with appropriate personal protective equipment to deliver healthcare to patients admitted to hospital with covid-19 and were involved in aerosol generating procedures. 77 healthcare professionals with no exposure history to covid-19 and 80 patients who had recovered from covid-19 were recruited to verify the accuracy of antibody testing. MAIN OUTCOME MEASURES: Covid-19 related symptoms (fever, cough, and dyspnoea) and evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, defined as a positive test for virus specific nucleic acids in nasopharyngeal swabs, or a positive test for IgM or IgG antibodies in the serum samples. RESULTS: The average age of study participants was 35.8 years and 68.1% (286/420) were women. These study participants worked 4-6 hour shifts for an average of 5.4 days a week; they worked an average of 16.2 hours each week in intensive care units. All 420 study participants had direct contact with patients with covid-19 and performed at least one aerosol generating procedure. During the deployment period in Wuhan, none of the study participants reported covid-19 related symptoms. When the participants returned home, they all tested negative for SARS-CoV-2 specific nucleic acids and IgM or IgG antibodies (95% confidence interval 0.0 to 0.7%). CONCLUSION: Before a safe and effective vaccine becomes available, healthcare professionals remain susceptible to covid-19. Despite being at high risk of exposure, study participants were appropriately protected and did not contract infection or develop protective immunity against SARS-CoV-2. Healthcare systems must give priority to the procurement and distribution of personal protective equipment, and provide adequate training to healthcare professionals in its use.

Preparedness of medical education in China: Lessons from the COVID-19 outbreak.

The COVID-19 outbreak can be seen as a 'big test' for China; a summative assessment of its preparedness on multiple fronts, including medical education. Being intimately involved in the coordinated response, the First Affiliated Hospital of Sun Yat-sen University has been a first-hand witness to the strengths and weaknesses of the current medical education system in China. On the one hand, we believe that the distinguished contributions in disease containment efforts by healthcare professionals indicated that our medical education system has achieved its intended outcomes and is socially accountable. On the other hand, we have also identified three major issues that need to be addressed from an educational standpoint: insufficient emphasis on public health emergency preparedness; unsophisticated mechanisms for interdisciplinary cooperation; and inadequate guidance in medical ethics. Whilst these reflections might be seen in its summative form, we would suggest changing it to that of a formative process, where we learn from our assessment through observation and feedback of the gaps, upon which improvement of our present situation can be made. We hope that these lessons may be helpful to our colleagues in the rest of China and around the world, who are engaged in medical educational reform.

Phenomapping of subgroups in hypertensive patients using unsupervised data-driven cluster analysis: An exploratory study of the SPRINT trial.

BACKGROUND: Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment. METHODS: An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters. RESULTS: Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55-0.98) and cluster 1 (HR 0.54, 95% CI 0.37-0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05-1.32). CONCLUSION: Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.

Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials.

BACKGROUND: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications. RESULTS: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant. CONCLUSIONS: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.

The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University.

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. Results and discussions: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

Comparative cardiovascular outcomes in the era of novel anti-diabetic agents: a comprehensive network meta-analysis of 166,371 participants from 170 randomized controlled trials.

BACKGROUND: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included. We used network meta-analysis to obtain estimates for the outcomes of interests. In addition, post hoc correlation analysis of severe hypoglycemia and primary outcome as per ranking order was conducted. Outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: A total of 170 trials (166,371 participants) were included. By class and by individual, sulfonylureas (SU) ranked last. Therefore, with SU as reference, categorically sodium-glucose co-transporter 2 inhibitor (SGLT2i), insulin (INS), glucagon-like peptide-1 receptor agonist, and dipeptidyl peptidase 4 inhibitor were significantly superior in term of MACE; as were SGLT2i and INS in term of all-cause mortality. Moreover, ranking orders of MACE and all-cause mortality were both positively correlated with that of severe hypoglycemia risk (by individual: R2 = 0.3178, P = 0.018; by class: R2 = 0.2574, P = 0.038). CONCLUSIONS: Novel anti-diabetic agents possess favorable CV safety profile, despite small but robust differences between individuals. In addition, increase in CV risk was again shown to be partly attributable to a concomitant increase in the risk of severe hypoglycemia, for which SU performed the worst.

Enhanced external counterpulsation inhibits endothelial apoptosis via modulation of BIRC2 and Apaf-1 genes in porcine hypercholesterolemia.

OBJECTIVES: Enhanced external counterpulsation (EECP) could improve endothelium-dependent vasodilatation of carotid artery and restore imbalance of nitric oxide and endothein-1 in patients with coronary artery disease. Our study was designed to test the hypothesis that long-term EECP may protect vascular endothelial cells from apoptosis by modifying apoptosis-related gene expression. METHODS: Eighteen male Yorkshire pigs were randomly assigned to three groups: usual diet (Normal), high cholesterol diet (HC) and high cholesterol diet plus EECP (HC+EECP). Vascular endothelial cells were isolated from the aortic endothelium and identified by CD31 staining and DiI-Ac-LDL reaction. Morphological changes were observed by both scanning and transmission electronic microscopes. TUNEL technique was applied to detect the apoptotic index of vascular endothelial cells. Two genes, Apaf-1 and BIRC2, were chosen for exploring the potential mechanisms of action at the molecular level. RESULTS: EECP brought a certain degree of alleviation from ultrastructural changes such as shrinking and blebbing of cytomembrane, marginalization, degeneration, and fragmentation of the nucleus. EECP also significantly reduced apoptotic indices while compared with that of control (177±12‰ vs. 237±23‰, P<0.05). The Apaf-1 expression at both protein and mRNA level in pigs of HC+EECP group was significantly decreased than those of the HC group (P<0.05), whereas the BIRC2 expression was significantly enhanced after EECP treatment, documented by immunostaining and semi-quantitative RT-PCR analysis, respectively (P<0.05). CONCLUSIONS: EECP could protect vascular endothelial cells from apoptosis, thereby delaying the progression of early atherosclerotic lesions possibly through transcriptional down-regulation of pro-apoptotic gene Apaf-1, and up-regulation of anti-apoptotic gene BIRC2.

