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Abstract  Injection of hematopoietic stem cells or endothelial progenitor cells (EPCs) expandedex vivohas been shown to augment neovascularization in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. The limited quantity of EPCs in the circulation has been the main obstacle to clinical trials. Several authors have therefore attempted to expand these cellsex vivoin order to obtain a homogeneous cell therapy product. One possible means of expanding EPCsex vivois to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation promotes cell proliferation and C-X-C chemokine receptor type 4 (CXCR4) dependent migration and differentiation, with an overall angiogenic effect. This review summarizes the results and rationale of clinical trials of angiogenic therapy, the nature of EPCs, the different methods ofex vivoexpansion, and current methods of quantification. [ABSTRACT FROM AUTHOR]

Background and Purpose: We aimed to report the characteristics of cerebral venous thrombosis (CVT) in elderly people (aged ≥65 years)., Methods: This multicenter retrospective cohort included elderly patients hospitalized for a first CVT in nine Paris-Ile-de-France hospitals between 2011 and 2021. The estimated incidence was compared to CVT recorded by the French health insurance data system. Lariboisière Hospital's CVT registry allowed comparisons of our elderly cohort with individuals younger than 65 years., Results: One hundred fourteen patients were included in this study (mean age = 74.2 years, range = 65-93, 61% female). The CVT annual incidence in Ile-de-France was 5.9-7.1 per million elderly individuals versus 8.5 per million nationwide. Headaches and focal deficits were the most common initial clinical features (50% and 51%, respectively), followed by seizures and confusion (40% and 27%). Treatment included anticoagulation (93%) and, rarely, endovascular procedure (2%) or craniectomy (1%). Compared with adult patients aged <65 years (younger adults), elderly patients presented fewer headaches (50% vs. 96%, p < 0.01) and intracranial hypertension (7% vs. 22%, p < 0.01) but more seizures and focal deficits (40% vs. 27% and 51% vs. 38%, respectively, p < 0.01). Underlying cancer, hemopathy, and locoregional infections were more frequent in elderly patients than among younger adults (p < 0.01). The prognosis of patients from our elderly cohort was poorer than that of younger adults; 8% died in the acute phase, and 73% had a favorable outcome at 1 year (vs. 1.7% and 87%, respectively, p < 0.01)., Conclusions: CVT in elderly patients has a specific clinical presentation, epidemiology, and risk factors such as cancer or hemopathy, justifying specialized management., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase., Patients and Methods: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup., Results: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p  < 0.0001), with similar sICH rate (3 vs 2, p  = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p  < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p  < 0.0001). Propensity score matching analyses supported all these associations., Conclusion: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation., Trial Registration: ClinicalTrials.gov Identifier: NCT05809921 ., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: I.S reports consultant fees for Bayer, BMS/Pfizer, Boehringer Ingelheim outside the submitted work, Medtronic, Novartis, Novo Nordisk, Bioprojet, Astra-Zeneca, Alexion and speaker activities for AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk; DS reports consultant fees for BMS/Pfizer, Boehringer-Ingelheim outside the submitted work, Novartis and speaker activities for BMS/Pfizer, Boehringer-Ingelheim, Novo Nordisk, Servier, Sanofi; Other authors do not report any conflicting interests.

Background: Despite its increasing use, there are limited data on the risk of intracranial hemorrhage (ICH) after intravenous thrombolysis with tenecteplase in the setting of acute ischemic stroke. Our aim was to investigate the incidence and predictors of ICH after tenecteplase administration., Methods: We reviewed data from the prospective ongoing multicenter TETRIS (Tenecteplase Treatment in Ischemic Stroke) registry. Patients with available day-1 imaging were included in this study. Clinical, imaging and biological variables were collected. Follow-up imaging performed 24 h after IVT was locally reviewed by senior neuroradiologists and neurologists. The incidence of parenchymal hematoma (PH) and any ICH were investigated. Potential predictors of PH and any ICH were assessed in multivariable logistic regressions. Subgroup analyses focusing on patients intended for endovascular treatment were performed., Results: PH and any ICH occurred in 126/1321 (incidence rate: 9.5%, 95% CI 8.1-11.2) and 521/1321 (39.4%, 95% CI 36.8-42.1) patients, respectively. Symptomatic ICH was observed in 77/1321 (5.8%; 95% CI 4.7-7.2). PH occurrence was significantly associated with poorer functional outcomes ( p  < 0.0001) and death ( p  < 0.0001) after 3 months. Older age (aOR = 1.03; 95% CI 1.01-1.05), male gender (aOR = 2.07; 95% CI 1.28-3.36), a history of hypertension (aOR = 2.08; 95% CI 1.19-3.62), a higher baseline NIHSS (aOR = 1.07; 95% CI 1.03-1.10) and higher admission blood glucose level (aOR = 1.12; 95% CI 1.05-1.19) were independently associated with PH occurrence. Similar associations were observed in the subgroup of patients intended for endovascular treatment., Conclusion: We quantified the incidence of ICH after IVT with tenecteplase in a real-life prospective registry and determined independent predictors of ICH. These findings allow to identify patients at high risk of ICH., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Limited data are available on long-term respiratory disabilities in patients following acute COVID-19., Patients and Methods: This prospective, monocentric, observational cohort study included patients admitted to our hospital with acute COVID-19 between 12 March and 24 April 2020. Clinical, functional and radiological data were collected up to 28 months after hospital discharge., Results: Among 715 patients hospitalised for COVID-19, 493 (69.0%) were discharged alive. We could access complete medical records for 268 out of 493 patients (54.4%); 138 out of 268 (51.5%) exhibited persistent respiratory symptoms and agreed with the data collection and follow-up. Patients were predominantly male (64.5%), with a mean±sd age of 58.9±15.3 years. At the last follow-up, the leading symptoms were asthenia (31.5%), dyspnoea (29.8%) and neuropsychological symptoms (17.7%). Lung function improved up to the last visit. Mean diffusing capacity of the lung for carbon monoxide ( D LCO ) was 77.8% of predicted value, total lung capacity (TLC) was 83.5% and O 2 desaturation during exercise (O 2 desaturation) was 2.3%. While D LCO improved over the entire period, TLC improved in the early phase and O 2 desaturation in the late phase. Except for those with lung comorbidities, only one patient presented with minor functional and chest radiological alterations at 28 months., Conclusion: Patients with acute COVID-19 discharged alive showed improved clinical symptoms, lung function parameters and radiological signs up to 28 months post-infection. Persistent symptoms consisted mainly of asthenia and dyspnoea, with lung function returning to normal. One patient without prior respiratory issues exhibited moderate pulmonary fibrosis., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

Background: Tirofiban has been shown to be superior to aspirin in achieving functional independence at 3 months for acute ischemic stroke of atheromatous or microatheromatous origin. As intravenous thrombolysis (IVT) has previously been shown to be nonsuperior to aspirin in achieving functional independence at 3 months for anterior choroidal or paramedian pontine infarction (ACI/PPI), we aimed to compare the outcomes of Caucasian patients receiving IVT plus tirofiban (IVT + T) with those receiving tirofiban alone for acute ACI/PPI., Methods: A retrospective study was conducted in patients aged ≥ 18 years with ACI/PPI treated in our stroke unit between December 1, 2020, and April 30, 2023, who received therapeutic intervention within 9 hours of symptom onset or after awakening with stroke symptoms. Modified Rankin Scale (mRS) ≤ 1 at 3 months was the primary endpoint. Secondary endpoints were National Institutes of Health Stroke Scale (NIHSS) ≤ 2 at day 7 or discharge and post-procedural neurological deterioration (PPND) within 72 hours. Symptomatic intracranial hemorrhage (SICH) and major systemic bleeding (MSB) were the safety measures of the study., Results: A total of 24 patients were enrolled in the tirofiban group and 43 patients in the IVT + T group. Compared to tirofiban alone, IVT + T was associated with a higher probability of achieving mRS ≤1 at 3 months (adjusted odds ratio [aOR], 8.79; 95% confidence interval [CI], 2.06-37.52; P = 0.003) and National Institutes of Health Stroke Scale ≤2 at day 7 or discharge (aOR, 3.70; 95% CI, 1.05-12.99; P = 0.041). No significant difference was seen between the two groups in preventing postprocedural neurological deterioration. One case of SICH and two cases of MSB occurred in the IVT + T group and no cases in the tirofiban group. One case of inhospital mortality was recorded in the IVT + T group., Conclusions: Our results showed that IVT + T may be safe and effective in Caucasian patients with acute ACI/PPI., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Brain Circulation.)

