Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass.

Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years. Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study. Patients with advanced peripheral artery disease (PAD) requiring above-the-knee femoropopliteal bypass surgery without available autologous graft options had undergone implantation with the HAV, a bioengineered human tissue replacement blood vessel. The patients who completed the 24-month primary portion of the study will be evaluated for ≤10 years after implantation. The present mid-term analysis was performed at the 6-year milestone (72 months) for patients followed up for 24 to 72 months. Results: HAVs were implanted in 20 patients at three sites in Poland. Seven patients had discontinued the study before completing the 2-year portion of the study: four after graft occlusion had occurred and three who had died of causes deemed unrelated to the conduit, with the HAV reported as functional at their last visit. The primary results at 24 months showed primary, primary assisted, and secondary patency rates of 58%, 58%, and 74%, respectively. One vessel had developed a pseudoaneurysm deemed possibly iatrogenic; no other signs of structural failure were reported. No rejections or infections of the HAV occurred, and no patient had required amputation of the implanted limb. Of the 20 patients, 13 had completed the primary portion of the study; however, 1 patient had died shortly after 24 months. Of the remaining 12 patients, 3 died of causes unrelated to the HAV. One patient had required thrombectomy twice, with secondary patency achieved. No other interventions were recorded between 24 and 72 months. At 72 months, five patients had a patent HAV, including four patients with primary patency. For the entire study population from day 1 to month 72, the overall primary, primary assisted, and secondary patency rate estimated using Kaplan-Meier analysis was 44%, 45%, and 60% respectively, with censoring for death. No patient had experienced rejection or infection of the HAV, and no patient had required amputation of the implanted limb. Conclusions: The infection-resistant, off-the-shelf HAV could provide a durable alternative conduit in the arterial circuit setting to restore the lower extremity blood supply in patients with PAD, with remodeling into the recipient's own vessel over time. The HAV is currently being evaluated in seven clinical trials to treat PAD, vascular trauma, and as a hemodialysis access conduit.

Collagen-Sealed Polyester Vascular Prostheses Functionalized by Polycatecholamine Coatings.

Collagen-sealed polyester (PET) prostheses are commonly used in reconstructive vascular surgery due to their self-sealing properties. To prevent post-surgical infection, different modification methods have been tested but so far none have showed long-term satisfactory efficiency. For this reason, in the present study, a commercial collagen-sealed PET prosthesis was coated by a highly adhesive poly (L-DOPA) layer maintaining the sealing protein without losing the original properties and functionality. This modified (as proven by SEM, FTIR, XPS and contact angle) graft exhibited comparable wettability and elasticity as pristine commercial graft, as well as reduced hemolysis-inducing effect, lowered toxicity against human endothelial cells and reduced toxicity in Danio rerio model. Poly (L-DOPA)-coated grafts were shown to bind six times more aminoglycoside antibiotic (gentamicin) than pristine graft. Poly (L-DOPA)-coated antibiotic-bound prostheses exhibited an improved antibacterial activity (bacterial growth inhibition and anti-adhesive capacity) in comparison with pristine antibiotic-bound graft. Overall, poly (L-DOPA)-coatings deposited on PET vascular grafts can effectively functionalize collagen-sealed prostheses without the loss of protein sealing layer and allow for antibiotics incorporation to provide higher safety in biomedical applications.

Effect of Reconstructive Procedures of the Extracranial Segment of the Carotid Arteries on Damage to the Blood-Brain Barrier.

INTRODUCTION: Endarterectomy and angioplasty of the internal carotid artery are surgical measures for the prevention of ischemic stroke. Perioperative complications are caused by concomitant embolism and reperfusion syndrome leading to damage of the blood-brain barrier. METHODS: The study included 88 patients divided into two groups, depending on the surgical technique used: internal carotid artery endarterectomy (CEA), 66 patients, and percutaneous carotid angioplasty and stenting (CAS), 22 patients. Blood was drawn 24 h before surgery, as well as 8, 24, and 48 h post-surgery. The assessment of damage to the blood-brain barrier was based on the evaluation of the concentration of claudin-1 and occludin, aquaporin-4, the measurements of the activity of metalloproteinase-2 (MMP-2) and -9 (MMP-9), and the assessment of central nervous system damage, measured by changes in the blood S100ß protein concentration. RESULTS: A significant increase in the concentration of the blood-brain barrier damage markers and increased MMP-2 and MMP-9 activity were found in patient blood. The degree of damage to the blood-brain barrier was higher in the CEA group. CONCLUSIONS: The authors' own research has indicated that revascularization of the internal carotid artery may lead to damage to the central nervous system secondary to damage to the blood-brain barrier.

