Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS. METHODS: Consecutive patients with non-disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary-care stroke centers during a 6-year period. The primary outcome events included stroke, myocardial infarction or death during the 30-day follow-up period. RESULTS: A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30-day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%-17.7%) and early (4.4%; 95% confidence interval 2.4%-7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4-6) vs. 10 days (interquartile range 7-14); P < 0.001]. CONCLUSIONS: Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non-significant increase in the risk of peri-procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.

Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence.

BACKGROUND: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. METHODS: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. RESULTS: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. CONCLUSION: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.

Nephrotoxicity issues of organophosphates.

Organophosphates are a large class of chemicals, initially invented in 1850 and since then they have been applied in numerous aspects of science to serve our purposes. Their mechanism of action in living organisms involves the irreversible inhibition of acetylcholinesterase, therefore they interfere with neuromuscular signal transmission. Due to the systematic and exaggerated use of these chemicals, there is massive exposure to them, hence there is great concern regarding the ramifications to all mammalian organisms. It has been widely accepted that over-exposure to organophosphates, has a deleterious impact on the renal tissue and subsequently on the renal function. Despite the significance of this global issue, limited knowledge exists, regarding the effect of these substances on our health. Therefore, new and extensive research is required to expand our knowledge and ensure proper guidance regarding the use of organophosphates as well the protection against their detrimental consequences. The aim of this review is to negotiate the effect of organophosphate exposure on renal tissue and kidney function.

Wire and extended ladder model predict THz oscillations in DNA monomers, dimers and trimers.

We call monomer a B-DNA base pair and study, analytically and numerically, electron or hole oscillations in monomers, dimers and trimers. We employ two tight binding (TB) approaches: (I) at the base-pair level, using the on-site energies of the base pairs and the hopping parameters between successive base pairs i.e. a wire model, and (II) at the single-base level, using the on-site energies of the bases and the hopping parameters between neighbouring bases, specifically between (a) two successive bases in the same strand, (b) complementary bases that define a base pair, and (c) diagonally located bases of successive base pairs, i.e. an extended ladder model since it also includes the diagonal hoppings (c). For monomers, with TB II, we predict periodic carrier oscillations with frequency [Formula: see text]-550 THz. For dimers, with TB I, we predict periodic carrier oscillations with [Formula: see text]-100 THz. For trimers made of identical monomers, with TB I, we predict periodic carrier oscillations with [Formula: see text]-33 THz. In other cases, either with TB I or TB II, the oscillations may be not strictly periodic, but Fourier analysis shows similar frequency content. For dimers and trimers, TB I and TB II are successfully compared giving complementary aspects of the oscillations.

Lack of evidence for use of heparin-bonded grafts in access surgery: a meta-analysis.

The aim of this study was to evaluate the efficacy of heparin-bonded vascular grafts to offer improved outcomes compared with standard prosthetic grafts in access surgery. A systematic review and meta-analysis was performed and eight studies (seven observational studies and one randomized controlled trial) were included. The pooled 6-month and 1-year primary patency was not significantly different between heparin-bonded arteriovenous (AV) grafts and standard prosthetic AV grafts in seven studies reporting on 1,209 access procedures. The assisted primary patency and secondary patency at 1-year was not significantly different either. Heparin-bonded AV grafts offer no distinct advantage over standard prosthetic AV grafts and their preferential use in access surgery cannot be recommended based on the available evidence.

The Necessity for Routine Pre-operative Ultrasound Mapping Before Arteriovenous Fistula Creation: A Meta-analysis.

