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1.
Ther Apher Dial ; 26(1): 185-190, 2022 Feb.
Article En | MEDLINE | ID: mdl-33891365

Central venous stenosis (CVS) is usually a late-diagnosed clinical entity that is common in hemodialysis patients. It causes various problems ranging from hemodialysis difficulty to loss of the arterio-venous (A-V) fistula. In the present study, we aimed to determine the effect of drug eluting balloon while excluding the influence of other variable factors by evaluating the same individuals with plain and paclitaxel-eluting balloons. This research was a prospective study of 18 symptomatic hemodialysis patients (age 50.9 ± 14.0 years, range 32-72 years; 11 male, 7 female) with CVS who underwent treatment by plain balloon angioplasty (PBA) and paclitaxel-eluting balloon angioplasty (PEBA) in our hospital from January 2016 to June 2017. First, third and sixth month central vein patency rates were compared. The median patency rates of central veins were 109.0 (range: 10-324) days after PBA and 238.5 (range: 157-501) days after PEBA (p < 0.001). There was no statistically significant difference between PBA and PEBA angioplasty in one-month patency (p Ëƒ 0.05). By contrast, a statistically significant difference was found between 3- and 6-month patency rates (p = 0.031 and p Ë‚ 0.001, respectively). Kaplan-Meier analysis revealed that the primary cumulative patency rate of PEBA was significantly longer than that of PBA (p ˂ 0.001). In this prospective study, PEBA patency is superior to PBA patency in the treatment of CVS in dialysis patients.


Angioplasty, Balloon/instrumentation , Angioplasty, Balloon/methods , Graft Occlusion, Vascular/drug therapy , Paclitaxel/administration & dosage , Renal Dialysis/adverse effects , Vascular Patency/drug effects , Adult , Aged , Constriction, Pathologic/complications , Constriction, Pathologic/drug therapy , Female , Graft Occlusion, Vascular/etiology , Humans , Male , Middle Aged , Prospective Studies , Renal Dialysis/instrumentation , Treatment Outcome , Tubulin Modulators/administration & dosage
2.
Clin Appl Thromb Hemost ; 27: 10760296211063882, 2021.
Article En | MEDLINE | ID: mdl-34873965

Hemodialysis is required for patients with end-stage renal disease (ESRD) that require arteriovenous (AV) grafts or fistulas for vascular access. These access points are prone to thrombosis. To determine the effect of medical adjuvant therapy on AV graft/fistula patency among patients with ESRD on hemodialysis. Adhering to the PRISMA 2020 statement, a systematic search was conducted until August 20, 2021, with keywords including arteriovenous graft, fistula, patency, thrombosis, hemodialysis, adjuvant treatment. The following databases were searched: PubMed, Scopus, Web of Science, CINAHL Plus, and Cochrane. A random-effects model was employed using Review Manager 5.4 for data analysis. The meta-analysis pooled in 1985 participants with 1000 (50.4%) in the medical adjuvant treatment group. At a snapshot, medical adjuvant therapy reduced the risk for graft thrombosis (RR = 0.64, P = .02). Notable medications included aspirin for graft thrombosis (RR = 0.36, P = .006) and ticlopidine for fistula thrombosis (RR = 0.53, P = .01). Certain antiplatelet therapies (aspirin and ticlopidine) reduced the number of patients with AV fistula/graft thrombosis among patients with high heterogeneity among the trials. Other therapies (fish oil, sulfinpyrazone, clopidogrel, and aspirin/dipyridamole) did not demonstrate significant improvement but may be promising once concrete evidence is available. Potential benefits of anti-platelet therapies may be explored to maintain the potency of AV grafts/fistulas through well-designed placebo-controlled trials and long-term follow-up.


Graft Occlusion, Vascular/drug therapy , Kidney Failure, Chronic/therapy , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Vascular Patency , Combined Modality Therapy , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Platelet Aggregation Inhibitors
3.
J Vasc Surg Venous Lymphat Disord ; 9(4): 881-887, 2021 07.
Article En | MEDLINE | ID: mdl-33122077

