Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores in stroke with atrial fibrillation: A nationwide multicenter registry study.

ABSTRACT: The performance of scoring systems for risk stratification in patients with atrial fibrillation (AF) was not validated well in patients with stroke. The purpose of this study was to evaluate whether the risk scoring systems predict vascular outcomes in stroke patients with AF.Data were obtained from a nationwide multicenter registry for acute stroke with AF from January 1, 2013, to December 31, 2015. We investigated the predictive power of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke scores in stroke patients with AF. The subjects were further stratified into groups according to treatment with or without oral anticoagulants (OACs).A total of 3112 stroke with AF subjects were included. The rate of recurrent ischemic stroke and any stroke were not associated with the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores. The risks of death and major adverse cerebrovascular and cardiovascular events (MACEs) increased sequentially with the increase of each risk score in OAC group. (the range of C-index 0.544-0.558 for recurrent ischemic stroke; 0.523-0.537 for any stroke; 0.580-0.597 for death; 0.564-0.583 for MACEs). However, in the group treated with OACs, all risk scores were significantly associated with the risk of MACEs. The C-statistics of the 4 scoring systems were 0.544 to 0.558, 0.523 to 0.537, 0.580 to 0.597, 0.564 to 0.583, respectively, for recurrent ischemic stroke, any stroke, death, and MACEs.The performance of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores for the prediction of recurrent stroke was unsatisfactory in stroke patients with AF whereas the performance for the prediction of recurrent stroke was not MACEs or death was good. A new risk stratification scheme that is specific for secondary stroke prevention in the AF population is needed.

Effect of Statin Therapy on Outcomes of Patients With Acute Ischemic Stroke and Atrial Fibrillation.

Background There is insufficient evidence on the effect of statins, particularly high-intensity statins, in patients with acute ischemic stroke and atrial fibrillation. We investigated the impact of statins on the outcomes in these patients, including those who might be vulnerable to statin therapy and those without clinical atherosclerotic cardiovascular diseases. Methods and Results A total of 2153 patients with acute ischemic stroke and atrial fibrillation were enrolled in the present nationwide, multicenter, cohort study. The primary composite end point was the occurrence of net adverse clinical and cerebral events (NACCE; death from any cause, stroke, acute coronary syndrome, or major bleeding) over a 3-year period based on statin intensity. NACCE rates were lower in patients receiving low- to moderate-intensity (adjusted hazard ratio 0.64; 95% CI: 0.52-0.78) and high-intensity statins (hazard ratio 0.51; 95% CI 0.40-0.66) than in those not receiving statin therapy. High-intensity statins were associated with a lower risk for NACCE than low- to moderate-intensity statins (hazard ratio 0.76; 95% CI 0.59-0.96). Subgroup analyses showed that the differences in hazard ratio for 3-year NACCE favored statin use across all subgroups, including older patients, those with low cholesterol levels, patients receiving anticoagulants, and patients without clinical atherosclerotic cardiovascular diseases. Magnified benefits of high-intensity statins compared with low- to moderate-intensity statins were observed in patients who underwent revascularization therapy and those under 75 years of age. Conclusions Statins, particularly high-intensity statins, could reduce the risk for NACCE in patients with acute ischemic stroke and atrial fibrillation; this needs to be further explored in randomized controlled trials.

Utility of temperature-sensitive indicators for temperature monitoring of red-blood-cell units.

BACKGROUND AND OBJECTIVES: The 30-min rule has been used to maintain a core temperature (CT) of red-blood-cell (RBC) units below 10°C during transportation. We evaluated the utility of temperature-sensitive indicators (TIs) to monitor the surface temperature (ST) of RBC units and to explore whether TIs can help with compliance with the 30-min rule by extrapolating or correlating temperature change with time. MATERIALS AND METHODS: Two US FDA-approved TIs, Safe-T-Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ, USA) and Timestrip Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK), were attached to 50 RBC units. After issue, their colour change indicating 10°C was monitored, and temperature excursions were measured by standard reading. In additional 18 RBC units, both ST and CT were monitored simultaneously. RESULTS: In 50 RBC units, 94% of STV10 and 100% of BT10 showed colour change indicating 10°C within 30 min; 4% of STV10 and 18% of BT10 showed it during transportation. The time for colour change indicating 10°C differed significantly between STV10 and BT10 (19·0 vs. 5·6 min, P < 0·001). In additional 18 RBC units, 83·3% of STV10, 100% of BT10 and 88·9% of CT reached 10°C within 30 min, and the time for colour change indicating 10°C was 24·4 min in STV10, 14·6 min in BT 10 and 24·2 min in CT (P < 0·001). CONCLUSION: In two TIs, the time for colour change indicating 10°C varied considerably. To enhance the utility of TIs, further improvement and standardization would be needed.

Relationship between the Angle of the Posterior Inferior Cerebellar Artery and Cardioembolic Stroke.

BACKGROUND: In patients with unilateral posterior inferior cerebellar artery (PICA) territory infarction, the absence of relevant vessel stenosis may make it difficult to determine the etiology of the infarction. The incidence of cardioembolic (CE) infarction and the factors associated with infarction in such patients remains largely unknown. We hypothesized that the PICA angle would affect the flow direction of embolic sources. Thus, we analyzed the association between high-risk CE sources and the PICA angle. METHODS: Patients with an isolated unilateral PICA territory infarction without relevant vessel stenosis who were admitted between 2014 and 2017 were included from the Korea University Stroke Registry, which includes data from 3 university hospitals. We classified patients according to the presence of CE sources. For each case, we measured the angle between the vertebral artery (VA) and the proximal PICA. RESULTS: In all, 71 patients met the final study entry criteria. Multivariable analysis showed that the PICA angle was independently associated with the risk of a CE source. The optimal cut-off value using Youden's index was 89°. We classified the PICA shape based on the optimal cut-off value. A CE source was identified in 83.3% of cases in which the PICA angle exceeded 89°. CONCLUSIONS: The angle between the PICA and VA was an independent predictor of unilateral PICA stroke with high-risk CE sources without relevant artery stenosis, suggesting that an angle greater than 89° could be a new image marker for determining the stroke subtype.