Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non–Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial

Background

Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non–small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone.

Exstirpation eines Beckenmelanomes

Ohne Zusammenfassung (Mit 1 Abbildung.)     

Myxofibrosarkom der Bursa achillea post

Ohne Zusammenfassung (Mit 3 Abbildungen.)     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

Hintergrund: Viele der antiglaukomat?sen Medikamente beeinflussen den okul?ren Blutflu?. Die Blutflu?ver?nderungen in der vorderen Uvea sind in der Literatur beschrieben. über den Effekt von Antiglaukomatosa auf den Blutflu? des hinteren Augenpols wird in neuerer Zeit vermehrt berichtet. Wir pr?sentieren eine Placebo-kontrollierte Studie mit Blick auf den kurz- und mittelfristigen Einflu? von topisch appliziertem Dipivefrin 0,1 % auf den retinalen und papill?ren Blutflu?.     

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial

Introduction

Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC).

Methods

The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH).

Results

The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6–4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44–1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31–0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34–1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18–1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups.

Conclusion

During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.     

Brood pouch-mediated polystyrene nanoparticle uptake during Daphnia magna embryogenesis

Nanoplastic debris is currently expected to be ubiquitously distributed in aquatic environments and an emerging environmental issue affecting organisms across trophic levels. While ingestion of particles receives most attention, other routes of uptake and cellular accumulation remain unexplored. Here, the planktonic filter feeder Daphnia magna was used to track routes of uptake and target tissues of polystyrene nanoparticles (PSNPs). A sublethal concentration of 5?mg L^?1 fluorescent PSNPs (25?nm) was used to monitor accumulation in adult animals as well as their embryos in the open brood pouch. A time series throughout embryonic development within the brood pouch revealed accumulation of PSNP in or on lipophilic cells in the early stages of embryonic development while the embryo is still surrounded by a chorion and before the beginning of organogenesis. In contrast, PSNP particles were neither detected in the gut epithelium nor in lipid droplets in adults. An ex vivo exposure of embryos to PSNP demonstrated a similar accumulation of PSNP in or on lipophilic cells, illustrating the likelihood of brood pouch-mediated PSNP uptake by embryos. By demonstrating embryo PSNP uptake via the brood pouch, data presented here give novel insights in bioaccumulation of nanoparticles and likely other lipophilic contaminants. Since this uptake route can occur within a diverse array of aquatic organisms, this study warrants consideration of brood pouch-mediated accumulation in efforts studying the hazards and risks of nanoparticle contamination.     

High frequency recombination betweenloxP sites in human chromosomes mediated by an adenovirus vector expressing Cre recombinase

An adenovirus vector (AdCre1) expressing Cre recombinase has been used to induce recombination betweenloxP sites in human chromosomes. G418 resistant cells with oneloxP site, generated by transfection with a plasmid containingloxP between the SV40 promoter and the G418 resistance (neo) gene, were infected with AdCre1 and transfected with a plasmid containingloxP adjacent to a promoterless hisD gene. This resulted in integration of hisD downstream of the SV40 promoter with gain of histidinol and loss of G418 resistance. Since AdCre1 is non-replicating and Cre expression transient, histidinol resistant cells containing the hisD gene flanked byloxP sites were stable. Reinfection of these cells with AdCre1 induced excision of hisD in over 90% of infected cells. This high efficiency of site-specific recombination suggests that AdCre1 may be exploited for temporal and tissue-specific regulation of gene expression and for chromosome engineering in vitro and in animals.