Bridging therapy for early surgery in patients on dual antiplatelet therapy after drug-eluting stent implantation

Objectives

To evaluate stent-related adverse cardiac events and bleeding complications within 30 days after surgical procedures in patients with recent drug-eluting stent (DES) implantation, in whom a bridging protocol was used.

Methods

In our centre a bridging protocol is used in patients scheduled for cardiac or non-cardiac surgery within 6 months after PCI with DES implantation. Clopidogrel and in some cases also acetylsalicylic acid is discontinued 5 days prior to the planned intervention and patients are admitted 2 to 3 days before the intervention for tirofiban infusion. This is discontinued 4 h before intervention. Close postoperative monitoring is performed and double antiplatelet therapy is restarted as soon as possible. Thirty-six consecutive patients were included in the protocol, 15 receiving coronary artery bypass graft and 21 non-cardiac interventions. Thrombotic and bleeding complications were studied for up to 30 days after the bridged procedure.

Results

No incidences of stent thrombosis or other adverse cardiac events (mortality, myocardial infarction) were seen in up to 30 days of follow-up. However, 6 bleeding events were reported of which 5 required a blood transfusion.

Conclusion

Our bridging protocol in patients requiring surgery after recent PCI with DES seems adequate to prevent stent thrombosis in this high-risk group. The bleeding risk is not insignificant but in our patient group controllable without major late sequelae. Larger studies should be performed to establish safety and efficacy in order to develop guidelines for these patients.     

A prospective,randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin

Background and Aim. Failure of primary anti‐H. pylori therapy results in a high rate of antimicrobial resistance. Here, we investigated the efficacy of high‐dose dual therapy and quadruple therapy as salvage treatments for eradication of H. pylori resistant to both metronidazole and clarithromycin. Patients and Methods. Patients with at least one treatment failure and infected with H. pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 × 40 mg and amoxicillin 4 × 750 mg; or omeprazole 2 × 20 mg, bismuthcitrate 4 × 107 mg, metronidazole 4 × 500 mg and tetracycline 4 × 500 mg. Both regimens were given for 14 days. In cases of persistent infection, a cross‐over therapy was performed. Results. Eighty‐four patients were randomized. Cure of H. pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9–93.8) and 92.1% (95% CI, 78.6–98.3), respectively (p = 0.71); intention to treat: 75.6% (95% CI: 59.7–87.6) and 81.4% (95% CI: 66.6–91.6), respectively (p = 0.60)). Cross‐over therapy was performed in six of nine patients, four of whom were cured of the infection. Conclusion. Both high‐dose dual therapy and quadruple therapy are effective in curing H. pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures.     

二联方案在幽门螺杆菌根除治疗中的应用进展

幽门螺杆菌(Helicobacter pylori,H.pylori)在世界范围内感染率高,随着H.pylori对常用抗生素的耐药率逐渐增加,高效的经验性治疗方案亟待探索。新近Maastricht V/Florence共识及我国第五次幽门螺杆菌感染处理共识均推荐含铋剂四联方案可作为一线治疗方案。但是,四联方案存在用药多、药物不良反应多、患者依从性差、部分老年人及肝、肾功能不全的患者无法耐受等缺点。近年来多项研究显示高剂量阿莫西林联合质子泵抑制剂(proton pump inhibitor,PPI)的二联方案与含铋剂四联方案的疗效相近,但用药少,不良反应少,患者依从性更高,有可能成为经验性的一线治疗方案,或成为一线、二线治疗失败后的补救方案。本文就二联方案在H.pylori根除治疗中的应用进展作一综述。     

Development of novel topical drug delivery system containing cisplatin and imiquimod for dual therapy in cutaneous epithelial malignancy

Context: Strategy of dual therapy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies.

Objective: The aim of this study was to develop an effective drug delivery system for the simultaneous topical delivery of two anti-tumor agents, cisplatin and imiquimod.