Polycatecholamine and gentamicin as modifiers for antibacterial and blood-biocompatible polyester vascular prostheses.

Polyester (PET) prostheses are commonly used in reconstructive vascular surgery. The most serious complication after implantation is early or late infection of the graft. Therefore, there is high demand to protect prosthesis against bacterial adhesion and biofilm development. For this reason, in this work PET prostheses were first coated by highly adhesive polycatecholamine layer. The grafts were then coupled with gentamicin and studied in relation to morphological and structural properties, biological safety (contact with blood, reaction of vascular endothelial cells (HUVEC), Danio rerio fish), drug release and antibacterial activity. Among two tested catecholamine monomers, L-DOPA was found to be more effective precursor in this process than dopamine. For L-DOPA, assistance of Cu2+, Mg2+ and Na+ ions seems to increase the amount of further immobilized drug. Coated prostheses exhibited greater human endothelial cell proliferation increase and lower cytotoxic effect than uncoated. The modification reduced the hemolysis observed for pristine commercial graft and limited the rate of abnormalities in D. rerio larvae, confirming the safety of the proposed modification. The coating allowed to double the amount of immobilized antibiotic in comparison with uncoated graft which resulted in increased antibacterial activity and reduced bacterial adhesion against 4 bacterial strains prevalent in biomaterials infections. Overall, poly(L-DOPA)-coatings deposited on PET vascular grafts can effectively functionalize these prostheses for higher safety in biomedical applications.

Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease.

OBJECTIVE: Vascular conduit is essential for arterial reconstruction for a number of conditions, including trauma and atherosclerotic occlusive disease. We have developed a tissue-engineered human acellular vessel (HAV) that can be manufactured, stored on site at hospitals, and be immediately available for arterial vascular reconstruction. Although the HAV is acellular when implanted, extensive preclinical and clinical testing has demonstrated that the HAV subsequently repopulates with the recipient's own vascular cells. We report a first-in-man clinical experience using the HAV for arterial reconstruction in patients with symptomatic peripheral arterial disease. METHODS: HAVs were manufactured using human vascular smooth muscle cells grown on a biodegradable scaffold. After the establishment of adequate cell growth and extracellular matrix deposition, the vessels were decellularized to remove human cellular antigens. Manufactured vessels were implanted in 20 patients with symptomatic peripheral arterial disease as above-knee, femoral-to-popliteal arterial bypass conduits. After HAV implantation, all patients were assessed for safety, HAV durability, freedom from conduit infection, and bypass patency for 2 years. RESULTS: Twenty HAVs were placed in the arterial, above-knee, femoral-to-popliteal position in patients with rest pain (n = 3) or symptomatic claudication (n = 17). All HAVs functioned as intended and had no evidence of structural failure or rejection by the recipient. No acute HAV infections were reported, but three surgical site infections were documented during the study period. Three non-HAV-related deaths were reported. One vessel developed a pseudoaneurysm after suspected iatrogenic injury during a balloon thrombectomy. No amputations of the HAV implanted limb occurred over the 2-year period, and no HAV infections were reported in approximately 34 patient-years of continuous patient follow-up. CONCLUSIONS: Human tissue engineered blood vessels can be manufactured and readily available for peripheral arterial bypass surgery. Early clinical experience with these vessels, in the arterial position, suggest that they are safe, have acceptable patency, a low incidence of infection, and do not require the harvest of autologous vein or any cells from the recipient. Histologic examination of tissue biopsies revealed vascular remodeling and repopulation by host cells. This first-in-man arterial bypass study supports the continued development of human tissue engineered blood vessels for arterial reconstruction, and potential future expansion to clinical indications including vascular trauma and repair of other size-appropriate peripheral arteries.

Replacement of infected aortoiliac vascular grafts with bifurcated BioIntegral Surgical No-React® bovine pericardial xenografts.

The infection of a vascular prosthesis is potentially fatal, and its effective treatment still remains the greatest challenge for vascular surgeons. We present our initial experience using bovine pericardial vascular prostheses to replace infected aortoiliac vascular grafts. Six consecutive patients with infection of the graft were prospectively included in this study. Infection of the vascular graft was confirmed by clinical symptoms, laboratory tests and the results of computed tomography and positron emission tomography/computed tomography. In all cases, the infected aortoiliac graft was surgically removed and replaced by the bovine-pericardial BioIntegral aortic-bifemoral prosthesis. Technical success was achieved in every case with no in-hospital or 30 days mortality. One patient required revision of distal anastomosis due to recurrent bleeding at day four after surgery. One patient presented with upper gastrointestinal tract bleeding during the postoperative period, which was managed endoscopically. The mean hospital stay was 14 days (range 9-19). The control CT scan performed 2 months after surgery showed significant regression of abscesses and periprosthetic inflammation. Two patients died within 32 months of follow-up: one due to heart attack, the other due to generalized sepsis, which was correlated with the previous infection. Four patients are still in follow-up. The BioIntegral prosthesis is patent in all four cases, with no clinical or ultrasonographic signs of infection. Our brief investigation shows that a bovine pericardial prosthesis may be a valuable option in the treatment of vascular grafts infections.

