Mei Dong

The beneficial effects of postconditioning on no-reflow phenomenon after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction

No-reflow phenomenon is a serious complication of percutaneous coronary intervention (PCI) which is closely related to the incidence of major adverse cardiovascular events. It has been demonstrated that Postconditioning (PostC) during primary PCI confers protection against ischemia–reperfusion injury and thus might reduce infarct size. However, whether PostC may exert its beneficial effects on acute myocardial infarction (AMI) patients by reducing no-reflow phenomenon is still unknown. Sixty two patients diagnosed with ST-elevation AMI were randomly assigned to study group (nxa0=xa032) or control group (nxa0=xa030). Blood samples were obtained and assayed for creatine kinase MB (CK-MB) and high-sensitive C-reactive protein (hs-CRP). Determinants of reflow, including final thrombolysis in myocardial infarction (TIMI) grade-3 flow, ST-segment resolution (STR), myocardial blush grades-3 (MBG-3) and corrected thrombolysis in myocardial infarction frame count (cTFC), were comparative between the two groups. Compared with control group, more patients in study group were identified as the final TIMI grade-3 flow (81.3 vs. 56.7xa0%, Pxa0=xa00.036), MBG-3 (23 vs. 14xa0%, Pxa0=xa00.043) and STR ≥50xa0% (93.8 vs. 73.3xa0%, Pxa0=xa00.029), while patients in study group had less cTFC (28.5xa0±xa09.1 vs. 37.4xa0±xa012.4, Pxa0=xa00.002) After PCI, study group was associated with lower levels of CK-MB (2,397.6xa0±xa0470.2 vs. 2,159.9xa0±xa0485.5, Pxa0=xa00.028), Troponin-I (197.5xa0±xa032.5 vs. 154xa0±xa043.1, Pxa0=xa00.041) and hs-CRP (5.5xa0±xa04.5 vs. 9.5xa0±xa05.2xa0mg/L, Pxa0=xa00.019) in comparison with control group. Left ventricle ejection fraction was better in the study group than in the control group (55.1xa0±xa09.8 vs. 42.9xa0±xa010.7, Pxa0=xa00.042). PostC could improve myocardial reperfusion in patients with ST-elevation AMI undergoing PCI by reducing no-reflow. However, due to the limited sample size, the results of our study should not be considered conclusive.

Association between local interleukin-6 levels and slow flow/ microvascular dysfunction

We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5xa0±xa010.3xa0years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5xa0%). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135–2.268; Pxa0=xa00.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (ORxa0=xa08.065, CI 1.244–52.632; Pxa0=xa00.029) and thrombus score (ORxa0=xa012.500, CI 1.100–142.857; Pxa0=xa00.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274–2.281, Pxa0<xa00.001; optimal threshold ≥11.3xa0pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73xa0% and specificity of 71xa0%. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI.

Prospective study of effects of endogenous estrogens on myocardial no-reflow risk in postmenopausal women with acute myocardial infarction.

The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no-reflow in postmenopausal women with ST-elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal-reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C-reaction protein (Hs-CRP) were significantly higher in the no-reflow group (Pu2009<u20090.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus scoreu2009≥u20094, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no-reflow (Pu2009<u20090.05). After adjusting for these factors, thrombus scoreu2009≥u20094 (ORu2009=u20094.994, CI 1.987-10.518; Pu2009=u20090.035), SHBG (ORu2009=u20090.800, CI 0.341-0.983; Pu2009=u20090.047), and estradiol levels (OR 4.091, CI 1.105-8.582; Pu2009=u20090.046) continued to demonstrate strong positive associations with the risk of no-reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no-reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no-reflow. However, our results need to be confirmed in a larger population.

