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1.  Arthrodesis Should Be Strongly Considered After Failed Two-stage Reimplantation TKA 
A two-stage reimplantation procedure is a well-accepted procedure for management of first-time infected total knee arthroplasty (TKA). However, there is a lack of consensus on the treatment of subsequent reinfections.
The purpose of this study was to perform a decision analysis to determine the treatment method likely to yield the highest quality of life for a patient after a failed two-stage reimplantation.
We performed a systematic review to estimate the expected success rates of a two-stage reimplantation procedure, chronic suppression, arthrodesis, and amputation for treatment of infected TKA. To determine utility values of the various possible health states that could arise after two-stage revision, we used previously published values and methods to determine the utility and disutility tolls for each treatment option and performed a decision tree analysis using the TreeAgePro 2012 software suite (Williamstown, MA, USA). These values were subsequently varied to perform sensitivity analyses, determining thresholds at which different treatment options prevailed.
Overall, the composite success rate for two-stage reimplantation was 79.1% (range, 33.3%–100%). The utility (successful outcome) and disutility toll (cost for treatment) for two-stage reimplantation were determined to be 0.473 and 0.20, respectively; the toll for undergoing chronic suppression was set at 0.05; the utility for arthrodesis was 0.740 and for amputation 0.423. We set the utilities for subsequent two-stage revision and other surgical procedures by subtracting the disutility toll from the utility each time another procedure was performed. The two-way sensitivity analysis varied the utility status after an additional two-stage reimplantation (0.47–0.99) and chance of a successful two-stage reimplantation (45%–95%). The model was then extended to a three-way sensitivity analysis twice: once by setting the variable arthrodesis utility at a value of 0.47 and once more by setting utility of two-stage reimplantation at 0.05 over the same range of values on both axes. Knee arthrodesis emerged as the treatment most likely to yield the highest expected utility (quality of life) after initially failing a two-stage revision. For a repeat two-stage revision to be favored, the utility of that second two-stage revision had to substantially exceed the published utility of primary TKA of 0.84 and the probability of achieving infection control had to exceed 90%.
Based on best available evidence, knee arthrodesis should be strongly considered as the treatment of choice for patients who have persistent infected TKA after a failed two-stage reimplantation procedure. We recognize that particular circumstances such as severe bone loss can preclude or limit the applicability of fusion as an option and that individual clinical circumstances must always dictate the best treatment, but where arthrodesis is practical, our model supports it as the best approach.
PMCID: PMC4182410  PMID: 24488752
2.  Hypoxia-Inducible Factor (HIF)-2 regulates Vascular Tumorigenesis in Mice 
Oncogene  2008;27(40):5354-5358.
The von Hippel-Lindau tumor suppressor pVHL regulates the stability of Hypoxia-Inducible Factors (HIF) -1 and –2, oxygen-sensitive basic helix-loop-helix transcription factors, which mediate the hypoxic induction of angiogenic growth factors such as vascular endothelial growth factor (VEGF). Loss of VHL function results in constitutive activation of HIF-1 and HIF-2 and is associated with the development of highly vascularized tumors in multiple organs. We have used a conditional gene targeting approach to investigate the relative contributions of HIF-1 and HIF-2 to VHL-associated vascular tumorigenesis in a mouse model of liver hemangiomas. Here we demonstrate genetically that conditional inactivation of HIF-2α suppressed the development of VHL-associated liver hemangiomas and that angiogenic gene expression in hepatocytes is predominantly regulated by HIF-2 and not by HIF-1. These findings suggest that HIF-2 is the dominant HIF in the pathogenesis of VHL-associated vascular tumors and that pharmacologic targeting of HIF-2 may be an effective strategy for their treatment.
PMCID: PMC2575082  PMID: 18490920

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