Endovascular-first approach is not associated with worse amputation-free survival in appropriately selected patients with critical limb ischemia

ObjectiveEndovascular interventions for critical limb ischemia are associated with inferior limb salvage (LS) rates in most randomized trials and large series. This study examined the long-term outcomes of selective use of endovascular-first (endo-first) and open-first strategies in 302 patients from March 2007 to December 2010.MethodsEndo-first was selected if (1) the patient had short (5-cm to 7-cm occlusions or stenoses in crural vessels); (2) the disease in the superficial femoral artery was limited to TransAtlantic Inter-Society Consensus II A, B, or C; and (3) no impending limb loss. Endo-first was performed in 187 (62%), open-first in 105 (35%), and 10 (3%) had hybrid procedures.ResultsThe endo-first group was older, with more diabetes and tissue loss. Bypass was used more to infrapopliteal targets (70% vs 50%, P = .031). The 5-year mortality was similar (open, 48%; endo, 42%; P = .107). Secondary procedures (endo or open) were more common after open-first (open, 71 of 105 [68%] vs endo, 102 of 187 [55%]; P = .029). Compared with open-first, the 5-year LS rate for endo-first was 85% vs 83% (P = .586), and amputation-free survival (AFS) was 45% vs 50% (P = .785). Predictors of death were age >75 years (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.7-6.6; P = .0007), end-stage renal disease (ESRD) (HR, 3.4; 95% CI, 2.1-5.6; P < .0001), and prior stroke (HR, 1.6; 95% CI, 1.03-2.3; P = .036). Predictors of limb loss were ESRD (HR, 2.5; 95% CI, 1.2-5.4; P = .015) and below-the-knee intervention (P = .041). Predictors of worse AFS were older age (HR, 2.03; 95% CI, 1.13-3.7; P = .018), ESRD (HR, 3.2; 95% CI, 2.1-5.11; P < .0001), prior stroke (P = .0054), and gangrene (P = .024).ConclusionsAt 5 years, endo-first and open-first revascularization strategies had equivalent LS rates and AFS in patients with critical limb ischemia when properly selected. A patient-centered approach with close surveillance improves long-term outcomes for both open and endo approaches

Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNγ, perforin, and TNFα, and due to the elimination of transduced cells

The adaptive immune response to viral vectors reduces vector-mediated transgene expression from the brain. It is unknown, however, whether this loss is caused by functional downregulation of transgene expression or death of transduced cells. Herein, we demonstrate that during the elimination of transgene expression, the brain becomes infiltrated with CD4 and CD8 T cells and that these T cells are necessary for transgene elimination. Further, the loss of transgene-expressing brain cells fails to occur in the absence of IFNγ, perforin, and TNFα receptor. Two methods to induce severe immune suppression in immunized animals also fail to restitute transgene expression, demonstrating the irreversibility of this process. The need for cytotoxic molecules and the irreversibility of the reduction in transgene expression suggested to us that elimination of transduced cells is responsible for the loss of transgene expression. A new experimental paradigm that discriminates between downregulation of transgene expression and the elimination of transduced cells demonstrates that transduced cells are lost from the brain upon the induction of a specific antiviral immune response. We conclude that the anti-adenoviral immune response reduces transgene expression in the brain through loss of transduced cellsFil: Zirger, Jeffrey M.. Cedars Sinai Medical Center; Estados Unidos. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Puntel, Mariana. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergeron, Josee. Cedars Sinai Medical Center; Estados Unidos. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Wibowo, Mia. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados UnidosFil: Moridzadeh, Rameen. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados UnidosFil: Bondale, Niyati. Cedars Sinai Medical Center; Estados Unidos. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Barcia, Carlos. Cedars Sinai Medical Center; Estados Unidos. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Kroeger, Kurt M.. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados UnidosFil: Liu, Chunyan. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados UnidosFil: Castro, Maria Graciela. University of California at Los Angeles. School of Medicine; Estados Unidos. Cedars Sinai Medical Center; Estados Unidos. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. Cedars Sinai Medical Center; Estados Unidos. University of California at Los Angeles. School of Medicine; Estados Unidos. University of Michigan; Estados Unido