Increased Platelet-leukocyte Aggregates Are Associated With Myocardial No-reflow in Patients With ST Elevation Myocardial Infarction

Objective We aimed to investigate the association between platelet‐leukocyte aggregates (PLA) levels on admission and the risk of myocardial no‐reflow in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Methods A total of 83 patients with STEMI undergoing primary PCI were included in the current study. Platelet‐leukocyte conjugates (PLA), including platelet‐monocyte aggregates (PMA), platelet‐neutrophil aggregates (PNA) and platelet‐lymphocyte aggregates were studied by flow cytometry in peripheral venous blood. No‐reflow was defined as coronary blood flow grade thrombolysis in myocardial infarction ≤2 or thrombolysis in myocardial infarction 3 and myocardial blush grade ≤2. Results No‐reflow was observed in 19 patients (22.9%). Compared with the reflow group, the level of PNA (76.5 ± 13.3) and PMA (90.3 ± 5.2) before PCI no‐reflow group was significantly higher than that in normal reflow (P < 0.001). Using multiple logistic regression analysis, PNA (odds ratio [OR] = 1.179; 95% CI: 1.035‐1.342; P = 0.013) and PMA (OR = 1.248; 95% CI: 1.040‐1.498; P = 0.017) were found to be a significant predictor of no‐reflow together with pain to balloon time (OR = 1.022; 95% CI: 1.002‐1.041; P = 0.028), estimated glomerular filtration rate (OR = 1.311; 95% CI: 1.009‐1.856; P = 0.047) and higher thrombus burden (OR = 0.061; 95% CI: 0.006‐0.658; P = 0.021). Receiver operating characteristic curve analysis revealed that PNA (area under the curve = 0.881; 95% CI: 0.809‐0.952; P < 0.001), PMA (area under the curve = 0.794; 95% CI: 0.699‐0.889; P < 0.001) have important predictive value for the myocardial no‐reflow. Conclusions Our study indicated that preprocedural increased PLA levels display a significantly independent association with no‐reflow phenomenon after PCI. Increased PLA levels may predict the development of no‐reflow phenomenon in patients with STEMI who underwent PCI.

Prognostic value of soluble ST2 postaortic valve replacement: a meta-analysis

Objectives Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family and a modulator of hypertrophic and fibrotic responses. Its prognostic value for patients undergoing aortic valve replacement (AVR) has been examined in prospective studies but to date, there has been no systematic evaluation or meta-analysis on this issue. Methods PubMed and Embase were searched until 1 October 2017 for studies that evaluated the relationship between sST2 levels and mortality after AVR. Results A total of 18 and 37 entries were retrieved from both databases, from which four studies were included in the final meta-analysis. In a total of 1154 subjects (50% male, mean age 80±10 years old, mean follow-up 14 months), elevated sST2 levels were significantly associated with a 44% increase in the risk of all-cause mortality (HR 1.44, 95%u2009CI 1.30 to 1.60, p<0.0001; I2: 44%). Conclusions sST2 significantly predicts all-cause mortality in patients who have undergone AVR, but this conclusion is limited by the small number of patients. Larger prospective studies are required to better elucidate its value for risk stratification in this patient population.

Association between preoperative serum insulin levels and lymph node metastasis in endometrial cancer-a prospective cohort study

Endometrial cancer is a common gynecological malignancy in developed countries. Insulin has been identified as a risk factor for endometrial cancer. However, whether insulin levels are related to the risk of lymph node metastasis (LNM) in endometrial cancer is unknown. We conducted a prospective cohort study in a regional hospital to examine the relationships between insulin levels and risk of LNM in premenopausal and postmenopausal women. A total of 668 patients were recruited. Of these, 206 were premenopausal (mean age: 42.01 ± 10.17) and 462 were postmenopausal (mean age: 62.13 ± 13.85). The incidence of LNM in both premenopausal and postmenopausal groups was comparable at 7% and 8%, respectively. In premenopausal women, multivariate logistic regression demonstrated that insulin levels (OR: 2.11, 95% CI: 1.48–2.85, P < 0.05) were significant predictors of LNM risk. In the same group, insulin levels remained significant predictors of LNM risk (cut‐off: 10.48 μIU/mL) when adjusted for body mass index (BMI) (OR: 3.51, 95% CI: 1.42–5.98; P < 0.05) or for waist‐to‐hip ratio (WHR) (OR: 1.87, 95% CI: 1.08–2.66; P < 0.05). Similarly, in postmenopausal women, multivariate logistic regression showed that insulin levels (OR: 1.99, 95% CI: 1.30–2.89; P < 0.05) also significantly predicted LNM risk. This relationship was maintained even after adjustment for BMI (cut‐off: 7.40 μIU/mL, OR: 1.99, 95% CI: 1.01–3.12, P < 0.05) or for WHR (cut‐off: 10.15 μIU/mL, OR: 1.61, 95% CI: 1.04–2.35; P < 0.05). Insulin levels are significantly associated with LNM risk in both premenopausal and postmenopausal women with endometrial cancer. Further prospective studies are needed to examine a potential causal relationship and determine whether its use can offer incremental value for risk stratification in this patient population.