OBJECTIVE: Endovascular treatment with percutaneous transluminal angioplasty and stenting has quickly gained popularity for treatment of deep venous obstructive disease. Early thrombosis after stenting in iliofemoral veins is uncommon. The treatment and analysis of the underlying factors leading to the rethrombosis of stents placed in the previous 14 days are reported in this study. METHODS: Patients diagnosed with early in-stent thrombosis after iliofemoral stenting were reviewed in this retrospective analysis. Patients with acute occlusion were routinely treated by catheter-directed thrombolysis (CDT), and the underlying causes of early occlusion were identified during the procedure. After successful CDT procedures, patients received additional interventions (percutaneous transluminal angioplasty with or without stenting) if indicated. RESULTS: A total of 527 patients underwent stenting in the iliofemoral veins, and 32 patients (20 men [63%]) with acute thrombosis in iliofemoral venous stents placed in the previous 14 days were treated in our center from January 2015 to December 2018. The mean time from the onset of symptoms to the intervention was 6 days. Successful thrombolysis was achieved in 31 of the 32 patients, and additional stents were implanted in 16 patients. Patency was achieved in all cases. The underlying factors of early stent thrombosis were technical failure of the initial procedure, such as suboptimal positioning, failure owing to stent characteristics (stent kinking, compression, and angulation), in-stent residual thrombus, and inadequate anticoagulation. In all cases, recanalization was achieved through successful thrombolysis with or without restenting. CONCLUSIONS: Treatment with CDT and stenting of early in-stent thrombosis is effective and feasible. Recanalization of stented segment(s) can be achieved in most cases of recent thrombosis (<14 days). Early stent-related occlusion is mainly caused by stent-related problems and technical inadequacies.


Femoral Vein/surgery , Graft Occlusion, Vascular/etiology , Iliac Vein/surgery , Prosthesis Failure , Stents/adverse effects , Adult , Aged , Angioplasty , Anticoagulants/therapeutic use , Female , Follow-Up Studies , Graft Occlusion, Vascular/drug therapy , Graft Occlusion, Vascular/surgery , Humans , Male , Middle Aged , Prosthesis Design , Recurrence , Retrospective Studies , Risk Factors , Thrombolytic Therapy/methods , Time Factors
4.
Int J Mol Sci ; 21(22)2020 Nov 20.
Article En | MEDLINE | ID: mdl-33233489

Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.


Atherosclerosis/metabolism , Graft Occlusion, Vascular/metabolism , Hypertension/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Reactive Oxygen Species/metabolism , Angiotensin II/genetics , Angiotensin II/metabolism , Antioxidants/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/genetics , Atherosclerosis/pathology , Biomarkers/metabolism , Cardiovascular Agents/therapeutic use , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Gene Expression Regulation , Graft Occlusion, Vascular/drug therapy , Graft Occlusion, Vascular/genetics , Graft Occlusion, Vascular/pathology , Humans , Hypertension/drug therapy , Hypertension/genetics , Hypertension/pathology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , Oxidative Stress/drug effects , Phenotype , Reactive Oxygen Species/antagonists & inhibitors , Signal Transduction
5.
Vasc Endovascular Surg ; 54(8): 752-755, 2020 Nov.
Article En | MEDLINE | ID: mdl-32783501

Compartment syndrome is caused by increased pressure within fascial compartment. We present a unique case of a thigh compartment syndrome that occurred after overnight catheter delivered Tissue plasminogen activator (tPA) thrombolysis of an acutely thrombosis femoral-to above knee popliteal artery Propaten® PTFE (WL Gore & Associates, Flagstaff, AZ) bypass graft. The condition was treated by emergency fasciotomy and the patient recovered uneventfully.


Blood Vessel Prosthesis Implantation/adverse effects , Compartment Syndromes/chemically induced , Fibrinolytic Agents/adverse effects , Graft Occlusion, Vascular/drug therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/therapy , Thigh/blood supply , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Compartment Syndromes/diagnostic imaging , Compartment Syndromes/physiopathology , Compartment Syndromes/surgery , Fasciotomy , Fibrinolytic Agents/administration & dosage , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/physiopathology , Tissue Plasminogen Activator/administration & dosage , Treatment Outcome
7.
Ann Vasc Surg ; 69: 317-323, 2020 Nov.
Article En | MEDLINE | ID: mdl-32502677

