Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

参七益气活血汤在心肌梗死患者中的临床效果及对患者生活质量的影响

目的 探讨参七益气活血汤治疗心肌梗死的临床效果及对生活质量的影响。方法 选取我院在2015年1月～2017年12月收治的心肌梗死患者100例，平均分为对照组和研究组，每组各50例。对照组采用常规西药进行治疗，研究组则在对照组基础上联合参七益气活血汤进行治疗，比较两组患者的临床效果。结果 研究组临床有效率要高于对照组（P＜0.05）；治疗前两组患者的中医证候积分无明显区别（P＞0.05），治疗后研究组低于对照组（P＜0.05）；治疗后两组患者的GCS以及QOL评分明显升高，研究组评分情况要优于对照组（P＜0.05）。 结论采用参七益气活血汤治疗心肌梗死能够取得比较理想的临床疗效，可以更好地改善患者胸闷胸痛、心悸、气短等临床症状，防止患者血栓的形成发生再梗死，能有效改善患者的生活质量，且安全性良好，临床上值得进一步推广和应用。     

Functional genetic evaluation of DNA house-cleaning enzymes in the malaria parasite: dUTPase and Ap4AH are essential in Plasmodium berghei but ITPase and NDH are dispensable

Background: Cellular metabolism generates reactive oxygen species. The oxidation and deamination of the deoxynucleoside triphosphate (dNTP) pool results in the formation of non-canonical, toxic dNTPs that can cause mutations, genome instability, and cell death. House-cleaning or sanitation enzymes that break down and detoxify non-canonical nucleotides play major protective roles in nucleotide metabolism and constitute key drug targets for cancer and various pathogens. We hypothesized that owing to their protective roles in nucleotide metabolism, these house-cleaning enzymes are key drug targets in the malaria parasite.

Methods: Using the rodent malaria parasite Plasmodium berghei we evaluate here, by gene targeting, a group of conserved proteins with a putative function in the detoxification of non-canonical nucleotides as potential antimalarial drug targets: they are inosine triphosphate pyrophosphatase (ITPase), deoxyuridine triphosphate pyrophosphatase (dUTPase) and two NuDiX hydroxylases, the diadenosine tetraphosphate (Ap4A) hydrolase and the nucleoside triphosphate hydrolase (NDH).

Results: While all four proteins are expressed constitutively across the intraerythrocytic developmental cycle, neither ITPase nor NDH are required for parasite viability. dutpase and ap4ah null mutants, on the other hand, are not viable suggesting an essential function for these proteins for the malaria parasite.

Conclusions: Plasmodium dUTPase and Ap4A could be drug targets in the malaria parasite.     

A randomized,triple‐blind,placebo‐controlled clinical trial,evaluating the sesamin supplement effects on proteolytic enzymes,inflammatory markers,and clinical indices in women with rheumatoid arthritis

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple‐blind, placebo‐controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200‐mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases‐3) and inflammatory biomarkers (hs‐CRP, IL‐1β, IL‐6, TNF‐α, and cyclooxygenase‐2) were measured with enzyme‐linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases‐3 decreased significantly in sesamin group. Also, serum levels of hs‐CRP, TNF‐α, and cyclooxygenase‐2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.     

Identification and human exposure prediction of two aldehyde oxidase-mediated metabolites of a methylquinoline-containing drug candidate

1. Aldehyde oxidase (AO enzymes)-mediated oxidation predominantly occurs at a carbon atom adjacent to the nitrogen on aromatic azaheterocycles. In the current report, we identified that AO enzymes oxidation took place at both the C-2 and C-4 positions of the methylquinoline moiety of Compound A based on data from mass spectrometric analysis, AO enzymes “litmus” test, and comparison with authentic standards.

2. To assess the potential for inadequate coverage for these two AO enzyme-mediated metabolites in nonclinical safety studies, given concerns due to differences in AO enzymes expression between preclinical species and humans, the human circulating levels of the two AO enzyme-mediated metabolites were predicted prospectively using in vitro and in vivo models. Both formation clearance and elimination clearance of the two metabolites were predicted based on in vitro to in vivo correlation and comparison with in vivo data from rats.

3. The result showed that the 4-OH metabolite of Compound A would account for less than 3% of the total drug-related exposure in human plasma, while the exposure to the 2-oxo metabolite would be relatively high (～70%).

4. The predicted human exposure levels for the two metabolites are in similar ranges as those observed in monkeys. These data taken together support the advancement to clinical development of Compound A.     

