Thrombectomy with embed aspiration in acute ischaemic stroke.

BACKGROUND: In addition to stent retrievers, direct aspiration has become a reasonable thrombectomy strategy. OBJECTIVES: We carried out the thrombectomy by guiding the aspiration catheter fully over the clot and performing immediate manual aspiration; we call this procedure "embed aspiration". METHODS: In this prospective, non-randomised, single-centre study, we included all patients treated at a high volume-of-care stroke centre between 2017 and 2018 for the TRIANA (Thrombectomy in Andalusia using Aspiration) registry. Thrombectomy was carried out by embed aspiration. Patients were classified according to the success (eTICI 2b67-2c-3) or failure (eTICI 0-1-2a-2b50) of the procedure. Baseline clinical data and outcomes were compared, and multivariate analysis was performed. RESULTS: The embed aspiration technique was used in 370 patients. Treatment was successful in 90.3% of patients. Mean puncture-to-recanalisation time was 25 minutes. The overall rate of good outcomes (mRS 0-2) at 3 months was 64%. CONCLUSIONS: This study supports real-life evidence that standardised embed aspiration may be an alternative to stent retrievers for thrombectomy.

Benefits in quality of life following an obstructive sleep apnea screening and treatment program in patients with acute ischemic stroke. / Beneficios en la calidad de vida de un programa de cribado y tratamiento de apnea obstructiva del sueño en pacientes con ictus isquémico agudo.

INTRODUCTION: Obstructive sleep apnea (OSA) has been proposed as a factor that worsens stroke prognosis. Our aim was to determine if an OSA intervention could improve quality of life (QOL, first objective) and modified Rankin score (mRS, second objective). PATIENTS AND METHODS: The intervention group of this quasi-experimental study included patients with acute ischemic stroke <72 hours who underwent polygraphy and Continuous Positive Airway Pressure (CPAP) and hygienic-dietary measures if required. The control group followed routine clinical practice. The Short Form 36 Health Survey (SF-36) and mRS were applied at the sixth month after stroke in both groups. RESULTS: Fifty-five vs. sixty-two patients were included in the intervention and control group respectively. In the intervention group, 64.71% of patients accepted the proposed CPAP (16 cases with a good adherence). An improvement in SF-36 items was detected in the intervention group: physical functioning (p = 0.008), role physical (p = 0.002), bodily pain (p = 0.008), general health (p <0.001), vitality (p = 0.001) and role emotional (p = 0.015). In a per-protocol analysis, all these improvements were verified in the group of patients treated with good CPAP adherence (p < 0.05 in all the same SF-36 items). The percentage of patients with physical component summatory = 50 was higher in the intervention group (p = 0.003). There were no differences in the median of mRS (p = 0.262). CONCLUSIONS: Although more evidence is needed, a significant improvement in QOL was suggested after our OSA intervention, particularly in patients with good CPAP adherence.

TITLE: Beneficios en la calidad de vida de un programa de cribado y tratamiento de apnea obstructiva del sueño en pacientes con ictus isquémico agudo.Introducción. La apnea obstructiva del sueño (AOS) se ha propuesto como un factor de mal pronóstico en el ictus. Pretendemos determinar si una intervención sobre la AOS puede mejorar las escalas de calidad de vida (primer objetivo) y de discapacidad (segundo objetivo). Pacientes y métodos. El grupo de intervención de este estudio cuasi experimental incluye a pacientes con ictus isquémico agudo menor de 72 horas de evolución a quienes se les realizó poligrafía, así como presión positiva continua en las vías aéreas (CPAP) y medidas higienicodietéticas si se requerían. En el grupo de control se siguió la práctica clínica habitual. Se aplicaron las escalas Short Form 36 Health Survey (SF-36) y modified Rankin Score (mRS) en el sexto mes del ictus en ambos grupos. Resultados. Se incluyó a 55 y a 62 pacientes en el grupo de intervención y en el de control, respectivamente. En el grupo de intervención, el 64,71% de los pacientes aceptó la CPAP indicada (16 casos con buena adhesión). Se detectó una mejoría en los ítems de la escala SF-36 en el grupo de intervención: funcionamiento físico (p = 0,008), rol físico (p = 0,002), dolor corporal (p = 0,008), salud general (p menor de 0,001), vitalidad (p = 0,001) y rol emocional (p = 0,015). En un análisis por protocolo, todas estas mejorías se comprobaron en el grupo de pacientes tratados con CPAP con buena adhesión (p menor de 0,05 en todos los ítems de la SF-36). El porcentaje de pacientes con el sumatorio del componente físico = 50 fue más alto en el grupo de intervención (p = 0,003). No había diferencias en la mediana de la mRS (p = 0,262). Conclusiones. Aunque se necesitan más evidencias, nuestro estudio sugiere una mejoría significativa de la calidad de vida tras nuestra intervención en la AOS, especialmente en pacientes con buena adhesión a la CPAP.

