Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale

Background: The use of thrombolytic therapy in the treatment of thrombosed infrainguinal native arteries and bypass grafts has increased over the years. Main limitation of this treatment modality, however, is the occurrence of bleeding complications. Low intensity ultrasound (US) has been shown to accelerate enzymatic thrombolysis, thereby reducing therapy time. So far, no randomized trials have investigated the application of US-accelerated thrombolysis in the treatment of thrombosed infra-inguinal native arteries or bypass grafts. The DUET study (Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thrombo-embolic infrainguinal disease) is designed to assess whether US-accelerated thrombolysis will reduce therapy time significantly compared with standard catheter-directed thrombolysis.Methods/design: Sixty adult patients with recently (between 1 and 7 weeks) thrombosed infrainguinal native arteries or bypass grafts with acute limb ischemia class I or IIa, according to the Rutherford classification for acute ischemia, will be randomly allocated to either standard thrombolysis (group A) or US-accelerated thrombolysis (group B). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infrainguinal native artery or bypass graft, with outflow through at least 1 crural artery.Discussion: The DUET study is a randomized controlled trial that will provide evidence of whether US-accelerated thrombolysis will significantly reduce therapy time in patients with recently thrombosed infrainguinal native arteries or bypass grafts, without an increase in complications. Trial registration: Current Controlled Trials ISRCTN72676102

Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts

Background Catheter-directed thrombolysis is a well-accepted treatment for acute lower extremity occlusions of native arteries and bypass grafts. Several variables that affect outcomes of thrombolysis have been identified. The hypothesis of this study was that the long-term outcome after catheter-directed thrombolysis would be better for acute lower extremity occlusions of native arteries compared with prosthetic bypass grafts. Methods This observational study retrospectively analyzed 159 consecutive patients (114 men), median age, 65 years (range 57–73 years), with 89 native artery (56%), and 70 prosthetic bypass graft (44%) occlusions of the lower extremity. All patients were treated with catheter-directed thrombolysis between 2006 and 2009 in 2 vascular referral centers in the Netherlands. The severity of ischemia was Rutherford class I (52%), class IIa (27%), class IIb (12%) and unknown (9%) in native arteries and class I (64%), class IIa (19%), class IIb (1%), and unknown (16%) in bypass grafts. Median (range) duration of symptoms before the start of thrombolysis was 3.5 (1–14) days in native arteries and 3 (1–9) days in bypass grafts. All patients were treated with a continuous dosage of urokinase (100,000 IU/h). Amputation-free survival was estimated by conduit type using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Results Complete (>95%) lysis was achieved in 69% of native arteries and bypass grafts (P = 1.00). Major hemorrhagic complications occurred in 12% (4% hemorrhagic strokes, of which 2% were fatal) of native arteries and in 7% (0% hemorrhagic stroke) of bypass grafts (P = 0.28). The 30-day mortality rate was 6% in native arteries and 1% in bypass grafts (P = 0.17), and the 30-day amputation rate was 10% in native arteries and 13% in bypass grafts (P = 0.45). Mean follow-up was 27 ± 19 months. Amputation-free survival at 1 year was 76% for native arteries and 78% for bypass grafts and at 5 years was 65% for native arteries and 51% for bypass grafts (P = 0.32). Multivariate analysis showed 2 negative predictors for amputation-free survival: age >65 years and cerebrovascular disease. Conduit type was not an independent predictor for amputation-free survival (P = 0.78). Conclusions Despite initial promising results, long-term follow-up of catheter-directed thrombolysis for acute lower extremity occlusions showed a disappointing amputation-free survival. In multivariate analysis, no significant differences in amputation-free survival between native arteries and prosthetic bypass grafts were determined

Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts

Background Catheter-directed thrombolysis is a well-accepted treatment for acute lower extremity occlusions of native arteries and bypass grafts. Several variables that affect outcomes of thrombolysis have been identified. The hypothesis of this study was that the long-term outcome after catheter-directed thrombolysis would be better for acute lower extremity occlusions of native arteries compared with prosthetic bypass grafts. Methods This observational study retrospectively analyzed 159 consecutive patients (114 men), median age, 65 years (range 57–73 years), with 89 native artery (56%), and 70 prosthetic bypass graft (44%) occlusions of the lower extremity. All patients were treated with catheter-directed thrombolysis between 2006 and 2009 in 2 vascular referral centers in the Netherlands. The severity of ischemia was Rutherford class I (52%), class IIa (27%), class IIb (12%) and unknown (9%) in native arteries and class I (64%), class IIa (19%), class IIb (1%), and unknown (16%) in bypass grafts. Median (range) duration of symptoms before the start of thrombolysis was 3.5 (1–14) days in native arteries and 3 (1–9) days in bypass grafts. All patients were treated with a continuous dosage of urokinase (100,000 IU/h). Amputation-free survival was estimated by conduit type using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Results Complete (>95%) lysis was achieved in 69% of native arteries and bypass grafts (P = 1.00). Major hemorrhagic complications occurred in 12% (4% hemorrhagic strokes, of which 2% were fatal) of native arteries and in 7% (0% hemorrhagic stroke) of bypass grafts (P = 0.28). The 30-day mortality rate was 6% in native arteries and 1% in bypass grafts (P = 0.17), and the 30-day amputation rate was 10% in native arteries and 13% in bypass grafts (P = 0.45). Mean follow-up was 27 ± 19 months. Amputation-free survival at 1 year was 76% for native arteries and 78% for bypass grafts and at 5 years was 65% for native arteries and 51% for bypass grafts (P = 0.32). Multivariate analysis showed 2 negative predictors for amputation-free survival: age >65 years and cerebrovascular disease. Conduit type was not an independent predictor for amputation-free survival (P = 0.78). Conclusions Despite initial promising results, long-term follow-up of catheter-directed thrombolysis for acute lower extremity occlusions showed a disappointing amputation-free survival. In multivariate analysis, no significant differences in amputation-free survival between native arteries and prosthetic bypass grafts were determined

A Regenerative Agricultural System at Scale: an Outline of Required Outcomes for the Netherlands

Regenerative agriculture is considered a more sustainable alternative to current farming practices, but it is not yetwell defined. Building on scientific literature we have defined regenerative agriculture as ‘an approach to farming thatuses soil conservation as the entry point to regenerate and contribute to multiple provisioning, regulating and supportingecosystem services, with the aspiration that this will enhance not only the environmental, but also the social andeconomic dimensions of sustainable food production’. In addition to this definition at farm level we propose thefollowing vision for a regenerative agricultural system at landscape or higher system levels: A regenerative agriculturalsystem enables production of food and biomass and enables ecosystems to maintain a healthy state and evolve, whilecontributing to biological diversity, integrity of the biosphere, human and farm animal well-being and economicprosperity of society. Based on this long-term vision we have defined a comprehensive outline of a regenerativeagricultural system that includes, and takes into account, all ecosystem services, soil functions and planetaryboundaries. This outline covers fourteen topics and describes the ‘outcomes’ that are needed to meet the objectives of a regenerative agricultural system, without being prescriptive on ‘how’ these outcomes should be achieved. Therefore, weuse the term ‘required outcomes’ which precisely and quantitatively describe the target performance of the regenerativeagricultural system. These ‘required outcomes’ are related to the inputs and use of resources, the output (i.e. food,biomass) and losses/emissions, and the preferred state of soils, water bodies, animals, biodiversity and society. Theoutcomes encompass environmental, social, and economic aspects, and are defined at five different system levels: 1)field (above and below ground), 2) farm, 3) local landscape (including air and water bodies), 4) the Netherlands and 5)international. All required outcomes are based on and supported by scientific literatur

A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome

Item does not contain fulltextBACKGROUND & AIMS: Treatment of patients with necrotizing pancreatitis has become more conservative and less invasive, but there are few data from prospective studies to support the efficacy of this change. We performed a prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis. METHODS: We collected data from 639 consecutive patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome. RESULTS: Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An intervention was performed in 242 patients (38%), with 27% mortality; this included early emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days, 26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003). Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and mortality (20% vs 9%, P<.001). CONCLUSIONS: Approximately 62% of patients with necrotizing pancreatitis can be treated without an intervention and with low mortality. In patients with infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome