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    Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use. Seiffge David J,Goeldlin Martina B,Tatlisumak Turgut,Lyrer Philippe,Fischer Urs,Engelter Stefan T,Werring David J Journal of neurology OBJECTIVE:To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset. METHODS:We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference. RESULTS:We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH. CONCLUSION:This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs. 10.1007/s00415-019-09536-1
    MRI for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis. Suh Chong Hyun,Jung Seung Chai,Cho Se Jin,Woo Dong-Cheol,Oh Woo Yong,Lee Jong Gu,Kim Kyung Won Acta radiologica (Stockholm, Sweden : 1987) BACKGROUND:Hemorrhagic transformation increases mortality and morbidity in patients with acute ischemic stroke. PURPOSE:The purpose of this study is to evaluate the diagnostic performance of magnetic resonance imaging (MRI) for prediction of hemorrhagic transformation in acute ischemic stroke. MATERIAL AND METHODS:A systematic literature search of MEDLINE and EMBASE was performed up to 27 July 2018, including the search terms "acute ischemic stroke," "hemorrhagic transformation," and "MRI." Studies evaluating the diagnostic performance of MRI for prediction of hemorrhagic transformation in acute ischemic stroke were included. Diagnostic meta-analysis was conducted with a bivariate random-effects model to calculate the pooled sensitivity and specificity. Subgroup analysis was performed including studies using advanced MRI techniques including perfusion-weighted imaging, diffusion-weighted imaging, and susceptibility-weighted imaging. RESULTS:Nine original articles with 665 patients were included. Hemorrhagic transformation is associated with high permeability, hypoperfusion, low apparent diffusion coefficient (ADC), and FLAIR hyperintensity. The pooled sensitivity was 82% (95% confidence interval [CI] 61-93) and the pooled specificity was 79% (95% CI 71-85). The area under the hierarchical summary receiver operating characteristic curve was 0.85 (95% CI 0.82-0.88). Although study heterogeneity was present in both sensitivity (I=67.96%) and specificity (I=78.93%), a threshold effect was confirmed. Studies using advanced MRI showed sensitivity of 92% (95% CI 70-98) and specificity of 78% (95% CI 65-87) to conventional MRI. CONCLUSION:MRI may show moderate diagnostic performance for predicting hemorrhage in acute ischemic stroke although the clinical significance of this hemorrhage is somewhat uncertain. 10.1177/0284185119887593
    Efficacy of neuroendoscopic surgery versus craniotomy for supratentorial hypertensive intracerebral hemorrhage: A meta-analysis of randomized controlled trials. Zhao Xu-Hui,Zhang Su-Zhen,Feng Jin,Li Zhen-Zhong,Ma Zeng-Lu Brain and behavior BACKGROUND:Hypertensive cerebral hemorrhage (HCH) is a potentially life-threatening neurological condition with an extremely high morbidity and mortality. In recent years, neuroendoscopy has been used to treat intracerebral hemorrhage (ICH). However, the choice of neuroendoscopic surgery versus craniotomy for patients with intracerebral hemorrhages is controversial. AIM:We conducted this meta-analysis to assess the efficacy of neuroendoscopic surgery compared with craniotomy in patients with supratentorial hypertensive ICH. METHODS:A systematic electronic search was conducted of online electronic databases: PubMed, Embase, and the Cochrane Library updated on December 2017. The meta-analysis only included randomized controlled studies. RESULTS:Three randomized controlled trials met our inclusion criteria. The pooled analysis of death showed that neuroendoscopic surgery decreased the rate of death when compared with craniotomy (RR = 0.58, 95% CI 0.26-1.29; p = .18). The pooled result of complications indicated that neuroendoscopic surgery has a tendency toward lower complications (RR = 0.37, 95% CI 0.28-0.49; p < .001). CONCLUSIONS:Our results suggested that neuroendoscopic surgery has lower complications, but no superior advantages in morbidity rates. Since the advantage of neuroendoscopic surgery has been performed in some area, the continuation of multi-center comparative investigation with craniotomy may be necessary. Moreover, some efforts need to be taken in selecting appropriate patients with different treatments. 10.1002/brb3.1471
