Evaluation of Bactec Mycosis IC/F and Plus Aerobic/F Blood Culture Bottles for Detection of Candida in the Presence of Antifungal Agents

Clinical practice guidelines recommend performing follow-up cultures for patients with candidemia in order to determine the time when Candida is cleared from the bloodstream. Since this requires culturing blood samples from patients undergoing antifungal treatment, we evaluated two blood culture bottles (the Bactec Mycosis IC/F [MICF], specifically adapted to the growth of fungi, and the Bactec Plus Aerobic/F [PAF], containing resins to inactivate anti-infective agents) for their effectiveness in detecting Candida albicans and Candida glabrata when seeded in concentrations of 1 CFU/ml and 10 CFU/ml, respectively, together with human whole blood and various antifungal agents in therapeutic peak serum concentrations (C_max). Significant differences between the MICF and PAF vials for the detection of Candida spp. were found when inoculated with caspofungin (0/12 versus 8/12) (P < 0.001) or amphotericin B (3/12 versus 12/12) (P < 0.001). Inoculation of fluconazole or voriconazole did not influence the effectiveness of detection in the MICF and PAF bottles (P = 1.0). Neither the MICF nor the PAF bottles detected Candida spp. reliably when seeded together with anidulafungin (1/12 versus 1/12) (P = 1.0) or micafungin (0/12 versus 1/12) (P = 1.0). The times to positivity of both bottles were significantly prolonged when antifungal agents were added compared to those of controls without antimycotic drugs (P < 0.001). Overall, the results of this in vitro study indicate that the PAF bottles detected Candida spp. more reliably than the MICF bottles when supplemented with certain antifungal agents. Consequently, clinical studies should evaluate whether this holds true when blood cultures from patients undergoing antifungal treatment are performed.     

Ephrin-B2 controls PDGFRβ internalization and signaling

B-class ephrins, ligands for EphB receptor tyrosine kinases, are critical regulators of growth and patterning processes in many organs and species. In the endothelium of the developing vasculature, ephrin-B2 controls endothelial sprouting and proliferation, which has been linked to vascular endothelial growth factor (VEGF) receptor endocytosis and signaling. Ephrin-B2 also has essential roles in supporting mural cells (namely, pericytes and vascular smooth muscle cells [VSMCs]), but the underlying mechanism is not understood. Here, we show that ephrin-B2 controls platelet-derived growth factor receptor β (PDGFRβ) distribution in the VSMC plasma membrane, endocytosis, and signaling in a fashion that is highly distinct from its role in the endothelium. Absence of ephrin-B2 in cultured VSMCs led to the redistribution of PDGFRβ from caveolin-positive to clathrin-associated membrane fractions, enhanced PDGF-B-induced PDGFRβ internalization, and augmented downstream mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) activation but impaired Tiam1–Rac1 signaling and proliferation. Accordingly, mutant mice lacking ephrin-B2 expression in vascular smooth muscle developed vessel wall defects and aortic aneurysms, which were associated with impaired Tiam1 expression and excessive activation of MAP kinase and JNK. Our results establish that ephrin-B2 is an important regulator of PDGFRβ endocytosis and thereby acts as a molecular switch controlling the downstream signaling activity of this receptor in mural cells.     

抑郁症的非药物治疗现状

抑郁症是一种发病率、复发率、致残率及致死率均较高的严重精神疾患。药物治疗抑郁症可以有效改善患者的临床症状,但起效滞后,且存在不良反应,从而影响了患者的治疗依从性。非药物治疗研究的不断发展为抑郁症的治疗开辟了新的有效途径。本文对抑郁症非药物治疗的研究现状进行了回顾与总结,了解非药物治疗的方法及优势,便于临床工作中尽快给予全面抗抑郁治疗,以提高临床缓解率。     

中国MSM中HIV原发耐药的Meta分析

目的了解中国男男性行为人群(MSM)中艾滋病病毒(HIV)原发耐药水平。方法检索5个数据(万方、CNKI、VIP、CBM及Pubmed)并提取HIV耐药的原始数据,根据异质性检验结果,选择模型对原始数据进行合并分析。结果共纳入28个研究。中国MSM未治疗HIV感染者总耐药率、蛋白酶抑制剂(PI)耐药率、核苷类反转录酶抑制剂(NRTI)耐药率、非核苷类反转录酶抑制剂(NNRTI)耐药率分别为3.59%[95%可信区间(CI):2.40%~4.96%]、1.69%(95%CI:0.74%~2.90%)、0.52%(95%CI:0.14%~1.05%)、0.54%(95%CI:0.16%~1.08%)。总耐药率及PI耐药率存在地区差异,华北、东北、华东地区耐药率更高些。结论当前中国MSM的HIV感染者原发耐药水平低,抗病毒治疗政策实际且可行。但是在一些高发地区,更需加强监测,以便提供最优治疗方案。     

Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen

Objective: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as adjunctive analgesics in cholecystectomy patients by comparing associated hospital length of stay (LOS), hospital costs, opioid use, and rates of nausea/vomiting, respiratory depression, and bowel obstruction.