Endovenous laser ablation is an effective treatment for great saphenous vein incompetence in teenagers.

OBJECTIVES: The current knowledge of chronic venous disease in teenagers and its treatment is very limited. The aim of the study is to present our experience and the available literature data on the treatment of varicose veins in teenagers with endovenous laser ablation of the great saphenous vein. METHODS: Five patients, aged 15-17 years, were qualified for surgery, based on typical signs and symptoms of chronic venous disease. Minimally invasive treatment with endovenous laser ablation of the great saphenous vein was applied. RESULTS: The technical success of surgery was achieved in all patients. Over a 2-year follow-up we did not observe any case of recanalisation of the great saphenous vein, recurrence of varicose veins, or serious complications, such as deep vein thrombosis or pulmonary embolism. One patient presented with resolving of post-operative bruising, and two cases of local numbness were transient. CONCLUSIONS: Endovenous laser ablation of the great saphenous vein in the treatment of chronic venous disease in teenagers is effective and safe. The method provides excellent cosmetic effects, very short recovery time and high levels of patient satisfaction.

Serum Neuron-Specific Enolase as a Marker of Brain Ischemia-Reperfusion Injury in Patients Undergoing Carotid Endarterectomy

In patients with atherosclerotic stenosis of the extracranial segment of internal carotid artery, surgical intervention is an effective method to prevent cerebral ischemic stroke. However, this surgical procedure may cause vascular brain damage. The aim of the study was to investigate consequential brain ischemia-reperfusion injury by measuring the cerebral specific marker, neuron-specific (NSE), in serum of patients having undergone internal carotid endarterectomy (CEA). The study involved 25 patients that underwent CEA due to internal carotid artery stenosis. Blood samples were obtained from each patient on three occasions: within 24 h prior to surgery, 12 h after surgery, and 48 h after surgery. Serum NSE levels were measured by a commercially available enzyme-linked immunosorbent assay. The study showed that serum NSE level was statistically significantly increased 48 h after CEA as compared with the level 12 h after surgery and the level before surgery (p<0.05). Difference in serum NSE between the level before surgery and 12 h after CEA was not statistically significant (p>0.05). Data from our study showed CEA to affect serum NSE in patients with significant internal carotid artery stenosis. Thus, serum NSE may be used as a biochemical marker of brain ischemia-reperfusion injury following CEA.

Axial splitting of the medial antebrachial cutaneous nerve facilitates second-stage elevation of basilic or brachial vein in patients with arteriovenous fistula.

We describe a novel surgical technique to facilitate the second-stage elevation of the basilic or brachial vein in patients with first-stage brachial-basilic or autogenous brachial-brachial arteriovenous fistula by axial splitting of the medial antebrachial cutaneous nerve (MABCN). Filaments of the MABCN typically traverse the anterior aspect of the basilic and brachial veins. The second-stage elevation/shelf superficialization of the basilic or brachial vein, so as not to cause an injury to the MABCN, requires division of these veins with transposition over the nerve branches and subsequent reanastomosis. Our method of axial splitting of the MABCN enables elevation and shelf superficialization of the basilic or brachial vein without the division and reanastomosis of the vein. Twenty-eight patients underwent this simplified elevation. The nerve perineurium was incised longitudinally, nerve fibers were divided intrafascicularly, and cutaneous nerve branches were retracted aside. The vein was elevated between the divided nerves. On discharge and at 1-month follow-up, only one patient complained of localized patch hypoesthesia as reported in a simplified neurologic assessment questionnaire and neurologic examination.

Carotid surgery affects plasma kynurenic acid concentration: a pilot study.

