Balancing efficacy and safety in the management of atopic dermatitis: the role of methylprednisolone aceponate

Although emollients can be sufficient to manage mild atopic dermatitis (AD), acute flares resulting in moderate‐to‐severe symptoms require treatment with anti‐inflammatory agents, such as topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs). This review examines the role of a member of the newest class of TCs, the fourth‐generation compound methylprednisolone aceponate (MPA) in AD management, with reference to the chemical structure, pharmacokinetics, efficacy in AD, safety assessed in preclinical and clinical trials and dosing considerations. MPA has an optimized efficacy/safety profile with minimal local or systemic adverse effects. In addition, it offers the opportunity for once‐daily dosing, which provides benefits in terms of patient compliance with treatment.     

Transampullary pancreatic duct stenting decreases pancreatic fistula rate following left pancreatectomy

BACKGROUND/AIMS: Significant improvements in mortality following pancreatic surgery have been noted by high-volume centers in recent years. Despite this, morbidity from pancreatic resection remains high, with postoperative pancreatic fistula remaining a common problem following distal pancreatectomy (DP). Rates of pancreatic fistula following distal pancreatectomy have ranged from 0 to 61% in a recent meta-analysis of surgical techniques and impact upon pancreatic fistula rates. We postulated that intraoperative placement of a transampullary pancreatic duct stent (TAPDS) at the time of distal pancreatectomy, would decrease ampullary complex-mediated elevation in pancreatic duct pressures, improve healing of the ligated pancreatic duct and result in a decrease in pancreatic fistula following distal pancreatectomy. METHODOLOGY: Sixteen consecutive patients underwent distal pancreatectomy plus TAPDS and were compared to 43 control patients who underwent distal pancreatectomy by the same surgeon, with identical management of the pancreatic remnant. Distal pancreatectomy was performed as the primary operation or as part of an en-bloc resection for a primary malignancy other than pancreatic adenocarcinoma. In patients who underwent transampullary pancreatic duct stenting (TAPDS), the pancreatic duct was identified after transection of the pancreatic parenchyma. A soft, pediatric feeding tube was inserted directly into the pancreatic duct and carefully fed into the duodenum (confirmed by palpation). The stent was placed distally, one centimeter from the cut-edge of the pancreatic duct, which was then ligated as described earlier. Closure of the pancreatic parenchyma was identical to those patients who did not undergo TAPDS placement. Common perioperative outcomes were assessed, including pancreatic fistula. RESULTS: No statistically significant differences where found between the rates of intraabdominal abscess, intraabdominal hemorrhage or need for reoperation. Pancreatic fistula rates and average length of stay were significantly decreased in patients undergoing distal pancreatectomy with TAPDS (p<0.05 and p<0.0001 respectively). CONCLUSIONS: Statistically significant reductions in pancreatic fistula and average length of stay were noted in patients who underwent stenting of the pancreatic duct with TAPDS.     

中孕期非整倍体染色体异常血清学筛查不同方案比较

目的：对中孕期非整倍体染色体异常血清学筛查不同方案的检出率进行探讨。方法选取513名2009年9月~2013年3月在攀枝花市妇幼保健院产科进行常规产前筛查的孕妇血清样本,分别采用化学发光法和时间分辨荧光免疫法对孕妇血清进行二联、三联、四联检查,比较阳性率及假阳性率。结果二联化学发光法检测唐氏综合征(DS)高危假阳性率为9.10豫,三联为7.36豫,四联为6.28豫,假阳性率呈递减趋势(字2=5.119,P约0.05);二联化学发光法筛查18-三体高危假阳性率(0.63豫)低于三联(0.82豫),差异有统计学意义(字2=4.776,P约0.05)。三联时间分辨荧光免疫法筛查DS、18-三体假阳性率(4.01豫、0.34豫)较二联(8.93豫、0.61豫)均明显降低(字2=6.992、4.776,P约0.05)。二联化学发光法检测DS、18-三体假阳性率分别为9.10豫、0.63豫,时间分辨荧光免疫法则分别为8.93豫、0.61豫,两种检测方法比较,差异无统计学意义(字2=1.787、0.000,P跃0.05);而三联时间荧光分辨法检测DS、18-三体假阳性率(4.01豫、0.34豫)均低于三联化学发光法(7.36豫、0.82豫),差异有统计学意义(字2=5.382、4.783,P约0.05)。结论化学发光法的检测系统发现筛查效率二联、三联及四联方案呈递增趋势。时间分辨荧光免疫法检测系统发现筛查效率三联高于二联方案,时间荧光分辨法三联筛查优于化学发光法。     

Feasibility and implications of an early discharge strategy after percutaneous intervention with abciximab in acute myocardial infarction (the CADILLAC Trial)

Early complications may hamper efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.     

