Konstantinos G. Moulakakis

Arterial stiffness and novel biomarkers in patients with abdominal aortic aneurysms

OBJECTIVES Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA). METHODS We enrolled 108 men with AAA (AAA group) candidates for endovascular repair. We excluded patients with Marfan syndrome or other collagen-related disorders. Forty-one age-matched men, with stable coronary artery disease (CAD), but without AAA, served as controls (CO group). PWV, clinical parameters and serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6) and IL-10 were determined. RESULTS With the exception of higher smoking rate and the lower statins usage in the AAA group, there were non-significant differences in the rest of demographic and clinical parameters (p>0.05). We found significantly higher levels of PWV in AAA than CO group (12.99±3.75 m/s vs 10.03±1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA group. PWV positively correlated with mean blood pressure, OPG concentrations and AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008). Finally, age and OPG remained independent determinants of AAA presence in the whole study cohort. CONCLUSIONS Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation.

Clinical Considerations of Primary Hydatid Disease of the Pancreas

Background: The pancreas is a rare primary location of hydatid disease. The purpose of our study is to gain more insight into this entity and to focus on the management and the diagnostic approach to the disease. Methods: The medical records of 5 patients with hydatid cysts of the pancreas were reviewed. Results: Four of the cysts were primary, while in 1 case a coexisting cyst was found in the liver. The body and tail of the pancreas were the most common locations. Clinical presentation varied according to the anatomic location of the cyst. Abdominal pain, discomfort and vomiting were the main clinical symptoms. One patient presented with obstructive jaundice, while another patient manifested a mild episode of anaphylactic shock. The indirect hemagglutination test was positive in 3 of 4 cases. A computed tomography scan successfully imaged all cysts and calcification of the cystic wall was found in 3 of 4 cases. All patients underwent surgical therapy. Hydatid cysts in the tail of the pancreas were successfully treated with distal pancreatectomy, while cysts in the body and head of pancreas were treated with proper evacuation, pericystectomy and omentoplasty. The postoperative course was uneventful in all patients except 1 who presented a pancreatic fistula and was re-operated. The mean length of hospitalization after surgery was 11–12 (range 10–13) days, except for the patient who needed to be re-operated. No evidence of cyst recurrence was observed during the follow-up period. Conclusions: Hydatid cystic masses of the upper abdomen might also originate from the pancreas especially in endemic countries. Surgical excision of the entire cystic lesion remains the optimal treatment, offering hope for a complete cure.

Changes in aortic pulse wave velocity of patients undergoing endovascular repair of abdominal aortic aneurysms.

Purpose To assess changes in pulse wave velocity (PWV), a valid index of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). Arterial stiffness is an independent marker of all-cause mortality and cardiovascular morbidity and mortality. Methods Forty-eight consecutive male patients (mean age 71 ± 4 years) underwent elective EVAR (AAA group) after exclusion of patients with Marfan syndrome or other collagen-related disorders. Thirty-one age-matched men (mean age 69 ± 5 years) without overt cardiovascular disease served as controls. PWV and clinical parameters were determined at baseline in both groups and after 6 months in the AAA group. Results At baseline, the groups did not differ in demographic characteristics, lipid profile, or blood pressure levels (p>0.05). PWV was considerably higher in AAA than controls (p<0.001). PWV positively correlated with mean blood pressure, AAA diameter, and age in univariate and multivariate analysis (R 2 =0.498, p=0.008). At 6 months after EVAR, PWV significantly increased from 13.11 ± 3.57 m/s to 16.41 ± 2.33 m/s (p<0.001) in the AAA group. Conclusion Patients with AAA present with significantly elevated PWV levels compared to controls, and stent-graft repair is associated with a significant increase in the PWV. Whether those changes contribute to the cardiovascular risk in AAA patients needs further investigation.

