Effect of CYP2C19 Polymorphisms on the Platelet Response to Clopidogrel and Influence on the Effect of High Versus Standard Dose Clopidogrel in Carotid Artery Stenting.

OBJECTIVES: Genetic background has been identified to be a major predictor of post-clopidogrel platelet inhibition in patients undergoing coronary stenting. However, there is a lack of data on clopidogrel response regarding genotype in patients undergoing carotid artery stenting (CAS). The influence of the most common allelic variants of CYP2C19 phenotypes and genotypes on response to baseline clopidogrel and on the pharmacodynamic effect of dose adjustment (high or standard dose of clopidogrel) in patients with high on-treatment reactivity after CAS was investigated. METHODS: Platelet reactivity was assessed before and 30 days after carotid stenting using the VerifyNow P2Y12 assay to obtain P2Y12 reactivity unit (PRU) values. RESULTS: A total of 209 patients (79.4% male, 44.1% currents smokers) were treated by CAS. Smokers improved responsiveness to clopidogrel (p = .034). With respect to CYP2C19 enzymatic function, 61 subjects (29.1%) were ultra-rapid metabolizers, 95 patients (45.5%) were extensive metabolizers, 51 (24.4%) were intermediate metabolizers, and two (0.96%) were poor metabolizers. Baseline PRU was significantly higher among intermediate-poor metabolizers compared with ultra-rapid (p = .001) or extensive metabolizers (p = .005). At 30 days follow up, in non-responding patients with the intermediate-poor metabolizer phenotype, the PRU value and inhibition percentage were significantly reduced with standard dose (p = .008; p = .0029) and high dose of clopidogrel (p = .00 0; p = .000). However, high dose clopidogrel did not achieve a more intense pharmacodynamic effect at 30 days (p = .994) compared with standard dose. CONCLUSIONS: In patients undergoing carotid stenting, those with the CYP2C19*2 allele had increased basal PRU values and in fact clopidogrel non-responders increased significantly among intermediate-poor metabolizers. Although high dose and standard dose clopidogrel therapy was effective in lowering the 30 day PRU values in patients with high on-treatment reactivity who are intermediate-poor metabolizers, the use of high dose clopidogrel did not result in statistically significantly greater reductions in reactivity compared with the standard dose.

Silent ischemia after neuroprotected percutaneous carotid stenting: a diffusion-weighted MRI study.

BACKGROUND AND PURPOSE: To assess by diffusion-weighted MR imaging (DWI) the efficacy of cerebral protection devices in avoiding embolization and new ischemic lesions in patients with severe internal carotid artery (ICA) stenosis undergoing carotid artery stent placement (CAS). METHODS: One hundred sixty-two CASs in the extracranial ICA were performed with the use of distal filters. Mean age of the patients was 68.5 years (range, 33-86) and 122 patients (75.3%) were symptomatic. MR imaging was performed in all patients during the 3-day period before CAS, and DWI was obtained within 24 hours after the procedure. Ninety-five patients (58.6%) were monitored by transcranial Doppler ultrasonography for microemboli detection in the territory of the middle cerebral artery (MCA), ipsilateral to the vessel being treated. RESULTS: Twenty-eight patients (17.3%) showed 58 new ischemic foci in DWI, and 13 patients (46.4%) had multiple foci. Location of new lesions was mainly in the vascular territory supplied by the treated vessel (19 patients; 67.9%), but also in the contralateral MCA (1 patient; 3.6%), and the posterior fossa (4 patients; 14.3%). A significant relationship (P < .03) was found between occurrence of transient ischemic attack (TIA) and appearance of new lesions. Microembolic signals (MES) were detected in 88 patients (92.6%), with no relationship between number of MES and the appearance of new ischemic foci. CONCLUSION: New ischemic foci were observed in 17.3% of the patients undergoing neuroprotected CAS. Appearance of new ischemic lesions were only significantly related to the occurrence of TIA but not to the number of MES registered or other variables. Despite the encouraging results, the incidence of new ischemic lesions should promote research for safer techniques and devices.

Modest adjunctive benefit with transcranial magnetic stimulation in medication-resistant depression.

BACKGROUND: Controverted results have been obtained using high frequency transcranial magnetic stimulation (HF-rTMS) as an antidepressant treatment. METHODS: Forty patients suffering from drug-resistant major depression received ten sessions of HF-rTMS at 90% of the motor threshold on the left prefrontal cortex or sham stimulation, added to their pharmacological treatment, in a randomized double-blind design. In a second open phase, patients still fulfilling criteria of inclusion received ten additional sessions of HF-rTMS at 90 or 110%. RESULTS: Real, but not sham HF-rTMS, was associated with a significant decrease in the Hamilton Depression Rating Scale, but only twelve patients decreased more than 50%. CONCLUSIONS: Left prefrontal HF-rTMS was effectively associated with antidepressant treatment, although the size effect was small. LIMITATIONS: Shortage of the sample and control difficulties of the placebo effect. CLINICAL RELEVANCE: Questionable in more than half of the patients studied.

Self-schemas and risk for depression: a prospective study.

