国产雷帕霉素洗脱支架治疗急性冠状动脉综合征：安全性和临床有效性

目的:分析国产雷帕霉素洗脱支架治疗急性冠状动脉综合征的安全性和有效性。方法:选择2004-11/2006-02在河北大学附属医院接受冠状动脉介入治疗的急性冠状动脉综合征患者102例,其中ST段抬高型心肌梗死54例,非ST段抬高型心肌梗死28例,不稳定型心绞痛20例。根据血管情况置入国产雷帕霉素药物洗脱支架(Firebird支架),支架选择原则为:支架长度应覆盖病变两端;血管直径:支架直径=1∶1.1。所有患者术前3d均口服阿司匹林100mg,氯吡格雷75mg,术中推注肝素8000￣10000U,手术每延迟1h,补充肝素1000u,术后皮下注射低分子肝素5￣7d;服用氯吡格雷75mg,1次/d,共服用9￣12个月,并长期服用阿司匹林100mg,1次/d。随访情况:术后6个月时随访64例;7个月时随访26例;8个月时随访12例;平均随访6.8个月,患者出院后定期进行门诊随访,记录一般情况及严重心脏不良事件(包括急性、亚急性、迟发支架内血栓形成;再发心肌梗死;急诊冠状动脉旁路移植术;死亡),术后6￣8个月行冠状动脉造影评价支架内再狭窄情况。并观察材料及宿主反应。结果:102例患者经皮冠状动脉介入治疗治疗均获得成功,共治疗靶血管102支,置入Firebird支架116枚,术中3例ST段抬高型心肌梗死患者出现无复流现象,2例发生室颤,电转复恢复窦性心律,3例因分支受压,出现心绞痛症状。术后4例出现穿刺部位血肿,经重新加压压迫后好转。随访6￣8个月所有患者未发生严重心血管事件;42例(41.2%)患者术后6￣8个月行冠状动脉造影复查,无一例发生支架内再狭窄。随访期间所有患者无全身毒性及超敏反应发生,生物相容性好。结论:国产药物洗脱支架治疗急性冠状动脉综合征安全,有效。     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.     

导致成人与儿童患者30天脑室腹腔分流失败的原因分析（英文）

OBJECTIVE The aim of this study was to provide a comprehensive benchmark of 30-day ventriculoperitoneal(VP)shunt failure rates for a single institution over a 5-year study period for both adult and pediatric patients,to compare this with the results in previously published literature,and to establish factors associated with shunt failure.METHODS A retrospective database search was undertaken to identify all VP shunt operations performed in a single,regional neurosurgical unit during a 5-year period.Data were collected regarding patient age,sex,origin of hydrocephalus,and whether the shunt was a primary or secondary shunt.Operative notes were used to ascertain the type of valve inserted,which components of the shunt were adjusted/replaced(in revision cases),level of seniority of the most senior surgeon who participated in the operation,and number of surgeons involved in the operation.Where appropriate and where available,postoperative imaging was assessed for grade of shunt placement,using a recognized grading system.Univariate and multivariate models were used to establish factors associated with early(30-day)shunt failure.RESULTS Six hundred eighty-three VP shunt operations were performed,of which 321 were pediatric and 362 were adult.The median duration of postoperative follow-up for nonfailed shunts(excluding deaths)was 1263 days(range 525-2226 days).The pediatric 30-day shunt failure rates in the authors'institution were 8.8%for primary shunts and 23.4%for revisions.In adults,the 30-day shunt failure rates are 17.7%for primary shunts and 25.6%for revisions.In pediatric procedures,the number of surgeons involved in the operating theater was significantly associated with shunt failure rate.In adults,the origin of hydrocephalus was a statistically significant variable.Primary shunts lasted longer than revision shunts,irrespective of patient age.CONCLUSIONS A benchmark of 30-day failures is presented and is consistent with current national databases and previously published data by other groups.The number of surgeons involved in shunt operations and the origin of the patient's hydrocephalus should be described in future studies and should be controlled for in any prospective work.The choice of shunt valve was not a significant predictor of shunt failure.Most previous studies on shunts have concentrated on primary shunts,but the high rate of early shunt failure in revision cases(in both adults and children)is perhaps where future research efforts should be concentrated.     

Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine

Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.