Transplantation of human umbilical cord-derived endothelial progenitor cells promotes re-endothelialization of the injured carotid artery after balloon injury in New Zealand white rabbits.

BACKGROUND: Cell transplantation has great potential for promoting endothelial repair and reducing the complications of percutaneous coronary intervention (PCI). The aim of this study was to investigate the effect of transplantation of human umbilical cord blood endothelial progenitor cells (EPCs) on injured arteries. METHODS: Umbilical cord blood mononuclear cells were obtained from post-partum lying-in women, and EPCs were isolated, cultured, expanded and identified by immunofluorescence. The carotid arterial endothelium of New Zealand white rabbits was injured by dilatation with a 3F balloon, and the EPCs were injected into the lumen of the injured artery in the transplanted group (n = 16), while an equal volume of phosphated buffered saline (PBS) was injected into the control group after balloon injury (n = 16). The animals were sacrificed after either 2 or 4 weeks, and the grafted cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibodies. Arterial cross sections were analyzed by pathology, immunohistochemistry and morphometry to evaluate the reparative effects of EPCs. Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF)-ß1 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fluorescence-labeled EPCs were found in the neointima. The neointimal area and the neointimal/medial area ratio were significantly lower in the transplanted group than in the control group (P < 0.05). von Willebrand factor (vWF) immunohistostaining showed more VWF-positive cells in the transplanted animals than in the controls (8.75 ± 2.92 vs. 4.50 ± 1.77, P < 0.05). Compared with the control group, the transplanted group had lower expression of PCNA mRNA (0.67 ± 0.11 vs. 1.25 ± 0.40, P < 0.01) and higher expression of TGF-ß1 mRNA (1.10 ± 0.21 vs. 0.82 ± 0.07, P < 0.05). CONCLUSIONS: EPCs derived from human umbilical cord blood were successfully transplanted into injured vessels. The transplanted EPCs inhibited neointimal hyperplasia and promoted vascular re-endothelialization.

Vasculoprotective properties of enhanced external counterpulsation for coronary artery disease: beyond the hemodynamics.

A growing pool of evidence has shown that enhanced external counterpulsation (EECP) is a non-invasive, safe, low-cost, and highly beneficial therapy for patients with coronary artery disease. However, the exact mechanisms of benefit exerted by EECP therapy remain only partially understood. The favorable hemodynamic effects of EECP were previously considered as the primary mechanism of action. Nevertheless, recent advances have shed light on the shear stress-increasing effects of EECP which are vasculoprotective and anti-atherosclerotic. EECP-induced endothelial shear stress increase may lead to improvement in endothelial function and morphology, attenuation of oxidative stress and inflammation, and promotion of angiogenesis and vasculogenesis. This review summarizes evidence of the potential mechanisms contributing to the immediate and long-term benefits of EECP, from the perspective of its shear stress-increasing effects.

Expanded human cord blood-derived endothelial progenitor cells salvage infarcted myocardium in rats with acute myocardial infarction.

1. Cell transplantation has promise as a therapeutic option for restoring impaired heart function after acute myocardial infarction (AMI). However, the optimal cell type to use remains controversial. We investigated the therapeutic efficacy and feasibility of intramyocardial transplantation of human umbilical cord blood-derived endothelial progenitor cells (hUCB-EPC) in rats with AMI. 2. The Wistar rats myocardial infarction model was established by ligating the left anterior descending artery. The labelled hUCB-EPC were transplanted through intramyocardial injection. Left ventricular function was assessed using a pressure-volume catheter and echocardiogram. Anti-VIII immunohistochemistry staining was used to reflect the degree of angiogenesis in peri-infarcted areas by calculating the average capillary density. The fibrosis degree of infarcted myocardium was analysed by Masson staining and the collagen volume fraction was calculated. 3. The labelled donor endothelial progenitor cells were detected in the new microvessels in host myocardium by double-positive staining with CM-Dil and FITC-UEA-l. An increase in left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-systolic pressure, first derivative of left ventricular pressure (+dP/dtmax and -dP/dtmax), as well as a decrease in the left ventricular end-diastolic pressure in rats with cell therapy indicated a significant improvement in global heart function. The cell therapy group had increased microvessel formation and a decreased degree of myocardial fibrosis compared to the control group. Moreover, the degree of myocardial fibrosis was less than that of the control group. 4. The improved global heart function and decreased cardiac fibrosis in rats with AMI implies the potential benefit of hUCB-EPC transplantation.

Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia.

BACKGROUND: Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+). METHODS: Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively. RESULTS: A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P < 0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P < 0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P < 0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups. CONCLUSIONS: The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.

Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction.

BACKGROUND: Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction. METHODS: Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-l). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization. RESULTS: The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted rats, associated with a significant improvement of global heart function in terms of the increase of left ventricular end-systolic pressure (LVESP), +dp/dtmax and -dp/dtmax as well as the decrease of LVEDP in rats with EPCs therapy comparing to the control rats (P < 0.05). Moreover, the expression of the rat PCNA mRNA and PECAM were both enhanced in the EPCs group compared with that of the control group. CONCLUSIONS: The human umbilical cord blood-derived EPCs could incorporate into new-born capillaries in rat myocardium, induce revascularization and improve the proliferation activity in the peri-infarct area, resulting in the improvement of global heart function. This may indicate a promising stem cell resource in cell-based therapy for ischaemic diseases.