Study protocol - Prospective case-control trial - Impact of significant carotid stenosis on retinal perfusion measured with automated retinal oximetry.

BACKGROUND: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

Peak systolic velocity ratio for evaluation of internal carotid artery stenosis correlated with plaque morphology: substudy results of the ANTIQUE study.

Background: Accurate assessment of carotid stenosis severity is important for proper patient management. The present study aimed to compare the evaluation of carotid stenosis severity using four duplex sonography (DUS) measurements, including peak systolic velocity (PSV), PSV ratio in stenosis and distal to stenosis (PSVICA/ICA ratio), end-diastolic velocity (EDV), and B-mode, with computed tomography angiography (CTA), and to evaluate the impact of plaque morphology on correlation between DUS and CTA. Methods: Consecutive patients with carotid stenosis of ≥40% examined using DUS and CTA were included. Plaque morphology was also determined using magnetic resonance imaging. Spearman's correlation and Kendall's rank correlation were used to evaluate the results. Results: A total of 143 cases of internal carotid artery stenosis of ≥40% based on DUS were analyzed. The PSVICA/ICA ratio showed the highest correlation [Spearman's correlation r = 0.576) with CTA, followed by PSV (r = 0.526), B-mode measurement (r = 0.482), and EDV (r = 0.441; p < 0.001 in all cases]. The worst correlation was found for PSV when the plaque was calcified (r = 0.238), whereas EDV showed a higher correlation (r = 0.523). Correlations of B-mode measurement were superior for plaques with smooth surface (r = 0.677), while the PSVICA/ICA ratio showed the highest correlation in stenoses with irregular (r = 0.373) or ulcerated (r = 0.382) surfaces, as well as lipid (r = 0.406), fibrous (r = 0.461), and mixed (r = 0.403; p < 0.01 in all cases) plaques. Nevertheless, differences between the mentioned correlations were not statistically significant (p > 0.05 in all cases). Conclusion: PSV, PSVICA/ICA ratio, EDV, and B-mode measurements showed comparable correlations with CTA in evaluation of carotid artery stenosis based on their correlation with CTA results. Heavy calcifications and plaque surface irregularity or ulceration negatively influenced the measurement accuracy.

Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction.

Influenza virus causes severe respiratory infection in humans. Current antivirotics target three key proteins in the viral life cycle: neuraminidase, the M2 channel and the endonuclease domain of RNA-dependent-RNA polymerase. Due to the development of novel pandemic strains, additional antiviral drugs targetting different viral proteins are still needed. The protein-protein interaction between polymerase subunits PA and PB1 is one such possible target. We recently identified a modified decapeptide derived from the N-terminus of the PB1 subunit with high affinity for the C-terminal part of the PA subunit. Here, we optimized its amino acid hotspots to maintain the inhibitory potency and greatly increase peptide solubility. This allowed thermodynamic characterization of peptide binding to PA. Solving the X-ray structure of the peptide-PA complex provided structural insights into the interaction. Additionally, we optimized intracellular delivery of the peptide using a bicyclic strategy that led to improved inhibition in cell-based assays.

Correlation between retinal oxygen saturation and the haemodynamic parameters of the ophthalmic artery in healthy subjects.

PURPOSE: The aim of the study was to obtain the values of oxygen saturation in retinal vessels and ophthalmic blood flow parameters in a healthy Caucasian population and assess whether the oximetry parameters are affected by the flow rate or the vascular resistance. METHODS: The spectrophotometric retinal oximetry and colour Doppler imaging (CDI) of retinal vessels were successfully performed with 52 healthy subjects (average age 29.7 ± 5.6 years). The retinal oximeter simultaneously measures the wavelength difference of haemoglobin oxygen saturation in retinal arterioles and venules. The arteriolar and venular saturation in both eyes was measured. The peak systolic (PSV) end diastolic (EDV) velocities, resistive (RI) and pulsatility (PI) indices were obtained for both eyes using CDI in the ophthalmic artery. A paired t-test and two sample t-tests were used for statistical analyses. The correlation was assessed using the Pearson coefficient correlation. RESULTS: The mean oxygen saturation level was 96.9 ± 3.0% for the retinal arterioles and 65.0 ± 5.1% for the retinal venules. The A-V difference was 31.8 ± 4.6%. The mean of the measured haemodynamic parameters was PSV 46.6 ± 9.4 cm/s, EDV 12.0 ± 3.5 cm/s, PI 1.68 ± 0.38 and RI 0.74 ± 0.05. No significant difference in oxygen saturation and haemodynamic parameters was found between the left and the right eyes or the dominant and non-dominant eye. The oximetry and ultrasound values were sex independent. The Pearson correlation coefficient demonstrated a significant yet weak negative correlation between A-V difference and RI (r = -0.321, p = 0.020). CONCLUSIONS: A negative correlation between A-V difference and resistance index was observed, suggesting that reduced oxygen consumption may reflect the increased vascular tone of the ophthalmic vessels, which is likely determined by autoregulatory mechanisms.

Retinal oxygen saturation is associated with HbA1c but not with short-term diabetes control, internal environment, smoking and mild retinopathy - ROXINEGLYD study.

PURPOSE: Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions. METHODS: Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2 . RESULTS: Wilcoxon signed-rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found. CONCLUSION: This study confirmed the association of venous SatO2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.

Evaluation of the insertion parameters and complications of the i-gel Plus airway device for maintaining patent airway during planned procedures under general anaesthesia: a protocol for a prospective multicentre cohort study.

INTRODUCTION: Supraglottic airway devices represent a less invasive method of airway management than tracheal intubation during general anaesthesia. Their continued development is focused mainly on improvements in the insertion success rate and minimalisation of perioperative and postoperative complications. The i-gel Plus is a novel, anatomically preshaped supraglottic airway device which achieves a perilaryngeal seal due to a non-inflatable cuff made of a soft thermoplastic elastomer. The purpose of this cohort study is to assess the success rate of the i-gel Plus use during elective procedures under general anaesthesia, its intraoperative performance, and the degree of postoperative complications. METHODS AND ANALYSIS: This is a multicentre, prospective, interventional cohort study. The enrolment will take place in seven centres in four European countries. We plan to enrol 2000 adult patients in total, who are scheduled for elective surgery under general anaesthesia, and with an indication for use of a supraglottic airway device for management of their airway. The study is projected to run over a period of 18 months. The primary outcome of the study is the total success rate of the i-gel Plus insertion in terms of successful ventilation and oxygenation through the device. Secondary outcomes include perioperative parameters, such as insertion time, seal/leak pressures, number of insertion attempts and postoperative adverse events and complications. Postoperative follow-up will be performed at 1 hour, 24 hours in all patients, and for selected patients at 3 and 6 months. ETHICS AND DISSEMINATION: The cohort study has received the following ethical approvals: General University Hospital Prague, University Hospital Olomouc, University Military Hospital Prague, University Hospital Barcelona, University Hospital Lodz, Antrim Area Hospital, Craigavon Area Hospital, Office for Research Ethics Committees Northern Ireland. The results will be published in peer-reviewed journals and presented at relevant anaesthesia conferences. TRIAL REGISTRATION NUMBER: ISRCTN86233693;Pre-results.

Socioeconomic status and lifestyle in young ischaemic stroke patients: a possible relationship to stroke recovery and risk of recurrent event.

