The relative importance of graft surveillance and warfarin therapy in infrainguinal prosthetic bypass failure

BackgroundWe sought to describe modes of failure and associated limb loss after infrainguinal polytetrafluoroethylene bypass grafting in patients lacking a saphenous venous conduit and to define specific clinical or hemodynamic factors prognostic for bypass failure.MethodsWe identified 121 patients (mean age, 67 years; 90 men and 31 women) with determinable outcomes (minimum follow-up, 2 months; mean, 17 months) after 130 prosthetic infrainguinal bypasses between 1997 and 2005. Ischemic presentation was rest pain in 52%, tissue loss in 34%, and disabling claudication and/or popliteal aneurysm in 14%, with 24% of patients requiring a redo bypass. Distal targets were the above-knee (n = 44), distal popliteal (n = 27), or tibial/pedal (n = 59) arteries. Sixty-six (77%) of the below-knee (BK) target (distal popliteal or tibial) bypasses had distal anastomotic adjuncts (vein cuff or patch). Duplex graft surveillance was performed at 1, 4, and 7 months after surgery and twice yearly thereafter, with recording of midgraft velocities and imaging encompassing inflow and outflow vessels. Arteriography and open/endovascular intervention was performed for stenoses identified by duplex scanning (peak systolic velocity >300 cm/s; velocity ratio >3.5). An attempt was made to salvage occluded grafts by using catheter-directed thrombolysis or open techniques. Eighty-six patients (74% of BK bypasses) were placed on chronic warfarin therapy with a target international normalized ratio range between 2 and 3. Prognostic factors were identified by using univariate statistics and multivariate logistic regression analysis.ResultsThree-year primary, assisted, and secondary patency rates were 39%, 43%, and 59%, respectively, for all bypasses, with no difference noted between above-knee and BK grafts (P = .5). At 3 years, freedom from limb loss was 75%, and patient survival was only 70%, with no adverse effect on survival imparted by amputation. Sixty-nine total adverse events occurred as a result of thrombotic occlusion (n = 51), duplex scan–detected stenosis (n = 13), or graft infection (n = 5). Forty-nine percent of all initial graft occlusions eventually led to amputation. Twenty-three grafts (27% of 86 patients) in patients maintained on chronic warfarin were subtherapeutic at the time of occlusion. Use of a distal anastomotic adjunct with BK bypasses reduced graft thrombosis (35% with vs 60% without) but did not impart a significant patency advantage (P = .07). Multivariate analysis revealed low graft flow (midgraft velocity ≤45 cm/s; odds ratio [OR], 6.1; 95% confidence interval [CI], 1.9-19.2), use of warfarin (OR, 8.4; 95% CI, 2.1-34.5), and therapeutic warfarin (OR, 24.6; 95% CI, 5.7-106) to be independently predictive for bypass patency. Graft patency was maintained in 89% of grafts remaining therapeutic on warfarin compared with only 55% of subtherapeutic or nonanticoagulated grafts (P < .001). Low-flow grafts (n = 61) occluded more frequently than higher-flow grafts (46% vs 13%; P < .001). Therapeutic warfarin augmented the patency of low-flow (P < .001) but not high-flow (P = .15) grafts.ConclusionsLow graft flow was a more common mode of prosthetic bypass failure than development of duplex scan–detected stenotic lesions during follow-up. Early duplex scanning may be more important for characterizing midgraft velocity and related thrombotic potential and selecting patients for chronic anticoagulation. Maintenance of therapeutic warfarin is paramount in optimizing prosthetic bypass patency and limb preservation

Plaque excision with the Silverhawk catheter: Early results in patients with claudication or critical limb ischemia

ObjectiveThis study was conducted to detail the early experience after infrainguinal atherectomy using the Silverhawk plaque excision catheter for the treatment of symptomatic peripheral vascular disease.MethodsA prospective database was established in August 2004 in which data for operations, outcomes, and follow-up were recorded for patients undergoing percutaneous plaque excision for peripheral arterial occlusive disease. Society for Vascular Surgery (SVS) ischemia scores and femoropopliteal TransAtlantic Inter-Society Consensus (TASC) criteria were assigned. A follow-up protocol included duplex ultrasound surveillance at 1, 3, and 6 months and then yearly thereafter. Standard statistical analyses were performed.ResultsDuring a 17-month period, 66 limbs of 60 patients (37 men [61.7%]) underwent 70 plaque excisions (four repeat procedures). Indications included tissue loss based on SVS ischemia at grades 5 and 6 (25/70), rest pain at grade 4 (22/70), and claudication at grades 2 to 3 (23/70). The mean lesion length was 8.8 ± 0.7 cm. The technical success rate was 87.1% (61/70). Adjunctive treatment was required in 17 procedures (24.3%), consisting of 14 balloon angioplasties and three stents. Femoropopliteal TASC criteria included 5 TASC A lesions, 14 TASC B lesions, 32 TASC C lesions, and 19 TASC D lesions. Although 17 plaque excisions included a tibial vessel, no patient underwent isolated tibial atherectomy. The mean increase in ankle-brachial index was 0.27 ± 0.04 and in toe pressure, 20.3 ± 6.9 mm Hg. Mean duplex ultrasound follow-up was 5.2 months (range, 1 to 17 months). One-year primary, primary assisted, and secondary patency was 61.7%, 64.1%, and 76.4%, respectively. Restenosis or occlusion developed in 12 patients (16.7%) and was detected at a mean of 2.8 ± 0.7 months. Restenosis or occlusion was significantly more common (P < .05) in patients with TASC C and D lesions compared with patients with TASC A and B lesions. Six (8.3%) of 12 patients underwent reintervention on the basis of duplex ultrasound surveillance results. Four (33.3%) of 12 patients experienced reocclusion during the same hospitalization, and amputation and open revascularization were required in two patients each.ConclusionsPercutaneous plaque excision is a viable treatment option for lower extremity revascularization. Outcomes are related to ischemia and lesion severity. Patency and limb salvage rates are equivalent to other endovascular modalities