    High incidence of asymptomatic cerebral microbleeds in patients with hemorrhagic onset-type moyamoya disease: a phase-sensitive MRI study and meta-analysis. Qin Ying,Ogawa Toshihide,Fujii Shinya,Shinohara Yuki,Kitao Shin-Ichiro,Miyoshi Fuminori,Takasugi Marie,Watanabe Takashi,Kaminou Toshio Acta radiologica (Stockholm, Sweden : 1987) BACKGROUND:Moyamoya disease is a relatively rare cerebrovascular occlusive disorder. Several studies have reported cerebral microbleeds (CMBs) in moyamoya disease patients using T2*-weighted imaging (T2*WI) and/or susceptibility-weighted imaging (SWI). PURPOSE:To investigate the incidence, distribution patterns, and influencing factors of asymptomatic CMBs in patients with moyamoya disease. MATERIAL AND METHODS:Phase-sensitive imaging (PSI) was used to investigate 27 consecutive moyamoya disease patients with a 3-T magnetic resonance imaging system, then a meta-analysis of 245 patients (asymptomatic moyamoya disease, n = 23; ischemic moyamoya disease, n = 161; hemorrhagic moyamoya disease, n = 61) from four previous individual studies and our PSI study was performed. The meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Based on the clinical and radiological data, we divided the studies into different model groups to calculate the incidence of CMBs and discuss the distribution patterns of CMBs. RESULTS:Thirty-five asymptomatic CMBs were demonstrated in 14 moyamoya disease patients (51.9%) in our PSI study. Of these, 45.7% were located in the periventricular white matter. In the meta-analysis, the pooled incidence of asymptomatic CMBs in moyamoya disease was 46% (95% confidence interval [CI], 28.2-63.8%) on SWI or PSI and 29.6% (95% CI, 17.4-41.7%) on T2*WI. Statistical analysis showed that PSI or SWI offered better detection of CMBs in moyamoya disease than T2*WI, and 3-T T2*WI offered better detection than 1.5-T T2*WI. Furthermore, hemorrhagic onset-type moyamoya disease correlated with a high incidence of asymptomatic CMBs. CONCLUSION:PSI or SWI can detect CMBs better than T2*WI, and 3-T T2*WI. Hemorrhagic onset-type moyamoya disease seems to correlate with a high incidence of asymptomatic CMBs. The meta-analysis indicates that asymptomatic CMBs may be an important factor for hemorrhagic stroke risk. Long-term evaluation of CMBs using PSI or SWI may contribute to the management of moyamoya disease. 10.1177/0284185114524198
    A randomized clinical trial and meta-analysis of early surgery vs. initial conservative treatment in patients with spontaneous lobar intracerebral hemorrhage. Starke Robert M,Komotar Ricardo J,Connolly E Sander Neurosurgery 10.1227/01.neu.0000442974.53712.26
    Vasospasm on transcranial Doppler is predictive of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Kumar Gyanendra,Shahripour Reza Bavarsad,Harrigan Mark R Journal of neurosurgery OBJECT The impact of transcranial Doppler (TCD) ultrasonography evidence of vasospasm on patient-centered clinical outcomes following aneurysmal subarachnoid hemorrhage (aSAH) is unknown. Vasospasm is known to lead to delayed cerebral ischemia (DCI) and poor outcomes. This systematic review and meta-analysis evaluates the predictive value of vasospasm on DCI, as diagnosed on TCD. METHODS MEDLINE, Scopus, the Cochrane trial register, and clinicaltrials.gov were searched through September 2014 using key words and the terms "subarachnoid hemorrhage," "aneurysm," "aneurysmal," "cerebral vasospasm," "vasospasm," "transcranial Doppler," and "TCD." Sensitivities, specificities, and positive and negative predictive values were pooled by a DerSimonian and Laird random-effects model. RESULTS Seventeen studies (n = 2870 patients) met inclusion criteria. The amount of variance attributable to heterogeneity was significant (I(2) > 50%) for all syntheses. No studies reported the impact of TCD evidence of vasospasm on functional outcome or mortality. TCD evidence of vasospasm was found to be highly predictive of DCI. Pooled estimates for TCD diagnosis of vasospasm (for DCI) were sensitivity 90% (95% confidence interval [CI] 77%-96%), specificity 71% (95% CI 51%-84%), positive predictive value 57% (95% CI 38%-71%), and negative predictive value 92% (95% CI 83%-96%). CONCLUSIONS TCD evidence of vasospasm is predictive of DCI with high accuracy. Although high sensitivity and negative predictive value make TCD an ideal monitoring device, it is not a mandated standard of care in aSAH due to the paucity of evidence on clinically relevant outcomes, despite recommendation by national guidelines. High-quality randomized trials evaluating the impact of TCD monitoring on patient-centered and physician-relevant outcomes are needed. 10.3171/2015.4.JNS15428