OBJECTIVE/BACKGROUND: Existing guidelines suggest routine use of pre-operative color Doppler ultrasound (DUS) vessel mapping before the creation of arteriovenous fistulae (AVF); however, there is controversy about its benefit over traditional clinical examination or selective ultrasound use. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing routine DUS mapping before the creation of AVF with patients for whom the decision for AVF placement was based on clinical examination and selective ultrasound use. A search of MEDLINE/PubMed, SCOPUS, and the Cochrane Library was carried out in June 2014. The analyzed outcome measures were the immediate failure rate and the early/midterm adequacy of the fistula for hemodialysis. Additionally, assessment of the methodological quality of the included studies was carried out. RESULTS: Five studies (574 patients) were analyzed. A random effects model was used to pool the data. The pooled odds ratio (OR) for the immediate failure rate was 0.32 (95% confidence interval [CI] 0.17-0.60; p < .01), which was significantly in favor of the DUS mapping group. The pooled OR for the early/midterm adequacy for hemodialysis was 0.66 (95% CI 0.42-1.03; p = .06), with a trend in favor of the DUS mapping group; however, subgroup analysis revealed that routine DUS mapping was more beneficial than selective DUS (p < .05). CONCLUSION: The available evidence, based mainly on moderate quality RCTs, suggests that the pre-operative clinical examination should always be supplemented with routine DUS mapping before AVF creation. This policy avoids negative surgical explorations and significantly reduces the immediate AVF failure rate.

The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system.

BACKGROUND: The oxaliplatin (ΟΧΑ)-based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ-based chemotherapy on the ANS. METHODS: We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3-4 months and 6-8 months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR). RESULTS: The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both P < 0.001), while patients had more often diastolic OH at the 6-8 month evaluation compared to baseline (P = 0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (P = 0.036 and P = 0.020). CONCLUSIONS: Oxaliplatin-based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.

Computational estimation of the influence of the main body-to-iliac limb length ratio on the displacement forces acting on an aortic endograft. Theoretical application to Bolton Treovance® Abdominal Stent-Graft.

AIM: The influence of the relative iliac limb length of an endograft (EG) on the displacements forces (DF) predisposing to adverse effects are under-appreciated in the literature. Therefore, we conducted a computational study to estimate the magnitude of the DF acting over an entire reconstructed EG and its counterparts for a range of main body-to-iliac limb length (L1/L2) ratios. METHODS: A customary bifurcated 3D model was computationally created and meshed using the commercially available ANSYS ICEM (Ansys Inc., Canonsburg, PA, USA) software. Accordingly, Fluid Structure Interaction was used to estimate the DF. The total length of the EG was kept constant, while the L1/L2 ratio ranged from 0.3 to 1.5. RESULTS: The increase in L1/L2 slightly affected the DF on the EG (ranging from 3.8 to 4.1 N) and its bifurcation (4.0 to 4.6 N). However, the forces exerted at the iliac sites were strongly affected by the L1/L2 values (ranging from 0.9 to 2.2 N), showing a parabolic pattern with a minimum for 0.6 ratio. CONCLUSION: It is suggested that the hemodynamic effect of the relative limb lengths should not be considered negligible. A high main body-to-iliac limb length ratio seems to favor hemodynamically a low bifurcation but it attenuates the main body-iliac limbs modular stability. Further clinical studies should investigate the relevant value of these findings. The Bolton Treovance(®) device is presented as a representative, improved stent-graft design that takes into account these hemodynamic parameters in order to achieve a promising, improved clinical performance.

Safety of early endarterectomy in patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: Although the latest recommendations suggest that carotid endarterectomy (CEA) should be performed in symptomatic carotid artery stenosis (sCAS) patients within 2 weeks of the index event, only a minority of patients undergo surgery within the recommended time-frame. The aim of this international multicenter study was to prospectively evaluate the safety of early CEA in patients with sCAS in everyday clinical practice settings. METHODS: Consecutive patients with non-disabling acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) due to sCAS (≥ 70%) underwent early (≤ 14 days) CEA at five tertiary-care stroke centers during a 2-year period. Primary outcome events included stroke, myocardial infarction (MI) or death occurring during the 30-day follow-up period and were defined according to the International Carotid Stenting Study criteria. RESULTS: A total of 165 patients with sCAS [mean age 69 ± 10 years; 69% men; 70% AIS; 6% crescendo TIA; 8% with contralateral internal carotid artery (ICA) occlusion] underwent early CEA (median elapsed time from symptom onset 8 days). Urgent CEA (≤ 2 days) was performed in 20 cases (12%). The primary outcomes of stroke and MI were 4.8% [95% confidence interval (CI) 1.5%-8.1%] and 0.6% (95% CI 0%-1.8%). The combined outcome event of non-fatal stroke, non-fatal MI or death was 5.5% (95% CI 2.0%-9.0%). Crescendo TIA, contralateral ICA occlusion and urgent CEA were not associated (P > 0.2) with a higher 30-day stroke rate. CONCLUSIONS: Our findings indicate that the risk of early CEA in consecutive unselected patients with non-disabling AIS or TIA due to sCAS is acceptable when the procedure is performed within 2 weeks (or even within 2 days) from symptom onset.

