Use of escitalopram to prevent depression and cognitive impairments in the acute phase of stroke

The purpose of the study was to comparatively analyze the rate of post-stroke depression and cognitive impairments in escitalopram (cipralex)-treated and untreated (control) patients. Emotional and affective cognitive symptoms, neurological deficit, and day-to-day activity were evaluated over time 1, 3, and 6 months after treatment. The results of the study indicated that escitalopram used to prevent depression in the acute phase of stroke provided a good effect. This drug caused a prompter recovery of cognitive impairments and reduced the pace of development of neurodegenerative disorders underlying the post-stroke 2D (depression and dementia) syndrome. The study group was recorded to have more favorable functional outcomes of stroke and patient mobility indicators associated with lower disability rates

Cerebrolysin as an Early Add-on to Reperfusion Therapy: Risk of Hemorrhagic Transformation after Ischemic Stroke (CEREHETIS), a prospective, randomized, multicenter pilot study

Abstract Background Cerebrolysin could mitigate reperfusion injury and hemorrhagic transformation (HT) in animal models of acute ischemic stroke. Methods This was a prospective, randomized, open-label, parallel-group with active control, multicenter pilot study. Cerebrolysin (30 mL/day over 14 days) was administered concurrently with alteplase (0.9 mg/kg) in 126 patients, whereas 215 control patients received alteplase alone. The primary outcomes were the rate of any and symptomatic HT assessed from day 0 to 14. The secondary endpoints were drug safety and functional outcome measured with the National Institutes of Health Stroke Scale (NIHSS) on day 1 and 14, and the modified Rankin scale (mRS) on day 90. Advanced brain imaging analysis was applied on day 1 and 14 as a marker for in vivo pharmacology of Cerebrolysin. Results Cerebrolysin treatment resulted in a substantial decrease of the symptomatic HT rate with an odds ratio (OR) of 0.248 (95% CI: 0.072–0.851; p = 0.019). No serious adverse events attributed to Cerebrolysin occurred. On day 14, the Cerebrolysin arm showed a significant decrease in the NIHSS score (p = 0.045). However, no difference in the mRS score was observed on day 90. A substantial improvement in the advanced brain imaging parameters of the infarcted area was evident in the Cerebrolysin group on day 14. Conclusions Early add-on of Cerebrolysin to reperfusion therapy was safe and significantly decreased the rate of symptomatic HT as well as early neurological deficit. No effect on day 90 functional outcome was detected. Improvements in the imaging metrics support the neuroprotective and blood–brain barrier stabilizing activity of Cerebrolysin. Trial registration Name of Registry: ISRCTN. Trial Registration Number: ISRCTN87656744 . Trial Registration Date: 16/02/2021

DataSheet1_Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial.XLSX

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair.Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk.Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method.Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%–56.7%; H2, 1.56–2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.</p

DataSheet3_Heterogeneous treatment effects of Cerebrolysin as an early add-on to reperfusion therapy: post hoc analysis of the CEREHETIS trial.docx

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair.Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk.Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method.Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%–56.7%; H2, 1.56–2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.</p

The hemorrhagic transformation index score: a prediction tool in middle cerebral artery ischemic stroke