BACKGROUND: Acute limb ischemia (ALI) is challenging to treat because of high morbidity and mortality. Endovascular-first options beginning with thrombolysis are technically feasible with similar results to open surgery. We examined our experience with thrombolysis to identify patients and target conduits that are predictive of improved outcomes. METHODS: We performed a retrospective review of our institutional database of thrombolysis cases for arterial lower extremity disease. Thrombolysis was the index procedure, and any subsequent treatment was a reintervention. Conversion to open surgery perioperatively such as thromboembolectomy or bypass was considered a technical failure. Primary outcomes included primary patency, secondary patency, amputation-free survival (AFS), and survival. Secondary outcomes included conversion to open, reintervention <30 days, and amputation <30 days. Descriptive statistics and analysis of variance were performed for preoperative and intraoperative risk factors. Kaplan-Meier estimation and Cox proportional hazard models were used for primary and secondary outcomes. RESULTS: Ninety-nine patients with ALI were treated with thrombolysis from 2007 to 2017. Thrombolysis was attempted on native artery (40%), vein bypass (7%), prosthetic bypass (33%), and stent (19%). Rutherford class distribution was 50% class 1, 41% class 2a, 5% class 2b, and 3% class 3. Technical success was 70%, characterized by an all-endovascular approach, patency at 30 days, and AFS for 30 days. Primary patency at 1- and 2-years was 31% and 22%, respectively. Secondary patency at 1- and 2-years was 39% and 27%, respectively. Overall, 30% required conversion to open surgery at the time of the index procedure, 7% reintervention <30 days, 5% mortality <30 days, and 5% major amputation <30 days. Prosthetic grafts and vein bypasses had the worst primary and secondary patency (P < 0.05). Five out of 7 vein bypasses required open conversion. Thrombolysis of native arteries was most successful maintaining primary patency (P < 0.05), secondary patency (P < 0.05), and AFS (P < 0.05). Patients who had adjunctive procedures at the time of thrombolysis had a significantly greater primary patency (P < 0.05) and secondary patency (P < 0.05) but not greater AFS. CONCLUSION: Outcomes in thrombolysis for ALI have not significantly improved 20 years after the STILE trial. Technical success and mid-term patency rates are modest at best. Thrombolysis of vein bypasses and prosthetic grafts have poor technical success and primary patency compared with native arteries. However, aggressive adjunctive interventions during thrombolysis appear to improve primary and secondary patency.


Graft Occlusion, Vascular/drug therapy , Ischemia/drug therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/drug therapy , Thrombolytic Therapy , Acute Disease , Aged , Amputation, Surgical , Databases, Factual , Female , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/mortality , Graft Occlusion, Vascular/physiopathology , Humans , Ischemia/diagnostic imaging , Ischemia/mortality , Ischemia/physiopathology , Limb Salvage , Male , Middle Aged , New York , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Peripheral Arterial Disease/physiopathology , Retrospective Studies , Risk Factors , Tertiary Care Centers , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome , Vascular Patency
8.
Am Heart J ; 220: 237-245, 2020 02.
Article En | MEDLINE | ID: mdl-31884246

RATIONALE: An estimated 15% of saphenous vein grafts (SVGs) occlude in the first year after coronary artery bypass grafting (CABG) despite aspirin therapy. Graft occlusion can result in symptoms, myocardial infarction, and death. SVG occlusion is primarily caused by atherothrombosis, in which platelet activation plays a pivotal role. Evidence regarding the effect of stronger platelet inhibition on SVG patency after CABG is limited. The main objective of the POPular CABG trial is to determine whether dual antiplatelet therapy with aspirin plus ticagrelor improves SVG patency when compared to aspirin alone. STUDY: The POPular CABG is a randomized, double-blind, placebo-controlled, multicenter trial investigating the effect of adding ticagrelor to standard aspirin therapy on the rate of SVG occlusion. A total of 500 patients undergoing CABG with ≥ 1 SVG are randomized to ticagrelor or placebo. The primary end point is SVG occlusion rate, assessed with coronary computed tomography angiography at 1 year. Secondary end points are stenoses and occlusions in both SVGs and arterial grafts and SVG failure at 1 year, defined as a composite of SVG occlusion on coronary computed tomography angiography or coronary angiography, SVG revascularization, myocardial infarction in the territory supplied by an SVG, or sudden death. Safety end points are bleeding events at 30 days and 1 year. CONCLUSION: The POPular CABG trial investigates whether adding ticagrelor to standard aspirin after CABG reduces the rate of SVG occlusion at 1 year.