OBJECTIVES: Socioeconomic status (SES) and lifestyle have impact on recovery after ischaemic stroke (IS) and on risk of recurrent ischaemic stroke (RIS) in elderly patients. With regard to currently available limited data on young people, we aimed to assess SES and parameters of lifestyle and evaluate their relationship to stroke recovery and risk of RIS in young patients. METHODS: We analysed consecutive young IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischaemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). Data were acquired from structured a self-evaluating multiple-choice questionnaire. Clinical outcome was assessed using the Modified Rankin Scale (MRS) after 3 months with score 0-1 for excellent outcome. RESULTS: Data were obtained from 297 (163 males, mean age 39.6 ± 7.8 years) young patients. Patients with MRS 0-1 (237, 79.8%) did not differ in SES except university education (21.1 vs. 3.3%; p = 0.001), less smoked (16.5 vs. 58.3%; p < 0.001), more of them did regular sport activities (79.1 vs. 51.6%; p = 0.02) and passed regular preventive medical checks (45.6 vs. 24.2%; p = 0.01). Twelve (4%) patients suffered from RIS during a follow-up with median of 25 months. They did not differ in SES but had higher body mass index (31.6 vs. 26.7; p = 0.007), reported less regular sport activities (16.7 vs. 73.0%; p < 0.001) and less regular medical checks (8.3 vs. 40.0%; p = 0.001). CONCLUSION: In young patients, SES had no relationship to clinical outcome after IS and to risk of RIS except education level. Some parameters of health lifestyle were presented more in patients with excellent outcome and without RIS during the follow-up.

Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors.

The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg2+ or Mn2+ ions located in the enzyme's catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin to be potent inhibitors. Through structural analysis, we identified the presence of a 3',4'-dihydroxyphenyl moiety as a crucial feature for sub-micromolar inhibitory activity. Here, we report results from a subsequent investigation exploring structural changes at the C-7 and C-8 positions of luteolin. Experimental IC50 values were determined by AlphaScreen technology. The most potent inhibitors were C-8 derivatives with inhibitory potencies comparable to that of luteolin. Bio-isosteric replacement of the C-7 hydroxyl moiety of luteolin led to a series of compounds with one-order-of-magnitude-lower inhibitory potencies. Using X-ray crystallography, we solved structures of the wild-type PA-N-terminal domain and its I38T mutant in complex with orientin at 1.9 Å and 2.2 Å resolution, respectively.

Brain Imaging Findings and Response to Intravenous Thrombolysis in Posterior Circulation Stroke.

INTRODUCTION: Intravenous thrombolysis (IVT) is a standard treatment for both anterior circulation ischaemic stroke (ACIS) and posterior circulation ischaemic stroke (PCIS). Our aim was to evaluate the predictors for a good clinical outcome and intracerebral haemorrhage (ICH) in patients undergoing posterior circulation IVT based on the initially performed CT or MR imaging. METHODS: The study cohort consisted of 1643 consecutive patients with acute ischaemic stroke (1440 ACIS, 203 PCIS cases) who underwent IVT. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) I protocol. Clinical outcome was assessed using the modified Rankin scale (mRS). Early ischaemic signs and pre-existing structural signs were assessed. RESULTS: Good clinical outcomes (mRS 0-1) were noted in 45.3% of patients with PCIS, with a mortality rate of 14.8%. ICH was noted in 8.3%, and a large haemorrhage was found in 2.4% of patients. Some early ischaemic signs and pre-existing structural signs on initial CT/MR imaging correlated significantly with the 90-day clinical outcome. CONCLUSIONS: Early ischaemic signs and pre-existing structural signs should be considered during the assessment of patients with PCIS eligible for IVT. Tissue hypoattenuation on initial CT scans correlates with an increased risk of death. Similarly to anterior circulation, atrophy on initial MRI may negatively predict good clinical outcome in posterior circulation.

Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients.

INTRODUCTION: In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients. METHODS: The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification. RESULTS: Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510-24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000). CONCLUSION: AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Young cryptogenic ischemic stroke: A descriptive analysis of clinical and laboratory characteristics, outcomes and stroke recurrence.