The role of soluble P selectin in the diagnosis of venous thromboembolism

INTRODUCTION Soluble P selectin (sPsel), a member of the selectin family of cell adhesion receptors, has been proposed as a key molecule in hemostasis and thrombosis mediating platelet rolling, generating procoagulant microparticles and enhancing fibrin deposition. The aim of this study was to examine the role of sPsel in the diagnosis of venous thromboembolism (VTE). MATERIALS AND METHODS We performed a systematic review and we used meta-analysis to synthesize data from published studies reporting sPsel levels in patients with i) VTE (deep venous thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated among patients and controls. Diagnostic performance of sPsel was tested with pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver operator characteristic (SROC) curve. RESULTS Eleven studies, comprising of 586 VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly increased after VTE (OR=2.89, 95%CI=2.31-3.61, p<0.001), or DVT only (OR=2.64, 95%CI=1.95-3.56, p<0.001). Subgroup analysis evidenced that sPsel was also increased after VTE when evaluating only studies with patients that had no prior medical history (OR=2.88, 95%CI=1.98-4.19, p<0.001). Exclusion of studies including patients with solid organ tumor, HIV or lupus anticoagulants positive patients did not alter findings. Pooled sensitivity and specificity of sPsel was 0.57 (95%CI=0.30-082, p<0.001) and 0.73 (95%CI=0.51-0.90, p<0.001), respectively and DOR was 4.31 (95%CI=2.22-8.37, p<0.01). SROC curve yielded in significant accuracy of sPsel performance (AUC=0.74, p=0.05). CONCLUSIONS The sPsel was significantly elevated in patients with DVT, both uncomplicated and complicated with PE and presented with high levels of diagnostic performance. sPsel is a plasma biomarker that may help in the diagnosis of VTE.

The Impact of Carotid Artery Stenting on Cognitive Function in Patients with Extracranial Carotid Artery Stenosis

BACKGROUND The effect of carotid artery stenting (CAS) on cognitive function in patients with extracranial carotid artery stenosis is equivocal. The aim of this study was to examine the impact of CAS on various domains of cognitive function. METHODS We performed a meta-analysis of the studies evaluating various domains of cognitive function before and after CAS, namely, (1) global cognition using Mini-Mental State Examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT), (2) executive function using Trail Making Test (TMT) A or Color Trails Test (CTT) A and TMT B or CTT B, (3) language ability using Boston Naming Test (BNT), (4) memory, (5) attention/psychomotor speed, and (6) functional ability, using various cognitive tests. Pooled weighted mean differences (WMDs) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were appropriately calculated using fixed or random effects models after assessing between-study heterogeneity. Meta-regression analysis was performed with number of patients per study; mean age (years); follow-up (months); proportion of men; proportion of patients with hypertension, diabetes mellitus, hyperlipidemia, smoking, and coronary artery disease; proportion of symptomatic patients; and degree of ipsilateral and degree of contralateral carotid stenosis as covariates. RESULTS Sixteen studies were eligible, including a total of 626 CAS patients. A statistically significant improvement of global cognition was detected with MMSE (WMD = 0.67, 95% CI = 0.29-1.05, P < 0.001; follow-up = 5.6 months), but not with RAVLT (SMD = 0.45, 95% CI = -0.03 to 0.93, P = 0.07; follow-up = 2.4 months). Significant improvement of memory (SMD = 0.33, 95% CI = 0.11-0.55, P < 0.01; follow-up = 4.1 months) and attention/psychomotor speed (SMD = 0.21, 95% CI = 0.04-0.39, P = 0.02; follow-up = 4 months) was also detected. No statistically significant effect on executive function (TMT A/CTT A and TMT B/CTT B; SMD = 0.08, 95% CI = -0.10 to 0.26, P = 0.39; follow-up = 3.9 months and SMD = -0.02, 95% CI = -0.20 to 0.16, P = 0.82, respectively; follow-up = 3.9 months), language ability (BNT; SMD = 0.24, 95% CI = -0.05 to 0.54, P = 0.10; follow-up = 4 months), and functional ability (SMD = -0.05, 95% CI = -0.25 to 0.15, P = 0.63; follow-up = 3.8 months) was observed. No significant effects of the examined covariates were demonstrated in the meta-regression analyses. CONCLUSIONS CAS may be associated with improvement in global cognition, memory, and attention/psychomotor speed. There was no positive effect on executive function, language, and functional ability, but CAS was not associated with a decline in any area of cognitive function. Future studies in larger groups of patients are probably needed to fully investigate the long-term effect of CAS on cognition in patients with carotid artery stenosis.