Aspirin/therapeutic use , Coronary Artery Bypass , Graft Occlusion, Vascular/drug therapy , Platelet Aggregation Inhibitors/pharmacology , Saphenous Vein/transplantation , Ticagrelor/pharmacology , Aged , Computed Tomography Angiography , Coronary Angiography/methods , Death, Sudden, Cardiac/etiology , Double-Blind Method , Drug Therapy, Combination , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/epidemiology , Humans , Myocardial Infarction/etiology , Placebos/pharmacology , Research Design , Sample Size , Vascular Patency/drug effects
9.
J Cardiovasc Surg (Torino) ; 61(2): 200-207, 2020 Apr.
Article En | MEDLINE | ID: mdl-28849898

BACKGROUND: Thrombolytic treatment has many potential indications in the era of modern vascular surgery. We aimed to analyze the contemporary experience in the catheter-directed, intraarterial thrombolysis in different clinical scenarios. METHODS: The available data of 121 patients with different types (acute, subacute, complications of vascular procedures) of lower limb ischemia treated by means of the intraarterial, catheter-directed thrombolysis between November 2011 and December 2016 were retrospectively analyzed. The basic treatment protocol, utilized in 92% of patients, was a catheter-directed infusion of 40 mg of alteplase within 3.5 hours. Pre- and intraprocedural factors (indications, demographic details, comorbidities, the dose of alteplase utilized, underlying lesions procedures), as well as postoperative outcomes (lysis grade, death, complications, reinterventions, and limb loss after 1-month observation), were analyzed. RESULTS: Successful thrombolysis was achieved in 76.1% (92 of 121) patients. The success rate was similar for acute, subacute limb ischemia and thrombotic complications of vascular procedures. Around 67.8% of patients (N.=82) had procedures to correct underlying lesions performed. Overall complication rate was 28.1%, but the major bleeding was observed in only 5% (6 patients). Neither intracranial bleeding nor gastrointestinal bleeding occurred. No mortality, 1.7% reintervention rate and 10.7% amputation rate were recorded during one-month follow-up. CONCLUSIONS: Accelerated intraarterial thrombolysis is an effective measure in the treatment of acute, sub-acute limb ischemia as well as thromboembolic complications of vascular procedures. It carries a low risk of major bleeding. The location of thrombus in the crural arteries adversely affects the treatment results. Atrial fibrillation increases the risk of amputation while complete thrombus lysis is protective.


Graft Occlusion, Vascular/drug therapy , Peripheral Arterial Disease/therapy , Tissue Plasminogen Activator/therapeutic use , Vascular Patency/physiology , Vascular Surgical Procedures/adverse effects , Acute Disease , Aged , Catheterization, Peripheral/methods , Databases, Factual , Female , Graft Occlusion, Vascular/diagnostic imaging , Humans , Infusions, Intra-Arterial , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Prognosis , Retrospective Studies , Risk Assessment , Severity of Illness Index , Thrombolytic Therapy/methods , Treatment Outcome , Vascular Patency/drug effects , Vascular Surgical Procedures/methods
10.
Eur J Pharmacol ; 868: 172856, 2020 Feb 05.
Article En | MEDLINE | ID: mdl-31836533

Saphenous vein grafts (SVG) patency is limited by intimal hyperplasia (IH) caused by endothelial dysfunction. This study aimed to explore the effect of placental growth factor (PlGF) on the endothelial function of SVG. In rat models of external jugular vein-carotid artery graft treated with PlGF or saline hydrogel, PlGF inhibited vein graft IH (day 28: 12.0 ± 1.9 vs. 61.7 ± 13.1 µm, P < 0.001), promoted microvessel proliferation (day 14: 33.3% 3+ vs. 50.0% 2+, P = 0.03), and increased nitric oxide (NO) production (P < 0.05 on days 1/3/5) and NO synthase (NOS) expression by immunohistochemistry. In human umbilical vein endothelial cells (HUVECs) cultured under hypoxia and treated or not with PlGF, PlGF restored the survival (50 ng/ml PlGF, 48 h: 91.7 ± 0.6% vs. 84.9 ± 0.5%, P < 0.01), migration (by Matrigel assay), and tube formation ability (junctions, tubules, and tubule total length; all P < 0.01) of HUVECs after hypoxia. PlGF increased NO production through increased eNOS expression (P < 0.05), without changes in iNOS expression. The mRNA expression of eNOS decreased after the addition of the PI3K inhibitor LY294002 (P < 0.05). PlGF promoted the protein expression of eNOS by up-regulating AKT, and the AKT and eNOS protein levels were decreased after adding LY294002 (all P < 0.05). In conclusion, PlGF is a candidate for the inhibition of IH in SVG after coronary artery bypass graft. The effects of PlGF are mediated by the upregulation of the eNOS mRNA and protein through the PI3K/AKT signaling pathway. PlGF promotes the secretion of NO by endothelial cells and thereby reduces the occurrence and development of IH.