BACKGROUND AND PURPOSE: Ischemic strokes (IS) occur also in young adults and despite an extensive work-up the cause of IS remains very often cryptogenic. Thus, effectiveness of secondary prevention may be unclear. We aimed to analyze a relationship among vascular risk factors (VRF), clinical and laboratory parameters, outcomes and recurrent IS (RIS) in young cryptogenic IS (CIS) patients. SUBJECTS AND METHODS: The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). All analyzed patients underwent transesophageal echocardiography, 24-h and 3-week ECG-Holter to assess cause of IS according to the ASCOD classification. Recurrent IS (RIS) was recorded during a follow-up (FUP). RESULTS: Out of 294 young enrolled patients, 208 (70.7%, 113 males, mean age 41.6 ± 7.2 years) were identified as cryptogenic. Hyperlipidemia (43.3%), smoking (40.6%) and arterial hypertension (37.0%) were the most frequent VRF. RIS occurred in 7 (3.4%) patients during a mean time of FUP 19 ± 23 months. One-year risk of RIS was 3.4% (95%CI: 1.4-6.8%). Patients with RIS were older (47.4 vs. 41.1 years, p = 0.007) and more often obese (71.4 vs. 19.7%, p = 0.006), and did not differ in any of other analyzed parameters and VRF. Multivariate logistic regression analysis showed obesity (OR: 9.527; 95%CI: 1.777-51.1) and the previous use of antiplatelets (OR: 15.68; 95%CI: 2.430-101.2) as predictors of recurrent IS. CONCLUSION: Despite a higher presence of VRF in young CIS patients, the risk of RIS was very low. Obesity and previous use of antiplatelet therapy were found the only predictors of RIS.

Risk of recurrent ischemic stroke in young cryptogenic patients with embolic stroke of undetermined source.

INTRODUCTION: Elderly cryptogenic ischemic stroke (IS) patients with embolic stroke of undetermined source (ESUS) have a high risk of recurrent IS (RIS) compared to other stroke subtypes. In young ESUS patients, different sources of embolism may be a cause and the risk of RIS remains not enough established. The aim was to assess and compare risk of RIS between ESUS and non ESUS patients <50 years. METHODS: The study set consisted of young acute IS patients <50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). In all analyzed patients, the brain ischemia was confirmed on CT or MRI. All patients underwent identical diagnostic protocol including TEE and long-term ECG-Holter. Cause of IS was assessed according to the ASCOD classification. RESULTS: Of 320 enrolled patients <50 years, 219 (68.4%) were identified as cryptogenic (119 males, mean age 41.4 ±â€¯7.2 years) and 122 (38.1%) patients fulfilled the ESUS criteria. During the follow-up with a median of 34 months, three (2.5%) ESUS and 5 (5.2%) non-ESUS patients suffered from RIS (p = .471). One-year risk of RIS was 0.008 (95% CI: 0-0.025) for ESUS and 0.036 (95% CI: 0-0.076) for non-ESUS patients (p = .262). CONCLUSION: The risk of RIS was very low in ESUS patients and did not differ from those with non-ESUS. Our finding may indicate that antiplatelet therapy can be effective in the secondary prevention in young ESUS patients if high-risk sources of embolization are excluded extensively.

Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis associated with multiple sclerosis in a 6-month follow-up.

PURPOSE: Optic neuritis (ON) is an inflammatory demyelinating disorder of the optic nerve, which can be the first manifestation of multiple sclerosis (MS). The main goal was to assess changes in the retinal nerve fibre layer (RNFL) and in retinal oxygen saturation [arterial (AS), venous (VS) and arterio-venous (A-V) difference] in the affected and unaffected eye. METHODS: Fifty patients with ON due to MS within 3 months of onset of symptoms were enrolled (17 males, mean age 35.3). All patients were examined at baseline (V1) and after 6 months (V2) using optical coherence tomography (OCT) to get RNFL values; automatic retinal oximetry to obtain saturation values; and ultrasound to exclude arterial stenosis, and orbital colour Doppler imaging was performed in the ophthalmic artery. RESULTS: At V1, AS was significantly increased in affected eye compared to unaffected eye (99.5% versus 98.0%, p = 0.03). Significant decrease in A-V difference from baseline was detected in both eyes for ON eye: 32.0% versus 29.0%, p = 0.004; for fellow eye: 31.4% versus 30.0%, p = 0.04. We did not observe any changes in retinal vessel diameter. There were no changes observed in blood flow in ophthalmic artery. At V1, there were no significant differences in RNFL, and significant loss of RNFL was confirmed in the affected eye at V2 (95 µm versus 86 µm, p = 0.0002) and in comparison with the fellow eye (86 µm versus 94 µm, p = 0.0002). There were no correlations between RNFL and saturation values at V1, although at V2, there was a negative correlation between the RNFL and AS (Spearman's rho = -0.480, p = 0.003) and between the RNFL and VS (rho = -0.620, p = 0.00007). CONCLUSION: Retinal oximetry is altered in both eyes in MS patients with unilateral ON. During the course of the disease, the retinal oxygen consumption decreases to a different degree in each eye and this change is not completely followed by changes in the RNFL thickness, suggesting either sub-clinical ON or systemic effects in the clinically unaffected eye. Since this is the first and initial longitudinal evaluation of the saturation changes in MS patients, the clinical value of these findings needs to be deeper evaluated in the future studies.