Objective: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce., Methods: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score., Results: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated., Interpretation: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment., Patients and Methods: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed., Results: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69)., Conclusion: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study aimed to evaluate the efficacy of ripasudil in managing various corneal edema conditions., Materials and Methods: This single-center retrospective analysis was conducted at Hadassah Medical Center and involved 16 patients with 17 eyes. Patients were selected based on diagnostic criteria, primarily corneal edema. The conditions were as follows, listed by frequency: postcataract surgery (31.25%), postpenetrating keratoplasty (25%), post-Descemet's membrane endothelial keratoplasty (18.75%), Fuchs' endothelial corneal dystrophy (12.5%), status post-Ahmed glaucoma valve (6.25%), and status posttrabeculectomy (6.25%). The treatment regimen involved topical administration of ripasudil hydrochloride hydrate (Glanatec ® 0.4%), administered three times a day or tailored to condition severity. Efficacy was assessed using pre- and posttreatment measurements of best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC), along with slit-lamp and optical coherence tomography examinations., Results: The average duration of ripasudil treatment was approximately 4.9 ± 2.2 months. Significant improvements were observed in BCVA, changing from a pretreatment value of 1.106 ± 0.817 logMAR to a posttreatment value of 0.56 ± 0.57 logMAR ( P = 0.0308). CCT also showed a significant reduction, from 619.50 ± 56.36 μm pretreatment to 572.5 ± 75.48 μm posttreatment ( P = 0.0479). ECC showed a marginal but not statistically significant increase, from 849.00 ± 570.72 cells/mm² pretreatment to 874.75 ± 625.59 cells/mm² posttreatment ( P = 0.9010)., Conclusion: The study provides robust evidence supporting the use of ripasudil in managing corneal edema. Significant improvements in key ocular metrics such as BCVA and CCT were observed, enhancing the overall quality of life for patients suffering from various forms of corneal edema., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2024 Taiwan J Ophthalmol.)

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing -4.02 ± 0.70 D, -4.18 ± 0.89 D, -3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (-0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (-1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (-0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.

Myopia (nearsightedness) and presbyopia (aging eye) are the most common refractive errors of the human eye. Technology has advanced toward correcting aberration using various surgical procedures, including laser surgery, as well as prescribing corrective lenses. Hence, the effect of various laser wavelengths on the eye has been extensively studied over the last few decades. Usually, excimer lasers are used for this purpose, which increases the cost of the procedure because they are unique and difficult to manufacture and require regular maintenance. Due to the absorption properties, visible wavelengths do not interact with the corneal layers and hence are currently not used for eye surgery. This study presents the first clinical evidence that a 532 nm laser in combination with an eye-safe fluorescein dye that is in wide clinical use in ophthalmology can be utilized for high-precision ablation purposes due to the photochemical reaction that occurs on an ex vivo porcine eye. Our results show the promise of utilizing inexpensive visible wavelength lasers in the ablation of biological tissues, reducing the high costs of ophthalmological surgical procedures, as well as in other applications., Competing Interests: The authors declare the following competing financial interest(s): Nanodrops partially funded this research and some of the authors have equity at nanodrops., (© 2023 The Authors. Published by American Chemical Society.)

This retrospective comparative study analyzes the early postoperative impact of laser vision correction for myopia on the optical quality and stability of functional vision using a double-pass aberrometer. Retinal image quality and visual function stability were assessed preoperatively, one and three months after myopic laser in situ keratomileuses (LASIK) and photorefractive keratectomy (PRK) using double-pass aberrometry (HD Analyzer, Visiometrics S.L, Terrassa, Spain). The parameters analyzed included vision break-up time (VBUT), objective scattering index (OSI), modulation transfer function (MTF), and Strehl ratio (SR). The study included 141 eyes of 141 patients, of whom 89 underwent PRK and 52 underwent LASIK. No statistically significant differences were noted between the two techniques in any analyzed parameters at three months postoperatively. However, a significant drop was observed in all parameters one month after PRK. Only the OSI and VBUT remained significantly altered from baseline at the three months follow-up visit, with an increased OSI by 0.14 +/- 0.36 ( p < 0.01) and a shortened VBUT by 0.57 +/- 2.3 s ( p < 0.01). No correlation was found between the changes in optical and visual quality parameters and age, ablation depth, or postoperative spherical equivalent. The stability and quality of the retinal images were similar between LASIK and PRK at three months postoperatively. However, significant degradation in all parameters was found one month after PRK.

Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder due to the presence of neutralizing autoantibodies directed against the coagulation factor VIII (FVIII). The reference method to detect and quantify anti-FVIII antibodies is the Bethesda assay (BA), but it presents some limitations such as a lack of sensitivity for low titers of inhibitor and the need for experienced laboratory. A commercially available ELISA detecting anti-FVIII antibodies has demonstrated excellent sensitivity and specificity. The aim of our study was to assess the performance of this ELISA for the detection of anti-FVIII IgG in AHA patients during the follow-up. In total, 11 acquired hemophilia A patients were recruited, and anti-FVIII antibody levels were monitored by BA and ELISA. Anti-FVIII IgG ELISA showed 100% sensitivity and 100% specificity, and it correlated with the BA. Discrepancies observed in 13.3% of cases were consistent with patients' biological evolution. All these data suggest the possible use of anti-FVIII IgG ELISA for both diagnosis and follow-up of AHA patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel technique for Descemet membrane endothelial keratoplasty (DMEK) graft handling and centration without the endothelium touching the posterior part of the anterior chamber (AC), is presented here. It is particularly suitable for vitrectomized eyes, deep AC, and AC intraocular lenses (ACIOLs), potentially reducing surgery time and endothelial cell loss during surgery. This retrospective interventional case series includes 27 eyes with complex ocular pathology. All utilized a “Wave maneuver” to center an early elevated graft without completing graft centration on the bottom of the AC. Successful graft attachment and centration were evaluated intra and post-operatively. Best-corrected visual acuity (BCVA), central corneal thickness (CCT), and donor endothelial cell density (ECD) were measured pre-operatively, and three and six months post-operatively. DMEK grafts were successfully attached and centered in all cases. No maneuver-related complications were observed intraoperatively. BCVA improved from a pre-operative 0.2 ± 0.63, to 0.43 ± 0.49 and 0.76 ± 0.51 at the three- and six-month follow-ups, respectively (p < 0.01). CCT decreased from a pre-operative 742 ± 118, to 546 ± 87 and 512 ± 67 at three and six months, respectively (p < 0.01). ECD decreased from 2878 ± 419 cells/mm2 to 1153 ± 466 cells/mm2 at three and six months, respectively (p < 0.01). The “Wave maneuver” may be very beneficial in DMEK cases where the AC is either very deep or the bottom of the AC is compromised. The “Wave maneuver” learning curve was brief.

Background: Stroke is a high burden illness and the second leading cause of worldwide disability with generally poor recovery rates. Robust benefits of hippotherapy, a novel neurorehabilitation approach, in functional recovery following various severe neurological disabling conditions has been shown. In the present study, we will analyze the effect of a hippotherapy program on the outcome of post-stroke patients in the first year post-stroke., Method: A randomized controlled clinical trial on the effectiveness of hippotherapy (4 weeks/18 weeks hippotherapy/conventional neurorehabilitation) versus conventional neurorehabilitation alone (22 weeks) will be conducted over 48 weeks. In the treated group, one-hour daily hippotherapy sessions will be exclusively conducted during the hippotherapy's cycles, alternated with periods of conventional neurorehabilitation. A test battery will measure both the functional and psychological outcomes. The primary endpoint will be the patient's functional independence. The secondary endpoints will measure the sensorimotor function, autonomy, and quality of life, as well as the caregivers' quality of life., Results and Conclusion: Individual brain connectome, life history and personality construct influence the brain's functional connectivity and are central to developing optimal tailored neurorehabilitation strategies. According to our current practice, hippotherapy allows the enhancement of substantial neuroplastic changes in the injured brain with significant neurological recovery. The protocol aims to confirm those issues. Trial registration in ClinicalTrials.gov NCT04759326 accessed on 19 February 2021.

Background: The occurrence of both ischaemic (IS) and haemorrhagic stroke in patients on anticoagulation is a major issue due to the frequency of their prescriptions in westernised countries and the expected impact of anticoagulant activity on recanalization during an IS or on the outcomes associated with intracerebral haemorrhage (ICH). Several guidelines are available but sometimes differ in their conclusions or regarding specific issues, and their application in routine emergency settings may be limited by particular individual issues or heterogeneous local specificities. Methods: Based on the current guidelines and additional published data, the algorithms proposed in this paper aim to help the decision-making process regarding stroke management in the setting of concurrent anticoagulants by addressing specific clinical situations based on clinical variables commonly encountered in real-world practise. Results: For patients on non-vitamin K oral anticoagulants, reversion can be achieved with specific antidotes, but only idarucizumab, the specific dabigatran antidote, is indicated in both IS and ICH. Due to the low risk of a prothrombotic effect, idarucizumab can be immediately used in IS patients eligible for thrombolysis before the dabigatran concentration is known. To optimise ICH management, the time since symptom onset, with thresholds proposed at 6 and 9 hours based on the expected timing of haematoma expansion, could also to be taken into account. Conclusions: Anticoagulant reversal in patients presenting with a stroke remains a major issue, and algorithms based on a step-by-step approach may be useful for clinical practise. Real-life studies strongly support the benefits of idarucizumab availability in stroke units and emergency departments., Competing Interests: IS received fees for editorial activities with Elsevier, served as advisor for Servier and Boehringer Ingelheim, received teaching honoraria from Medtronic, BMS-Pfizer, AstraZeneca and Bayer, as well as research support from the University Hospital of Bordeaux and the French Health Ministry. MM received speaker's honoraria from Boehringer Ingelheim and consulting honoraria from Boehringer Ingelheim, Acticor Biotech, Air Liquide and Amgen. DS received speaker's honoraria and consulting honoraria from Boehringer Ingelheim., (Copyright © 2022 Sibon, Mazighi and Smadja.)

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns., Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors., Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients., Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

Background and Purpose: Carotid web (CaW) is an intimal variant of fibromuscular dysplasia responsible for ipsilateral cerebral ischemic events (CIE). Symptomatic CaW likely has a high risk of recurrent CIE, but no salient prospective data are available. We aimed to assess recurrence rate and its predictors after a first-ever CIE., Methods: Consecutive Afro-Caribbean patients who had cryptogenic first-ever CIEs (ischemic stroke [IS] or transient ischemic attack [TIA]) associated with ipsilateral CaW were included in this multicenter observational cohort study. The follow-up (January 2008 to March 2019) focused on CIE recurrences. Kaplan-Meier method assessed rates of recurrences and Cox proportional hazards regression analyzed risk factors., Results: Ninety-two patients (79 first-ever ISs and 13 TIAs; mean age±standard deviation, 49.8±9.9 years; 52 [56.5%] women) were included. During a mean follow-up of 50.5±29.6 months, 19 (20.7%) patients experienced recurrent ipsilateral CIEs (16 ISs and three TIAs). Of 23 patients receiving surgery/stenting treatment, no recurrence occurred after the intervention (median follow-up, 39.8 months [interquartile range, 27.6 to 72.4]). Under medical treatment alone, the annual recurrent CIE rate was 6.9%, and the cumulative rate was 4.4% at 30-day, 10.8% at 1-year, 19.8% at 2-year, 23.2% at 3-year, and 27.3% at 5-year. Presence of silent cerebral infarctions was the only independent risk factor of CIE recurrences (hazard ratio, 6.99; 95% confidence interval, 2.4 to 20.4; P=0.004)., Conclusions: Under medical treatment alone, symptomatic CaW was associated with a high rate of recurrence that reached 27.3% at 5-year. Surgery/stenting seems to be efficient, and randomized control trials are required to confirm the benefit of these interventions.

Purpose: To employ a finite element (FE) stress model to simulate laser in situ keratomileusis (LASIK) surgery and its biomechanical consequences., Methods: The basic geometrical model we used for the cornea was patient-specific on which we manually incorporated seven simulations: three simulations evaluating the effect of a 120, 140 and 180 μm flap (without ablation); three simulations evaluating ablation depths of 40, 80 and 120 μm (with a 120 μm flap); and one control model, without any simulated surgical intervention., Results: In all simulations, stress values were greatest in the centre of the cornea. Furthermore, when comparing the different treatments, stress values were highest in the cornea with the deepest ablation, and were lowest in the non-treated cornea. Specifically, peak effective stresses were 0.031, 0.028 and 0.025 MPa in 120, 80 and 40 µm ablation depths, respectively., Conclusions: In our model, the depth of tissue penetration using ablation or flap creation was correlated with tissue loads-the thinner the residual stromal bed is, the greater are the stresses occurring as a result of the same IOP., Relevance: We based our model geometry on patient specific scans, allowing for customisation of the treatment to the patient's corneal structure.

Background: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed., Objectives: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke., Methods: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema., Results: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]., Conclusions: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke., (© 2019 The Association for the Publication of the Journal of Internal Medicine.)

Factor V serves an important role in the regulation of blood coagulation. The rs6025 (R534Q) and rs4524 (K858R) polymorphisms in the F5 gene, are known to influence the risk of venous thrombosis. While the rare Q534 (factor V Leiden) allele is associated with an increased risk of venous thrombosis, the minor R858 allele is associated with a lower risk of disease. However, no study has deeply examined the cumulative impact of these two variations on venous thrombosis risk. We study the association of these polymorphisms with the risk of venous thrombosis in 4 French case-control populations comprising 3719 patients and 4086 controls. We demonstrate that the Q534 allele has a dominant effect over R858. Besides, we show that in individuals not carrying the Q534 allele, the protective effect of the R858 allele acts in a dominant mode. Thrombin generation-based normalized activated protein C sensitivity ratio was lower in the 858R/R homozygotes than in the 858K/K homozygotes (1.92 ± 1.61 vs 2.81 ± 1.57, p = 0.025). We demonstrate that the R858 allele of the F5 rs4524 variant protects from venous thrombosis only in non-carriers of the Q534 allele of the F5 rs6025. Its protective effect is mediated by reduced factor VIII levels and reduced activated protein C resistance.

