Igor Koncar

Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: Preliminary study

OBJECTIVE Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue. METHODS The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR. RESULTS In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; S.E. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003). CONCLUSION Our preliminary results indicate that MMP-8 -381A/G and -799C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis.

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence.

OBJECTIVES Matrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population. DESIGN AND METHODS Study enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms -1607 1G/2G, -519 A/G and -340 T/C were genotyped by PCR and RFLP methods. RESULTS Individuals carrying MMP-1 -1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR=1; OR=1.87 95% CI 1.29-2.07; OR=3.49 95% CI 1.67-7.30, p=0.0009, respectively). Compared to the referent haplotype 2G(-1607)-T(-340)-A(-519), the haplotypes 1G(-1607)-T(-340)-A(-519), 1G(-1607)-T(-340)-G(-519) and 2G(-1607)-C(-340)-A(-519) had statistically significant protective effect on CP presence (OR=0.41, 95% CI 0.29-0.81, p=0.01; OR=0.56, 95% CI 0.44-0.89, p=0.01; OR=0.43, 95% CI 0.27-0.86, p=0.02, respectively). CONCLUSIONS MMP-1 -1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.

Surgical Treatment of Carotid Restenosis After Eversion Endarterectomy—Serbian Bicentric Prospective Study

BACKGROUND The increased number of carotid endarterectomies performed worldwide in recent years is associated with a greater need for carotid restenosis evaluation. Carotid restenosis rate ranges from 0.6% to 3.6% in symptomatic patients and from 8.8% to 19% in asymptomatic patients. Carotid angioplasty and stenting is a preferable therapeutic choice for carotid restenosis treatment, but whenever it is not technically feasible (tortuosities of supra-aortic branches, calcifications, pathological elongation, or very extensive lesions), redo surgical treatment is indicated. The aim of our study was to examine outcome of redo surgical treatment in patients with symptomatic and asymptomatic carotid restenosis, in whom carotid angioplasty could not be done, and its impact on early and late morbidity and mortality. METHODS The study included 52 patients who were surgically treated for significant carotid restenosis from January 2000 to December 2008 in two high-volume vascular surgery university clinics. Surgical techniques included redo eversion endarterectomy, standard endarterectomy with Dacron patch closure, and Dacron tubular graft interposition. The patients were followed for significant events (transient ischemic attack, stroke, cranial nerve injuries, surgical site hematoma, the occurrence of carotid re-restenosis, or occlusion), and mortality after 1 month, 6 months, 1 year, and annually afterward. RESULTS In the early postoperative period (within 30 days), there were no lethal outcomes. Transient ischemic attack was diagnosed in four patients (7.6%), minor stroke in two patients (3.8%), and cranial nerve injury in four patients (7.6%). After 4 years, three patients died (5.7%), two due to a fatal myocardial infarction (3.8%) and one after a major stroke (1.9%); four patients (7.6%) had ipsilateral stroke; and graft occlusion was verified in one patient (1.9%). CONCLUSION Carotid angioplasty might be a primary option for carotid restenosis treatment, but whenever it cannot be performed, redo surgical treatment is indicated, owing to its acceptable rate of early and late postoperative complications.

Incidence and relevance of groin incisional complications after aortobifemoral bypass grafting.

BACKGROUND Aortobifemoral bypass (ABFB) for aortoiliac occlusive disease (AIOD) is traditionally accompanied by substantial groin incisional morbidity, which poses a threat to an underlying prosthetic graft. We performed a study to investigate the frequency and define the clinical course and significance of such problems. METHODS One hundred twenty consecutive patients undergoing primary elective ABFB for AIOD were enrolled in a prospective study. The healing of groin wounds was systematically assessed, the occurrence of incisional complications of any type noted, and their clinical course and economic consequences documented and analyzed. RESULTS Early postoperative complications (30 days) affected 35 (15%) groin wounds in 29 (24.8%) patients. Lymph fistulas/lymphoceles were observed in 15 (6.4%), infection in 11 (4.7%), and noninfectious wound dehiscence in 9 (3.8%) of groin incisions. The only significant predictor of groin healing impairment was preoperative length of stay. Groin incision-related morbidity significantly increased the duration and cost of hospitalization. Sixty percent of groin healing problems were diagnosed after discharge and they represented the most common cause for early readmissions. CONCLUSIONS The incidence of groin wound complications after ABFB is considerable, their financial impact significant, and delayed onset frequent. Femoral incisional morbidity after ABFB still represents an unremitting nuisance, necessitating further improvements in preventive strategies and techniques and strict adherence to conventional ones, including the minimization of preoperative length of stay.