Endothelium, Vascular/drug effects , Graft Occlusion, Vascular/drug therapy , Placenta Growth Factor/administration & dosage , Vascular Grafting/adverse effects , Animals , Cell Hypoxia , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/pathology , Endothelium, Vascular/pathology , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/pathology , Human Umbilical Vein Endothelial Cells , Humans , Hyperplasia/drug therapy , Hyperplasia/pathology , Jugular Veins/transplantation , Male , Rats , Saphenous Vein/transplantation
11.
Urology ; 134: 143-147, 2019 Dec.
Article En | MEDLINE | ID: mdl-31542462

OBJECTIVES: To assess the postoperative complication rate and overall survival when bovine pericardium is used as graft material for inferior vena cava (IVC) reconstructions in patients with renal cell carcinoma (RCC). The ideal graft material is yet to be established, with synthetic grafts widely studied and used in the current literature. METHODS: We performed a retrospective cohort analysis of consecutive patients who underwent IVC reconstructions as part of resection for RCC, using bovine pericardium as either a patch repair or tubular interposition graft. RESULTS: A total of 15 patients underwent resection with IVC reconstruction between 2010 and 2018. Nine patients had tubular interposition grafts and 6 had patch repairs. Three patients had Clavien-Dindo grade 3 or higher short-term complications. There was no difference in Comprehensive Complications Index between those who had interposition grafts and patch repairs. Two patients had a long-term graft-associated thrombus requiring temporary anticoagulation. Overall survival was 46.5 months (95% confidence interval [CI] 36.9-56.1). There were no perioperative deaths. All long-term deaths were due to disease progression. CONCLUSION: Reconstruction of the IVC with a bovine pericardium graft is safe in experienced centers. Bovine pericardium could be considered as the material of choice, given its safety in the immediate postoperative period, ease of use, and patency without routine long-term anticoagulation. Advanced surgical management leads to good overall survival in this cohort with high tumor burden.


Bioprosthesis , Blood Vessel Prosthesis , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/pathology , Vena Cava, Inferior/surgery , Aged , Animals , Anticoagulants/therapeutic use , Carcinoma, Renal Cell/mortality , Cattle , Cohort Studies , Disease Progression , Female , Graft Occlusion, Vascular/drug therapy , Graft Occlusion, Vascular/etiology , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Neoplasm Invasiveness , Pericardium/transplantation , Postoperative Complications , Retrospective Studies , Thrombosis/drug therapy , Thrombosis/etiology
12.
Ann Vasc Surg ; 61: 48-54, 2019 Nov.
Article En | MEDLINE | ID: mdl-31075461

BACKGROUND: In case of acute thrombosis, lower limb bypasses can, in certain cases, be cleared by local intra-arterial fibrinolysis (LIF). The aim of this study is to evaluate the secondary patency of thrombosed bypasses after fibrinolysis. METHODS: This retrospective study includes all patients hospitalized for thrombosed bypasses of the lower limbs that were treated with in situ fibrinolysis using urokinase, between 2004 and 2013, in 2 French university hospital centers. Fibrinolysis was indicated in case of recent thrombosis (<3 weeks) provoking acute limb ischemia without sensory-motor deficit and in the absence of general contraindications. The secondary patency of the grafts was defined as the time after fibrinolysis without a new thrombotic event. RESULTS: There were 207 patients, hospitalized for recent thrombosis of 244 bypasses. The LIF was efficient in 74% of the cases (n = 180). Secondary patency of these bypasses was 54.2% and 32.4% overall, 68.3% and 50.3% for the suprainguinal bypasses, and 48.3% and 21.5% for the infrainguinal bypasses at 1 and 5 years, respectively. There is a significant difference (P = 0.002) regarding the permeability of the suprainguinal and infrainguinal bypasses. The survival rate was 75% (±6.4%) at 5 years and the limb salvage rate was 89% (±3.3%), 78.2% (±5.1%), and 75% (±5.8%) at 1, 3, and 5 years, respectively. The only independent factor influencing the secondary patency of infrainguinal bypasses that was significant in a multivariate analysis was the infragenicular localization of the distal anastomosis (P = 0.023). CONCLUSIONS: LIF is an effective approach that often allows the identification of the underlying cause, permitting elective adjunctive treatment of the underlying cause. Although LIF is at least as effective as its therapeutic alternatives described in the literature, the secondary patency of the bypasses remains modest and encourages close monitoring, particularly in patients with an infragenicular bypass.