Antiplatelet treatment and prothrombotic diathesis following endovascular abdominal aortic aneurysm repair.

Prothrombotic diathesis expressed by elevated levels of coagulation-specific biomarkers has been reported in patients with abdominal aortic aneurysm (AAA) and after AAA endovascular repair (EVAR). This study investigates the effect of antiplatelet agents (APLs) on the prothrombotic diathesis in the post-EVAR period. Forty elective EVAR patients had thrombin-antithrombin complex, d-dimer, fibrinopeptide A, and high-sensitivity C-reactive protein measured before, at 24 hours, 1 month, and 6 months after EVAR. Patients receiving APLs postoperatively were compared with those not receiving APLs. All biomarkers were above the normal limits preoperatively and increased significantly 24 hours postoperatively followed by a drop at 1 and 6 months. No statistically significant changes were noted among patients receiving APLs in comparison with those not receiving APLs. The preoperative and postoperative prothrombotic diathesis of AAA following EVAR was confirmed in line with other reports. There was however no significant alteration of the examined biomarkers in patients receiving APLs.

The hemodynamic impact of misalignment of fenestrated endografts: a computational study.

OBJECTIVE: The hemodynamic consequences of misaligned stent-grafts (SG) in fenestrated endografts (EG) have not been adequately studied. Our aim was to study the hemodynamic effects of positional variations of SG, investigating the potential influence on the total displacement forces acting on the EG and the shear stress values at the stented segments. METHODS: This was a computational study. An idealized EG model with two renal fenestrations was computationally reconstructed and centrally extended up to the suprarenal level to treat a suprarenal aneurysm. The misalignment of SG was represented by a variable take-off angle between the SG and the EG centerline axis, corresponding to angles of 90°, 176°, 142°, 38°, and 4°, respectively. Accordingly, the maximum EG displacement forces and the shear stress within the stented segments were calculated, using commercially available software. RESULTS: The variable positions of the SG caused no effect on the maximum displacement force acting on the EG, being quite steady and equal to 5.55 N. On the contrary, the values of maximum shear stress acting on the stented segments were influenced by their orientation. The narrow transition zone between the distal end of the mating stent and the target artery showed higher stresses than any other segment. The right-angle take off SG position (90°) was associated with the lowest stresses (12.5 Pa), whereas the highest values were detected at 38° and 142° (16.5 and 16.1 Pa, respectively). The vessel segments distal to the SG exhibited constantly lower stress values (1.9-2.2 Pa) than any other segment. CONCLUSION: We detected differences in the values of shear stress exerted on the stented arteries, depending on different positions that SG can adapt after the deployment of fenestrated EG. The pathophysiologic implication of our findings and their potential association with clinical events deserve further investigation and clinical validation.

Writing a research abstract: eloquence in miniature.

Abstracts are summaries, usually of a full article or conference presentation, and may be classified into structured and unstructured ones. The former have a predefined layout necessitating the use of headings. Most journals and conferences now use the structured abstract format. Research abstracts are increasingly vital for scientific communication and are expected to continue playing a key role for the dissemination of medicine in the near future. Abstracts take time and need meticulous preparation. They must aptly summarise the content of the study or presentation and avoid vague statements and poor style. Moreover, they must comply with provided instructions. Finally, they should be pleasant to read and encourage study of the corresponding full work.

Sympathetic skin response in Parkinson's disease before and after mental stress.