    Meta-Analysis of Pre-Clinical Trials of Therapeutic Hypothermia for Intracerebral Hemorrhage. Melmed Kara R,Lyden Patrick D Therapeutic hypothermia and temperature management Therapeutic hypothermia (TH) is a potent neuroprotectant for experimental ischemic stroke, but studies of TH for intracerebral hemorrhage (ICH) are emerging. We systematically reviewed the experimental literature to assess TH efficacy for ICH. We found 18 suitable papers; quality scores were moderately good. Compared with normothermia, TH reduced measures of edema (mean effect size (95% CI) -1.6873 (-2.3640, -1.0106), p < 0.0001) or blood-brain barrier leakage (p < 0.0001) and improved behavioral outcomes (p < 0.0001). There was no evidence of publication bias. In this meta-analysis of available preclinical studies of ICH, TH is potently effective for reducing perihematomal edema and for improving behavioral outcomes. 10.1089/ther.2016.0033
    Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy. Perry Luke A,Lucarelli Tom,Penny-Dimri Jahan C,McInnes Matthew Df,Mondello Stefania,Bustamante Alejandro,Montaner Joan,Foerch Christian,Kwan Patrick,Davis Stephen,Yan Bernard International journal of stroke : official journal of the International Stroke Society BACKGROUND AND AIMS:Glial fibrillary acidic protein (GFAP) has shown promise in several studies for its ability to diagnose intracerebral hemorrhage (ICH). We evaluated the diagnostic accuracy of blood GFAP level to differentiate (ICH) from acute ischemic stroke (AIS) and stroke mimics, both overall, and in the first three hours after symptom onset. METHODS:We searched multiple databases, without language restriction, from inception until December 2017. Hierarchical summary receiver operating characteristic (HSROC) modeling was used to meta-analyze results. We conducted subgroup analyses restricted to blood samples collected within 0-60, 60-120, and 120-180 min time groups after symptom onset, to evaluate diagnostic accuracy in the early pre-hospital phase. Between and within study heterogeneity was explored using meta-regression. RESULTS:The search identified 199 potentially relevant citations from which 11 studies involving 1297 participants (350 ICH, 947 AIS, or mimic) were included. The pooled sensitivity, specificity, and area under the HSROC curve were 0.756 (95% CI 0.630-0.849), 0.945 (95% CI 0.858-0.980), and 0.904 (95% CI 0.878-0.931), respectively. Differences in assays used, but not the other covariates, partially explained between-study heterogeneity ( = 0.034). The summary estimates for the 0-60, 60-120, and 120-180 min subgroups were comparable to the primary analysis and there was no statistically significant difference in diagnostic accuracy between subgroups. CONCLUSIONS:GFAP is a promising diagnostic biomarker for ICH diagnosis in the early pre-hospital phase. Test accuracy is affected by assay subtype, but there are still unexplained sources of heterogeneity. High quality, international multi-center trials are warranted to develop and validate a point-of-care GFAP assay for the rapid triage and evaluation of acute stroke in the pre-hospital setting. 10.1177/1747493018806167
    Predictive Accuracy of Alpha-Delta Ratio on Quantitative Electroencephalography for Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Analysis. Yu Zhiyuan,Wen Dingke,Zheng Jun,Guo Rui,Li Hao,You Chao,Ma Lu World neurosurgery OBJECTIVE:Delayed cerebral ischemia (DCI) is significantly related to death and unfavorable functional outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). The association between alpha-delta ratio (ADR) on quantitative electroencephalography (EEG) and DCI has been reported in several previous studies, but their results are conflicting. This meta-analysis was conducted to assess the accuracy of ADR for DCI prediction in patients with aneurysmal SAH. METHODS:PubMed and Embase were systematically searched for related records. Study selection and data collection were completed by 2 investigators. Sensitivity, specificity, and their 95% confidence intervals (CIs) were pooled. A summary receiver operating characteristic curve was plotted to show the pooled accuracy. Deeks funnel plot was used to evaluate publication bias. RESULTS:Five studies were included in this meta-analysis. The pooled sensitivity and specificity of worsening ADR for DCI prediction in patients with aneurysmal SAH were 0.83 (95% CI 0.44-0.97) and 0.74 (95% CI 0.50-0.89), respectively. In addition, the area under the summary receiver operating characteristic curve was 0.84 (95% CI 0.81-0.87). No obvious publication bias was found using Deeks funnel plot (P = 0.29). CONCLUSIONS:Worsening ADR on quantitative EEG is a reliable predictor of DCI in patients with aneurysmal SAH. Further studies are still needed to confirm the role of quantitative EEG in DCI prediction. 10.1016/j.wneu.2019.02.082
    CT Perfusion for Identification of Patients at Risk for Delayed Cerebral Ischemia during the Acute Phase after Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis. Sun Haogeng,Ma Junpeng,Liu Yi,You Chao Neurology India Background:It has been acknowledged that delayed cerebral ischemia (DCI) can be diagnosed by computed tomography perfusion (CTP) when it occurs following aneurysmal subarachnoid hemorrhage (aSAH); however, the clinical role of CTP in the prediction of DCI remains unclear. We performed a meta-analysis to investigate the role of CTP in the identification of patients at risk for DCI during the acute phase (<4 days) after aSAH. Materials and Methods:Relevant articles were systematically searched for analysis on PubMed, EMBASE, and Cochrane databases. The best CTP parameter or the definition of abnormal CTP scan result were collected, and the data with the greatest overall predictive value for DCI was extracted to assess the strength of association between a positive CTP result and an impending DCI. In addition, pooled estimates of sensitivity and specificity were determined. Results:Three relevant articles involving 128 patients were included in the analysis wherein DCI developed in 48 patients (37.5%). The pooled odds ratio was 32.15 (95% CI, 9.92-104.21), suggesting that the patients with a positive CTP test in the acute phase after aSAH were approximately 32 times as likely to develop DCI compared with those without aSAH. The pooled sensitivity and specificity of CTP for detecting impending DCI after aSAH was 65% (95% CI: 0.49-0.78) and 91% (95% CI: 0.83-0.96). Conclusions:CTP can detect abnormal brain perfusion before the occurrence of DCI. This may allow close monitoring and preemptive therapy for improvement in the prognosis in patients with aSAH. 10.4103/0028-3886.271235
    Hyperglycemia and Mortality Risk in Patients with Primary Intracerebral Hemorrhage: A Meta-Analysis. Guo Xiaoming,Li Helin,Zhang Zhiwen,Li Shouchun,Zhang Lizhi,Zhang Jiajing,Han Guiqing Molecular neurobiology Hyperglycemia may be associated with worse functional outcomes in patients with primary intracerebral hemorrhage. We performed a systematic review and meta-analysis to investigate the relationship between hyperglycemia and mortality risk in patients with primary intracerebral hemorrhage. We searched PubMed and Embase databases for studies investigating the association between hyperglycemia and mortality risk in patients with primary intracerebral hemorrhage. We estimated the pooled relative risk (RR) with its 95% confidence interval (95% CI) to assess the impact of hyperglycemia on mortality risk. Seventeen studies with a total of 6527 primary intracerebral hemorrhage patients were included. Meta-analysis of those studies showed that hyperglycemia significantly increased risk of mortality in patients with primary intracerebral hemorrhage (RR = 2.36, 95% CI 1.79-3.12). Subgroup analysis by time of follow-up showed that hyperglycemia significantly increased risk of short-term mortality (RR = 3.97, 95% CI 2.13-7.43) and long-term mortality (RR = 1.53, 95% CI 1.14-2.05). The RR of mortality for per 1-mmol/L increment in glucose level was 1.14 (95% CI 1.06-1.22). In patients with primary intracerebral hemorrhage, hyperglycemia significantly increases risk of both short-term mortality and long-term mortality. 10.1007/s12035-015-9184-4
