Ioannis A. Tsolakis

Human abdominal aortic aneurysm is characterized by decreased versican concentration and specific downregulation of versican isoform V0

Abdominal aortic aneurysm (AAA) is a common disease of human aorta with increased incidence. It is a complication to atherosclerosis and it is closely associated with alterations in extracellular macromolecules. In this study, the levels of mRNA for versican--the major extracellular arterial proteoglycan (PG)--present in AAA and normal aortas were evaluated by reverse-transcriptase polymerase chain reaction. The concentration of versican was also examined in corresponding tissue samples. Versican was almost completely extracted with 4 M guanidine hydrochloride in the presence of Triton X-100, isolated by chromatography on DEAE-Sephacel and characterized using treatment with specific chondro-/dermato-lyases and agarose gel electrophoresis. Versican localization in tissue as well as the variation and distribution of smooth muscle cells (SMCs) and macrophages were also investigated immunohistochemically. The mRNAs coding for versican isoforms V(0) and V(1) were identified in both tissues, whereas V(2) was absent. The expression of V(0) was decreased 40% in aneurysmal vessel wall, whereas that for V(1) remained constant. This change was simultaneous with a significant decrease in versican concentration by 89%. In normal aortas, most versican was seen in the intima, whereas in AAA, this layer is characterized by advanced atherosclerotic lesion, rich in lipids and macrophages but poor in versican. The decreased transcription and the still lower amount of versican in the AAA may correlate to (i) a decrease in density of SMCs, these cells being the major source of versican in aorta, and (ii) the presence of macrophages, which may induce versican degradation and modulate versican synthesis. It is proposed that the decreased synthesis and increased degradation of versican, particularly of isoform V(0), and the resulting low concentration in the intima are crucial factors contributing to the altered viscoelastic and compressive properties and thereby to the deformity and dilatation of aorta.

Human abdominal aortic aneurysm is closely associated with compositional and specific structural modifications at the glycosaminoglycan level

Human abdominal aortic aneurysm (AAA) is a commonly occuring disease of blood vessels and is related to alterations in extracellular matrix molecules. In this study we report on the type and fine structural characterization of glycosaminoglycans (GAGs) present in AAA as compared with those present in normal abdominal aorta. Hyaluronan (HA), the galactosaminoglycans-chondroitin sulfate (CS) and dermatan sulfate (DS) with average molecular size (Mr) of 35-kDa-as well as heparan sulfate (HS) with Mr of 40-kDa were identified in both tissues. No significant intrabatch differences in total GAG content were identified in normal and aneurysmal aortas. Comparing, however, tissue composition and structure of GAGs between AAAs and normal aortas, significant differences (P < or = 0.001) were found. The overall GAG content in AAAs was approx. 60% lower than the normal ones. A 90% decrease in HS content, and 65 and 73% in CS and HA, respectively, were also recorded. In contrast, only a slight decrease in the amount of DS was noted (8%). Structural alterations in disaccharide composition of GAGs correspond mainly to significant decreases (P < or = 0.001) of HS-derived N-sulfated disaccharides, CS-derived 6-sulfated disaccharide and DS-derived disulfated disaccharides. These results demonstrate that the development of AAA is related to dramatic quantitative and structural modifications at the GAG level and this may well be attributed to the destruction of arterial wall architecture and further significant functional inadequacies of the tissue.

Chondroitin sulfate as a key molecule in the development of atherosclerosis and cancer progression.

Publisher Summary This chapter discusses the molecular involvement of CS in the progression of two main human diseases: cancer and atherosclerosis. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) composed of repeating disaccharides of glucuronic acid and N ‐acetyl‐galactosamine, which are variously substituted by sulfate groups. It is covalently attached on several core proteins creating a variety of proteoglycans (PGs) found in the extracellular matrix (ECM) and cell membrane, but also intracellularly. Chondroitin sulfate interacts with a wide variety of key molecules, such as growth factors, cytokines, chemokines, adhesion molecules and lipoproteins via specific saccharide domains within the chain. These interactions regulate several biological processes and cell behavior. Several diseases are often associated with a biosynthetic imbalance of chondroitin sulfate proteoglycans (CSPGs). CSPGs are markedly increased in early atherosclerotic lesions, playing important roles in lipid retention, modification, and finally accumulation. In addition, CSPGs participate in inflammatory process associated with atherosclerosis and influence arterial smooth muscle cell behavior. They also directly affect elastogenesis and proper formation of the extracellular matrix. CSPGs are markedly accumulated also in tumor stroma and its deposition is often correlated to poor prognosis of the disease.

