Constantine N. Antonopoulos

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.

Association between Carotid Artery Occlusion and Ultrasonographic Plaque Type

BACKGROUND Internal carotid artery (ICA) occlusion is associated with acute stroke and carries significant morbidity and mortality. The aim of this study was to examine whether ultrasonographic carotid plaque type may be associated with ICA occlusion. METHODS Two hundred eleven patients (85% men, mean age 66.0±9.5 years, 28.9% asymptomatic) with ICA occlusion were included in this case-control study. Ultrasonographic Gray-Weale plaque type (I-IV, echolucent to echogenic) characterization was obtained in both the occluded and the contralateral ICA. Univariate and conditional logistic regression analyses with 1:1 pair matching per artery were undertaken. Each contralateral carotid artery with stenosis was treated as control to the ipsilateral-occluded ICA of the same patient. RESULTS A total of 261 ICAs (61.9%) were recorded with type I-II plaque, of which 165 (63.2%) were among the occluded and 96 (36.8%) were among the contralateral ICAs with stenosis (P<0.001). Mean contralateral ICA stenosis was 58.2%±20.4%. Regression analysis showed that carotid plaque type I-II was significantly associated with carotid artery occlusion compared with plaque type III-IV (crude odds ratio [OR]=4.29, 95% confidence intervals [CI]=2.81-6.57%, P<0.001, adjusted OR=5.60, 95% CI=3.23-9.70, P<0.001). Previous neurological events did not seem to be significantly associated with plaque echolucency (OR=0.62, 95% CI=0.29-1.35, P=0.23). CONCLUSIONS A significant association between echolucent plaque and ICA occlusion was observed. This observational hypothesis may prompt for further investigation of the causal mechanism between carotid plaque type and ICA occlusion by larger cohort studies.

Safety and efficacy of polyurethane vascular grafts for early hemodialysis access

Background: Arteriovenous grafts made of polyurethane (PU) have the advantage of early cannulation obviating the placement of a central vein catheter in patients with an acute need for long‐term hemodialysis. The aim of the present study was to evaluate the safety, efficacy and complication rate of PU vascular grafts for dialysis access in patients in whom early cannulation was performed. Methods: Between January 2007 and December 2015, 125 straight brachial‐axillary grafts were placed in patients with an acute thrombosis of a previous arteriovenous access. Sixty‐four were PU and 61 were polytetrafluoroethylene (PTFE) grafts. Patency and complications rates were compared between the two groups. Results: The median interval from implantation to cannulation was 1 day in the PU group vs 28 days in the PTFE group. Cumulative infection rate at 5 years was 13% and 8% in the PU and the PTFE groups, respectively (P = .6). None of the patients in the PU group developed a pseudoaneurysm necessitating intervention, compared with one patient in the PTFE group. Primary and secondary patency rates did not differ significantly between the two groups. The cumulative median primary patency was 23 months in the PU group vs 26 months in the PTFE group. Median secondary patency was 42 vs 33 months, respectively. Diabetes mellitus was the only factor adversely affecting graft patency in both groups. Conclusions: PU grafts offer the advantage of early cannulation with infection, pseudoaneurysm formation and patency rates similar to those of the PTFE grafts.

Development of an animal model of fibrous cholangitis in pigs.

ABSTRACT Introduction: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Material and Methods: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0–5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Results: Statistically significant differences were observed for most of the histopathological markers between the group of pigs’ offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Conclusions: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

Effect of Oestrogen Exposure, Obesity, Exercise and Diet on Breast Cancer Risk

Intense research efforts have been devoted to the exploration of breast cancer risk factors aiming at subsequent use in the development of prevention strategies. Age at menarche/menopause and childbearing patterns are proxies of exposure to endogenous oestrogens; circulating hormone levels, depending also on the use of exogenous oestrogens, are involved in the causation of the disease due to proliferative effects on breast epithelial tissue. Several modifiable lifestyle-related risk factors have been identified including obesity, alcohol consumption and physical inactivity, which increase breast cancer risk, especially in postmenopausal women, by up to 40%. Findings regarding the effect of diet remain inconclusive, apart from the established linear association of alcohol consumption with breast cancer risk. Exploration of specific components and the impact of these factors on disease outcome remains also to be established.

