老年急性心肌梗死急诊PCI术后联合服用尼可地尔与曲美他嗪对改善心功能的短期随访研究

目的：观察急诊经皮冠状动脉介入术(PCI)后联合服用尼可地尔、曲美他嗪对对老年多支病变ST段抬高型心肌梗死(STEMI)心功能的改善效果。方法：将2014年6月-2016年12月期间105例急诊PCI有效病例据随机数字分为观察组(52例)、对照组(53例),对照组出院后服用盐酸曲美他嗪片,每次20mg,每日3次,连服6个月,观察组在对照组基础上加服尼可地尔片,每次5mg,每日3次,术后随访6个月,比较两组血清学心肌损伤标志物、顿抑心肌血流灌注、心功能及不良心血管事件。结果：两组术后6个月BNP、Hs-CRP、MMP-9均显著低于本组术后3个月水平(P<0.05);术后3个月,观察组BNP(202.7±42.6 vs. 225.7±48.3) pg/ml显著低于对照组(P<0.05),术后6个月观察组BNP(137.9±36.5 vs. 165.9±41.1) pg/ml、Hs-CRP(4.19±1.23 vs. 5.01±1.55) mg/L、MMP-9(82.8±13.6 vs. 95.7±17.4) μg/L均显著低于对照组(P<0.05)。心肌核素显像显示两组术后6个月SRS、TPD%均显著低于术后3个月水平(P<0.05);术后3个月观察组SRS(15.6±3.8 vs. 17.9±4.3)显著低于对照组,术后6个月观察组SRS(8.9±2.3 vs. 13.5±2.8)、TPD%(18.2±4.9 vs. 22.4±5.7)%均显著低于对照组(P<0.05)。超声心动图检查显示两组术后LVEF、PER均较出院前显著提高(P<0.05),LVESVI、LVEDVI均显著降低(P<0.05);术后3个月观察组LVEF(56.1±4.5 vs. 53.9±4.6)%显著高于对照组,术后6个月观察组LVEF(58.8±4.7 vs. 56.5±4.7)%、PER(1.82±0.13 vs. 1.77±0.11) EDV/s均显著高于对照组(P<0.05),而LVESVI(38.5±6.3 vs. 42.1±7.8) ml/m₂、LVEDVI(85.6±12.5 vs. 92.4±14.4)ml/m₂均显著低于对照组水平(P<0.05)。观察组随访期内心绞痛发生率(7.7% vs.17.0%)、靶血管血运重建比例(1.9% vs.5.7%)、再入院比例(5.8% vs.9.4%)低于对照组,差异均无统计学意义(P＞0.05)。结论：尼可地尔、曲美他嗪对改善心肌灌注作用协同,急诊PCI术后口服曲美他嗪基础上加服尼可地尔有助于减轻心肌损伤,提高心功能,联合用药长期效果更为显著。     

The effect of age on blood pressure response by 4‐week treatment perindopril: A pooled sex‐specific analysis of the EUROPA,PROGRESS, and ADVANCE trials

Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron‐MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4‐week run‐in phase in which all patients were treated with the perindopril‐based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1–5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55–65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55–65: 2.8 mmHg [95% CI = 1.8–3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7–4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age‐adjusted perindopril dosages.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Previous animal studies have shown that the response to antihypertensive treatment targeting the renin angiotensin aldosterone system (RAAS) might be different after reproductive senescence.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Are there differences in perindopril‐based treatment response to RAAS inhibitor perindopril in different age categories in women and men?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In both women and men, the effects of perindopril on systolic blood pressure decrease and on diastolic blood pressure increase with age.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

More research is needed to find out whether it would be beneficial to use age‐adjusted perindopril dosages in isolated systolic hypertension.     

