F. Rosenfeldt

Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation

BACKGROUND Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. METHODS Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. RESULTS Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. CONCLUSIONS The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation.

Safety and efficacy of extended‐release bupivacaine local anaesthetic in open hernia repair: a randomized controlled trial

Background:  Pain relief remains a major problem in hernia surgery. SABER‐Bupivacaine is an investigational extended‐release formulation of bupivacaine in a resorbable matrix, which may provide up to 72 h of local pain relief.

A systematic review of cost-effectiveness of percutaneous coronary intervention vs. surgery for the treatment of multivessel coronary artery disease in the drug-eluting stent era

Aims The suitability of percutaneous coronary intervention (PCI), compared with coronary artery bypass grafting (CABG), for patients with complex multivessel coronary artery disease (MVCAD) remains a contentious topic. While the body of evidence regarding the clinical effectiveness of these revascularization strategies is growing, there is limited evidence concerning their long-term cost-effectiveness. We aim to critically appraise the body of literature investigating the cost-effectiveness of CABG compared with PCI using stents, and to assess the quality of the economic evidence available. Methods and results A systematic review was performed across six electronic databases; Medline, Embase, the NHS Economic Evaluation Database, the Database of Abstracts of Reviews of Effects, the health technology assessment database, and the Cochrane Library. All studies comparing economic attractiveness of CABG vs. PCI using bare-metal stents (BMS) or drug-eluting stents (DES) in balanced groups of patients were considered. Sixteen studies were included. These comprised studies of conventional CABG vs. BMS (n = 8), or DES (n = 4); off-pump CABG vs. BMS (n = 2), or DES (n = 1); and minimally invasive direct CABG vs. BMS (n = 2). The majority adopted a healthcare payer perspective (n = 14). The incremental cost-effectiveness ratios (ICERs) reported across studies varied widely according to perspective and time horizon. Favourable lifetime ICERs were reported for CABG in three trials. For patients with left main coronary artery disease, however, DES was reported as the dominant (more effective and cost-saving) strategy in one study. Conclusion Overall, CABG rather than PCI was the favoured cost-effective treatment for complex MVCAD in the long term. While the evidence base for the cost-effectiveness of DES compared with CABG is growing, there is a need for more evaluations adopting a societal perspective, and time horizons of a lifetime or 10 or more years.