Abstract Background We aimed to develop a tool, the hemorrhagic transformation (HT) index (HTI), to predict any HT within 14 days after middle cerebral artery (MCA) stroke onset regardless of the intravenous recombinant tissue plasminogen activator (IV rtPA) use. That is especially important in the light of missing evidence-based data concerning the timing of anticoagulant resumption after stroke in patients with atrial fibrillation (AF). Methods We retrospectively analyzed 783 consecutive MCA stroke patients. Clinical and brain imaging data at admission were recorded. A follow-up period was 2 weeks after admission. The patients were divided into derivation (DC) and validation (VC) cohorts by generating Bernoulli variates with probability parameter 0.7. Univariate/multivariate logistic regression, and factor analysis were used to extract independent predictors. Validation was performed with internal consistency reliability and receiver operating characteristic (ROC) analysis. Bootstrapping was used to reduce bias. Results The HTI was composed of 4 items: Alberta Stroke Program Early CT score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), hyperdense MCA (HMCA) sign, and AF on electrocardiogram (ECG) at admission. According to the predicted probability (PP) range, scores were allocated to ASPECTS as follows: 10–7 = 0; 6–5 = 1; 4–3 = 2; 2–0 = 3; to NIHSS: 0–11 = 0; 12–17 = 1; 18–23 = 2; >23 = 3; to HMCA sign: yes = 1; to AF on ECG: yes = 1. The HTI score varied from 0 to 8. For each score, adjusted PP of any HT with 95% confidence intervals (CI) was as follows: 0 = 0.027 (0.011–0.042); 1 = 0.07 (0.043–0.098); 2 = 0.169 (0.125–0.213); 3 = 0.346 (0.275–0.417); 4 = 0.571 (0.474–0.668); 5 = 0.768 (0.676–0.861); 6 = 0.893 (0.829–0.957); 7 = 0.956 (0.92–0.992); 8 = 0.983 (0.965–1.0). The optimal cutpoint score to differentiate between HT-positive and negative groups was 2 (95% normal-based CI, 1–3) for the DC and VC alike. ROC area/sensitivity/specificity with 95% normal-based CI for the DC and VC were 0.85 (0.82–0.89)/0.82 (0.73–0.9)/0.89 (0.8–0.97) and 0.83 (0.78–0.88)/0.8 (0.66–0.94)/0.87 (0.73–1.0) respectively. McDonald’s categorical omega with 95% bias-corrected and accelerated CI for the DC and VC was 0.81 (0.77–0.84) and 0.82 (0.76–0.86) respectively. Conclusions The HTI is a simple yet reliable tool to predict any HT within 2 weeks after MCA stroke onset regardless of the IV rtPA use

Efficacy of valdoxan in the prevention and treatment of post-stroke depression

The efficacy of valdoxan (agomelatine) used to prevent and treat post-stroke depression was analyzed. The study enrolled 49 patients (21 men and 28 women; mean age 61+5.5years) in the acute period of ischemic stroke in different vascular basins (a study group). A control group included 50 patients (24 men and 26 women; mean age 64+4.8 years) who were comparable with the study group of patients and who did not receive valdoxan. The duration of a follow-up was 6 months. During valdoxan therapy, there were better changes in recovery with a rapider regression of neurological disorders in patients with moderate stroke as compared with the control group (according to the National Institute of Health Stroke Scale (NIHSS). The administration of valdoxan prevents depression, sleep disorders, pain syndromes, and cognitive impairments in the acute and early rehabilitation period of stroke

Prediction of Optimal Conditions of Hydrogenation Reaction Using the Likelihood Ranking Approach

The selection of experimental conditions leading to a reasonable yield is an important and essential element for the automated development of a synthesis plan and the subsequent synthesis of the target compound. The classical QSPR approach, requiring one-to-one correspondence between chemical structure and a target property, can be used for optimal reaction conditions prediction only on a limited scale when only one condition component (e.g., catalyst or solvent) is considered. However, a particular reaction can proceed under several different conditions. In this paper, we describe the Likelihood Ranking Model representing an artificial neural network that outputs a list of different conditions ranked according to their suitability to a given chemical transformation. Benchmarking calculations demonstrated that our model outperformed some popular approaches to the theoretical assessment of reaction conditions, such as k Nearest Neighbors, and a recurrent artificial neural network performance prediction of condition components (reagents, solvents, catalysts, and temperature). The ability of the Likelihood Ranking model trained on a hydrogenation reactions dataset, (similar to 42,000 reactions) from Reaxys(R) database, to propose conditions that led to the desired product was validated experimentally on a set of three reactions with rich selectivity issues

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

International audienc