Blood Vessel Prosthesis Implantation/adverse effects , Fibrinolytic Agents/administration & dosage , Graft Occlusion, Vascular/drug therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/surgery , Thrombolytic Therapy , Thrombosis/drug therapy , Vascular Patency/drug effects , Aged , Amputation, Surgical , Blood Vessel Prosthesis Implantation/mortality , Female , Fibrinolytic Agents/adverse effects , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/mortality , Graft Occlusion, Vascular/physiopathology , Humans , Limb Salvage , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/mortality , Peripheral Arterial Disease/physiopathology , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Time Factors , Treatment Outcome
13.
J Vasc Surg ; 70(4): 1205-1216, 2019 10.
Article En | MEDLINE | ID: mdl-30922746

OBJECTIVE: The objective of this study was to assess the technical and short- and long-term clinical outcomes of catheter-directed thrombolysis (CDT) with urokinase for occluded infrainguinal bypass grafts. In addition, factors associated with technical success and amputation-free survival were assessed. METHODS: A retrospective analysis of a cohort of patients treated with catheter-directed urokinase-based thrombolysis for occluded infrainguinal bypass grafts was conducted between January 2000 and December 2015. Demographics, procedural data, and short- and long-term outcome data, including patency rates of the bypasses, limb salvage, and overall survival, were collected. Statistical models for clustered data were applied to assess predictive factors. RESULTS: In 177 patients, 251 CDTs were performed on 204 bypasses. In 209 procedures (83.3%), the occluded bypass was reopened; clinical disappearance of ischemic symptoms occurred after 157 procedures (62.6%). Premature cessation of thrombolysis occurred in 33 procedures (13.2%), and periprocedural and postprocedural complications were noted in 91 patients (36.3%). Factors associated with long-term limb salvage are fewer vascular interventions before CDT (P = .0003), higher number of patent outflow vessels before start of CDT (P < .0001), and higher number of patent outflow vessels after CDT (P < .0001). The 1- and 5-year patency rates of bypasses after successful CDT were 64.6% and 48.9%; amputation-free survival after 1 year, 5 years, and 7 years was 81.5%, 71.3%, and 70.5%, respectively. CONCLUSIONS: Clinical success after CDT was observed in 62% of procedures with an associated complication rate of 36%. Patent outflow vessels before and after CDT are factors associated with long-term limb salvage. Amputation-free survival after 5 years is 71.3%.


Fibrinolytic Agents/administration & dosage , Graft Occlusion, Vascular/drug therapy , Peripheral Arterial Disease/surgery , Thrombolytic Therapy , Thrombosis/drug therapy , Urokinase-Type Plasminogen Activator/administration & dosage , Vascular Grafting/adverse effects , Vascular Patency , Aged , Amputation, Surgical , Catheterization, Peripheral , Female , Fibrinolytic Agents/adverse effects , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Limb Salvage , Male , Middle Aged , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/physiopathology , Progression-Free Survival , Retrospective Studies , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Time Factors , Urokinase-Type Plasminogen Activator/adverse effects
14.
Arterioscler Thromb Vasc Biol ; 39(4): 799-809, 2019 04.
Article En | MEDLINE | ID: mdl-30700130

Objective- Factor XI (FXI) contributes to thrombotic disease while playing a limited role in normal hemostasis. We generated a unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting FXI activation by thrombin or the procoagulant function of FXIa. We sought to confirm the antithrombotic activity of AB023 in a baboon thrombosis model and to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult subjects. Approach and Results- In a primate model of acute vascular graft thrombosis, AB023 reduced platelet and fibrin accumulation within the grafts by >75%. To evaluate the safety of AB023, we performed a first-in-human study in healthy adult volunteers without any serious adverse events. Overall, 10 of 21 (48%) subjects experienced 20 treatment-emergent adverse events, with 7 of 16 (44%) subjects following active treatment and 3 of 5 (60%) subjects following placebo. AB023 did not increase bleeding or prothrombin times. Anticoagulation was verified by a saturable ≈2-fold prolongation of the partial thromboplastin time for over 1 month after the highest dose. Conclusions- AB023, which inhibits contact activation-initiated blood coagulation in vitro and experimental thrombus formation in primates, produced a dose-dependent duration of limited anticoagulation without drug-related adverse effects in a phase 1 trial. When put in context with earlier observations suggesting that FXI contributes to venous thromboembolism and cardiovascular disease, although contributing minimally to hemostasis, our data further justify clinical evaluation of AB023 in conditions where contact-initiated FXI activation is suspected to have a pathogenic role. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03097341.


Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Factor XI/antagonists & inhibitors , Factor XIa/physiology , Fibrinolytic Agents/therapeutic use , Adult , Animals , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/immunology , Antibodies, Monoclonal, Humanized/pharmacology , Anticoagulants/adverse effects , Anticoagulants/immunology , Anticoagulants/pharmacology , Area Under Curve , Dose-Response Relationship, Drug , Double-Blind Method , Factor XI/immunology , Factor XIIa/physiology , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/immunology , Fibrinolytic Agents/pharmacology , Graft Occlusion, Vascular/drug therapy , Humans , Papio , Partial Thromboplastin Time
15.
Intern Med ; 58(9): 1287-1293, 2019 May 01.
Article En | MEDLINE | ID: mdl-30626836

A 61-year-old man with essential thrombocythemia (ET) presented with acute myocardial infarction (AMI) and underwent primary percutaneous coronary intervention. After stent deployment from the left main (LM) to the left anterior descending artery, intravascular ultrasound revealed thrombi formation in the whole stent. Two days later, optical frequency domain imaging confirmed stent malapposition and thrombi remaining in only the LM. The stent malapposition and ET might have contributed to this phenomenon. He underwent an additional stent expansion and aggressive anti-thrombotic regimen. AMI complicated with ET carries increased risks of in-stent thrombi formation and requires careful revascularization and aggressive pharmacotherapy.


Drug-Eluting Stents , Graft Occlusion, Vascular/etiology , Prosthesis Failure/etiology , Thrombocythemia, Essential/complications , Thrombosis/etiology , Anticoagulants/therapeutic use , Coronary Angiography/methods , Coronary Occlusion/surgery , Graft Occlusion, Vascular/drug therapy , Humans , Intraoperative Complications/drug therapy , Intraoperative Complications/etiology , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , Thrombosis/drug therapy
17.
J Vasc Access ; 20(5): 501-506, 2019 Sep.
Article En | MEDLINE | ID: mdl-30585114

BACKGROUND: Percutaneous pharmacomechanical thrombolysis is increasingly used to salvage thrombosed hemodialysis access. We aim to evaluate the effectiveness of alteplase compared to urokinase in percutaneous pharmacomechanical thrombolysis clotted access. METHODS: Records of patients who underwent pharmacomechanical thrombolysis at Interventional Nephrology Suite in a tertiary teaching hospital from 1 January 2016 to 31 December 2016 were reviewed. Technical and clinical success rates, thrombosis-free and cumulative survivals, procedure time, and radiation dose imparted to patients were compared for pharmacomechanical thrombolysis with urokinase versus alteplase. RESULTS: A total of 122 incident patients underwent pharmacothrombolysis (n = 53 for urokinase, n = 69 for alteplase) during the study period. The mean dose of urokinase and alteplase used was 176,897 ± 73,418 units and 3.7 ± 0.8 mg, respectively. Pharmacomechnical thrombolysis using urokinase versus alteplase has similar technical success rate (98.1% vs 97.1%, p = 0.599), clinical success rate (88.7% vs 97.1%, p = 0.068), complication rate (9.4% vs 13.0%, p = 0.373), and primary patency rates at 3 months (57.1% vs 70.1%, p = 0.106). Thrombosis-free survivals of the vascular access were 113.2 (35.3, 196) days versus 122 (84, 239) days (p = 0.168). Cumulative survivals were 239 (116, 320) vs 213 (110.5, 316.5) days (p = 0.801). Procedure time, fluoroscopy time, skin dose, and dose were significantly lower for pharmacomechanical thrombolysis using alteplase compared to urokinase (p = 0.045, p < 0.0001, p = 0.006, p = 0.001, respectively). Stenting was found to be associated with successful dialysis following thrombolysis on univariate analysis (odds ratio: 9.167, 95% confidence interval: 1.391-19.846, p = 0.021), although this was no longer significant in multivariate analysis (p = 0.078). CONCLUSION: Alteplase is an effective and safe alternative to urokinase for pharmacomechanical thrombolysis of clotted vascular access.


