Optimization of risk stratification for anticoagulation-associated intracerebral hemorrhage: net risk estimation.
- 作者列表："Lioutas VA","Goyal N","Katsanos AH","Krogias C","Zand R","Sharma VK","Varelas P","Malhotra K","Paciaroni M","Karapanayiotides T","Sharaf A","Chang J","Kargiotis O","Pandhi A","Palaiodimou L","Schroeder C","Tsantes A","Boviatsis E","Mehta C","Serdari A","Vadikolias K","Mitsias PD","Selim MH","Alexandrov AV","Tsivgoulis G
BACKGROUND:Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether combining ischemic and hemorrhagic stroke risk in individual patients might provide a meaningful paradigm for risk stratification. METHODS:We enrolled consecutive patients with anticoagulation-associated ICH in 15 tertiary centers in the USA, Europe and Asia between 2015 and 2017. Each patient was assigned baseline ischemic stroke and hemorrhage risk based on their CHA2DS2-VASc and HAS-BLED scores. We computed a net risk by subtracting hemorrhagic from ischemic risk. If the sum was positive the patient was assigned a "Favorable" indication for anticoagulation; if negative, "Unfavorable". RESULTS:We enrolled 357 patients [59% men, median age 76 (68-82) years]. 31% used non-vitamin K antagonist (NOAC). 191 (53.5%) patients had a favorable indication for anticoagulation prior to their ICH; 166 (46.5%) unfavorable. Those with unfavorable indication were younger [72 (66-80) vs 78 (73-84) years, p = 0.001], with lower CHA2DS2-VASc score [3(3-4) vs 5(4-6), p < 0.001]. Those with favorable indication had a significantly higher prevalence of most cardiovascular risk factors and were more likely to use a NOAC (35% vs 25%, p = 0.045). Both groups had similar prevalence of hypertension and chronic kidney disease. CONCLUSIONS:In this anticoagulation-associated ICH cohort, baseline hemorrhagic risk exceeded ischemic risk in approximately 50%, highlighting the importance of careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining 50% suffered an ICH despite excess baseline ischemic risk, stressing the need for biomarkers to allow more precise estimation of hemorrhagic complication risk.
背景: 每个抗凝治疗决定都有出血的固有风险; 脑出血 (ICH) 是最具破坏性的出血并发症。我们研究了个体患者合并缺血性和出血性卒中风险是否可能为风险分层提供有意义的范例。 方法: 我们于 2017 和 2015年在美国、欧洲和亚洲的 15 个三级中心连续入选了抗凝相关 ICH 患者。每个患者根据其 CHA2DS2-VASc 和 HAS-BLED 评分分配基线缺血性卒中和出血风险。我们通过从缺血性风险中减去出血性来计算净风险。如果总和为阳性，则为患者指定 “有利” 抗凝指征; 如果阴性，则为 “不利”。 结果: 我们入组了 357 例患者 [59% 例男性，中位年龄 76 (68-82) 岁]。31% 使用非维生素k 拮抗剂 (NOAC)。191 (53.5%) 患者在 ICH 前有良好的抗凝指征; 166 (46.5%) 不利。指征不利者较年轻 [72 (66-80) vs 78 (73-84) 岁，p = 0.001]，CHA2DS2-VASc 得分较低 [3(3-4) vs 5(4-6)，p <0.001]。那些有良好适应症的患者大多数心血管危险因素的患病率显著较高，更有可能使用 NOAC (35% vs 25%，p = 0.045)。两组高血压和慢性肾脏疾病的患病率相似。 结论: 在这个抗凝相关 ICH 队列中，基线出血风险超过缺血风险约 50%，强调了在抗凝决策前仔细考虑风险/获益比的重要性。其余 50% 的患者尽管基线缺血风险过大，但仍患有 ICH，强调需要生物标志物来更精确地估计出血并发症风险。
METHODS:BACKGROUND:People with stroke are not meeting recommended levels of physical activity. The modifiable factors associated with post-stroke physical activity levels need to be identified to develop targeted interventions. OBJECTIVE:The objective of this study was to investigate the factors at discharge from inpatient rehabilitation that are associated with physical activity levels at 3 months following discharge. DESIGN:This was a prospective cohort study. METHODS:Sixty-four people with stroke completed baseline assessments at discharge from inpatient rehabilitation and 55 completed the follow-up 3 months later. The candidate factors (i.e. gait speed, balance, strength, cognition, mood and motivation) were measured at discharge. The primary outcome measure at follow-up was walking related activity (measured by wrist-worn accelerometer). Secondary outcome measures were physical activity participation (Activity Card Sort) and intensity of physical activity (International Physical Activity Questionnaire - Short 7 days). Adjusted separate multivariable linear regression models or proportional odds regression models were used to evaluate the associations between candidate factors and physical activity. RESULTS:Gait speed and balance were associated with all aspects of physical activity. Higher level of intrinsic motivation was also associated with higher physical activity participation. Anxiety demonstrated a significant non-linear relationship with physical activity participation. LIMITATIONS:Inclusion of fatigue and individual muscle strength could have provided further insights into associations with steps per day. CONCLUSION:The results demonstrated that better physical function at discharge from inpatient rehabilitation was associated with future increased levels of physical activity. Additionally, higher levels of motivation impacted on increased physical activity participation. The influence of anxiety on physical activity participation requires further exploration. Mixed-method study designs can be utilized to further understand the factors associated with post-stroke physical activity.