    Accuracy of Shape Irregularity and Density Heterogeneity on Noncontrast Computed Tomography for Predicting Hematoma Expansion in Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. Yu Zhiyuan,Zheng Jun,Xu Zhao,Li Mou,Wang Xiaoze,Lin Sen,Li Hao,You Chao World neurosurgery OBJECTIVE:This systematic review and meta-analysis was aimed to evaluate the predictive values of shape irregularity and density heterogeneity of hematoma on noncontrast computed tomography (NCCT) for hematoma expansion (HE). METHODS:A literature search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library. Studies about predictive values of shape regularity or density heterogeneity of hematoma on NCCT for HE in spontaneous intracerebral hemorrhage were included. Meta-analysis was performed to pool the data. Publication bias assessment, subgroup analysis, and univariate meta-regression were conducted. RESULTS:A total of 7 studies with 2294 patients were included. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of shape irregularity were 67%, 47%, 1.30, and 0.71, respectively. In contrast, the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of density irregularity were 52%, 69%, 1.70, and 0.69, respectively. CONCLUSIONS:Considering the relatively low sensitivity and specificity, the predictive values of shape irregularity and density heterogeneity of hematoma for HE are limited. Further studies are still needed to find optimal NCCT predictors for HE in spontaneous intracerebral hemorrhage patients. 10.1016/j.wneu.2017.09.022
    An Update on the Efficacy and Safety Profile of Clazosentan in Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis. Song Jie,Xue Yue-Qin,Wang Yan-Ju,Xu Peng,Sun De-Ke,Chen Wei World neurosurgery OBJECTIVE:The present meta-analysis was conducted to provide an update on the efficacy and safety profile of clazosentan with different doses in aneurysmal subarachnoid hemorrhage (aSAH). METHODS:We performed a comprehensive and electronic search updated to September 2018 of The Cochrane Library, Embase, and PubMed to identify relevant clinical trials. Trials of the effectiveness of clazosentan in treating cerebral vasospasm after aSAH were studied. The main outcomes included new cerebral infarction (NCI), delayed ischemic neurologic deficit (DIND), vasospasm associated with morbidity/mortality, angiographic vasospasm, rescue therapy, and adverse events. We applied RevMan 5.3 software for this meta-analysis to analyze the combined pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed- or random-effects model on the basis of heterogeneity. RESULTS:A total of 5 randomized placebo-controlled trials were included in this meta-analysis. Beneficial outcome was found in patients who received higher doses of clazosentan (>5 mg/h) after aSAH based on decreased incidence of DINDs (OR, 1.76; 95% CI, 1.16-2.69; P = 0.008), NCIs (OR, 2.31; 95% CI, 1.34-3.95; P = 0.002), and angiographic vasospasms (OR, 1.85; 95% CI, 1.19-2.89; P = 0.007). Meanwhile, other parameters, such as vasospasm-related morbidity/mortality, rescue therapy, and adverse events, showed no statistical significance (P > 0.05) between high and low doses of clazosentan. CONCLUSIONS:The significant beneficial outcomes of high-dose clazosentan have been proven in preventing cerebral vasospasm and subsequent cerebral infarction compared with low-dose clazosentan, with a manageable safety profile. However, high doses of clazosentan had no significant effect on rescue therapy and vasospasm-related morbidity/mortality. 10.1016/j.wneu.2018.11.143
    Effects of Prior Antiplatelet Therapy on the Prognosis of Primary Intracerebral Hemorrhage: A Meta-analysis. Yu Hai-Han,Pan Chao,Tang Ying-Xin,Liu Na,Zhang Ping,Hu Yang,Zhang Ye,Wu Qian,Deng Hong,Li Gai-Gai,Li Yan-Yan,Nie Hao,Tang Zhou-Ping Chinese medical journal BACKGROUND:Antiplatelet therapy (APT) was prevalently being used in the prevention of vascular disease, but the influence of prior APT on the prognosis of patients with intracerebral hemorrhage (ICH) remains controversial. This meta-analysis was to explore the effects of prior APT on the prognosis of patients with primary ICH. METHODS:PubMed and Embase were searched to identify the eligible studies. The studies comparing the mortality of ICH patients with or without prior APT were included. The quality of these studies was evaluated by the Newcastle-Ottawa quality assessment scale. The adjusted or unadjusted odds ratio (OR) for mortality between ICH patients with and without prior APT were pooled with 95% confidence interval (95% CI) as the effect of this meta-analysis. RESULTS:Twenty-two studies fulfilled the inclusion criteria and exhibited high qualities. The pooled OR was 1.37 (95% CI: 1.13-1.66, P = 0.001) for univariate analysis and 1.41 (95% CI: 1.05-1.90, P = 0.024) for multivariate analysis. The meta-regression indicated that for each 1-day increase in the time of assessment, the adjusted OR for the mortality of APT patients decreased by 0.0049 (95% CI: 0.0006-0.0091, P = 0.026) as compared to non-APT patients. CONCLUSION:Prior APT was associated with high mortality in patients with ICH that might be attributed primarily to its strong effect on early time. 10.4103/0366-6999.220302
