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.).

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.

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.

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.

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.

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.

Patent Foramen Ovale and the Risk of Cerebral Infarcts in Acute Pulmonary Embolism-A Prospective Observational Study.

BACKGROUND: Pulmonary embolism (PE) is associated with a risk of consecutive paradoxical embolism with brain infarction through a patent foramen ovale (PFO). The aims of this study were to assess the rate of new ischemic brain lesions (IBLs) using magnetic resonance imaging (MRI) during a 12-month follow-up period with anticoagulation and to evaluate the potential relationship with the presence of PFO on transesophageal echocardiography (TEE). SUBJECTS AND METHODS: Seventy-eight patients with acute PE underwent baseline contrast TEE with brain MRI. After the 12-month follow-up, 58 underwent brain MRI. The rates of MRI documenting new IBLs were measured based on the presence of PFO. RESULTS: PFO was detected in 31 patients (39.7%). At baseline MRI, IBL was present in 39 of 78 patients (50%). The presence of IBL was not significantly higher in patients with PFO than in patients without PFO (20 [64.5% patients with PFO] versus 19 [40.4% without PFO] of 39 patients with baseline IBL, P = .063). At the follow-up MRI, in the group with new IBL (9 of 58 patients, 15.5%), the number of patients with PFO was significantly higher than that without PFO (7 [33.3%] versus 2 [5.4%], P = .008). PFO was identified as an independent predictor of new IBL (odds ratio 4.6 [1.6-47.4], P = .008). CONCLUSIONS: The presence of PFO was associated with new IBL in patients with PE. These patients are at a higher risk of ischemic stroke despite effective anticoagulation therapy.

Atrial fibrillation in young ischemic stroke patients: an underestimated cause?

BACKGROUND: Undetected atrial fibrillation (AF) is often suspected as the possible cause in patients with cryptogenic ischemic stroke (IS), especially in elderly population. In young IS patients, the prevalence of AF, particularly paroxysmal form, remains still not enough established. Our aim was to assess the presence of AF in young patients using a long-term electrocardiography (ECG) Holter monitoring. METHODS: The study set consisted of acute IS patients ≤50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study (NCT01541163). In all patients, admission ECG, serum cardiac markers, transesophageal echocardiography, 24-h and 3-week ECG Holter monitoring were performed. RESULTS: Out of 634 enrolled patients in the HISTORY study, 98 were ≤50 years (56 males, mean age 39.7 ± 8.4). In total, AF was detected in 10.2% of patients and 70% of them had a paroxysmal form of AF. The elevated serum cardiac markers were present in 70% of patients with detected AF (p = 0.0001). CONCLUSION: AF was detected in 10.2% of young stroke patients and paroxysmal form of AF prevailed. Using of long-term ECG Holter monitoring improved the detection of AF. Patients with presence of AF had more frequently elevated serum specific cardiac markers.

Outcome predictors in acute basilar artery occlusion.

OBJECTIVE: to identify predictors of good outcome in acute basilar artery occlusion (Bao). Background: acute ischemic stroke (aiS) caused by Bao is often associated with a severe and persistent neurological deficit and a high mortality rate. METHODS: the set consisted of 70 consecutive aiS patients (51 males; mean age 64.5 ± 14.5 years) with Bao. the role of the following factors was assessed: baseline characteristics, stroke risk factors, pre-event antithrombotic treatment, neurological deficit at time of treatment, estimated time to therapy procedure initiation, treatment method, recanalization rate, change in neurological deficit, post-treatment imaging findings. 30- and 90-day outcome was assessed using the modified rankin scale with a good outcome defined as a score of 0­ 3. RESULTS: the following statistically significant differences were found between patients with good versus poor outcomes: mean age (54.2 vs. 68.9 years; p=0.0001), presence of arterial hypertension (52.4% vs. 83.7%; p=0.015), diabetes mellitus (9.5% vs. 55.1%; p=0.0004) and severe stroke (14.3% vs. 65.3%; p=0.0002), neurological deficit at time of treatment (14.0 vs. 24.0 median of national institutes of health Stroke Scale [nihSS] points; p=0.001), successful recanalization (90.0% vs. 54.2%; p=0.005), change in neurological deficit (12.0 vs. 1.0 median difference of nihSS points; p=0.005). Stepwise binary logistic regression analysis identified age (or=0.932, 95% Ci=0.882­0.984; p=0.012), presence of diabetes mellitus (or=0.105, 95% Ci=0.018-0.618; p=0.013) and severe stroke (or=0.071, 95% Ci=0.013-0.383; p=0.002) as significant independent negative predictors of good outcome. CONCLUSIONS: in the present study, higher age, presence of diabetes mellitus and severe stroke were identified as significant independent negative predictors of good outcome.