Antithrombotic Treatment after Carotid Stenting in Patients with Concomitant Atrial Fibrillation.

BACKGROUND AND PURPOSE: Antithrombotic therapy following carotid artery stent placement with concomitant atrial fibrillation is not well-established. Our aim was to assess the safety and efficacy of the combination of direct oral anticoagulants and a P2Y12 inhibitor at 30 days after carotid artery stent placement in patients with atrial fibrillation. MATERIALS AND METHODS: We designed an observational single-center study including patients who underwent carotid artery stent placement with concomitant atrial fibrillation. We studied 3 groups according to antithrombotic therapy: 1) the direct oral anticoagulants plus clopidogrel (DC) group: receiving direct oral anticoagulants plus a P2Y12 inhibitor; 2) the triple therapy group: anticoagulation and dual antiplatelet therapy; and 3) the dual antiplatelet therapy group: following dual antiplatelet therapy alone. The safety outcome was a major or clinically relevant non-major bleeding event at the first month. The efficacy outcomes were the thromboembolic events (myocardial infarction, stroke, systemic embolism, or stent thrombosis). RESULTS: Of 959 patients with carotid artery stent placement, 91 met the inclusion criteria, including 24 patients in the DC group, 42 patients in the triple therapy group, and 25 in the dual antiplatelet therapy group. The mean age was 72.27 (SD, 8.1 ) years, with similar baseline characteristics. The median CHA2DS2-VASc score for each group was 6 (interquartile range = 5-6), 5 (interquartile range = 4-6), and 5 (interquartile range = 4-6), respectively. The median HAS-BLED score was 4 in the 3 groups (P = .17). The primary safety end point was 23.8% in the triple therapy group compared with 4% in the dual antiplatelet therapy group (P = .032), with no bleeding events in the DC group (P = .007). There was 1 stent thrombosis in DC group and a cardioembolic stroke in the dual antiplatelet therapy group (P = .41). CONCLUSIONS: Among patients with carotid artery stent placement with atrial fibrillation, triple therapy confers a high bleeding risk. A regimen of direct oral anticoagulants plus a P2Y12 inhibitor might confer a good safety profile with significantly lower rates of bleeding and optimal efficacy.

Inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico: Documento de consenso y aplicaciones prácticas / Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance

Introducción: Los pacientes, tras un ictus o un ataque isquémico transitorio, presentan un riesgo muy elevado de sufrir nuevos episodios vasculares. La reducción del nivel de colesterol unido a lipoproteínas de baja densidad (cLDL) reduce la incidencia de nuevos episodios, si bien una proporción importante de pacientes no alcanza los objetivos terapéuticos recomendados con los tratamientos hipolipemiantes actuales. El objetivo de este documento de consenso es actualizar el papel de los inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9; alirocumab y evolocumab) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico previo. Métodos: Se realizó una revisión bibliográfica para identificar las principales evidencias sobre el uso de iPCSK9 en estos pacientes y los objetivos terapéuticos recomendados de cLDL. Los resultados se discutieron en 2 reuniones de consenso, que constituyeron la base para la elaboración del documento. Conclusiones: Los iPSCSK9 son eficaces en la reducción del riesgo vascular en prevención secundaria y, específicamente, evolocumab ha demostrado esta reducción en pacientes con ictus isquémico previo. Ambos fármacos han demostrado un buen perfil de seguridad, incluso en pacientes que alcanzaron un nivel de cLDL < 20 mg/dL. En este sentido, en el subestudio de episodios neurocognitivos con evolocumab no se observó ninguna señal de empeoramiento de la función cognitiva en pacientes con nivel muy bajo de cLDL. Con base en estas evidencias, en el documento se presentan recomendaciones prácticas sobre el uso de iPCSK9 para la prevención secundaria y seguimiento de episodios vasculares en pacientes con ictus isquémico previo. (AU)