Dietary heme injures surface epithelium resulting in hyperproliferation, inhibition of apoptosis and crypt hyperplasia in rat colon

Epidemiological and animal model studies suggest that a high intake of heme, present in red meat, is associated with an increased risk of colon cancer. The aim of this study was to elucidate the effects of dietary heme on colonic cell homeostasis in rats. Rats were fed a purified, humanized, control diet or a similar diet supplemented with 0.5 mmol heme/kg for 14 days. Fecal water cytolytic activity was determined with a bioassay, and colon epithelial cell proliferation was evaluated with (3)H-thymidine or 5-bromo-2'-deoxyuridine incorporation into DNA or by Ki-67 immunohistochemistry. Exfoliation of colonocytes was measured as the amount of rat DNA in feces, and caspase-3 expression and activity were measured to study colonic mucosal apoptosis. Dietary heme induced a >10-fold increased cytolytic activity of the fecal water and a 100-fold lower excretion of host DNA. Colons of heme-fed rats showed injured surface epithelium and an approximately 25% increase in crypt depth. Finally, dietary heme doubled colonocyte proliferation, shown by all three markers, but inhibited colonic mucosal apoptosis. In conclusion, our results demonstrate that dietary heme injures colonic surface epithelium, which is overcompensated by inhibition of apoptosis and hyperproliferation of cells in the crypts, resulting in crypt hyperplasia. This disturbed epithelial cell homeostasis might explain why a high intake of dietary heme is associated with an increased risk of colon cancer.     

Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: a feasibility study

PURPOSE: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. METHODS AND MATERIALS: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. RESULTS: Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. CONCLUSIONS: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.     

Early results and long-term follow-up after corrective surgery for total anomalous pulmonary venous return.

OBJECTIVE: An ever increasing number of patients with an operated congenital cardiac anomaly is reaching adulthood. Insight in the long-term characteristics of these patients is steadily growing for the more common anomalies, but is still scarce for the less frequent entities. In this regard we report our results and long-term follow-up of surgically treated total anomalous pulmonary venous return (TAPVR). METHODS: Since 1973 44 patients with TAPVR were treated with surgery. There were 23 girls and 21 boys. Hospital mortality concerned six patients and additionally one patient died 2.5 months after surgery. Follow-up data could be collected from all the surviving patients at last outpatient visit or by phone contact. The mean duration of the follow-up was 12 years (range 1 month to 24 years). RESULTS: The Kaplan-Meier estimate of survival at 15 years was 84% (95% CI 73-95%). Reoperations were performed for five patients at 7 days to 4.5 years after surgery. In one patient this involved obstruction of pulmonary venous return, in four complications of the primary repair. The reoperation-free survival at 15 years was 74% (95% CI 61-87%). At the end of follow-up all survivors were in NYHA functional class I and, at appropriate age, normally attended school or were employed. None of the patients was using cardiac medication. CONCLUSIONS: We conclude that, despite a possible hectic initial postoperative course of surgery for TAPVR, only a limited number of reoperations is necessary relatively short after initial surgery. The long-term perspective for those surviving surgical treatment is good.     

微重力条件下动态三维诱导骨髓间充质干细胞分化为软骨细胞：与静态培养的比较

目的:观察微重力条件下动态三维诱导骨髓间充质干细胞向软骨细胞的分化,并与静态培养作比较。方法:实验于2005-08/2006-04在哈尔滨医科大学附属第一医院中心实验室完成。穿刺抽取2月龄新西兰大白兔骨髓,密度梯度离心法分离纯化,体外培养扩增。取第3代骨髓间充质干细胞分组诱导培养:三维动态培养组:1%藻酸钠溶液洗涤并重新悬浮细胞,细胞密度为5×1010L-1,滴入200mmol/L氯化钙溶液,立即形成藻酸钙凝胶微球,细胞被悬浮固定于球内部,静止5min,取出凝胶微球,磷酸盐缓冲液充分洗涤,置于旋转式细胞培养系统,微重力条件下动态诱导。二维动态培养组:细胞直接接种于平面培养瓶,置于旋转式细胞培养系统,微重力条件下动态诱导。三维静态培养组:藻酸钙凝胶微球悬浮细胞静态培养。二维静态培养组:细胞直接接种于平面培养瓶静态培养。诱导培养2周后取材,甲苯胺蓝染色、Ⅰ、Ⅱ型胶原免疫组织化学染色,测定胶原和蛋白多糖含量。结果:①藻酸钠接触钙离子迅速形成透明凝胶微球,直径约为1.0mm,均匀一致,有光泽,易于操作。倒置显微镜下见凝胶微球中的细胞呈球形,核仁清晰,动、静态培养后立体结构相似。甲苯胺蓝染色阳性,表达Ⅱ型胶原,无明显Ⅰ型胶原表达。平面培养组细胞形态由梭形向多角形、多边形转变,核周可见黑色颗粒。甲苯胺蓝染色弱阳性,仅少数细胞表达Ⅱ型胶原。②与静态培养相比,动态培养出现明显软骨分化,动态培养组胶原和蛋白多糖产量均高于静态培养培养组,以三维动态培养组效果最佳[胶原:0.078±0.004,0.069±0.003,0.048±0.002,0.035±0.004;蛋白多糖:0.111±0.003,0.092±0.002,0.069±0.003,0.058±0.002,(P<0.05)]。结论:立体诱导优于平面诱导,微重力动态培养可提高细胞诱导分化质量。     