Combined (mechanical and pharmacological) modalities for the prevention of venous thromboembolism in joint replacement surgery

We performed a systematic review and meta-analysis to compare the efficacy of intermittent mechanical compression combined with pharmacological thromboprophylaxis, against either mechanical compression or pharmacological prophylaxis in preventing deep-vein thrombosis (DVT) and pulmonary embolism in patients undergoing hip or knee replacement. A total of six randomised controlled trials, evaluating a total of 1399 patients, were identified. In knee arthroplasty, the rate of DVT was reduced from 18.7% with anticoagulation alone to 3.7% with combined modalities (risk ratio (RR) 0.27, p = 0.03; number needed to treat: seven). There was moderate, albeit non-significant, heterogeneity (I(2) = 42%). In hip replacement, there was a non-significant reduction in DVT from 8.7% with mechanical compression alone to 7.2% with additional pharmacological prophylaxis (RR 0.84) and a significant reduction in DVT from 9.7% with anticoagulation alone to 0.9% with additional mechanical compression (RR 0.17, p < 0.001; number needed to treat: 12), with no heterogeneity (I(2) = 0%). The included studies had insufficient power to demonstrate an effect on pulmonary embolism. We conclude that the addition of intermittent mechanical leg compression augments the efficacy of anticoagulation in preventing DVT in patients undergoing both knee and hip replacement. Further research on the role of combined modalities in thromboprophylaxis in joint replacement and in other high-risk situations, such as fracture of the hip, is warranted.

Endovascular Management of Arterioenteric Fistulas: A Systemic Review and Meta-Analysis of the Literature

Purpose: To present a systemic review and meta-analysis investigating the outcomes of endovascular management of arterioenteric fistula (AEF). Methods: Literature review on AEF management with endovascular surgery using MEDLINE search, including two cases managed by the authors. Results: Fifty-nine patients (50 men; mean age 68 years, range 23–90) were identified. AEF was successfully managed in 55 (93%) patients and 30-day mortality was 8.5% (5/59). During follow-up, 10 (19%) patients developed recurrent bleeding, which occurred more often in AEFs due to cancer. The freedom from recurrence rate at 12 and 24 months was 71.5%. Seventeen (32%) patients developed sepsis, which was managed conservatively in 8 (7 successful). Freedom from sepsis at 12 and 24 months was 64%, while the freedom from combined recurrence and sepsis at 12 and 24 months was 59%. Patients who did not have intestinal repair had a higher rate of combined recurrence and sepsis compared to patients who did; the freedom from combined recurrence and sepsis at 12 months was 52% for patients not having intestinal repair versus 100% in patients who did (p=0.022). Total AEF-related mortality rates at 12 and 24 months were 15% and 19%, respectively, significantly worse when AEF recurred (p=0.001). Overall survival rates at 12 and 24 months were 68% and 52%; prognosis was worse in patients with perioperative sepsis, large bowel fistulization, tube graft placement, no intestinal repair, and recurrent AEF. Conclusion: Endovascular management of AEF can achieve satisfactory short and midterm results, better than those historically reported for open surgery, despite the high rate of recurrent bleeding and sepsis. Further investigation of the role played by intestinal repair is warranted.

Seasonal variation in the incidence of superficial venous thrombophlebitis

INTRODUCTION Previous studies have demonstrated an increased frequency and severity of symptoms due to varicose veins during summer. However there is no data on their complications, including superficial venous thrombophlebitis (SVT). The aim of this study was to test the hypothesis that SVT follows a seasonal pattern. MATERIALS AND METHODS During the two-year period between January 2007 and December 2008, inclusive, 123 patients with SVT were evaluated, including 60 females and 63 males. In 8 patients (6.5%) an additional and/or other predisposing factor was present. On presentation, SVT was complicated by thrombus extension to the proximal deep system in 5 cases (4.1%); above-knee SVT was present in 4 of these 5 cases. RESULTS SVT occurred more often during the months of May through October (monthly incidence of 7.3 cases) compared to remaining of the year (monthly incidence of 2.9 cases). SVT showed a peak in June and July with 33.3% of all SVTs occurring during these two months (monthly incidence of 10.25 cases). Using time-series statistics SVT occurrence showed a periodical seasonal pattern (p=0.003). Although a seasonal pattern was evident in all patient subgroups, this was significant only in males and patients with below-knee SVT. CONCLUSIONS SVT showed a clear seasonal pattern of occurrence, with a significant rise during summer time. Although a possible explanation of this observation could be poor patient compliance and suboptimal usage of elastic stockings during the hot Mediterranean summer, further studies to investigate the cause, clinical significance and preventive methods of this complication are justified.