Introduction: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. Methods: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. Conclusions: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients. (AU)

Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance.

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

Immunological and virological response to initial antiretroviral therapy among older people living with HIV in the Canadian Observational Cohort (CANOC).

OBJECTIVES: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable. METHODS: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/µL, (2) CD4 ≥ 500 cells/µL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL). RESULTS: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted ß = -31 cells/µL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/µL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57-0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05-1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3-0.71) compared with those aged ≤ 30 years. CONCLUSIONS: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.

[Delayed administration of thrombolytic therapy in minor stroke]. / Retraso en la administración de tratamiento trombolítico en el ictus minor.

INTRODUCTION: Minor strokes are considered to be those that present with few symptoms, although up to 40% of them entail long-term disability. The rate of thrombolysis in these patients is also lower than in other strokes. The aim of this study is to explore whether there are any differences in intravenous thrombolysis care times in minor strokes. PATIENTS AND METHODS: We conducted a retrospective review of strokes treated with intravenous thrombolysis at our centre and a comparative analysis of the care times in minor strokes and in the other types. RESULTS: Longer times were found in minor strokes in terms of door-to-CT scan and door-to-needle time. This was not the case, however, for the time from the onset of symptoms to arrival at the hospital. CONCLUSIONS: The presence of few symptoms in minor strokes can make them difficult to recognise and could be a reason for delaying treatment. Training among staff caring for these patients is essential to improve this aspect.

TITLE: Retraso en la administración de tratamiento trombolítico en el ictus minor.Introducción. Se considera ictus minor a aquel que se presenta con escasos síntomas; sin embargo, hasta un 40% presenta discapacidad a largo plazo. La tasa de trombólisis en estos pacientes también es inferior a la del resto de ictus. En este estudio se pretende explorar si existen diferencias en los tiempos de atención en la trombólisis intravenosa en los pacientes con ictus minor. Material y métodos. Revisión retrospectiva de los ictus tratados con trombólisis intravenosa en nuestro centro y análisis comparativo de los tiempos de asistencia entre ictus minor y el resto. Resultados. Se encontraron tiempos más alargados en los casos de ictus minor en cuanto al tiempo puerta-tomografía computarizada y puerta-aguja. No fue así, sin embargo, para el tiempo desde el inicio de los síntomas hasta la llegada al hospital. Conclusiones. La presencia de escasos síntomas en el ictus minor puede hacer difícil su reconocimiento y podría ser un motivo de retraso en el tratamiento. La formación entre el personal que atiende a estos pacientes es fundamental para mejorar este aspecto.

B-type natriuretic peptide over N-terminal pro-brain natriuretic peptide to predict incident atrial fibrillation after cryptogenic stroke.

BACKGROUND AND PURPOSE: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients. METHODS: Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers. RESULTS: From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model. CONCLUSIONS: Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance. / Inhibidores de la proproteína convertasa subtilisina/kexina tipo 9 (iPCSK9) en la prevención secundaria de episodios vasculares en pacientes con ictus isquémico: Documento de consenso y aplicaciones prácticas.

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels <20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

A parsimonious score with a free web tool for predicting disability after an ischemic stroke: the Parsifal Score.

BACKGROUND: Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality. METHODS: Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The "polr" function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6). RESULTS: The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80-76% (discovery-replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90-80% (discovery-replication cohorts); while, the sensitivity was 64-74% (discovery-replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80. CONCLUSIONS: The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort.

