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Abstract: Background: Statins reduce the risk for transplant vasculopathy and mortality among heart transplant recipients. Interactions between commonly used statins (ie, simvastatin, atorvastatin) and immunosuppressant drugs lead to side effects or withdrawal of statin therapy. Fluvastatin shows fewer interactions with the immunosuppressant agents because it is not metabolized via the cytochrome P-450 3A4 pathway like most immunosuppressants, steroids, or other statins. This study investigated the impact of a switch from other statins to fluvastatin in heart transplant recipients who revealed elevated creatine-kinase levels. Methods: A total of 23 heart transplant patients with elevated creatine-kinase levels were included in this study. Statins were replaced with an equal dosage of fluvastatin. We measured on the day of replacement as well as there after at 3, 6, 9, and 12 months creatine-kinase, lipid status, ALT, AST, and creatinine levels. Results: After 6 months creatine-kinase showed a significant reduction of 25% (P < .05) and after 9 months of 38% (P < .05). The HDL-cholesterol levels were significantly reduced at 6 months (8%; P < .05) and 9 months (23%; P < .05). At 3 months, triglyceride levels were significantly elevated (18%; P < .05). No differences were observed in ALT, AST, creatinine, total, and LDL-cholesterol at any time. Conclusion: A conversion from commonly used statins to fluvastatin in heart transplant patients with elevated creatine-kinase was safe, leading to a significant reduction in creatine-kinase levels. Except for an initial raise in triglycerides and a lowering of HDL-cholesterol, no changes in lipid status were seen. This conversion might help to maintain lipid-lowering therapy in transplant recipients who show side effects using conventional statins. [Copyright &y& Elsevier]

Abstract: Administration of perioperative antibiotic prophylaxis is a routine procedure in orthopedic surgery. Besides systemic prophylaxis, only few techniques are established for local application of antibiotics to reduce infection related to orthopedic implants. The aim of this study was to evaluate the efficacy of locally versus systemically applied gentamicin in a rat model (n = 60). For local application, the antibiotic was delivered from a biodegradable poly(d,l-lactide) (PDLLA) coating of titanium implants. The efficacy of local prophylaxis was compared to a systemic single shot application of gentamicin as well as a combination of both administrations. Half of the animals received a weight-adopted single shot application of gentamicin 30 min prior to surgery. At surgery, the medullary cavities of the tibiae were contaminated with Staphylococcus aureus (102 colony forming units /CFU) and titanium Kirschner wires were implanted into the medullary canals. The implants were either uncoated, PDLLA coated, or coated with PDLLA + 10% w/w gentamicin. The animals were followed up for 42 days. X-ray examinations were performed; body weight, temperature, and the clinical condition were determined. After sacrifice, infection was evaluated by histological and microbiological analysis. All animals treated with uncoated or PDLLA-coated Kirschner wires without systemic application of the antibiotic developed osteomyelitis and all cultures of implants were tested positive on S. aureus. Implant-related osteomyelitis could be prevented by prophylaxis of systemically applied gentamicin in 15% of animals. In contrast, local application of gentamicin delivered from a PDLLA coating was more effective. Onset of infection could be prevented in 90% of animals treated with gentamicin coated Kirschner wires, and in 80% of the animals that were treated with a combination of local and systemic application. The local application from PDLLA-coated implants might support systemic antibiotic prophylaxis in preventing implant-associated osteomyelitis. [Copyright &y& Elsevier]

Abstract: Background: Thromboembolism is a major complication in patients with ventricular assist devices (VADs). Drug anticoagulation and the use of biocompatible surfaces, such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin-induced thrombocytopenia (HIT) type II, mainly through heparin/platelet factor 4 (PF4) antibodies. We assessed the presence of PF4 antibodies in VAD thrombi of patients with heparin-coated VADs and HIT II. Methods: Thrombi (n = 6) were obtained from the replaced Excor ventricles of patients with HIT II after biventricular VAD implantation (Excor Adult; Berlin Heart, Germany). Excor ventricles were changed after clinical examination and suspicion of thrombi in the polyurethane valves. Expression of PF4- antibodies was assessed with the use of a polyclonal rabbit antibody (anti-PF4 antibody; Abcam, USA). Expression was assessed by 2 independent observers. Results: Biopsies of all thrombi showed an extreme positive immunoreaction for PF4. No differences between the different thrombi and localization (left/right Excor ventricle) were observed. The thrombi were organized, without lamination of fibrin and cellular layers. Conclusions: Platelet surface expression of PF4 in the thrombi reflects HIT antigen presentation. The physical relationship between the PF4-positive thrombi and the heparin-coated surface suggests that onset of HIT II could be influenced by the immobilized heparin coating. [Copyright &y& Elsevier]