Material and methods: The preformulation studies were carried out in terms of tests for identification, solubility profile, determination of partition coefficient and simultaneous estimation of both drugs by UV–Visible spectrophotometer and High Performance Liquid Chromatography (HPLC). Drug–drug and drug-excipients interactions were examined by thin layer chromatography, infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Provesicular drug delivery system (protransfersome gel formulation) have been prepared and characterized by in vitro and in vivo parameters.

Results: The mean size, poly dispersity index (PDI) and zeta potential of transfersomal vesicles formed by protransfersome hydration were 429.5?nm, 0.631 and ?68.1 Mv, respectively. The prepared formulation showed toxicity on cutaneous squamous cell carcinoma cell line (A-431) at 200?µg (cisplatin) and 1?mg (imiquimod) concentration of drug in combination against control. The cisplatin- and imiquimod-loaded provesicular dual–drug delivery system achieved an optimal antitumor effect, increase in lifespan, antiviral, and toxicity reduction, revealing the advantage of site specific drug delivery and the modified combination therapy.

Discussion: Cisplatin delivery through protransfersome gel in combination with imiquimod may potentiate the activity against solid tumors of epidermal origin.

Conclusion: Data revealed that combination therapy considerably enhances antitumor efficacy of the drug for skin-cited malignancies.     

Novel siRNA-based molecular beacons for dual imaging and therapy

Short interfering RNAs (siRNAs) have become a mainstream tool reliably used to study and silence protein expression. We offer a proof-of-principle demonstration that siRNAs may be modified into a siRNA-based molecular beacon that activates upon binding to sequence-specific mRNA in cells while mediating RNA interference. We successfully demonstrate detection and knockdown of telomerase expression in human breast cancer cells. This probe provides a novel look at siRNA target validation that is not currently possible in live cells and holds promising potential in biological applications for disease detection and therapy based on mRNA expression, such as a telomerase-targeted siRNA probe in cancer.     

Nonbismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and versus sequential therapy for clarithromycin-resistant strains

Background:  Using quadruple clarithromycin‐containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance. Aim:  To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple (concomitant) therapy in a setting with cure rates <80% for triple and sequential therapies. Methods:  209 consecutive naive H. pylori‐positive patients without susceptibility testing were empirically treated with 10‐day concomitant therapy (proton pump inhibitors (PPI), amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg; all drugs b.i.d.). Simultaneously, 89 patients with positive H. pylori culture were randomized to receive triple versus concomitant therapy for clarithromycin‐susceptible H. pylori, and sequential versus concomitant therapy for clarithromycin‐resistant strains. Eradication was confirmed with ¹³C‐urea breath test or histology 8 weeks after completion of treatment. Results:  Per‐protocol (PP) and intention‐to‐treat eradication rates after empirical concomitant therapy without susceptibility testing were 89% (95%CI:84–93%) and 87% (83–92%). Antibiotic resistance rates were: clarithromycin, 20%; metronidazole, 34%; and both clarithromycin and metronidazole, 10%. Regarding clarithromycin‐susceptible H. pylori, concomitant therapy was significantly better than triple therapy by per protocol [92% (82–100%) vs 74% (58–91%), p = 0.05] and by intention to treat [92% (82–100%) vs 70% (57–90%), p = 0.02]. As for antibiotic‐resistant strains, eradication rates for concomitant and sequential therapies were 100% (5/5) vs 75% (3/4), for clarithromycin‐resistant/metronidazole‐susceptible strains and 75% (3/4) vs 60% (3/5) for dual‐resistant strains. Conclusions:  Empirical 10‐day concomitant therapy achieves good eradication rates, close to 90%, in settings with multiresistant H. pylori strains. Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin‐susceptible H. pylori and at least as effective as sequential therapy for resistant strains.     