Acute cellular rejection and infection rates in alemtuzumab versus traditional induction therapy agents for lung and heart transplantation: a systematic review and meta-analysis

BACKGROUND AND OBJECTIVESnHeart and lung transplantation is a high-risk procedure, requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific monoclonal antibody, is increasingly used for induction therapy compared with conventional agents. However, there has been no systematic review comparing its efficacy with traditional therapeutic drugs.nnnMETHODSnPubMed and EMBASE were searched to October 1, 2017, for articles on alemtuzumab in cardiothoracic transplant surgery. Of the 433 studies retrieved, 8 were included in the final meta-analysis.nnnRESULTSnIn lung transplantation, alemtuzumab use was associated with lower odds of acute cellular rejection compared with antithymocyte globulin (odds ratio [OR], 0.21; 95% CI, 0.11-0.40; Pxa0< .001), lower acute rejection rates (OR, 0.12; 95% CI, 0.03-0.55; Pxa0< .01), and lower infection rates (OR, 0.69; 95% CI, 0.35-1.36; Pxa0= .33) when compared with basiliximab. Multivariate meta-regression analysis found that mean age, male sex, single lung transplant, double lung transplant, cytomegalovirus or Epstein-Barr virus status, idiopathic pulmonary fibrosis, cystic fibrosis, and mean ischemic time did not significantly influence acute rejection outcomes. For heart transplantation, alemtuzumab use was associated with lower acute rejection rates when compared with tacrolimus (OR, 0.44; 95% CI, 0.30-0.66; Pxa0< .001).nnnCONCLUSIONSnAlemtuzumab use was associated with lower rejection rates when compared with conventional induction therapy agents (antithymocyte globulin, basiliximab, and tacrolimus) in heart and lung transplantation. However, this was based on observational studies. Randomized controlled trials are needed to verify its clinical use.

Synergistic effect of metformin and medroxyprogesterone 17‑acetate on the development of endometrial cancer

Accumulating data indicate that insulin resistance and unopposed estrogen are important risk factors of endometrial cancer (EC). Medroxyprogesterone 17‑acetate (MPA) has been used in the treatment of EC for many years. However, the therapeutic effect of this agent on EC has not been satisfactory. 36 arMetformin was recently reported to be a promising agent for the treatment of malignant diseases including EC. However, information on the synergistic effect of the two agents in EC is limited. With the aim to evaluate the synergistic effect of metformin and MPA, we conducted the present study inxa0vitro and inxa0vivo. We found that the combined application of metformin and MPA significantly inhibited the proliferation of the Ishikawa cells and arrested the cells in the G0/G1 phase. Furthermore, the apoptosis rate of the Ishikawa cells was significantly increased. In the animal study, the development of the xenograft tumors was significantly suppressed by the combined application of the two agents. Further investigation revealed that the synergistic inhibitory effect of the two agents on EC can be at least partly, explained by the decreased expression of cyclin D1 and cyclinxa0E. The results of the current study provide novel insights into the treatment of EC.