Low Levels of Glycemia within the First 48 Hours after Mechanical Thrombectomy for Acute Ischemic Stroke May be Associated with Better Clinical Outcome.

INTRODUCTION: Many different factors may have an impact on clinical outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aimed to investigate levels of serum glycemia (GLY) within the first 48 hours after MT. SUBJECTS AND METHODS: Consecutive AIS patients were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale with a score 0-2 for good outcome. Presence of symptomatic intracerebral hemorrhage was assessed according to the SITS- MOST criteria. RESULTS: In total, 868 patients (442 males, mean age 69.7 ± 12.2 years) with a median of admission NIHSS 17 points were enrolled in the study and 253 (29.1%) of them were diabetics. Recanalization was reached in 758 (87.3%) patients. Patients with good outcome (412, 47.5%) had lower median of GLY (6.5 versus 7.4 mmol/L, P < .0001) within the first 48 hours after MT. Similar results were found also in diabetics (8.1 versus 9.6 mmol/L, P < .0001) and in patients with achieved recanalization (6.5 versus 7.5 mmol/L, P < .0001). Multivariate regression analysis with adjustment for potential confounders showed median of GLY (P = .0001, odds ratio: 0.830, 95% confidence interval: 0.755-0.913) as a predictor of good outcome after MT. CONCLUSION: Lower levels of GLY within the first 48 hours after MT may be associated with better functional outcome after 3 months.

Intravenous Thrombolysis in Posterior Circulation Stroke.

Background: Intravenous thrombolysis (IVT) is a standard treatment for both anterior circulation ischemic stroke (ACIS) and posterior circulation ischemic stroke (PCIS). PCIS is a clinical syndrome associated with ischemia-related changes in the territory of the posterior circulation arteries. Embolism is the most common stroke mechanism in posterior circulation. PCIS represents 12-19% of all IVT-treated strokes. Methods and Results: We searched the PubMed database for assessments of intracerebral hemorrhage (ICH) and clinical outcome in PCIS patients treated with IVT. ICH occurs in 0-6.9% of posterior ischemic stroke depending on the definition of symptomatic ICH, and any ICH in 17-23.4% of posterior ischemic stroke. For patients with PCIS, 38-49% have a favorable outcome (mRS 0-1) after IVT. Better clinical outcomes occur more often in patients with PCIS than in those with ACIS. The mortality rate among PCIS patients treated with IVT ranges from 9 to 19%; it does not differ significantly between PCIS and ACIS. Conclusions: Up to date, no data about PCIS and IVT are available from RTCs. Based on limited results from retrospective clinical studies and case series, IVT is safer for use in PCIS than in ACIS. Patients with brainstem ischemia, vertebral artery occlusion, and absence of basilar or posterior cerebral artery occlusion could be considered for treatment with IVT even in borderline cases. Time to IVT in PCIS seems to be a less crucial factor than in ACIS. IVT for PCIS may be beneficial even after 4.5 h from symptom onset.

Impact of blood pressure levels within first 24 hours after mechanical thrombectomy on clinical outcome in acute ischemic stroke patients.