Large vessel occlusion is independently associated with atrial fibrillation detection.

BACKGROUND AND PURPOSE: Covert paroxysmal atrial fibrillation (pAF) is the most frequent cause of cardiac embolism. Our goal was to discover parameters associated with early pAF detection with intensive cardiac monitoring. METHOD: Crypto-AF was a multicentre prospective study (four Comprehensive Stroke Centres) to detect pAF in non-lacunar cryptogenic stroke continuously monitored within the first 28 days. Stroke severity, infarct pattern, large vessel occlusion (LVO) at baseline, electrocardiography analysis, supraventricular extrasystolia in the Holter examination, left atrial volume index and brain natriuretic peptide level were assessed. The percentage of pAF detection and pAF episodes lasting more than 5 h were registered. RESULTS: Out of 296 patients, 264 patients completed the monitoring period with 23.1% (61/264) of pAF detection. Patients with pAF were older [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08], they had more haemorrhagic infarction (OR 4.03, 95% CI 1.44-11.22), they were more likely to have LVO (OR 4.29, 95% CI 2.31-7.97) (P < 0.0001), they had a larger left atrial volume index (OR 1.03, 95% CI 1.01-1.1) (P = 0.0002) and they had a higher level of brain natriuretic peptide (OR 1.01, 95% CI 1.0-1.1). Age and LVO were independently associated with pAF detection (OR 1.06, 95% CI 1.00-1.16, and OR 4.58, 95% CI 2.27- 21.38, respectively). Patients with LVO had higher cumulative incidence of pAF (log rank P < 0.001) and more percentage of pAF > 5 h [29.6% (21/71) vs. 8.3% (12/144); OR 4.62, 95% CI 2.11-10.08; P < 0.001]. In a mean follow-up of 26.82 months (SD 10.15) the stroke recurrence rate was 4.6% (12/260). CONCLUSIONS: Large vessel occlusion in cryptogenic stroke emerged as an independent marker of pAF.

Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study.

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

Prevalence and Correlates of Reporting Difficulty Taking Antiretroviral Treatment Among HIV-Positive Illicit Drug Users in Vancouver, Canada: A Longitudinal Analysis.

People living with HIV who use illicit drugs continue to experience high rates of suboptimal treatment outcomes from antiretroviral therapy (ART). Although previous studies have identified important behavioural, social and structural barriers to ART adherence, the effects of patient-level factors have not been fully evaluated. Thus, we sought to investigate the prevalence and correlates of reporting ART was difficult to take among a cohort of illicit drug users in Vancouver, Canada. We accessed data from the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), an ongoing prospective cohort of HIV-positive illicit drug users linked to comprehensive HIV clinical monitoring records. We used generalized linear mixed-effects modeling to identify factors longitudinally associated with periods in which individuals reported they found ART difficult to take. Between December 2005 and May 2014, 746 ART-exposed illicit drug users were recruited and contributed at least one study interview. Finding ART hard to take was reported by 209 (28.0%) participants at baseline, and 460 (61.7%) participants throughout the study period. Patients ingesting a greater daily pill count (adjusted odds ratio [AOR] = 1.12 per pill, 95% confidence interval [CI] 1.08-1.17) and experiencing barriers to healthcare (AOR = 1.64, 95% CI 1.34-2.01) were more likely to report difficulty taking ART. Patients less likely to report satisfaction with their HIV physician (AOR = 0.76, 95% CI 0.58-1.00) and achieve a non-detectable HIV viral load (AOR = 0.62, 95% CI 0.51-0.74) were more likely to report finding ART hard to take. In this community-recruited cohort of ART-exposed illicit drug users, a substantial proportion reported they found HIV treatment hard to take, which was clearly linked to higher dissatisfaction with healthcare experiences and, most importantly, a lower likelihood of experiencing optimal virologic outcomes. Our findings reveal a number of opportunities to improve HIV treatment experiences and outcomes for people who use illicit drugs, including the use of treatment regimens with lower pill burdens, as well as reducing barriers to healthcare access.