Role of JNK signalling pathway and platelet‑lymphocyte aggregates in myocardial ischemia‑reperfusion injury and the cardioprotective effect of ischemic postconditioning in rats

In myocardial ischemia‑reperfusion injury (MIRI), increased activity of the c‑Jun N‑terminal kinase (JNK) pathway and the activation of platelets that leads to the formation of platelet‑leukocyte aggregates (PLAs) have been observed. It was hypothesized that ischemic postconditioning in MIRI exerts cardioprotective effects by altering JNK activity, which in turn leads to reduced PLA levels. A total of 60 rats were randomly divided into 6 groups (n=10 for each group): i)xa0Control; ii)xa0ischemia‑reperfusion injury alone; iii)xa0ischemia‑reperfusion with postconditioning (PostC group), iv)xa0treatment with the JNK inhibitor‑SP600125; v)xa0postC and treatment with anisomycin; and vi)xa0treatment with the JNK activator‑anisomycin. Subsequently, the levels of PLA, infarct size, myocardial injury markers (creatinine kinase‑muscle/brain and troponin I) and were measured. Western blotting was used to determine the protein expression of phosphorylated‑JNK. MIRI led to increased myocardial infarct size that was associated with raised troponin I and creatine kinase‑muscle/brain. At different time points of MIRI, the level of PLA gradually increased. Compared with the injury‑reperfusion group, the level of PLA in the PostC and Inhibitor‑JNK groups was significantly reduced at 60xa0min and 3xa0h following reperfusion. MIRI was able to increase the expression of phosphorylated JNK. These effects were significantly reduced by ischemic postC or by treatment with SP600125. By contrast, the addition of anisomycin attenuated these protective effects. JNK is a critical mediator of MIRI. Ischemic postC can reduce the level of PLA during reperfusion by inhibiting the phosphorylation of JNK MAPK, thereby reducing MIRI. Pharmacological inhibition and activation of JNK can improve and reduce cardioprotective effects, respectively. These results explained the mechanism of the cardioprotection of postC and provided novel insight and target for the therapeutic strategy of MIRI.

Impact of Coronary Artery Chronic Total Occlusion on Arrhythmic and Mortality Outcomes: A Systematic Review and Meta-Analysis

OBJECTIVESnThis study aimed to examine the relationship between chronic coronary artery total occlusion (CTO) status and the occurrence of ventricular tachycardia (VT)/ventricular fibrillation (VF) or appropriate implantable cardioverter-defibrillator (ICD) therapy.nnnBACKGROUNDnCTO is a significant problem in patients with ischemic heart disease. However, the extent to which it predisposes affected individuals to VT/VF and whether these arrhythmic events could be prevented by revascularization are unclear. Therefore, a systematic review and meta-analysis were conducted to examine the relationship between CTO status and the occurrence of VT/VF or appropriate ICD therapy.nnnMETHODSnPubMed and Embase databases were searched until November 16, 2017, identifying 137 studies.nnnRESULTSnSeventeen studies involving 54,594 subjects (mean age, 61 ± 21 years of age, 81% male) with a mean follow-up of 43 ± 31 months were included. The presence of CTO was associated with higher risk of VT/VF or appropriate ICD therapy (adjusted hazard ratio [aHR]: 1.99; 95% confidence interval (CI): 1.53 to 2.59; pxa0< 0.0001, I2xa0= 3%) but not in cardiac mortality (aHR: 2.59; 95% CI: 0.64 to 10.59; pxa0= 0.18, I2xa0= 86%) or in all-cause mortality (aHR: 1.70; 95% CI: 0.84 to 3.46; pxa0= 0.14; I2xa0= 64%). Compared to patients with non-infarct-related CTOs, those with infarct-related CTOs have a higher risk of VT/VF or appropriate ICD therapy (aHR: 2.47; 95% CI: 1.76 to 3.46; pxa0< 0.0001; I2xa0= 14%), cardiac mortality (aHR: 2.73; 95% CI: 1.02 to 7.30; pxa0< 0.05; I2xa0= 79%) and higher all-cause mortality (aHR: 1.69; 95% CI: 1.19 to 2.40; pxa0< 0.01; I2xa0= 40%). Nonrevascularization of CTOs tended to be associated with an increased risk of all-cause mortality compared to successful revascularization (unadjusted HR: 1.52; 95% CI: 0.96 to 2.43; pxa0= 0.08; I2xa0= 76).nnnCONCLUSIONSnCTOs, especially infarct-related, are associated with high risk of VT/VF or appropriate ICD therapy and mortality. ICD implantation could be beneficial. However, it is not clear that revascularization has an impact on the outcome of patients with CTOs.