Metallobacteriochlorophylls as potential dual agents for photodynamic therapy and chemotherapy

A theoretical analysis of bacteriochlorophyll a containing its non-native divalent metal ions: Co, Ni, Cu, Zn, Ru, Rh, Pd, and Pt, has been carried out by means of density functional theory (DFT) calculations. The main stress was put on the derivatives with metals, which already found applications as coordination compounds in anti-tumor therapy (Ru, Pt, Pd, and Rh). The idea was to combine their cytotoxic properties with the known suitability of bacteriochlorophylls macrocycle for photodynamic therapy. The geometries of the studied systems are compared and reveal a number of similarities. The cores of the modified bacteriochlorophylls are flat, and the introduced metal ions lie in plane of the macrocycle, showing its large ability to accommodate metal ions of different sizes. However, four metal–nitrogen bonds, linking the central ions with the macrocycle ligand, are not equivalent. Metals are the strongest attached to nitrogens, which come from the pyrrole, which is fused with isocyclic ring. Based on the known spectroscopic data, the absorption properties of the proposed systems are predicted. Finally, it is found that all studied metal–macrocycle adducts are stable in aqueous media. The only exceptions are Mg-BChla (the finding is reflected by experimental facts) and Zn-BChla. The predicted high stability of Ru-, Rh-, Pt- and Pd-bacteriochlorophylls might turn out beneficial for therapeutic purposes.     

Effectiveness and safety of repeated quadruple therapy in Helicobacter pylori infection after failure of second-line quadruple therapy: repeated quadruple therapy as a third-line therapy

Backgrounds: Quadruple therapy using a proton‐pump inhibitor, bismuth, metronidazole, and tetracycline is a standard second‐line therapy for Helicobacter pylori infection, achieving an eradication rate of about 80% in Korea. A standard third‐line therapy is not currently established, although various protocols have been proposed. We performed this study to evaluate the effectiveness of a retrial with quadruple therapy before starting a third‐line treatment with new drugs. Materials and Methods: In 80 of 746 patients treated with a second‐line quadruple therapy at the Korea University Ansan Hospital between January 2002 and September 2010, treatment for H. pylori had failed, and 45 of these patients were eligible for this study. Eradication of H. pylori was assessed by repeated endoscopy or by the ¹³C‐urea breath test at least 4 weeks after therapy. The patients with treatment failure were treated again with quadruple regimen for 2 weeks and reevaluated for treatment effectiveness and safety. Results: The eradication rate with second‐line quadruple therapy was 86.9%. Of the 80 patients who failed treatment for H. pylori with the initial second‐line quadruple therapy, 64 patients were treated again with the same regimen. Of the 45 retreated patients in this study, three patients were lost to follow‐up and two complied poorly with medication. The eradication rate in the 40 patients retreated was 75.0% at per‐protocol analysis. Seventeen patients experienced mild adverse events. Conclusions: A retrial of quadruple therapy before use of a third‐line therapy may be safe and effective for patients who fail to respond to second‐line quadruple therapy.     

MRI-guided gene therapy

MRI has the ability to generate high-contrast and high-resolution images, to obtain multiple diagnostic evaluations of organ function and morphology, and to provide multiple image planes with no risk of ionizing radiation. Recent efforts have focused on using MR technology to monitor gene delivery, to enhance gene transfection/transduction, and to track gene expression. This review summarizes the current status of MRI-guided gene therapy.     

人体粪便中药与粪微生态疗法述略

在漫长的历史中,中国的医药学家对粪便类药物持续不断地在进行研究,尤其是在过去的几百年间积累了越来越多的经验,是中国传统医药学极其宝贵的财富。应用粪便类药辨治疾病是中医诊疗特色之一。广泛而丰富的临床治疗信息为现代医学积累了大量的诊疗依据和启示,尤其是目前的粪菌移植治疗研究,它拓展了粪便类中药治疗的新概念,明确其疗效机制乃至为新产品的研发提供依据。现代微生态学的发展也为祖国医学的研究带来了新的契机和前景。     

Safety of dual antiplatelet therapy in daily cardiology practice

Dual antiplatelet therapy has become the cornerstone of the treatment of acute coronary syndromes with or without stent implantation.