Outcome of carotid stent-assisted angioplasty versus open surgical repair of recurrent carotid stenosis

AbstractPurposeWe compared outcome and durability of carotid stent-assisted angioplasty (CAS) with open surgical repair (ie, repeat carotid endarterectomy [CEA]) to treat recurrent carotid stenosis (RCS).MethodsA retrospective review of anatomic and neurologic outcomes was carried out after 27 repeat CEA procedures (1993-2002) and 52 CAS procedures (1997-2002) performed to treat high-grade internal carotid artery (ICA) RCS after CEA. The incidence of intervention because of symptomatic RCS was similar (repeat CEA, 63%; CAS, 60%), but the interval from primary CEA to repeat intervention was greater (P < .05) in the repeat CEA group (83 ± 15 months) compared with the CAS group (50 ± 8 months). In the CAS group, 17 of 52 arteries (33%) were judged not to be surgical candidates because of surgically inaccessible high lesions (n = 8), medical comorbid conditions (n = 4), neck irradiation (n = 3), or previous surgery with cranial nerve deficit or stroke (n = 2). Three patients who underwent repeat CEA had lesions not appropriate for treatment with CAS.ResultsOverall 30-day morbidity was similar after CAS (12%; death due to ipsilateral intracranial hemorrhage, 1; nondisabling stroke, 1; reversible neurologic deficits or transient ischemic attack, 2; access site complication, 2) and repeat CEA (11%; no death; nondisabling stroke, 1; reversible cranial nerve injury, 1; cervical hematoma, 1). Combined stroke and death rate was 3.7% for repeat CEA and 5.7% for CAS (P > .1). All duplex ultrasound scans obtained within 3 months after CEA and CAS demonstrated patent ICA and velocity spectra of less than 50% stenosis. During follow-up, no repeat CEA (mean, 39 months) or CAS (mean, 26 months) repair demonstrated ICA occlusion, but two patients (8%) who underwent repeat CEA and 4 patients (8%) who underwent CAS required balloon or stent angioplasty because of 80% RCS. At last follow-up, no patient had ipsilateral stroke and all ICA remain patent. At duplex scanning, stenosis-free (<50% diameter reduction) ICA patency at 36 months was 75% after repeat CEA and 57% after CAS (P = .26, log-rank test).ConclusionsCarotid angioplasty for treatment of high-grade stenotic ICA after CEA resulted in similar anatomic and neurologic outcomes compared with open surgical repair. Most lesions are amenable to endovascular therapy, and CAS enabled treatment in patients judged not to be suitable surgical candidates. Duplex scanning surveillance after repeat CEA or CAS is recommended, because stenosis can recur after either secondary procedure

Fragmentative and stereochemical isomerization probes for homolytic carbon to phosphorus bond scission catalyzed by bacterial carbon-phosphorus lyase

Three bacterial strains, Agrobacterium radiobacter, Klebsiella oxytoca, and Kluyvera ascorbata, isolated by enrichment culture for carbon to phosphorus bond cleavage ability, were analyzed for the mode of C---P bond fission. The cleavage of alkyl phosphonic acids to alkanes and inorganic phosphates proceeded both aerobically and anaerobically, and growth on trideuteromethylphosphonic acid yielded trideuteromethane as product. These data indicate that functionalization of the organic moiety does not precede carbon to phosphorus bond cleavage. As probes for radical intermediates, cyclopropylmethylphosphonic acid and cis-1,2-dideutero-1-propenylphosphonic acid were used in growth experiments and the gaseous hydrocarbon products were examined. With the cyclopropylmethylphosphonic acid probe, all three bacteria produced methylcyclopropane, but only K. oxytoca and K. ascorbata also generated the acyclic olefin 1-butene, and then only in very low quantity (0.6 and 0.3% versus methylcyclopropane, respectively). With the propenylphosphonic acid probe, cis-1,2-dideuteropropene was formed with greater than 98% retention of configuration with each bacterial strain. Only for K. oxytoca was the alternate product, in this case trans-1,2-dideuteropropene, clearly detected at 1.5%. Thus, C---P bond fission may yield radical intermediates that are trapped efficiently at the enzyme active site or, alternatively, homolysis of the C---P bond may occur as a minor reaction pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26489/1/0000025.pd

NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition

The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pigmented melanoma but not in prostate cell lines. We also found that loss of the tumor suppressor p53 increased NeuroD1 expression in normal human bronchial epithelial cells and cancer cells with neuroendocrine features. Although we found that a major mechanism of action of NeuroD1 is by the regulation of TrkB, effective targeting of TrkB to inhibit invasion may depend on the cell of origin. These findings suggest that NeuroD1 is a lineage-dependent oncogene acting through its downstream target, TrkB, across multiple cancer types, which may provide new insights into the pathogenesis of neuroendocrine cancers