Background : Little is known about the costs associated with vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (NVAF) in France. Objectives : To evaluate monthly per-patient costs attributable to VKA treatment in NVAF patients from a French societal perspective. Study design : Retrospective data were obtained from 7 international normalised ratio (INR) monitoring centres in France. Patients older than 18 years of age with NVAF treated with VKA were recruited. Additional patient-level data assessing resource use corresponding with VKA treatment were collected via self-completed questionnaires. Unit costs applicable to 2015 were multiplied by resource use and summed to generate VKA treatment costs. Results : 363 patients were included; 53% were men. The majority of patients received fluindione (72%). The number of INR tests per patient per month was 1.69 (95% CI, 1.59-1.80). The monthly patient cost was €39.72 (€36.23-43.21) from the French societal perspective. Direct medical costs comprised 76% of overall costs, with drug costs representing 7.4% (€2.4); direct non-medical and indirect costs comprised 10% and 14% respectively. Conclusions : Costs associated with VKA treatment in NVAF cannot be estimated only with drug costs. When direct and indirect attributable costs associated with VKA treatment are considered, the VKA treatment costs are more substantial.

Objective: To analyze the safety and efficacy of high-myopic PRK as an alternative to LASIK surgery in patients with a high preoperative percentage tissue altered (PTA)., Design: Retrospective interventional case series., Participants: Charts of 256 consecutive eyes that underwent PRK with application of mitomycin-C 0.02% for high myopia were retrospectively reviewed., Methods: Refractive (refraction and refractive accuracy) and visual outcomes (uncorrected and corrected visual acuities), as well as occurrence of haze in the eyes with preoperative PTA expected to be higher than 40% with a 110-micron flap if undergoing LASIK surgery, were analyzed., Results: Mean follow-up was 7.3 ± 4.8 months. A total of 187 of 256 eyes (73.0%) were included in the analysis because they were expected to have a PTA greater than 40%, should they have undergone LASIK surgery. The actual mean PTA of those eyes following PRK was 31.8 ± 2.2%, and none had a PTA ≥ 40%. UDVA of 20/16, 20/20, and 20/25 or better was achieved in 1.2% (2 eyes), 65.5% (112 eyes), and 85.4% (146 eyes), respectively. The percentage of eyes with postoperative SE within ±0.5 D and ±1.0 D of planned SE was 71% and 93%, respectively. None of the eyes lost 2 or more lines of CDVA. The rate of stromal haze, managed successfully with topical steroids only, was 4.8%., Conclusion: High-myopic PRK with application of mitomycin-C in the eyes at risk of developing ectasia because of high preoperative PTA was demonstrated to be a safe and effective alternative to the LASIK procedure.

Background and Purpose- Acute ischemic strokes under vitamin K antagonist (VKA) treatment are not uncommon, but intravenous thrombolysis (IVT) is not recommended for international normalized ratio (INR) >1.7 because of the excess bleeding risk. However, VKA-induced anticoagulation can be easily reversed by IV infusions of 4-factor prothrombin complex concentrate bolus and vitamin K. Our pilot study aimed to determine whether IVT immediately after anticoagulation reversal could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Methods- Consecutive acute ischemic stroke patients, otherwise eligible for IVT except for VKA intake and INR >1.7, were given IVT after infusing 4-factor prothrombin complex concentrate and vitamin K. Safety and efficacy were assessed clinically and by cerebral imaging at 24 hours. Results- Twenty-six patients (age, 77.8±12.8 years; atrial fibrillation, 84.6%; initial National Institutes of Health Stroke Scale, 11.6±5.6) were prospectively included. INR values were 2.3±0.6 initially and 1.3±0.2, 5 minutes postreversal. No symptomatic intracranial hemorrhage or thrombotic events occurred during the first 3 days. One patient developed major systemic hemorrhoidal bleeding that required blood transfusion; 61.5% of the patients were independent (modified Rankin Scale score of ≤2) at 3 months. Conclusions- A reversal strategy of 4-factor prothrombin complex concentrate bolus and vitamin K before IVT could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Well-designed, randomized controlled trials are warranted to confirm these preliminary findings.