INTRODUCTION: Despite early management and technical success of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), not all patients reach a good clinical outcome. Different factors may have an impact and we aimed to evaluate blood pressure (BP) levels in the first 24 hours after MT. METHODS: Consecutive AIS patients treated with MT were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale (mRS) with a score 0-2 for good outcome. The presence of symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Of 703 treated patients, completed BP levels were collected in 690 patients (350 males, mean age 71±13 years) with median of admission NIHSS 17 points. Patients with mRS 0-2 had a lower median of systolic BP (SBP) compared with those with poor outcome (131 vs 140 mm Hg, P<0.0001). The rate of SICH did not differ between the patients with a median of SBP <140 mm Hg and ≥140 mm Hg. (5.1% vs 5.1%, P=0.980). Multivariate regression analysis with adjustment for potential confounders showed a median of distolic BP (P=0.024, OR: 0.977, 95% CI: 0.957 to 0.997) as a predictor of good functional outcome after MT, and a median of maximal SBP (P=0.038; OR: 0.990, 95% CI: 0.981 to 0.999) in the patients with achieved recanalization. CONCLUSION: Lowering of BP within the first 24 hours after MT may have a positive impact on clinical outcome in treated patients.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Author Correction: Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.

In the original publication of the article, there was a switched order of author names.

Mechanical Thrombectomy in Patients with Acute Ischemic Stroke on Anticoagulation Therapy.

INTRODUCTION/PURPOSE: Mechanical thrombectomy (MT) for acute ischemic stroke (IS) can be performed also in patients on anticoagulation therapy (AT); however, sufficient and reliable data about safety and efficacy of MT are still missing. Thus, we aimed to compare these parameters between patients treated on AT and without AT. MATERIALS AND METHODS: All consecutive IS patients treated with MT using stent retrievers were included in the retrospective analysis. Neurological deficit was scored using National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale with a score 0-2 for good outcome. Recanalization was rated using Thrombolysis in Cerebral Infarction (TICI) scale. Symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Out of 703 patients treated with MT, 88 (12.5%) patients (46% males, mean age 75.5 ± 11.8 years) were on AT with an admission median NIHSS of 17 points. Recanalization (TICI 2b-3) was achieved in 80% and complete (TICI 3) in 65% of patients on AT and in 80 and 65% of patients without AT (p-1.000). SICH after MT was detected in 9% of AT and 5% of non-AT patients (p-0.136). Good outcome was present in 36% of AT patients (p-0.03). AT patients with poor outcome had more frequently atrial fibrillation (93%, p-0.005), higher admission NIHSS (17, p-0.004) and higher rate of SICH (14.5%, p-0.047). CONCLUSION: MT seems to be safe also in patients on AT. Poor outcome may be related to higher admission NIHSS, higher rate of SICH and presence of atrial fibrillation.

Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.

Intravenous thrombolysis (IVT) is a standard treatment for anterior (ACS) and posterior circulation stroke (PCS). However, due to the low occurrence of PCS and of intracranial hemorrhage (ICH) in PCS, the knowledge about ICH predictors following IVT in PCS is sparse. Our aim was to identify predictors for ICH following IVT in PCS. The set consisted of 1281 consecutive ischemic stroke (IS) patients treated with IVT, out of which 158 (103 males; mean age 65.6 ± 12.3 years) had PCS. Collected data include baseline characteristics, common stroke risk factors, pre-medication, stroke severity, admission blood glucose level, blood pressure and treatment with intravenous antihypertensive therapy before and during IVT, occlusion of arteries, recanalization rate, time to treatment, and clinical outcome at day 90. Overall, 11 (7%) patients had ICH. Atrial fibrillation (p = 0.004), neurological deficit at time of treatment in the National Institutes of Health Stroke Scale (p = 0.016), decreased level of consciousness (p = 0.003), occlusion of basilar artery (p = 0.007), occlusion of PCA (p = 0.001), and additional endovascular therapy (p = 0.001) were identified by logistic regression analysis as significant predictors for ICH in PCS. Patients with ischemic lesion in the brainstem, occlusion of vertebral artery, or absence of basilar and posterior cerebral artery occlusion might be considered for treatment with IVT even in borderline cases. Those patients seem to have less frequently favorable outcomes without an increase in ICH rate. Time to IVT in PCS seems not to influence ICH risk or chances for favorable outcomes as significantly as it does in ACS.