Inflammatory Response and Renal Function Following Endovascular Repair of the Descending Thoracic Aorta

Purpose: To evaluate inflammatory response and renal function after thoracic endovascular aortic repair (TEVAR) of lesions in the descending thoracic aorta. Methods: Thirty-two consecutive patients treated with TEVAR from January 2010 to August 2013 were enrolled in this prospective study. Two were excluded owing to dissecting thoracic aortic aneurysm (TAA) extending into the renal arteries with renal failure in one and a saccular TAA in which a multilayer flow-modulating stent was implanted in the other. This left 30 patients (28 men; mean age 68.8±5.9 years) with 28 TAAs, an aortic dissection, and an aortic ulcer for the analysis. Temperature and serum levels of white blood cells (WBCs), C-reactive protein (CRP), interleukin-10 (IL-10), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), creatinine, urea, and cystatin C were measured preoperatively and at 24 and 48 hours postoperatively. Results: Statistically significant increases in temperature and serum levels of WBCs, CRP, IL-10, and IL-6 were observed 24 and 48 hours postoperatively compared to baseline (all p<0.05). The number of endografts and the coverage of the celiac or subclavian artery did not affect the magnitude of the inflammatory response. No significant differences were observed concerning serum levels of IL-8, TNF-α, creatinine, or cystatin C from baseline to 24 or 48 hours postoperatively. Conclusion: Endograft implantation in the thoracic aorta may propagate an inflammatory response during the early postoperative period. No clinical adverse events related to the increased inflammatory response were observed. Renal function does not seem to be deteriorated after TEVAR in the descending thoracic aorta.

A network meta-analysis of randomized controlled trials comparing treatment modalities for de novo superficial femoral artery occlusive lesions

Background: Treatment of superficial femoral artery (SFA) lesions remains challenging. We conducted a network meta‐analysis of randomized controlled trials aiming to explore the efficacy of treatment modalities for SFA “de novo” lesions. Methods: Eleven treatments for SFA occlusive disease were recognized. We used primary patency and binary restenosis at 12‐month follow‐up as proxies of efficacy for the treatment of SFA lesions. Results: A total of 33 studies (66 study arms; 4659 patients) were deemed eligible. In terms of primary patency, odds ratios (ORs) with 95% confidence intervals (CIs) were statistically significantly higher in drug‐eluting stent (DES; OR, 10.05; 95% CI, 3.22‐31.39), femoropopliteal bypass surgery (BPS; OR, 7.15; 95% CI, 2.27‐22.51), covered stent (CS; OR, 3.56; 95% CI, 1.33‐9.53), and nitinol stent (NS; OR, 2.83; 95% CI, 1.42‐5.51) compared with balloon angioplasty (BA). The rank order from higher to lower primary patency in the multidimensional scaling was DES, BPS, NS, CS, drug‐coated balloon, percutaneous transluminal angioplasty with brachytherapy, stainless steel stent, cryoplasty (CR), and BA. Combination therapy of NS with CR and drug‐coated balloon were the two most effective treatments, followed by NS, CS, percutaneous transluminal angioplasty with brachytherapy, cutting balloon, stainless steel stent, BA, and CR in terms of multidimensional scaling values for binary restenosis. Conclusions: DES has shown encouraging results in terms of primary patency for SFA lesions, whereas BPS still maintains its role as a principal intervention. On the contrary, BA and CR appear to be less effective treatment options.