The use of anticoagulants in patients with cancer is challenging as several co-morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug interactions with concomitant anti-neoplastic therapies may lead to PK variability resulting in increased risk of thrombosis or bleeding. Data on the management of patients with cancer-associated thrombosis (CAT) in real life are scarce since patients with cancer presenting with significant comorbidities tend to be excluded from large trials. This review is mostly based on case-reports and pharmacokinetics in an attempt to provide oncologists, with relevant orientation based on our best knowledge to date. Overall, low-molecular-weight heparins (LMWH) are the preferred option for the long-term prophylaxis and treatment of CAT as their benefit-risk was shown superior to vitamin K antagonists (VKA). Direct oral anticoagulants (DOAC) may represent an alternative to LMWH provided that a favorable benefit-risk in patients with CAT is evidenced in the future. We recommend a systematic risk-assessment including body composition, multiple medication, and renal function. Moreover a systematic and early discussion between pharmacist and oncologist should optimize the benefit-risk ratio for each patient., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Human T-lymphotropic virus type 1 (HTLV-1) has been discovered in 1980 and has been linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique over 25 years., Methods: Martinique is a Caribbean French West Indies island deserved by a unique Neurology Department involved in HAM/TSP diagnosis and management. A registry has been set up since 1986 and patients diagnosed for a HAM/TSP were prospectively registered. Only patients with a definite HAM/TSP onset between 1986 and 2010 were included in the present study. The 25-year study time was stratified in five-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. Age-standardized rates were calculated using the direct method and the Martinique population census of 1990 as reference. Standardized incidence rate ratios with 95% CIs and P trends were assessed from simple Poisson regression models. Number of HTLV-1 infection among first-time blood donors was retrospectively collected from the central computer data system of the Martinique blood bank. The HTLV-1 seroprevalence into this population has been calculated for four 5-year periods between 1996 and 2015., Results: Overall, 153 patients were identified (mean age at onset, 53+/-13.1 years; female:male ratio, 4:1). Crude HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010 periods were 10.01 (6.78-13.28), 13.02 (9.34-16.70), 11.54 (8.13-14.95), 4.27 (2.24-6.28) and 2.03 (0.62-3.43). Age-standardized 5-year incidence rates significantly decreased by 69% and 87% in 2001-2005 and 2006-2010 study periods. Patients characteristics did not differ regarding 1986-2000 and 2001-2010 onset periods. Between 1996-2000 and 2011-2015 study periods, the HTLV-1 seroprevalence significantly decreased by 63%., Conclusion: Martinique faces a sudden and rapid decline of HAM/TSP incidence from 2001 in comparison to 1986-2000 periods. Reduction of HTLV-1 seroprevalence, that may result from transmission prevention strategy, could account for HAM/TSP incidence decrease.

Background: Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS)., Methods and Results: Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP)., Conclusions: As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events.

Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 [4.06-10.64] (p = 1.73 10 -14 ). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without [72 + 13 vs 91 + 21 UI/dL; p = 1.86 10 -6 , mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively]. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.

Background and Purpose: Carotid bulb diaphragm (CBD) has been described in young carotid ischemic stroke (CIS) patients, especially in blacks. However, the prevalence of CBD in CIS patients is unknown, and whether CBD is a risk factor for CIS remains unclear. We assessed the association between CBD and incident CIS in a population-based study., Methods: We selected all young (<55 years) CIS patients from a 1-year population-based cohort study in the Afro-Caribbean population of Martinique in 2012. All patients had a comprehensive work-up including a computed tomographic angiography. We calculated CIS associated with ipsilateral CBD incidence with 95% confidence intervals using Poisson distribution. We then selected age- and sex-matched controls among young (<55 years) Afro-Caribbean stroke-free patients admitted for a road crash who routinely had computed tomographic angiography. Odds ratio (ORs) were calculated by conditional logistic regression adjusted for hypertension, dyslipidemia, diabetes and smoking., Results: CIS associated with ipsilateral CBD incidence was 3.8 per 100 000 person-years (95% confidence interval, 1.4-6.1). Prevalence of ipsilateral CBD was 23% in all CIS and 37% in undetermined CIS patients. When restricted to undetermined CIS, CBD prevalence was 24 times higher than that in controls (adjusted OR, 24.1; 95% confidence interval, 1.8-325.6)., Conclusions: CBD is associated with an increased risk of ipsilateral CIS in young Afro-Caribbean population., (© 2016 American Heart Association, Inc.)