A combination of statins and beta-blockers is independently associated with a reduction in the incidence of perioperative mortality and nonfatal myocardial infarction in patients undergoing abdominal aortic aneurysm surgery.

OBJECTIVE: To investigate the combined beneficial effect of statin and beta-blocker use on perioperative mortality and myocardial infarction (MI) in patients undergoing abdominal aortic aneurysm surgery (AAA). BACKGROUND: Patients undergoing elective AAA-surgery identified by clinical risk factors and dobutamine stress echocardiography (DSE) as being at high-risk often have considerable cardiac complication rate despite the use of beta-blockers. METHODS: We studied 570 patients (mean age 69+/-9 years, 486 males) who underwent AAA-surgery between 1991 and 2001 at the Erasmus MC. Patients were evaluated for clinical risk factors (age>70 years, histories of MI, angina, diabetes mellitus, stroke, renal failure, heart failure and pulmonary disease), DSE, statin and beta-blocker use. The main outcome was a composite of perioperative mortality and MI within 30 days of surgery. RESULTS: Perioperative mortality or MI occurred in 51 (8.9%) patients. The incidence of the composite endpoint was significantly lower in statin users compared to nonusers (3.7% vs. 11.0%; crude odds ratio (OR): 0.31, 95% confidence interval (CI): 0.13-0.74; p=0.01). After correcting for other covariates, the association between statin use and reduced incidence of the composite endpoint remained unchanged (OR: 0.24, 95% CI: 0.10-0.70; p=0.01). Beta-blocker use was also associated with a significant reduction in the composite endpoint (OR: 0.24, 95% CI: 0.11-0.54). Patients using a combination of statins and beta-blockers appeared to be at lower risk for the composite endpoint across multiple cardiac risk strata; particularly patients with 3 or more risk factors experienced significantly lower perioperative events. CONCLUSIONS: A combination of statin and beta-blocker use in patients with AAA-surgery is associated with a reduced incidence of perioperative mortality and nonfatal MI particularly in patients at the highest risk.     

Prevalence and Factors Associated with Sarcopenia in Patients on Maintenance Dialysis in Australia—A Single Centre,Cross-Sectional Study

Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopenia in patients on maintenance dialysis by using the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria of sarcopenia and to identify associated risk factors. Methods: We evaluated adult patients on maintenance haemodialysis and peritoneal dialysis in this single-centre cross-sectional study in Australia. Patient’s clinical (age, gender, dialysis modality and diabetic status) and laboratory parameters (serum albumin, calcium, phosphate, 25-hydroxy-vitamin D and parathyroid hormone levels) were investigated. We employed bioimpedance spectroscopy, hand grip dynamometer and the timed up and go test (TUG) to evaluate muscle mass, strength and function, respectively. Results: We evaluated 39 dialysis patients with a median age of 69 years old. The prevalence of sarcopenia was 18%. Sarcopenia was associated with low serum albumin (p = 0.02) and low serum phosphate level (p = 0.04). Increasing age and female sex were potential risk factors for sarcopenia (p = 0.05 and 0.08, respectively). Low lean muscle mass, reduced hand grip strength and prolonged TUG were present in 23.1%, 41% and 40.5%, respectively, of the cohort. The hand grip test had good correlation with lean muscle evaluation and the TUG. Conclusions: Sarcopenia was prevalent in 18% of maintenance haemodialysis patients from an Australian single-centre cohort, with low serum albumin and phosphate as significant risk factors.