METHODS:Cerebral ischemia-reperfusion (I/R) is characterized by initial transient cerebral ischemia followed by reperfusion. Various pathophysiological processes are involved in brain injury and functional recovery during cerebral I/R. There are few studies on dynamic metabolic process after cerebral I/R. The present study was to observe dynamic alteration of brain injury, functional recovery, and metabolites after cerebral I/R in rats and discover potential metabolic markers. The cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 90 min, following reperfusion in rats. The results of cerebral infarction area, cerebral edema, and behavior test showed that there were dynamic changes in brain injury and functional recovery at different periods after cerebral I/R. Further analysis showed that the brain injury was severe on the first day of cerebral I/R, and there was a significant functional recovery from the 7th day of cerebral I/R, followed by an aggravation trend of brain injury from the days 7 to 28. Furthermore, Matrix-assisted laser desorption ionization mass spectrometry imaging analysis showed that the expression of ATP, glucose, and citric acid on 7th day was the highest during cerebral I/R, which indicated that energy metabolism and oxidative phosphorylation played important roles during cerebral I/R. In addition, the untargeted metabolomic results showed that the level of isocitric acid, the ratio of oxyglutaric acid/glutamic acid, and the level of pyruvic acid associated with the TCA cycle were also the highest on the 7th day during cerebral I/R, which indicated that the transient spontaneous recovery of ischemic brain on the 7th day after ischemia-reperfusion might be related to oxidative phosphorylation and energy metabolism in the brain in this period. In conclusion, the results suggest that some small molecule metabolites participate in the brain injury and functional recovery during cerebral I/R, which is of great significance to the development of therapeutic drugs and diagnostic markers.
METHODS:The aims of this study were to study the effects of miR-2 on cerebral ischemia–reperfusion rats and to explore its further mechanism. Rats were assigned into sham, model, miR-22 control and miR-22 groups. Observation of neurological behaviors at 24 h after operation found that neurological functions were severely damaged in the model and miR-22 control groups and these damages were improved by miR-22. RT-PCR indicated that miR-22 mRNA level in the brain tissue was significantly decreased in the model and miR-22 control groups, but increased in the miR-22 group. TTC staining showed increased percentage of cerebral infarction volume in the model and miR-22 control groups and this increase was reduced by miR-22. Immunohistochemistry showed increased densities of CD34^+ and VEGF^+ microvessels in the cortex in the model and miR-22 control groups, which were further increased in the miR-22 group. ELISA showed increased serum VEGF and Ang-1 levels in the model and miR-22 control groups, which were also further increased in the miR-22 group. Western blot analysis showed increased phosphorylation level of PI3K and Akt in brain tissue in the model and miR-22 control groups, which were further increased in the miR-22 group. Administration of LY294002, a specific PI3K pathway inhibitor, significantly reversed all the effects of miR-22 on rats in the model group. miR-22 exerts its neuroprotective and angiogenic functions via the PI3K/Akt signaling pathway, at least partly, in rats under cerebral ischemia–reperfusion.