Open repair of thoracoabdominal aortic aneurysms in experienced centers

Objective: We performed a systematic review and meta‐analysis aiming to assess the mortality and morbidity of all published case series on thoracoabdominal aortic aneurysms (TAAAs) in experienced centers treated with open repair. Methods: A systematic search of the literature published until April 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Separate meta‐analyses were conducted for overall in‐hospital mortality for TAAA, mortality according to the type of TAAA, spinal cord ischemia, paraplegia and paraparesis, cardiac events, stroke, acute kidney failure, and bowel ischemia. A metaregression analysis was performed with volume of the center, percentage of ruptured cases among the series, length of in‐hospital stay, and publication year as covariates. Results: A total of 30 articles were included in the meta‐analysis, corresponding to a total of 9963 patients who underwent open repair for TAAAs (543 ruptured). The pooled mortality rate among all studies was 11.26% (95% confidence interval [CI], 9.56‐13.09). Mortality was 6.97% (95% CI, 3.75‐10.90), 10.32% (95% CI, 7.39‐13.63), 8.02% (95% CI, 6.37‐9.81), and 7.20% (95% CI, 4.19‐10.84) for Crawford types I, II, III, and IV, respectively. Pooled spinal cord ischemia rate was estimated at 8.26% (95% CI, 6.95‐9.67), whereas paraparesis and paraplegia rates were 3.61% (95% CI, 2.25‐5.25) and 5% (95% CI, 4.36‐5.68), respectively. We estimated a pooled cardiac event rate of 4.41% (95% CI, 1.84‐7.95) and a stroke rate of 3.11% (95% CI, 2.36‐3.94), whereas the need for permanent dialysis rate was 7.92% (95% CI, 5.34‐10.92). Respiratory complications after surgery were as high as 23.01% (95% CI, 14.73‐32.49). Metaregression analysis evidenced a statistically significant inverse association between mortality and the volume of cases performed in the vascular center (t = −2.00; P = .005). Interestingly, a more recent year of study publication tended to be associated with decreased in‐hospital mortality (t = −1.35; P = .19). Conclusions: Our study showed that despite the advances in open surgical techniques, the morbidity and mortality of the technique continue to remain considerable. Despite the focus on mortality and spinal cord ischemia, respiratory complications, permanent postoperative renal dialysis, stroke rate, and cardiac events also affect the outcome. The estimated trend of lower mortality in high‐volume centers suggests that perhaps this type of service should be provided in a few reference centers that have an established record and experience in the management of these patients.

ARE ROAD TRAFFIC ACCIDENTS PREVENTABLE AMONG SLEEP APNOEA PATIENTS

Background Drowsiness and lack of concentration among obstructive sleep apnoea (OSA) patients may strongly contribute to road traffic accidents (RTAs). Aims/Objectives/Purpose A meta-analysis was conducted in order to estimate whether RTAs can be prevented after treatment with continuous positive airway pressure (nCPAP) among (OSA) patients. Methods Real accidents, near miss accidents and accident-related events in the driving simulator were used as the primary outcomes after nCPAP treatment. Pooled ORs, incidence rate ratios (IRRs), standardised mean differences (SMDs), risk differences (RDs) and numbers needed to treat (NNTs) were appropriately calculated. Results/Outcome Concerning real accidents (10 studies, 1221 patients), a statistically significant reduction in RTAs was recorded (OR=0.21, 95% CI 0.12 to 0.35, random effects model; IRR=0.45, 95% CI 0.34 to 0.59, fixed effects model). A stronger reduction on near miss accidents (5 studies, 769 patients; OR=0.09, 95% CI 0.04 to 0.21, random effects model; IRR=0.23, 95% CI 0.08 to 0.67, random effects model) was also observed. With respect to the preventable fraction of RTAs, it was estimated that five (NNT=5, 95% CI 3 to 8) and two (NNT=2, 95% CI 1 to 4) OSA patients should be treated with nCPAP to prevent one patient reporting real and near miss road traffic accidents, respectively. Significance/Contribution to the Field It seems that nCPAP treatment may offer a sizeable protective effect upon RTAs prevention. The clinical role of health professionals in accident prevention should include identification of accident risks or medical conditions conferring risk (OSA), treatment of accident-causing conditions (nCPAP treatment) and reinforcement of advocacy and policy making towards promoting accident prevention education and training (OSA patients).