Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC0–8_muscle)/AUC0–8_serumof 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC0–8_{adipose tissue}/AUC0–8_serum of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus,Enterobacter cloacae, and Serratia marcescensfor which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

Background: The microvascular anastomosis remains a technically sensitive and critical determinant of success in free tissue transfer. The microvascular anastomotic coupling device is an elegant, friction-fit ring pin device that is becoming more widely used. Objective: To systematically review the literature to examine the utility of the microvascular coupler in free tissue transfer. Methods: A comprehensive database search was performed to identify eligible publications. Inclusion criteria were anastomotic coupler utilization and free-tissue transfer. Recorded information from eligible studies included patient age, follow-up, radiation history, number of free-flaps and failure rates, reconstruction subsites, number of coupled venous and arterial anastomoses, coupling time, conversion to sutured anastomosis, coupler size and thrombosis rates. Results: Twenty-five studies reporting on 3207 patients were included in the analysis. A total of 3576 free-flaps were performed within the following subsites: 1103 head and neck, 2094 breast, 300 limb or body, and 79 nonspecified. There were only 26 reported flap failures (0.7%). A total of 3497 venous and 342 arterial coupled anastomoses were performed. The primary outcome measure was thrombosis rates, and there were 61 venous (1.7%) and 12 arterial (3.6%) thromboses reported. Mean coupling time was 5 min, and 30 anastomoses (0.8%) were converted to suture. Conclusion: Flap survival and revision-free application of the microvascular coupler occurred in more than 99% of cases. There is a substantial time savings with coupler use. Venous and arterial thrombosis rates are comparable with the best results achieved by sutured anastomosis and, when used by experienced surgeons, the coupler achieves superior results.

Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long‐term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of ‘tumor stem cells’ that exhibit a capacity for self‐renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with ‘more mature’ tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy. Cancer 2006. © 2006 American Cancer Society.