Distance to HIV care and treatment adherence: Adjusting for socio-demographic and geographical heterogeneity.

Distance to health services plays an important role in determining access to care and an individual's health. This study aims to examine the relationship between distance to antiretroviral therapy (ART) prescribing physician and adherence to HIV treatment in British Columbia, Canada. Only participants who provided highly accurate locational data for both place of residence and their physician were used in the analysis. Using logistic regression, a multivariable confounder model was created to assess the association between distance and adherence. A geographically weighted logistic regression was also performed to adjust for spatial dependency. There were 1528 participants in the analysis, for a median distance of 17.85km. The final model showed further away from ART prescribing physician had a higher chance of incomplete adherence to ART (adjusted odds ratio 1.31; 95% Confidence Interval 1.04-1.65). Mobile services could potentially increase adherence rates for population residing further away from their ART prescribing physician.

CCL23: a new CC chemokine involved in human brain damage.

BACKGROUND: CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6. METHODS: Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia. RESULTS: Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (ORadj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia. CONCLUSIONS: Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.

Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach.

This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012), with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA-positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies.

The UCP2-866G/A Polymorphism Could be Considered as a Genetic Marker of Different Functional Prognosis in Ischemic Stroke After Recanalization.

Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization. We investigate a hospital-based prospective cohort of patients with acute ischemic stroke due to occlusion of the middle cerebral artery diagnosed by transcranial Doppler who obtained a partial/complete recanalization 24 h after administration of intravenous thrombolysis. The main end point of the study was functional independence defined as modified Rankin Scale 0-2 on day 90. A total of 80 patients were enrolled. The UCP2-866G/A polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism technique (14 genotype A/A (18%), 45 genotype A/G (56%) and 21 genotype G/G (26%). The percentage of patients with good functional outcome at 3 months was significantly higher in patients harboring the A/A genotype than in those with A/G or G/G genotypes (85 vs 41%, p = 0.01). The A/A genotype was found to be an independent marker of good prognosis after adjustment for secondary variables (age, sex, glucose level, NIHSS score at baseline, complete recanalization and early neurological improvement) in a logistic regression analysis (OR 0.05, 95% CI 0.01-0.48, p = 0.01). Our results suggest that the AA genotype of UCP2-866 may predict a better functional outcome in ischemic stroke after recanalization of proximal MCA occlusion.

Proteomic discovery and verification of serum amyloid A as a predictor marker of patients at risk of post-stroke infection: a pilot study.

BACKGROUND: Post-stroke infections occur in 20-36% of stroke patients and are associated with high morbidity and mortality rates. Early identification of patients at risk of developing an infection could improve care via an earlier treatment leading to a better outcome. We used proteomic tools in order to discover biomarkers able to stratify patients at risk of post-stroke infection. METHODS: The post hoc analysis of a prospective cohort study including 40 ischemic stroke patients included 21 infected and 19 non-infected participants. A quantitative, isobaric labeling, proteomic strategy was applied to the plasma samples of 5 infected and 5 non-infected patients in order to highlight any significantly modulated proteins. A parallel reaction monitoring (PRM) assay was applied to 20 additional patients (10 infected and 10 non-infected) to verify discovery results. The most promising protein was pre-validated using an ELISA immunoassay on 40 patients and at different time points after stroke onset. RESULTS: Tandem mass analysis identified 266 proteins, of which only serum amyloid A (SAA1/2) was significantly (p = 0.007) regulated between the two groups of patients. This acute-phase protein appeared to be 2.2 times more abundant in infected patients than in non-infected ones. These results were verified and validated using PRM and ELISA immunoassays, which showed that infected patients had significantly higher concentrations of SAA1/2 than non-infected patients at hospital admission, but also at 1, 3, and 5 days after admission. CONCLUSIONS: The present study demonstrated that SAA1/2 is a promising predictor, at hospital admission, of stroke patients at risk of developing an infection. Further large, multicenter validation studies are needed to confirm these results. If confirmed, SAA1/2 concentrations could be used to identify the patients most at risk of post-stroke infections and therefore implement treatments more rapidly, thus reducing mortality.