Arteriovenous Shunt, Surgical/adverse effects , Fibrinolytic Agents/administration & dosage , Graft Occlusion, Vascular/drug therapy , Kidney Failure, Chronic/therapy , Renal Dialysis , Thrombolytic Therapy/methods , Thrombosis/drug therapy , Tissue Plasminogen Activator/administration & dosage , Urokinase-Type Plasminogen Activator/administration & dosage , Aged , Female , Fibrinolytic Agents/adverse effects , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Time Factors , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , Urokinase-Type Plasminogen Activator/adverse effects , Vascular Patency
18.
Heart Vessels ; 33(12): 1423-1433, 2018 Dec.
Article En | MEDLINE | ID: mdl-29967954

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.


Blood Platelets/metabolism , Clopidogrel/administration & dosage , Drug-Eluting Stents/adverse effects , Everolimus , Percutaneous Coronary Intervention/adverse effects , Prasugrel Hydrochloride/administration & dosage , Tomography, Optical Coherence/methods , Aged , Blood Platelets/drug effects , Coronary Artery Disease/surgery , Coronary Vessels/diagnostic imaging , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Graft Occlusion, Vascular/diagnosis , Graft Occlusion, Vascular/drug therapy , Humans , Male , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome
19.
Biomed Res Int ; 2018: 3519596, 2018.
Article En | MEDLINE | ID: mdl-29682536

AIM: The aim of this study was to evaluate short-term patency of the new prosthetic graft and its structural changes after explantation. METHODS: The study team developed a three-layer conduit composed of a scaffold made from polyester coated with collagen from the inner and outer side with an internal diameter of 6 mm. The conduit was implanted as a bilateral bypass to the carotid artery in 7 sheep and stenosis was created in selected animals. After a period of 161 days, the explants were evaluated as gross and microscopic specimens. RESULTS: The initial flow rate (median ± IQR) in grafts with and without artificial stenosis was 120 ± 79 ml/min and 255 ± 255 ml/min, respectively. Graft occlusion occurred after 99 days in one of 13 conduits (patency rate: 92%). Wall-adherent thrombi occurred only in sharp curvatures in two grafts. Microscopic evaluation showed good engraftment and preserved structure in seven conduits; inflammatory changes with foci of bleeding, necrosis, and disintegration in four conduits; and narrowing of the graft due to thickening of the wall with multifocal separation of the outer layer in two conduits. CONCLUSIONS: This study demonstrates good short-term patency rates of a newly designed three-layer vascular graft even in low-flow conditions in a sheep model.


Collagen/metabolism , Graft Occlusion, Vascular/drug therapy , Vascular Patency/drug effects , Animals , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/methods , Carotid Arteries/drug effects , Prospective Studies , Prosthesis Design/methods , Plastic Surgery Procedures/methods , Sheep
20.
J Cardiovasc Surg (Torino) ; 59(6): 804-809, 2018 Dec.
Article En | MEDLINE | ID: mdl-28747047

BACKGROUND: It is imperative to gain safe access into the occluded targeted vessel and begin treating acute extremity limb ischemia. Often the origin of the targeted native artery or bypass graft will have a flush occlusion making it difficult to cannulate. This paper looks at the novel use of portable ultrasound to evaluate the origin of the artery or bypass graft to help facilitate the start of thrombolysis. METHODS: We reviewed our last 2 years of acute limb ischemia in our patients with high risk factors and comorbidities. We reviewed the use of ultrasound in these cases from the initial use of gaining femoral access to real time ultrasound and fluoroscopic guidance into the targeted native artery or bypass graft to begin needed thrombolysis. RESULTS: We had 26 acute limb ischemia in 10 patients with native arterial circulation and in 16 patients with either saphenous or prosthetic bypass grafts. Ultrasound was used in gaining safe access with no complications in 22 contralateral and 2 antegrade femoral and 4 direct-graft accesses. Ultrasound was used in 6 of these cases to help gain access in the occluded graft (4 cases) and saphenous veins (2 cases). It was successful in all cases but one case which had bleeding. CONCLUSIONS: Ultrasound is increasing in its application including acute limb ischemia with flush occlusions of native arteries and bypass grafts.


Femoral Artery/diagnostic imaging , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/drug therapy , Ischemia/diagnostic imaging , Ischemia/drug therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/drug therapy , Thrombolytic Therapy , Ultrasonography, Interventional , Aged , Angiography, Digital Subtraction , Female , Femoral Artery/physiopathology , Graft Occlusion, Vascular/physiopathology , Humans , Ischemia/physiopathology , Male , Middle Aged , Peripheral Arterial Disease/physiopathology , Predictive Value of Tests , Punctures , Regional Blood Flow , Time Factors , Treatment Outcome , Vascular Patency
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