Intravascular brachytherapy for native coronary ostial in-stent restenotic lesions

OBJECTIVES: We analyzed the effects of vascular brachytherapy (VBT) on ostial in-stent restenosis (ISR). BACKGROUND: In-stent restenosis has a high recurrence rate after percutaneous reintervention. The recurrence rate of ostial ISR lesions and the impact of VBT remain unknown. METHODS: We evaluated 133 patients with native coronary ostial ISR from a pooled database of 990 patients enrolled in randomized VBT trials. Independent quantitative angiography was performed at baseline and follow-up in 45 gamma, 27 beta, and 61 placebo patients. RESULTS: Binary restenosis was significantly higher in placebo than radiated patients (75.4% vs. 17.8% in gamma vs. 22.2% in beta, p < 0.0001). The treatment effect of both gamma (odds ratio [OR] 0.06; 95% confidence interval [CI] 0.02 to 0.17) and beta VBT (OR 0.10; 95% CI 0.03 to 0.31) was maintained after controlling for differences in baseline lesion length. Proximal and distal radiation edge restenosis rates were similar among the groups. Vascular brachytherapy of true aorto-ostial lesions (n = 34) was similarly beneficial: restenosis rates of placebo versus gamma or beta patients of 83.3% versus 6.7% versus 28.6%, p = 0.0002. CONCLUSIONS: Conventional treatment of ostial ISR is associated with a recurrence rate of over 75%. Vascular brachytherapy with either gamma or beta sources results in significant and similar reductions in restenosis compared with placebo. Similar benefits after VBT prevail in true aorto-ostial lesions.     

Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice

An amphotropic retroviral vector, LgAL(delta Mo + PyF101) containing a human adenosine deaminase (ADA) cDNA was used to optimize procedures for the lasting genetic modification of the hematopoietic system of mice. The highest number of retrovirally infected cells in the hematopoietic tissues of long-term reconstituted mice was observed after transplantation of bone marrow (BM) cells that had been cocultured in the presence of both interleukin-1 alpha (IL-1 alpha) and IL-3. A significantly lower number was detected when IL-1 alpha was omitted from such cocultures. The yield of cells that generate spleen colony-forming cells (CFU-S) in the BM of lethally irradiated recipients (MRA-CFU-S) significantly improved on inclusion of the adherent cell fraction of cocultures in the transplant. Retroviral integration patterns in MRA-CFU-S-derived spleen colonies showed that an MRA-CFU-S can produce many CFU-S during BM regeneration. Expression of hADA was detected in the circulating white blood cells of long-term reconstituted animals, demonstrating that the LgAL(delta Mo + PyF101) vector is capable of directing the sustained expression of hADA, and in approximately 35% of the transduced MRA-CFU-S-derived spleen colonies. These results should facilitate the development of gene therapy protocols for the treatment of severe combined immunodeficiency caused by a lack of functional ADA.     

孟根乌森乌日乐对小鼠的急性毒性研究

目的：了解孟根乌森乌日乐的急性毒性作用剂量及给药后的急性毒性反应和死亡分布情况,确定孟根乌森乌日乐的半数致死量（ LD50）。方法用孔氏综合法（改进寇氏法）分为14．30,9．28,6．04,3．92,2．55,1．66 g? kg－16个剂量组,以0．4 mL／10 g的量灌胃给药1次。实验后观察14 d,记录体重变化及不良反应情况。结果孟根乌森乌日乐小鼠半数致死量为5．1597 g? kg－1（95％CI：3．6652～7．2637 g? kg－1）。14 d内未出现明显不良反应症状且体重有增长趋势。结论孟根乌森乌日乐的急性毒性实验的半数致死量为临床用药量的100倍,提示单次口服较为安全。     

Argatroban for therapeutic anticoagulation for heparin resistance associated with Covid-19 infection

Journal of Thrombosis and Thrombolysis -     

五种布鲁氏菌核酸检测试剂盒检测性能的评价北大核心CSCD

目的比较5种布鲁氏菌核酸实时荧光PCR检测试剂盒的一致性和检出能力,为临床实验室选择检测方法和布鲁氏菌的诊断提供参考依据。方法选用经病原学检测确定为布鲁氏菌阳性的血液样本38份,健康人的血液样本24份,潘氏变形杆菌、溶藻弧菌、河弧菌、铜绿假单胞菌、肺炎克雷伯菌DNA各1份,使用5种试剂盒(编号A-E)分别进行核酸检测,比较5种试剂盒临床样本检测的一致性;选择1份阳性样本核酸用无RNA酶水梯度稀释得到5个浓度(浓度1:4453.13 fg/μL,浓度2:1113.28 fg/μL,浓度3:278.32 fg/μL,浓度4:69.58 fg/μL,浓度5:17.40 fg/μL),每个浓度使用5种试剂盒(编号A-E)分别进行3次检测,比较5种试剂盒的阳性检出率及批内重复性。结果5种试剂盒检测67份DNA样品的符合率稍有不同,试剂盒ABDE的符合率均为100%,试剂盒C的符合率为98.51%。批内重复性显示5种试剂盒在浓度1、浓度2、浓度3水平重复检测DNA的Ct值变异系数均<5%;在浓度1与浓度4梯度区间,试剂盒的阳性检出能力比较显示试剂盒A、B、D较高,为11/12,试剂盒C和E较低,为8/12。结论5种试剂盒的真实性和可靠性较好,灵敏度和符合率稍有差别,特异度均为100%;重复性较好,检测性能良好。部分试剂盒对弱阳性样本的检出能力不强,该类样本可使用多种试剂盒复核,以保障结果的准确性。     

Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV- positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV- positive lymphoma blastoid cells rather than actual RS cells.