Treatment of in-stent restenosis with sirolimus-eluting-stents: results from the prospective German Cypher stent registry

Aims  Drug-eluting stents have been reported to effectively reduce in-stent restenosis (ISR). However, the effectiveness and safety have yet been investigated only in small trials or case series. The aim of this prospective large scale registry was to show that treatment of ISR with sirolimus eluting stents (SES) is safe, effective and feasible in daily routine. Methods and results  The German Cypher registry prospectively enrolled 6,555 patients undergoing implantation with SES for various indications, including 1,533 patients treated for ISR. Follow-up data (median 6.6 months) of this cohort was available for 1,531 patients (99.8%). Of these patients 75.8% were male. Of these patients 36.5% (n = 552) presented with acute coronary syndromes. In total, 1,932 SES were used with successful implantation in 98.9%. MI during hospitalization was observed in 0.7% (n = 11) while in-hospital mortality was only 0.1% (n = 2). MACE-rate at follow-up was 13.8% (n = 211) including a mortality of 1.3% (n = 20) and MI in 1.9% (n = 29). Total revascularization procedures including CABG (1.7%) were necessary in 12.3% (n = 186). Target vessel revascularization (TVR) rate was 9.3% (n = 139) and thus similar to patients with de novo lesions (8.1%, P = 0.69). Ten patients (0.65%) suffered from subacute stent thrombosis Vs. 0.24% observed in patients with de novo lesions (P = 0.03). Conclusion  This large registry confirms that treatment of ISR with sirolimus-eluting-stents is effective and save with good clinical results at index procedure and follow-up. TVR was not different from de novo lesions.     

Sequential combination therapy leads to biochemical and histological improvement despite low ongoing intrahepatic hepatitis B virus replication

BACKGROUND: We previously reported that 48 weeks of combination therapy with pegylated interferon-alpha2b (PEG-IFN-alpha2b) and adefovir dipivoxil (ADV) in patients with chronic hepatitis B led to marked decreases of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) (-2.4 log10 copies/ml). Combination therapy was followed by 96 weeks of ADV monotherapy. METHODS: Here, we report on the final outcome after 144 weeks of sequential antiviral treatment. Twenty-four patients were analysed, triplet liver biopsies (taken at baseline, week 48 and week 144) were available from 16 patients. RESULTS: At week 144, 12/15 patients positive for hepatitis B virus e antigen (HBeAg) had lost HBeAg, alanine transaminase (ALT) levels were normal in 23 patients (96%), median serum HBV DNA had decreased by -4.9 log10 copies/ml and was undetectable (<100 copies/ml) in 11/24 individuals (46%). Median total intrahepatic HBV DNA had decreased by -2.2 log. Although no further significant cccDNA changes occurred between week 48 and week 144, two years of ADV monotherapy proved capable of controlling cccDNA levels in most patients. Analysis of intrahepatic HBV DNA species demonstrated that combination therapy with PEG-IFN-alpha2b and ADV inhibited viral productivity by 99% and subsequent ADV monotherapy by 76%, respectively. Virus suppression to undetectability within the first 12 weeks of treatment was strongly associated with long-term virological response and HBeAg and hepatitis B virus surface antigen HBsAg seroconversion. Histological improvement was determined in 11/16 patients at week 144. Two patients developed ADV resistance during the third year of treatment. CONCLUSIONS: Reduction of intrahepatic viral load achieved after 48 weeks of combination therapy with PEG-IFN-alpha2b and ADV was maintained in the following 96 weeks of ADV monotherapy and translated into long-term clinical benefit for most of the treated patients.     

Ultrasound confidence maps using random walks

Advances in ultrasound system development have led to a substantial improvement of image quality and to an increased use of ultrasound in clinical practice. Nevertheless, ultrasound attenuation and shadowing artifacts cannot be entirely avoided and continue to challenge medical image computing algorithms. We introduce a method for estimating a per-pixel confidence in the information depicted by ultrasound images, referred to as an ultrasound confidence map, which emphasizes uncertainty in attenuated and/or shadow regions. Our main novelty is the modeling of the confidence estimation problem within a random walks framework by taking into account ultrasound specific constraints. The solution to the random walks equilibrium problem is global and takes the entire image content into account. As a result, our method is applicable to a variety of ultrasound image acquisition setups. We demonstrate the applicability of our confidence maps for ultrasound shadow detection, 3D freehand ultrasound reconstruction, and multi-modal image registration.     

Cobalt–chrome MULTI-LINK VISION™-stent implantation in diabetics and complex lesions: results from the DaVinci-Registry

Aims

Restenosis in bare-metal stents is in part related to stent design and material. Optimized strut design of cobalt–chrome (CoCr) stents may yield nearly comparable results to drug-eluting stents (DES) in selected lesions. The prospective multicenter DaVinci registry investigates the clinical outcome of a CoCr coronary stent (MULTI-LINK VISION?), particularly in terms of patients with diabetes and complex lesions (B1, B2, C).

Methods and results

The prospective internet-based registry included 1,344 patients (76% males, aged 66 ± 10 years) undergoing stent implantation (n = 1,642) in 32 centres from July 2003 to June 2004. Follow-up data (median 9 ± 1 months) of this cohort were available for 1,289 patients (98.1%). Of these patients 327 (26.2%) were diabetics. In total, 1,429 de-novo lesions (A 11.9%, B1 47.7%, B2 31.6%, C 8.8%) were treated with the CoCr stent. The predefined primary endpoint was defined as a composite of death, Q-wave myocardial infarction (STEMI), non-STEMI (NSTEMI), target vessel revascularization (TVR) by coronary bypass graft (CABG) or PCI at 270 days (target vessel failure, TVF). Secondary endpoints include death, time to the first myocardial infarction, TVR and CABG. The cumulative incidence of major adverse cardiac events (MACE) was 12.4% with 0.8% deaths, 1.5% non-fatal MI, and 9.7% TVR. TVF in the overall cohort was documented in 137 (10.8%) patients. For diabetics and complex lesions TVF was 13.8% (95% CI 4.2–18) and 11.4% (95% CI 2.0–13.3), respectively.

Conclusion

This large registry confirms good acute and long-term success of CoCr stents making this strategy valuable, particularly in a special cohort (diabetics and complex lesions) as long as late stent thrombosis with DES plays a role and short-term antiplatelet therapy is favoured.     

Clinical phase I and pharmacokinetic trial of vinorelbine administered as single intravenous bolus every 21 days in cancer patients

Summary We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine administered as a bolus injection every 21 days. The aim was to evaluate a schedule with longer treatment intervals than one week and to determine the toxicity pattern of such a schedule. A total of 13 patients (pts) with solid tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2 pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were entered [9 male, 4 female, median age: 56 years (range: 37–69)]. Dose levels were 35, 40 and 45 mg/m² with a total of 26 cycles administered. At 40 mg/m², 2/6 pts developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m² developed a grade 4 leuko- and granulocytopenia. Non-hematological toxicities were mild to moderate. Neurologic toxicity except for constipation was mild. Constipation occurred at 35 mg/m² in 1/6 pts WHO grade 4, at 40 mg/m² in 2/6 pts WHO grade 3 and at 45 mg/m² in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor response was observed. Vinorelbine pharmacokinetics were analysed in whole blood and plasma and were similar to previously published studies using 30 mg/m². Our results confirm a high affinity of vinorelbine to corpuscular blood elements. We conclude that the MTD of vinorelbine administered once every 21 days as bolus injection is 40 mg/m², the dose-limiting toxicities are constipation and granulocytopenia and the recommended dose for subsequent Phase II trials is 35 mg/m².