Mycotic aneurysm of the internal carotid artery presenting with multiple cerebral septic emboli.

Mycotic aneurysms of the extracranial carotid artery are uncommon and always warrant surgical treatment to prevent eventual rupture and death. Septic embolization to the brain is an even rarer complication of these aneurysms. We present a case of a 79-year-old male with an extracranial internal carotid artery mycotic aneurysm during Staphylococcus aureus bacteremia. He presented with hemiparesis owing to brain embolism from multiple septic emboli originating from the aneurysm. Multidetector computed tomographic angiography contributed to the diagnosis. Resection of the aneurysm and restoration of arterial supply to the brain by vein graft interpositioning was the therapeutic procedure along with long-term antibiotic treatment. A high index of suspicion is required for the diagnosis of a mycotic carotid aneurysm and aggressive treatment is always needed to prevent lethal complications.

Randomized controlled trial comparing primary and staged basilic vein transposition

Objective It is unclear if brachio-basilic vein fistula should be performed as a primary or staged procedure, particularly for smaller basilic veins. Our aim was to report on a randomized controlled trial comparing these two techniques. Methods Sixteen patients with a basilic vein ≥2.5 mm were randomized into primary transposed brachio-basilic vein (TBBV) fistula (n = 9) and staged TBBV fistula (n = 7). Patients with basilic veins enlarged by previous arteriovenous fistulas were excluded. Baseline characteristics of the two study groups, including vein size, were comparable (median basilic vein diameter 3.5 mm, range 2.8–4.1 mm). The staged group had a brachio-basilic vein fistula performed first followed by the transposition procedure performed at least 6 weeks later to allow the basilic vein to enlarge. TBBV fistula maturation at 10 weeks, primary, assisted-primary, and secondary patency were the primary outcome measures. Early failures were included in the calculation of patency rates. Results Transposed brachio-basilic vein fistula maturation rate after primary procedures (3/9, 33%) was lower compared to maturation rate after staged procedures (7/7, 100%, P = 0.011, Fisher’s exact test), which led to premature termination of the trial. Time to hemodialysis [median (interquartile range)] of primary and staged procedures was 54 (51.5–113.5) days and 97 (93–126) days, respectively (P = 0.16). One-year primary and assisted-primary patency rates of primary and staged procedures were equivalent (44 vs 57%, P = 0.76 and 44 vs 71%, P = 0.29, respectively); however, there was a trend toward a better 1-year secondary patency after staged procedures (86 vs 44% for primary procedures, P = 0.09). Conclusions Among candidates for TBBV fistula with a small basilic vein, staged transposition achieves higher maturation rates compared to primary procedures, a difference reflected in long-term secondary patency. Trial registration www.ClinicalTrials.gov, identifier NCT01274117.

Intravenous fentanyl patient-controlled analgesia for perioperative treatment of neuropathic/ischaemic pain in haemodialysis patients: a case series

Background and objective:  Use of opioids is common in perioperative haemodialysis patients because they often suffer from intractable ischaemic or neuropathic lower extremity pain. Intravenous (IV) fentanyl, patient‐controlled analgesia (PCA) does not appear to have been evaluated in this setting; hence this study.

Open Versus Endovascular Repair of Inflammatory Abdominal Aortic Aneurysms A Comparative Study and Meta-Analysis of the Literature

Objectives: Open surgical repair (OSR) of inflammatory abdominal aortic aneurysms (IAAAs) can have significant morbidity. The aim of the present investigation was to compare IAAA outcome after OSR and endovascular aneurysm repair (EVAR) and perform a meta-analysis of the literature. Methods: Twenty-seven patients with an intact IAAA operated on during a 21-year period were included. Results: Nine patients were managed with EVAR and 18 with OSR. In the EVAR group, the number of transfused red blood cell units (P = .001), procedure duration (P < .001), and postoperative hospitalization (P = .004) were significantly reduced compared to OSR. A trend for decreased morbidity with EVAR (11% vs 33% for OSR, P = .36) was observed. On literature review and meta-analysis, morbidity after EVAR was 8.3%, significantly lower compared to OSR (27.4%, P = .047). Mortality for nonruptured IAAAs was 0% after EVAR and 3.6% after OSR (P = 1.00). Conclusions: Endovascular aneurysm repair of IAAAs is associated with decreased procedure duration, transfusion needs, hospitalization, and morbidity compared to OSR.