BACKGROUND: An increase in plasma kynurenic acid (KYNA) concentration has been observed following surgery, inflammation, and cerebral pathologies. The aim of the present study was to analyze the changes in plasma KYNA concentration in patients undergoing carotid surgery (CS). MATERIAL AND METHODS: Adult patients undergoing elective carotid endarterectomy (CEA) or carotid angioplasty with stent placement (CAS) were studied. Plasma KYNA concentrations were analyzed before surgery and at 4 time points after CS. The amount of inflammation was measured as neutrophil-lymphocyte ratio (NLR). RESULTS: Forty patients (10 female and 30 male) aged 55-86 years of age were evaluated in this study. In patients with unstable carotid plaque, the plasma KYNA concentration was higher than in patients with stable carotid plaque. Moreover, the NLR was significantly higher in patients with unstable carotid plaque undergoing CEA than in patients undergoing CAS. Plasma KYNA concentration increased after surgery in patients undergoing CEA and CAS. There was a strong correlation between plasma KYNA concentration and NLR in patients with postoperative neurological disorders. CONCLUSIONS: CS increases plasma KYNA concentration, and changes in plasma KYNA concentration can indicate neurologic outcomes in patients undergoing CS.

Minimally invasive, endovenous laser treatment of varicose veins in patients with von Willebrand disease.

The presented report presents a minimally invasive approach for the treatment of varicose veins in patients with chronic venous disease and coexisting von Willebrand disease, the most common inherited bleeding disorder. Conventional stripping of an insufficient great saphenous vein and varicose vein surgery, carries a potential risk of serious bleeding complications in this specific group of patients. It is related to the extent of open surgery, significant tissue trauma, and possible post-operative bleeding of wounds. Less aggressive techniques, such as endovenous laser treatment or radiofrequency ablation, gain increasing popularity as a valuable and equally efficient alternative to conventional surgery in patients with varicose veins. Both of these endovenous techniques seem to have special indications in patients with bleeding disorders. Shortening of hospitalization, quick recovery time and return to normal daily activities, optimal cosmetic effect of the procedure, are also advantageous. The paper presents the technique and results of endovenous laser treatment of great saphenous vein insufficiency and varicose veins in a patient with type I von Willebrand disease. Available data on peri-operative care standards, optimization of the safety of procedures, and prevention of bleeding complications in surgical patients with von Willebrand disease, specifically undergoing varicose veins surgery are analysed.

Percutaneous endovascular abdominal aortic aneurysm repair within the infrarenal region. Preliminary report.

UNLABELLED: The aim of the study was to thoroughly evaluate the closure device ProStar XL in terms of its efficiency and safety in the percutaneous endovascular treatment of abdominal aortic aneurysms in the infrarenal section of the body. Additionally, it was crucial to assess if there were any occurrences of regional complications at any step of the procedure. It was also important to stipulate the estimated hospitalization period as well as the overall cost of the PEVAR treatment with the use of ProStar XL. MATERIAL AND METHODS: The analysis included 21 cases with PEVAR performed in the infrarenal region. The final success was achieved in 98.2% of the cases. One PEVAR case (that constituted 0.2% of this group) was unsuccessful because of the bleeding while the placement of the sutures with the use of ProStar XL was being performed. RESULTS: This resulted in the emergency treatment of the CFA with the continuous stitch (Prolene 5-0). During the postoperative period the above described patient was given 2 units of the Packed Red Blood Cells (PRBC). However, this complication (unexpected bleeding) did not influence the length of the hospitalization period in any significant way. CONCLUSIONS: Percutaneous vascular closure device ProStar XL used in the treatment of the common femoral artery (CFA) constitutes a necessary and safe supplement for Endovascular Aortic Aneurysm Repair (EVAR). The implementation of ProStar XL closure device proves to significantly shorten the hospitalization period after the EVAR treatment. Additionally, the safety of the entire procedure is exponentially linked to the experience of the operating surgeon.

Selected factors of fibrinolysis in the Buerger's disease.

UNLABELLED: Thrombangiitis obliterans (TAO marked by coexistence of thrombotic and inflammatory changes of neurovascular tract has evoked a considerable dispute concerning pathogenesis of this disease. The aim of the study was to define the level of activation of fibirinolitic system in course of TAO disease by means of determination its basic constituents as well as to examine the essence of level of fibrinolysis disorders in pathogenesis and development of this disease. MATERIAL AND METHODS: Fifty patients with thrombangiitis obliterans (TAO), 30 patients with peripheral occlusive disease - PAOD (ASO) and 20 healthy volunteers (K) have been subjected to the examination. We determined the activity some factors of fibrinolysis: t-PA, PAI-1, PAP, plasminogen, α2-antiplasminogen, D-dimmer as well as euglobulin lysis time. The analysis comprised 7 features and 8 factors of variability: a membership to a group of patients, sex, age, smoking, aggravation of the disease within last 3 months, occurrence of Raynaud's symptom, a degree of ischemia according to Fontaine, time the disease lasted. RESULTS: The significant differences between the average were checked by means of t-Student test or variance analysis (ANOVA) and co-relation rate r (Pearson). We concluded that the average value of PAI-1 in the group TAO was significantly higher than in comparison with ASO group. The increased values were revealed in case of 76 % of patients. The euglobulin lysis time was vitally extended in case of 60% of patients in ASO group. In all three groups higher levels of α2-antiplasmin were detected in case of elderly patients compared to the younger ones. CONCLUSIONS: The obtained results allow us to ascertain the state of potentially weakened fibrinolysis in case of patients with Buerger's disease as well as with PAOD.