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.

Acute combined revascularization in acute ischemic stroke with intracranial arterial occlusion: self-expanding solitaire stent during intravenous thrombolysis.

PURPOSE: To investigate the safety and efficacy of the self-expanding Solitaire stent used during intravenous thrombolysis (IVT) for intracranial arterial occlusion (IAO) in acute ischemic stroke (AIS). MATERIALS AND METHODS: Consecutive nonselected patients with AIS with IAO documented on computed tomographic angiography or magnetic resonance angiography and treated with IVT were included in this prospective study. Stent intervention was initiated and performed during administration of IVT without waiting for any clinical or radiologic signs of potential recanalization. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS), and 90-day clinical outcome was assessed by modified Rankin scale (mRS), with a good outcome defined as an mRS score of 0-2. Recanalization was rated by thrombolysis in cerebral infarction (TICI) scale. RESULTS: Fifty patients (mean age, 66.8 y ± 14.6) had a baseline median NIHSS score of 18.0. Overall recanalization was achieved in 94% of patients, and complete recanalization (ie, TICI 3 flow) was achieved in 72% of patients. The mean time from stroke onset to maximal recanalization was 244.2 minutes ± 87.9, with a median of 232.5 minutes. The average number of device passes was 1.5, with a mean procedure time to maximal recanalization of 49.5 minutes ± 13.0. Symptomatic intracerebral hemorrhage occurred in 6% of patients. The median mRS score at 90 days was 1, and 60% of patients had a good outcome (ie, mRS score 0-2). The overall 3-month mortality rate was 14%. CONCLUSIONS: Combined revascularization with the Solitaire stent during IVT appears to be safe and effective in the treatment of acute IAO.

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.

Prior use of antiplatelet therapy can be associated with a higher chance for early recanalization of the occluded middle cerebral artery in acute stroke patients treated with intravenous thrombolysis.

BACKGROUND: The early recanalization (ER) of an occluded cerebral artery is important for clinical improvement in acute ischemic stroke. The aim of the study was to assess the possible association between the prior use of antiplatelets (AP) and ER of occluded middle cerebral artery (MCA) after intravenous thrombolysis (IVT). METHODS: In 146 consecutive acute ischemic stroke patients presenting with occluded MCA and treated with IVT, the ER and incidence of symptomatic intracerebral hemorrhage (SICH) were compared according to the presence or absence of prior AP use. ER was assessed by transcranial Doppler or digital subtraction angiography within 2 h after the end of IVT. RESULTS: Fifty-six patients (28 males, mean age: 69.8 ± 9.8 years) used AP and 90 patients were AP naïve (51 males, mean age: 65.8 ± 12.5 years). Prior AP use was associated with a higher rate of early MCA recanalization (53.6 vs. 29.5% in AP naïve, p = 0.007) and was shown as a predictor of ER (OR: 2.30, 95% CI: 1.14-4.65; p = 0.020) in unadjusted analysis. No difference was found in the occurrence of SICH. CONCLUSION: Prior use of AP was associated with a higher rate of ER of occluded MCA, but with no increase of SICH after IVT.

Coronary artery disease is not associated with stroke recurrence.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of long-term mortality in Europe and it negatively influences the outcome after stroke. However, its influence on stroke recurrence which endangers stroke patients mostly in the first months following stroke, is unclear. Previous studies have found no association between CAD and ischemic stroke recurrence. However, assessment of the relationship was not the primary endpoint of these investigations. The aim of this study was to assess the possible association between CAD and stroke recurrence. PATIENTS AND METHODS: In a hospital-based, retrospective study, the set consisted of 190 patients - 105 patients with a first ever stroke (48 males; age 37-88, mean 70.7±12.5 years) and 85 patients with stroke recurrence (36 males; age 46-94, mean 88.0±9.6 years). CAD was correlated with the following other risk factors (age, sex, occurrence of arterial hypertension, atrial fibrillation, diabetes mellitus, plasma levels of total cholesterol, triglycerides, low-density cholesterol, high-density cholesterol, body mass index, presence of carotid plaques). Logistic regression analysis was used for the statistical evaluation. RESULTS: No significant association was found between CAD and stroke recurrence. Of all of the other observed risk factors, only age showed a significant association with stroke recurrence (OR 1.04, 95% CI: 1.02-1.07). CONCLUSION: The results of the presented study indicate that CAD does not influence stroke recurrence.

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.

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.

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.

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.

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.

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.