OBJECTIVES: This study aims to evaluate sympathetic sudomotor activity in Parkinson's disease (PD) by means of the sympathetic skin response (SSR) and explore its possible changes due to mental stress. METHODS: Sudomotor function was evaluated using SSR in 29 patients with PD (Hoehn and Yahr stage I-IV) without any clinical evidence of autonomic dysfunction. Twenty-seven healthy matched controls were also evaluated. SSR was elicited by electrical stimulation of the right median nerve and simultaneously recorded on the palms of both hands. Arithmetic mental stress was evoked by means of the WAIS-R arithmetic subscale. Latency and amplitude of SSR were evaluated before and after arithmetic mental stress. RESULTS: The SSR was obtained in all patients and controls. There were no significant differences in its mean latency and amplitude between patients and controls. SSR parameters were significantly correlated with disease duration, UPDRS score, and disease stage. There were also significant correlations with rigidity and bradykinesia, but not with tremor. Mental stress had no effect on SSR parameters in any group. CONCLUSIONS: SSR parameters in PD without autonomic dysfunction were comparable to matched controls. Although PD patients are sensitive to mental stress, the arithmetic task had no effect on SSR parameters. Consequently, SSR as a method of evaluation of sympathetic sudomotor function is not sufficient for exploration of subclinical autonomic dysfunction in PD, but should be combined with other tests of autonomous nervous system.

Endovascular management of peripheral arterial trauma in patients presenting in hemorrhagic shock.

AIM: This study investigated patients who sustained peripheral arterial trauma, presented with clinical signs of shock, and underwent urgent endovascular repair (endo-R). METHODS: Eighteen patients (11 men) aged 62.8 ± 17.5 y (range: 24-78 years) with severe peripheral arterial injuries or spontaneous ruptures who presented with clinical signs of shock were treated on an emergency basis at two institutions from August 2003 to August 2009. The injury mechanism and clinical presentation were assessed in all patients. The time interval from the initial event to the procedure, the time interval from hemodynamic instability to endo-R (HI-to-endo-RTI), the artery involved in the approach to the injured vessel, the method of endo-R, and the endo-R duration were recorded. Stent grafting and/or embolization of the injured vessel were performed. The outcome was assessed mainly by clinical examination and duplex scanning. The duration of follow-up ranged from 6 d to 60 mo (27.4 ± 17.8 mo, mean ± SD). RESULTS: Mechanisms of injury included 13 iatrogenic (9 catheter-related) injuries, 2 spontaneous hemorrhages, and 1 case each of gunshot wound, fall injury, and car accident. Traumatic lesions were in the external carotid (N.=1), vertebral (N.=1), subclavian (N.=3), common iliac (N.=1), external iliac (N.=5), internal iliac (N.=3), profunda femoral (N.=1), superficial femoral (N.=2), and popliteal (N.=1) arteries. Stent grafts and embolotherapy were successfully deployed in 12 and 4 patients, respectively, with complete exclusion of the bleeding site. One patient received both treatments and another patient received balloon occlusion therapy. Technical success with no procedural complications occurred in all cases. The mean event-to-procedure time interval, HI-to-endo-RTI, and operative time were 147 min, 42.2 ± 48.2 min (range: 3-180 min), and 40.0 ± 29.6 min (range: 5-110 min), respectively. Thirteen patients had an uneventful postoperative course while three patients died (mortality rate: 17%). One patient had below-knee amputation and another one suffered hemiparesis (morbidity rate: 11%). The durations of the hospital and intensive-care-unit stays were 16.6 ± 19.5 d (range: 2-62 d) and 6.4 ± 14.6 d (range: 0-60 d), respectively. The follow-up duration was 27.4 ± 17.8 mo (range: 0.2-60 mo). Freedom from early or late endo-R major events occurred in 71.4% and 65.6% of cases at 6 mo and 12 mo, respectively, and the rate of primary patency of endografts was 91.7% and 81.8%. CONCLUSION: Endo-R of traumatic non-aortic arterial injuries or spontaneous ruptures might be considered as a treatment option-in preference to open repair-even in emergency settings such as in shock patients. However, the safety of endovascular treatment in unstable trauma patients must be proved after comparison with open surgical treatment.

An open-label, multicenter observational study for patients with Alzheimer's disease treated with memantine in the clinical practice.

BACKGROUND/AIMS: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer's disease (AD). METHODS: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs) were also recorded to evaluate the safety profile of memantine. RESULTS: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≥1 ADRs, and treatment was discontinued due to ADR in 0.7%. CONCLUSION: Memantine was well tolerated and had a positive effect on the patient's cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.