A Review of Open and Endovascular Treatment of Superior Vena Cava Syndrome of Benign Aetiology

BACKGROUND The widespread use of central venous catheters, ports, pacemakers, and defibrillators has increased the incidence of benign superior vena cava syndrome (SVCS). This study aimed at reviewing the results of open and endovascular treatment of SVCS. METHOD Medical literature databases were searched for relevant studies. Studies with more than five adult patients, reporting separate results for the SVC were included. Nine studies reported the results of endovascular treatment of SVCS including 136 patients followed up for a mean of 11-48 months. Causes of SVCS were central venous catheters and pacemakers (80.6%), mediastinal fibrosis (13.7%), and other (5.6%). Percutaneous transluminal angioplasty (PTA) and stenting was performed in 73.6%, PTA only in 17.3%, and thrombolysis, PTA, and stenting in 9%. Four studies reported the results of open repair of SVCS including 87 patients followed up between 30 months and 10.9 years. The causes were mediastinal fibrosis (58.4%), catheters and pacemakers (28.5%), and other (13%). Operations performed included a spiral saphenous interposition graft, other vein graft, PTFE graft, and human allograft. Thirteen patients required re-operations (15%) before discharge mainly for graft thrombosis. RESULTS In the endovascular group technical success was 95.6%. Thirty day mortality was 0%. Regression of symptoms was reported in 97.3%. Thirty-two patients (26.9%) underwent 58 secondary procedures. In the open group the 30 day mortality was 0%. Symptom regression was reported in 93.5%. Twenty-four patients (28.4%) underwent a total of 33 secondary procedures. CONCLUSIONS Endovascular is the first line treatment for SVCS caused by intravenous devices, whereas surgery is most often performed for mediastinal fibrosis. Both treatments show good results regarding regression of the symptoms and mid-term primary patency, with a significant incidence of secondary interventions.

Coexistence of Primary Adrenal Hydatid Cyst and Arterial Hypertension : Report of a case and review of the literature

Abstract Adrenal gland has been considered as an atypical localization of Echinococcus Granulosus and the reported incidence is 0.5%. We report a rare case of coexistence of primary adrenal hydatid cyst and arterial hypertension. The patient underwent surgical excision of the adrenal gland with a slight improvement of blood pressure’s regulation, requiring antihypertensive medication postoperatively. Till today, two cases of coexistence of primary adrenal hydatid cyst and arterial hypertension have been reported in the literature. However there is not clear and acceptable explanation about the relation and the involved pathogenetic mechanism. Resection of the cyst with conservation of the gland remains the optimal procedure. In case of haemorrhage or failure to perform a cystectomy, ablation of the entire adrenal gland including the cyst should be performed.

The Mechanical Performance and Histomorphological Structure of the Descending Aorta in Hyperthyroidism

Thyroid hormones decrease systemic vascular resistance by directly affecting vascular smooth muscle relaxation. There is limited literature about their effect on the mechanical performance of the aortic wall. Therefore, the authors determined the influence of hyperthyroidism on the mechanical properties and histomorphological structure of the descending thoracic aorta in rats. Severe hyperthyroidism was induced in 20 male Wistar rats by administering L-thyroxine (T4) in their drinking water for 8 weeks; age-matched normal euthyroid rats acted as controls. Animals were sacrificed, and the mechanical and histomorphometrical characteristics of the descending thoracic aorta were studied. The aortic wall of hyperthyroid rats was stiffer than that of euthyroid animals at the upper physiologic levels of stress or strain (p < 0.05) but less stiff at the lower physiologic and lower levels (p < 0.05). The aorta of hyperthyroid animals compared with that of euthyroid ones showed an increase of the internal and external diameters (p < 0.05), the media area (p < 0.05), the number of smooth muscle cell nuclei (p < 0.05), and the collagen density (p < 0.05) and a decrease in the elastin laminae thickness (p < 0.001) and elastin density (p < 0.001). In hyperthyroid rats, the aortic wall was stiffer at the upper physiologic and higher levels of stress and strain. These changes correlated with microstructural changes of the aortic wall. The coexistence of hyperthyroidism with disease states or clinical conditions that predispose to increased arterial pressure may be associated with increased arterial stiffness and have undesirable consequences on the mechanical performance of the thoracic aorta and hemodynamic homeostasis. These changes could lead to an increased risk for developing vascular complications.