Methods: We conducted a retrospective analysis of the Premier Database (January 2012 to September 2015) including cholecystectomy patients who received either IV APAP or oral APAP. Differences in LOS, hospitalization costs, mean daily morphine equivalent dose (MED), and potential opioid-related adverse events were estimated. Multivariable logistic regression was performed for the binary outcomes and instrumental variable regressions, using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for continuous outcomes. Models were adjusted for patient demographics, clinical risk factors, and hospital characteristics.

Results: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP. Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter LOS (95% CI?=?–0.58 to –0.27; p?p?p?=?.0005), and lower rates of respiratory depression (odds ratio [OR]?=?0.89, 95% CI?=?0.82–0.97; p?=?.006), and nausea and vomiting (OR?=?0.86, 95% CI?=?0.86–0.86; p?Conclusions: In patients having cholecystectomy, the addition of IV APAP to perioperative pain management is associated with shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting and respiratory depression compared to oral APAP. These findings should be confirmed in a prospective study comparing IV and oral APAP.     

RAS基因突变对结直肠癌肝转移患者肝切除术后预后的影响

目的分析RAS基因突变对结直肠癌肝转移行肝切除患者预后的影响。方法回顾分析北京大学肿瘤医院肝胆胰外一科2008年1月1日至2016年12月31日连续收治的545例结直肠癌肝转移行肝切除的患者资料,依据纳入和排除标准最终纳入356例,男性232例,女性124例,年龄21〜83岁。比较RAS基因野生型和突变型患者的临床和随访资料。采用Kaplan-M eier法进行生存分析,比较采用log-rank检验。单因素和多因素Cox回归分析患者生存的影响因素。结果RAS基因野生型和突变型患者分别为247例和109例。RAS基因野生型患者中位生存期为74个月,突变型为30个月。RAS基因野生型患者累积生存率和累积无病生存率均优于突变型,差异有统计学意义(均P<0.05)。多因素Cox回归分析,肝转移出现间隔≤12个月(HR=1.673,95%CI:1.016~2.637)、肝转移瘤最大直径>5cm(HR=1.717,95%(CI:1.102〜2.637)、RAS基因突变型(HR=1.836,95%CI:1.322〜2.550)是结直肠癌肝转移患者手术切除后生存的独立危险因素。结论RAS基因突变是结直肠癌肝转移患者肝切除术后生存的危险因素,RAS基因突变型患者预后更差。     

贬低-歧视感知量表中文版测评社区人群病耻感的信效度

目的:考察贬低-歧视感知量表(PDD)测评社区人群病耻感的信效度。方法:采用多阶段分层整群抽样,于2011年7月-12月对抽取的天津市1621位18岁及以上社区居民进行贬低-歧视感知量表及心理健康知识问卷调查,按照40%的比例随机抽取被试完成美国精神障碍诊断及统计手册第4版(DSM-IV)轴I诊断临床定式检查患者版(SCID-I/P)的定式访谈,共有668人完成精神科诊断访谈,401人不存在任何精神障碍诊断,267人有精神障碍诊断。使用Cronbachα系数及条目与总分之间的相关系数检验量表的内部效度;探索性因素分析和验证性因素分析PDD量表的因子结构;在无任何DSM-IV轴I障碍诊断的人群中使用多元线性回归分析PDD总分的相关因素。结果:PDD的Cronbachα系数为0.70。各条目与总分呈相关系数在0.31~0.56之间。设定2个因子进行探索性因子分析发现两因子分别为肯定语句条目与否定语句条目。验证性因子分析发现在5个模型中,用潜在方法因子调整肯定与否定语句带来的方法效应时,单一因子(感知的贬低-歧视)模型4与2个独立的因子(感知的贬低,感知的歧视)模型5拟合程度好(GFI=0.96,TLI=0.83,CFI=0.88,RMSEA=0.06;GFI=0.97,TLI=0.84,CFI=0.89,RM SEA=0.06)。在无任何DSM-IV诊断人群中多元线性回归分析显示,PDD量表总分与城乡、性别、职业、婚姻状况、年龄、平均收入及教育程度的相关无统计学意义,仅有心理健康知识问卷得分进入回归方程(β=-0.40,R2=0.02)。结论:贬低-歧视感知量表具有可接受的内部一致性信度,回归分析结果符合构建此量表的"修正标签"理论,可用于国内社区人群精神疾病病耻感研究。