The evaluation of the effectiveness of Tachosil in the treatment of lymphorrhea of the postoperative wound in the selected group of patients, after vascular reconstructive surgeries--preliminary report.

UNLABELLED: Lymphorrhea of a postoperative wound after vascular reconstructive surgeries does not occur frequently but it accounts for a major complication. It should be brought to attention that during the intraoperative period it is impossible to diagnose any damages within the lymphatic system of the operated area. Additionally, the treatment of lymphorrhea with thermal abrasion does not usually bring the desired outcome. Therefore, the extended time of the postoperative wound treatment with the lymphatic drainage constitutes a standard method in such cases. The aim of the study was to evaluate the effectiveness of Tachosil surgical patch in the treatment of lymphorrhea of the postoperative wound in a selected group of patients who have undergone vascular reconstructive surgeries. Additionally, the aim of the study was to analyze the results and draw conclusions pertaining to the validity and effectiveness of the treatment with the use of Tachosil surgical patch. MATERIAL AND METHODS: The observed group included 10 patients with lymphorrhea developed during the postoperative period. 6 of the observed patients have undergone the vascular reconstructive surgery with the implantation of the vascular prosthesis (distal femoropopliteal reconstruction bridge - 3 patients; iliofemoral reconstruction bridge - 1 patient; angioplasty of the common femoral artery (CFA) with the use of the prosthetic patch - 1 patient; the implantation of the bifurcated (type Y) aortofemoral prosthesis - 1 patient). The remaining patients in the observed group have undergone the restoration of patency of the CFA. Additionally, 1 patient has undergone the resection of the pseudo aneurysm in the distal part of the iliofemoral prosthesis. The vascular reconstructive surgery required the denudation and isolation of the common femoral artery from the surrounding tissue as a step 1. The persisting lymphorrhea of the postoperative wound, in the volume of more than 200 ml per day during the first 3 postoperative days, indicated the necessity for the inguinal wound revision. In addition, Tachosil surgical patch was applied at that time. The drain was placed over Tachosil patch. RESULTS: Complete stop of lymphorrhea was shorter by 4.87 days in patients treated with the use of Tachosil in comparison to control group. These patients also had an average hospitalization time shorter by 3.88 days than patients in the control group. CONCLUSIONS: Early intervention in the cases of lymphorrhea of the postoperative wound allows planning and conducting successful treatment. The use of Tachosil surgical patch in the treatment of lymphorrhea of the postoperative wound shortens the treatment and hospitalization periods. The use of Tachosil in the treatment of postoperative lymphorrhea appeared to be significantly more effective than the standard drainage method of treatment. Results obtained through this study pave the way for the research on other possible applications of Tachosil in the cases of lymphorrhea after vascular reconstructive surgeries.

[The role of matrix metalloproteinases and their tissue inhibitors in angiogenesis]. / Rola metaloproteaz macierzy i ich tkankowych inhibitorów w angiogenezie.

Cellular aspect of angiogenesis - the multilevel process involving the growth of new blood vessels from pre-existing vessels--includes migration and proliferation of the cells as well as remodelling of their environment--extracellular matrix (ECM). The key role in ECM remodelling is played by proteolytic enzymes classified as matrix metalloproteinases (MMPs). Recent research shows that performed by MMPs degradation of vascular ECM components is a significant event ocurring during angiogenesis. This process enables migration of endothelial cells that is crucial part in new vessel formation. MMPs also release sequestered angiogenic molecules, such as VEGF, bFGF and TGF-beta. Angiogenesis is a normal process in growth and development, as well as in wound healing, monthly reproductive cycle and during pregnancy. However, this is also a fundamental step in such conditions as malignancies, inflammation or ischaemia. The influence of MMPs on agiogenesis as terminal agents in many physio- and pathological events makes this group of enzymes very promissing aim of new therapeutic strategies based on modulation of angiogenesis.