二维斑点追踪成像技术结合心肌做功评价蒽环类药物对乳腺癌患者左心室功能的影响#br#

背景与目的：应用二维斑点追踪成像（two-dimensional speckle tracking imaging，2D-STI）结合心肌做功评价蒽环类药物对乳腺癌患者左心室功能的影响。方法：前瞻性选择2019年9月—2020年3月在复旦大学附属肿瘤医院行蒽环类药物治疗的35例乳腺癌患者，分别于化疗前、化疗2个周期后、4个周期后行常规超声心动图检查并获取动态二维图像，同时使用肱动脉袖带血压计测量患者收缩期及舒张期血压值，测量左房内径（left atrial diameter，LAD）、左心室舒张末期内径（left ventricular end-diastolic diameter，LVEDD）、左心室收缩末期内径（left ventricular end-systolic diameter，LVESD）、舒张末期室间隔厚度（diastolic interventricular septal depth，IVSD）、左心室舒张末期容积（left ventricular end-diastolic volume，LVEDV）、左心室收缩末期容积（left ventricular end-systolic volume，LVESV）、左心室射血分数（left ventricular ejection fraction，LVEF）、二尖瓣口舒张早期峰值流速（early diastolic peak velocity，E峰）、舒张晚期峰值流速（late diastolic tissue velocity，A峰）、二尖瓣环间隔处舒张早期峰值速度（early diastolic tissue velocity，e’），并计算E/A、E/e’；应用EchoPac软件脱机分析，获取左心室整体纵向应变（global longitudinal strain，GLS）、左心室分层纵向应变（GLSendo、GLSmid、GLSepi），以及左心室心肌整体做功指数（global myocardial work index，GWI）、整体有用功（global constructive work，GCW）、整体无用功（global wasted work，GWW）、整体做功效率（global myocardial work efficiency，GWE）；并行统计学分析。结果：与化疗前比较，化疗2个周期乳腺癌患者GLSeondo、GLS有所减低，但差异无统计学意义（P＞0.05）；GWW增加，GWE降低（P＜0.05）；化疗4个周期后GLS、GLSendo、GWI、GCW、GWE均降低，GWW增加。与化疗2个周期后比较，化疗4个周期后乳腺癌患者GLS、GLSendo、GWI、GCW、GWE降低，GWW增加（P＜0.05）。与化疗前比较，化疗4个周期后乳腺癌患者E/e’升高（P＜0.05）。各周期结束后的其余各项超声心动图参数与化疗前比较差异均无统计学意义（P＞0.05）。结论：2D-STI能早期检测乳腺癌患者在蒽环类药物化疗中左心室功能的早期改变， GWW及GWE较其他参数更敏感。     

The role of peer support education model on the quality of life and self-care behaviors of patients with myocardial infarction

ObjectiveThis study aimed to assess the effect of peer education on the quality of life and self-care behaviors of patients with myocardial infarction.MethodsIn this clinical trial, 70 patients with myocardial infarction meeting the inclusion criteria were assigned to experimental (n = 35) or control (n = 35) groups using block randomization. Patients in the intervention group received two one-hour training sessions on the third day after myocardial infarction during the CCU stay along with routine care. Education intervention was performed by peers. The control group will follow routine care. All patients selected were assessed using McNews' quality of life questionnaire and Miller self-care questionnaire, respectively before the intervention and also one month after discharge. Chi-square and t-test were used to analyze the data.ResultsAfter the intervention, the mean of quality of life and the mean score of self-care behaviors in the experimental group were significantly higher compared to the control group.ConclusionsAccording to the results, to improve the quality of life and promote the self-care behaviors in such patients, using peer education along with healthcare professionals is recommended.Practice ImplicationThis patient education approach had a significant impact on quality of life and self-care behavior.     

Clinical characteristics and prognosis of postpartum acute kidney injury

ObjectiveTo investigate the clinical characteristics and prognoses of patients with postpartum acute kidney injury (PPAKI).MethodsWe retrospectively reviewed the clinical presentations, laboratory examinations, treatments, and outcomes of patients with PPAKI admitted to our hospital from January 2013 to December 2017. We then analyzed the clinical characteristics and prognoses of the mothers and their infants.ResultsOf 37 patients diagnosed with PPAKI, 26 (70.3%) received treatment in the intensive care unit, mainly for hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome (28/37, 75.7%), pre-eclampsia (26/37, 70.3%), and postpartum hemorrhage (22/37, 59.5%). Twenty patients required renal replacement treatment (RRT), but renal recovery times were similar in the RRT and non-RRT groups. Renal function recovered completely in 30 patients (81.1%) and partially in one patient (2.7%), and was not re-examined in two patients (5.4%). Three patients (8.1%) were lost to follow-up. Only one patient (2.7%) remained dialysis-dependent, and no maternal deaths occurred. The preterm birth, low birth weight, and infant survival rates were 70.7% (29/41), 68.3% (28/41), and 78.0% (32/41), respectively.ConclusionRRT does not reduce renal recovery time compared with non-RRT. Overall, the prognoses of both mothers and their fetuses are good following treatment for PPAKI.