This review outlines risk factors of post-laser in situ keratomileusis (LASIK) ectasia that can be detected preoperatively and presents a new metric to be considered in the detection of ectasia risk. Relevant factors in refractive surgery screening include the analysis of intrinsic biomechanical properties (information obtained from corneal topography/tomography and patient's age), as well as the analysis of alterable biomechanical properties (information obtained from the amount of tissue altered by surgery and the remaining load-bearing tissue). Corneal topography patterns of placido disk seem to play a pivotal role as a surrogate of corneal strength, and abnormal corneal topography remains to be the most important identifiable risk factor for ectasia. Information derived from tomography, such as pachymetric and epithelial maps as well as computational strategies, to help in the detection of keratoconus is additional and relevant. High percentage of tissue altered (PTA) is the most robust risk factor for ectasia after LASIK in patients with normal preoperative corneal topography. Compared to specific residual stromal bed (RSB) or central corneal thickness values, percentage of tissue altered likely provides a more individualized measure of biomechanical alteration because it considers the relationship between thickness, tissue altered through ablation and flap creation, and ultimate RSB thickness. Other recognized risk factors include low RSB, thin cornea, and high myopia. Age is also a very important risk factor and still remains as one of the most overlooked ones. A comprehensive screening approach with the Ectasia Risk Score System, which evaluates multiple risk factors simultaneously, is also a helpful tool in the screening strategy.

Background and Purpose: An atypical form of fibromuscular dysplasia located in the internal carotid-bulb (CaFMD) is thought to be uncommon and is poorly described as a cause of ischemic stroke in the young. This study aimed to obtain a better description of CaFMD in Afro-Caribbean population, who could be particularly affected by it., Methods: This study included consecutive patients <55 years consulting at Fort-de-France University Hospital Stroke Center (Martinique, FWI) found to have CaFMD as the only cause after a comprehensive work-up. CaFMD was diagnosed when computed tomographic angiography showed a bulbar spur without calcification., Results: Twenty-five patients with stroke and CaFMD were identified. Computed tomographic angiography showed 2 CaFMD patterns: a thin (n=15) or thick (n=10) spur. Three patients initial computed tomographic angiography images showed a mural thrombus overlying the CaFMD. CaFMD was surgically removed from 7 of 25 and 20 of 25 patients who received antiplatelet therapy; after mean follow-up of 25.3±19.5 months, their respective recurrence rates were 0% and 30%., Conclusions: CaFMD could be a common condition in young Afro-Caribbeans with carotid-territory ischemic stroke. Recurrences were frequent under antiplatelet treatment, while surgical CaFMD removal seemed more effective., (© 2014 American Heart Association, Inc.)

Background and Purpose: Seldom studies are available on trends in stroke incidence in blacks. We aimed to evaluate whether stroke risk prevention policies modified first-ever stroke incidence and outcomes in the black Afro-Caribbean population of Martinique., Methods: Etude Réalisée en Martinique et Centrée sur l'Incidence des Accidents Vasculaires Cérébraux (ERMANCIA) I and II are 2 sequential prospective population-based epidemiological studies. There have assessed temporal trends in first-ever stroke incidence, risk factors, pathological types, and early outcomes in the black Afro-Caribbean population of Martinique comparing two 12-month periods (1998-1999 and 2011-2012). Crude and age-standardized incidence and 30-day outcomes for stroke in the 2 study periods were compared using Poisson regression., Results: We identified 580 and 544 first-ever strokes in the 2 studies. World age-standardized incidence rates decreased by 30.6% in overall (111 [95% confidence interval, 102-120] versus 77 [95% confidence interval, 70-84]). Rate decline was greater in women than in men (34% versus 26%) particularly in women aged 65 to 74 years (-69%) and 75 to 84 years (-43%). Frequencies of hypertension and diabetes mellitus were unchanged, whereas dyslipidemia, smoking, and atrial fibrillation significantly increased. Only ischemic stroke types showed significant rate reduction in overall and in women, incidence rate ratio (95% confidence intervals) of 0.69 (0.50-0.97) and 0.61 (0.42-0.88), respectively. The overall 30-day case-fatality ratio remained stable (19.3%/17.6%), whereas a better 30-day outcome was found (modified Rankin Score, ≤2 in 47%/37.6%; P=0.03)., Conclusions: Over 13 years, there has been a significant decrease (30.6%) in the age-specific first-ever stroke incidence in our Afro-Carribean population. Although prevention policies seem effective, we need to focus on new risk factors limitation and on male population adherence to prevention program., (© 2014 American Heart Association, Inc.)