The role of depressive self-schemas in vulnerability to depression was explored in a longitudinal design. Five groups of subjects hypothesized to be at differential risk for depression according to a schema model were identified: depressed schematic, depressed nonschematic, nondepressed schematic, nondepressed nonschematic, and a psychopathology control. They were followed regularly for 4 months with self-report and clinical interview measures of depression. There was no evidence of risk for depression associated with schema status apart from initial mood and no interaction of life stress events and schemas. In a second experiment with the same subjects, it was shown that depressive self-schemas do not exert an ongoing, active influence on everyday information processing; instead current mood affected information processing. Remitted depressed persons resembled nondepressed rather than depressed ones. The results support Kuiper and colleagues' distinction between concomitant and vulnerability schemas, and help to clarify differences between cognitions that are symptoms or correlates of depression and those that may play a causal role under certain conditions.

[Hyperperfusion syndrome as a complication of percutaneous transluminal angioplasty of the internal carotid artery]. / Síndrome de hiperperfusión como complicación de la angioplastia transluminal percutánea de la arteria carótida interna.

INTRODUCTION: The hyperperfusion syndrome (HS) is described as an infrequent complication of carotid endarterectomy. It may also occur in percutaneous transluminal carotid angioplasty with a similar causal mechanism and clinical features to those seen in HS related to carotid endarterectomy. CLINICAL CASE: We describe the case of a 69 year old man who developed HS at the time of transluminal carotid angioplasty and 'stenting' of symptomatic, pre-occlusive stenosis of the left internal carotid artery. This complication was not detected on the postoperative arteriography. On CT the presence of a hemispheric hematoma was confirmed. It is thought that HS is caused by a fault in autoregulation of the cerebral blood flow following correction of vascular stenosis in previously ischemic territory. CONCLUSIONS: Most of the early complications of transluminal carotid angioplasty are ischemic. HS is rare but is a possible complication of transluminal carotid angioplasty and therefore meticulous control of the blood pressure is necessary. A CT scan after any atypical complication of angioplasty may be considered to be essential.

Internal carotid artery stenting in patients with near occlusion: 30-day and long-term outcome.

BACKGROUND AND PURPOSE: The natural history of the carotid NO is poorly characterized, and the management of patients remains controversial. We report the results and complications associated with CAS and follow-up. MATERIALS AND METHODS: Between March 2000 and March 2009, 116 of 836 CAS procedures were performed in patients with carotid NO (13.9%). A total of 99 men (85.3%) and 17 women (14.7%) with a mean age of 65.8 years were included. Presenting symptoms were TIA in 44 patients (37.9%) and minor stroke or noninvalidating stroke in 61 (52.6%). One hundred five patients (90.5%) were symptomatic. RESULTS: A distal filter was used for cerebral protection in 92 patients (79.3%). Transient hemodynamic alterations were frequent during balloon inflation: hypotension (37.1%), bradycardia (48.3%), and asystole in 24.1%. Four patients (3.4%) developed a TIA after CAS. Stroke in progression was arrested in the 1 patient (0.9%). The median follow-up period for patients was 36 months. Asymptomatic restenosis >70% occurred in 5 patients (4.3%); asymptomatic occlusion occurred in 3 patients (2.6%). During follow-up, 3 patients (2.6%) experienced a stroke, 1 ipsilateral (at 19 months) and 2 contralateral (at 6 and 30 months, respectively). Thirteen patients (11.2%) died, 7 from vascular causes. CONCLUSIONS: Our study showed that carotid NO is an under-recognized condition, and CAS would seem to be beneficial when performed by an experienced neurointerventional team.

Volume and composition of emboli in neuroprotected stenting of the carotid artery.

BACKGROUND AND PURPOSE: Periprocedural microembolization is a major and permanent risk for patients treated by angioplasty and stent placement of high-grade carotid stenoses. Little is known however about the characteristics and significance of these embolized particles. Our aim was to assess the volume and composition of debris captured by filters during carotid angioplasty and stent placement (CAS) of severe internal carotid artery (ICA) stenoses. MATERIALS AND METHODS: Institutional review board approval and informed consent from all subjects were obtained. Two hundred one patients (mean age, 66.2 years; range, 35-82 years) with > or = 70% stenosis of the ICA underwent filter-protected CAS. Ultrastructural and semiquantitative analysis of the volume of filters was obtained. Multifactorial statistical analysis was performed to determine factors related to debris volume and composition. RESULTS: Transient ischemic attack occurred in 6 patients (3%), and a major stroke, in 1 (0.5%). Debris was found in 117 filters (58.2%), with volume <1 lambda (0.001 mL) in 71%. The number of balloon dilations, age older than 65 years, and calcified plaques in pre-CAS angiography were significantly associated with the presence of particulates inside the filters (P < .03, P < .004, and P < .05, respectively). CONCLUSIONS: Vessel wall and atheromatous plaques are the main source of microemboli during CAS. Embolization is mainly related to the number of balloon dilations during CAS. Planning a proper and individualized strategy for the procedure in each patient is essential to minimize the potential effects of manipulation during CAS.