False Anastomotic Aneurysms

This retrospective study covers the period from 1991 to 2002, during which 3,623 patients were operated on because of aneurysmal or occlusive disease of aortoiliac and femoropopliteal segments. Among them, 87 patients (2.4%) developed a false anastomotic aneurysm in the 12-year follow-up period and were treated operatively. Most frequently, in 53 patients (6.9%), a false anastomotic aneurysm developed after aortobifemoral bypass performed owing to aortoiliac occlusive disease. The cause of false anastomotic aneurysm was infection in 21 cases (24.7%); resection and revascularization were performed with a Dacron graft in 46 cases (52.9%), with a polytetrafluoroethylene graft in 10 cases (11.5%), and with the great saphenous vein in 16 cases (18.4%). Homograft implantation in 4 patients (4.6%) or extra-anatomic bypasses in 11 cases (12.6%) were performed when graft infection was suspected. Of 87 patients who underwent surgery, 74 (85.5%) had good early results without infection, reintervention, limb loss, and mortality. The presence of infection as a cause of false anastomotic aneurysm and comorbidity increased the mortality rate significantly after the reoperation, whereas the type of graft used in treatment had no influence on early results.

CXCL16 haplotypes in patients with human carotid atherosclerosis: preliminary results.

AIM Chemokine CXC ligand 16 (CXCL16) has chemoattractive, adhesive and scavenging properties and may play a role in the formation of atherosclerotic lesions. However, studies of CXCL16 polymorphisms in patients with atherosclerosis are scarce. The missense polymorphisms I123T and A181V are potentially important factors in the regulation of presentation and shedding of the CXCL16 chemokine domain. The aim of this study was to analyze the association between I123T and A181V polymorphism haplotypes and the accumulation of carotid plaque as well as the effect of the haplotype on the CXCL16 mRNA expression in carotid plaques in patients with advanced atherosclerosis. Additionally, we performed a bioinformatic prediction analysis of the impact of CXCL16 protein sequence variation on CXCL16-CXCR6 interactions and analyzed the soluble CXCL16 plasma levels according to the CXCL16 haplotype. METHODS This study evaluated a total of 733 participants, including 283 controls and 450 patients with carotid atherosclerosis (CA) undergoing endarterectomy. Analyses of the polymorphisms and the gene expression were performed using real-time PCR. The soluble CXCL16 levels were measured with ELISA. RESULTS The missense allele haplotype, T123V181, was found to be significantly and independently associated with the occurrence of CA plaque (OR=1.27;1.02-1.57, p=0.03). This haplotype was predicted to significantly change the CXCL16-CXCR6 interaction, compared to I123A181. Neither the CXCL16 mRNA expression in the human plaques nor the soluble CXCL16 plasma levels differed according to the haplotype. CONCLUSIONS These results indicate that the CXCL16 T123V181 haplotype is a moderate genetic risk factor for the development of carotid plaque. Further functional and replication studies are needed to clarify the mechanisms by which this combination of alleles promotes advanced CA and validate its impact on disease progression.

Role of recombinant factor VIIa in the treatment of intractable bleeding in vascular surgery

BACKGROUND Most recent publications have shown that the recombinant form of activated factor VII (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsværd, Denmark) induces excellent hemostasis in patients with severe intractable bleeding caused by trauma and major surgery. The purpose of this study was to determine the influence of rFVIIa on the treatment of intractable perioperative bleeding in vascular surgery when conventional hemostatic measures are inadequate. MATERIALS AND METHODS There were two groups of patients: the NovoSeven group (group N), 10 patients with ruptured abdominal aortic aneurysms (RAAAs) and 14 patients operated on due to thoracoabdominal aortic aneurysms (TAAAs); the control group (group C), 14 patients with RAAAs and 17 patients with TAAAs. All patients suffered intractable hemorrhage refractory to conventional hemostatic measures, while patients from group N were additionally treated with rFVIIa. RESULTS Postoperative blood loss was significantly lower in group N treated with rFVII (P < .0001). Postoperative administration of packed red blood cells, fresh frozen plasma, and platelets was lower in patients from group N, (P < .0001). Successful hemorrhage arrest was reported in 21 patients (87.5%) treated with rFVIIa, and in 9 patients (29.03%) in group C (P < .001). Thirty-day mortality in these two groups significantly differed. The mortality rate was 12.5% (3 patients) in group N and 80.65% (25 patients) in group C (P < .0001). CONCLUSION Our findings suggest that rFVIIa may play a role in controlling the intractable perioperative and postoperative bleeding in surgical patients undergoing a repair of RAAAs and TAAAs. Certainly, prospective randomized trials are necessary to further confirm the efficacy and cost-effectiveness of rFVIIa in these patients.

