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Objective: Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment to aortic valve replacement (AVR) for selected patients with severe aortic stenosis. A systematic reviewwas conducted to analyse the cost-effectiveness of this novel technique within reimbursed healthcare systems. Methods and results: Two reviewers used seven electronic databases from January 2000 to November 2012 to identify relevant cost-effectiveness studies onTAVI versus AVR or medical therapy. The primary endpoints were the incremental cost-effectiveness ratio (ICER) and the probability of cost-effectiveness. Eligible studies included those in which cost-effectiveness data was measured or projected for TAVI and either medical therapy or AVR. All forms of TAVI were included and all retrieved publications were limited to English language. Eight studies were included for quantitative assessment. The ICER for TAVI compared with medical therapy for surgically inoperable patients ranged between US$26,302 and US$61,889 per quality adjusted life year gained (PQG). The probability of TAVI being cost-effective compared to medical therapy ranged between 0.03 and 1.00. ICER values for TAVI in comparison to AVR for high-risk surgical candidates ranged between US$32,000 and US$975,697 PQG. The probability of TAVI being cost-effective in this cohort ranged between 0.116 and 0.709. Conclusions: Based on the accepted Australian ICER threshold of AU $69,900 (US $71,882) PQG, TAVI is potentially justified on medical and economic grounds in comparison to medical therapy for inoperable patients. However, in the high-risk surgical patient cohort, there is currently insufficient evidence to economically justify the use of TAVI in preference to AVR.

8046 Background: BAY 43–9006 is a multikinase inhibitor. The RAS/BRAF/MEK/MAPK pathway (pw) is a major pw for transmitting extracellular growth factor signals to the nucleus. Activating mutations in any of the pw kinases would be expected to result in uncontrolled cell proliferation. Approximately 60% of melanomas carry B-Raf mutations. The primary trial goals are: 1) determine if treatment (tx) with BAY 43–9006 can disrupt the RAS/BRAF/MEK/MAPK pw by depleting intra-tumor stores of B-Raf and/or CDK4; and 2) determine if tx with BAY 43–9006 results in differential anti-tumor responses in pts whose tumors have been molecularly characterized. Methods: Eligibility criteria: Biopsy (bx)-accessible, untreated metastatic melanoma. Measurable disease (RECIST). Adequate hematologic and serologic parameters. Signed ICF. All pts had tumor bx for B-Raf status determined by PCR sequencing prior to tx. Exon 3 of N-Ras and exon 15 of B-Raf were sequenced. Pts stratified by B-Raf. Tx: BAY 43–9006 was administered at 400 mg po BID. D1–28 q4w. Repeat bx was done on Day 28. Re-imaging was done every 2 cycles and pts treated until POD. Stats: Stratification by B-Raf mutation status. 2 stage study design with accrual of 13 pts/arm in first stage and total of 29 pts/arm if ≥ 1 objective response (OR) in initial cohort. Results: 8 pts (2-M1a, 1-M1b, 5-M1c) enrolled. 7 wild type (WT) and 1 mutant (M) B-Raf. Median age: 54 (range 22–91). No pts with LDH ≥ 1.5 × nl. 2 withdrew prior to tx. Responses: M B-Raf (1 evaluable)-PR (lymph nodes and large SQ arm masses); WT B-Raf-1 POD during cycle 1 (NE), 1PD, 3 too early. Toxicity: Grade I diarrhea, Grade II hypertension, fatigue and oral mucositis. Correlative immunoassays of tumor B-Raf, CDK4, phospho-MAPK and cyclin-D1 and correlation of DNA extracted from peripheral blood cells assayed by fluorescent, mutant-specific PCR and tumor B-RAF are being evaluated. Conclusions: This Phase II trial will molecularly characterize tumors for B-Raf status prior to tx with BAY 43–9006 and assess the effects on Ras-Raf signaling and correlate clinical responses. This trial will address potential differences in sensitivity to BAY 43–9006 based on B-Raf. While premature, 1 pt with M B-Raf has had an OR with a significant decrease in tumor volume. Supported by NCI N01-CM17103 and TRI. No significant financial relationships to disclose.

Arthrogryposis multiplex congenita is a crippling congenital abnormality of muscle development characterized by marked muscle contracture and nonprogressive, limb joint deformity. The incidence is 1/3,000 births. The most frequent isolated contractures are clubfoot and congenital hip dislocation. 1 Arthrogryposis is seen in a number of syndromes with or without central nervous system involvement and is associated with multiple developmental defects. However, vascular complications with arthrogryposis multiplex congenita are not well described. 1 We report on a renal transplant recipient with arthrogryposis multiplex congenita. Unexpected severe blood vessel hypoplasia complicated transplant revascularization and led to acute thrombosis of the allograft, necessitating reperfusion and revascularization to the aortic bifurcation and common iliac vein. CASE REPORT A 20-year-old man with arthrogryposis multiplex congenita presented for renal transplantation. He had a small body habitus and classical locomotor findings. At birth he had an imperforate anus for which he underwent perinatal colostomy. The correction was complicated by a vesicorectal fistula necessitating self-catheterization and treatment for recurrent urinary tract infections. Chronic pyelonephritis developed with subsequent renal failure. He underwent a native nephrectomy of a horseshoe kidney for chronic pyelonephritis in preparation for renal transplantation. Cardiac, urological and general assessment for transplantation revealed no contraindications but pelvic angiography was not done. Live related renal transplantation was performed with the biological father of the patient as a kidney donor. Donor nephrectomy was uncomplicated. At the time of the extraperitoneal transplant procedure the iliac vessels of the patient were hypoplastic. The renal artery was anastomosed to the external iliac artery and the renal vein was anastomosed to the external iliac vein. Upon revascularization the graft initially became pink and then gradually turned dusky within a few minutes. The graft was subsequently removed and reperfused with cold Ringer’s lactate, and the external iliac vein was transected and ligated. After reperfusion, the donor kidney was subsequently reanastomosed intraperitoneally to the bifurcation of the aorta and the renal vein was anastomosed end to end to the common iliac vein, followed by reconstruction of the femoral artery. This second anastomosis was successful with fair perfusion of the donor kidney. Upon completion of the procedure, the kidney was perfused in a patchy manner. Postoperatively, the patient required dialysis and intensive care monitoring but recovered and subsequently was discharged home with normal serum creatinine. Coagulation studies performed after transplant were normal. Three months after healthy independent living, he died unexpectedly. Autopsy did not reveal the cause of death.