Endovascular stent-graft treatment of an iatrogenic vertebral arteriovenous fistula.

We present a high-flow vertebral arteriovenous fistula caused by percutaneous catheterisation of the internal jugular vein. Endovascular transarterial treatment with a self-expanding covered stent was used to close the fistula successfully with preservation of the parent artery.

Angioplasty and stenting for total symptomatic atherosclerotic occlusion of the subclavian or innominate arteries.

Bypass grafting is considered the treatment of choice for occlusions of supraaortic vessels. Percutaneous transluminal angioplasty (PTA) is a well-established treatment for patients with subclavian stenosis, but its efficacy in total subclavian or innominate occlusions is so far not well established. Since 1995, we have carried out 9 PTA revascularizations in 9 patients with total symptomatic atherosclerotic occlusion of supraaortic vessels. The technical success rate was 100%, without any major (death or stroke) or minor complications. In the follow-up period (mean 37.4 months), 1 patient had a symptomatic left internal carotid artery occlusion and an asymptomatic occlusion of the treated subclavian artery. In expert hands, stenting-PTA should be considered as the primary therapeutic option.

Angioplasty of symptomatic high-grade internal carotid artery stenosis with intraluminal thrombus: therapeutic approach.

Intraluminal thrombus in the internal carotid artery (ICA) is usually found in patients with severe atheromatous stenosis. Having reviewed 300 carotid angioplasties for symptomatic >70% ICA stenosis, we found three patients (1%) with intraluminal thrombus. Conservative treatment with anticoagulants and double antiplatelet coverage can result in lysis of the thrombus without severe risks. Percutaneous transluminal angioplasty and stenting, preferably with distal protection, can be an excellent alternative to carotid endarterectomy.

Effective management of marked lymphedema of the leg.

BACKGROUND: Several conservative and surgical treatment methods have been demonstrated to be useful in the management of lymphedema. METHODS: In a patient with an enormous lymphedema of the leg, we first used complex decongestive physiotherapy as proposed by Földi et al. in 1989, and then followed it with surgery. RESULTS: Satisfactory results were obtained in a short period of time and were maintained during the 2-year follow-up. CONCLUSIONS: We recommend a combined medical, surgical, and physiotherapeutic approach in patients with marked lymphedema.

Percutaneous transluminal angioplasty of the symptomatic atherosclerotic carotid arteries. Results, complications, and follow-up.

BACKGROUND AND PURPOSE: Carotid endarterectomy reduces stroke risk in patients with > 70% symptomatic stenosis. We present our results of percutaneous transluminal angioplasty (PTA) as an alternative treatment. METHODS: Ninety-eight patients with symptomatic > 70% stenosis of the internal carotid artery were considered for PTA. Details of the procedure, complications, and 4-year follow-up were registered. RESULTS: Eighty-five PTAs were performed in a 4-year period. Transient cardiovascular effects were frequent: hypotension (54.1%), bradycardia (67.1%), asystole (25.9%), and syncope (16.5%). Transient ischemic attack occurred in 3 of 82 patients (3.7%), and disabling stroke occurred in 4 (4.9%); mortality was 0%. After a mean follow-up period of 18.7 months, 4 patients died, 1 due to fatal stroke. The overall probability of surviving any stroke or death was 86.7%. Restenosis (> 70%) was seen in 6 cases (7.4%). CONCLUSIONS: PTA may be a reasonable treatment for symptomatic atherosclerotic stenosis, at least in patients at high risk for carotid endarterectomy.

Prefrontal repetitive transcranial magnetic stimulation as add on treatment in depression.

A growing number of studies report antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) in patients with major depression. The hypothesis that high frequency (20 Hz) rTMS (HF-rTMS) may speed up and strengthen the therapeutic response to sertraline in MD was tested. Twenty eight patients who had not yet received medication for the present depressive episode (n=12) or had failed a single trial of an antidepressant medication (n=16) were started on sertraline and randomised to receive either real of sham HF-rTMS. HF-rTMS was applied to the left dorsolateral prefrontal area in daily sessions (30 trains of 2 s, 20-40 s intertrain interval, at 90% motor threshold) on 10 consecutive working days. The results suggest that in this patient population, HF-rTMS does not add efficacy over the use of standard antidepressant medication.

CD34+ cell dose and CD33- subsets: collection and engraftment kinetics in autologous peripheral blood stem cells transplantation.

BACKGROUND AND OBJECTIVE: We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery. DESIGN AND METHODS: From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology. RESULTS: Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional prior chemotherapy and absence of prior radiation therapy also influenced the yield of PBSC. The number of CD34+ cells, CD34+CD33- cell subsets, the mobilization schedule, and the conditioning regimen correlated significantly with time to hematopoietic recovery. In the multivariate analysis only the CD34+CD33- cell content and the total number of CD34+ were related with rapid neutrophil and platelet recovery, respectively. Use of G-CSF after transplant significantly shortened the neutrophil recovery time only in patients transplanted with suboptimal dose of PBSC. INTERPRETATION AND CONCLUSIONS: These data suggest the utility of quantitation of CD34+ cells subsets to predict quick engraftment.