Dacron or ePTFE graft for above-knee femoropopliteal bypass reconstruction. A bi-centre randomised study

BACKGROUND The objective of this study was to compare polyester (Dacron) and expanded polytetrafluorethilene (ePTFE) grafts for above-knee femoropopliteal bypass. PATIENTS AND METHODS Eighty five patients with disabling claudications or limb threatening ischemia suitable for above-knee femoropopliteal reconstruction were randomized into two groups. In the first group the surgery was performed using 8 mm Dacron graft, whereas the patients in the second group were operated using ePTFE grafts. RESULTS The primary patency rates for Dacron and ePTFE were 100 %, and 88.37 % (p < 0.05), while secondary patency rates were 83.3 % and 75 % (p > 0.05) respectively. The early limb salvage rates for Dacron and ePTFE were 100 % and 97.7 % (p > 0.05). Early (30-day) complications (bleeding 2.38 % and 2.32 %; wound infection 11.9 % and 11.63 %) occurred in both groups with similar frequency (p > 0.05). The patients were followed up over a period of 6 to 12 months (mean 8.3 +/- 3.6 months). The overall mortality rate in the follow-up period was 2.38 % (one patient) for Dacron and 6.98 % (three patients) for ePTFE group (p > 0.05). Late graft infection was noted in three patients (7.1 %) in Dacron, and two patients (4.65 %) in ePTFE group (p > 0.05). Primary patency rates were not significantly influenced by obesity, diabetes, hypertension, hyperlipidemia, cigarette smoking, (p > 0.05). However, poor run-off (only one crural artery patent on preoperative angiography) significantly decreased patency of both grafts and favored the use of ePTFE graft (p < 0.05). CONCLUSIONS This study confirms that both materials are suitable for above-knee femoropopliteal reconstructions. Above-knee femoropopliteal bypass does not have a good long-term prognosis in the presence of poor run-off.

The Benefits of Internal Thoracic Artery Catheterization in Patients With Chronic Abdominal Aortic Occlusion

Occlusion of the abdominal aorta may be caused by an embolic lesion, but more commonly by thrombotic disease at the aortoiliac area, progressing retrograde. However, the visualization of the distal run-off via internal thoracic-epigastric inferior artery collateral channel may be a very important diagnostic tool, especially in countries with poor technical equipment. This study was designed to show the benefit of the selective internal thoracic angiography in cases with complete aortic occlusion. We present 30 patients with chronic aortic abdominal occlusion who were submitted to the transaxillary aortography and selective ITA angiography with purpose of distal run off evaluation. Angiographic evaluation was performed by two independent radiologists according to previously defined classification. Good angiographic score via internal thoracic angiography by first observer was achieved in 19 (63.3%) patients and in 18 (60%) by a second observer. Transaxillary aortography showed inferior results: good angiographic score by the first observer in six (20%) patients and by the second observer in three (3%) patients. Low extremity run-off is better visualized during internal thoracic angiography than during transaxillary aortography.

Aorto-left renal vein fistula is a rare complication of abdominal aortic aneurysm with unique clinical presentation

Spontaneous aorto-left renal vein fistulas (ALRVF) are extremely rare, with only 30 cases presented in the literature. In the majority of the reported cases, the fistula involved an anomalous retroaortic left renal vein. In some aspects, the clinical findings differ from those of aortocaval fistulas, often making the correct diagnosis difficult and contributing to the delay in treatment. In this article, we present 2 such cases, review previously reported data, and discuss clinical features and treatment options of this rare condition.