    Meta-Analysis of Accuracy of the Spot Sign for Predicting Hematoma Growth and Clinical Outcomes. Phan Thanh G,Krishnadas Natasha,Lai Vivian Wai Yun,Batt Michael,Slater Lee-Anne,Chandra Ronil V,Srikanth Velandai,Ma Henry Stroke Background and Purpose- The computed tomography angiographic spot sign refers to contrast leakage within intracerebral hemorrhage (ICH). It has been proposed as a surrogate radiological marker for ICH growth. We conducted a meta-analysis to study the accuracy of the spot sign for predicting ICH growth and mortality. Methods- PubMed, Medline, conference proceedings, and article references in English up to June 2017 were searched for studies reporting "computed tomography angiography" and "spot sign" or "intracerebral hemorrhage" and "spot sign." Each study was ranked on 27 criteria resulting in a quality rating score. Bivariate random effect meta-analysis was used to calculate positive and negative likelihood ratios and area under summary receiver operating characteristics curve for ICH growth and mortality. Hematoma growth was defined using the change in ≥6 mL or ≥33% increase in volume. Results- There were 26 studies describing 5085 patients, including 15 studies not used in previous meta-analyses. Positive likelihood ratio and negative likelihood ratio for ICH growth were 4.85 (95% CI, 3.85-6.02; I=76.1%) and 0.49 (95% CI, 0.40-0.58) and mortality were 4.65 (95% CI, 3.67-5.90) and 0.55 (95% CI, 0.40-0.69), respectively. For ICH growth, the pooled sensitivity was 0.57 (95% CI, 0.49-0.64) and pooled false positive rate was 0.12 (95% CI, 0.09-0.14). The post-test probability of ICH growth was 0.57. The area under the curve for ICH growth and mortality was 0.86 and 0.87 (CIs are not provided in bivariate method). Meta-regression showed sensitivity of the test to decline significantly with subsequent year of publication (β=-0.148; 95% CI, -0.295 to -0.001; P=0.05). Higher quality assessment is associated with lower false positive rate (β=-0.074; 95% CI, -0.126 to -0.022; P=0.006). Conclusions- The high area under the curve potentially suggests that the spot sign can predict hematoma growth and mortality. Caution is recommended in its application given the heterogeneity across studies, which is appropriate given the data. 10.1161/STROKEAHA.118.024347
    Heterogeneity Signs on Noncontrast Computed Tomography Predict Hematoma Expansion after Intracerebral Hemorrhage: A Meta-Analysis. Zhang Danfeng,Chen Jigang,Xue Qiang,Du Bingying,Li Ya,Chen Tao,Jiang Ying,Hou Lijun,Dong Yan,Wang Junyu BioMed research international Background and Purpose:Hematoma expansion (HE) is related to clinical deterioration after intracerebral hemorrhage (ICH) and noncontrast computed tomography (NCCT) signs are indicated as predictors for HE but with inconsistent conclusions. We aim to clarify the correlations of NCCT heterogeneity signs with HE by meta-analysis of related studies. Methods:PubMed, Embase, and Cochrane library were searched for eligible studies exploring the relationships between NCCT heterogeneity signs (hypodensity, mixed density, swirl sign, blend sign, and black hole sign) and HE. Poor outcome and mortality were considered as secondary outcomes. Odds ratio (OR) and its 95% confidence intervals (CIs) were selected as the effect size and combined using random effects model. Results:Fourteen studies were included, involving 3240 participants and 435 HEs. The summary results suggested statistically significant correlations of heterogeneity signs with HE (OR, 5.17; 95% CI, 3.72-7.19, < 0.001), poor outcome (OR, 3.60; 95% CI, 1.98-6.54, < 0.001), and mortality (OR, 4.64; 95%, 2.96-7.27, < 0.001). Conclusions:Our findings suggested that hematoma heterogeneity signs on NCCT were positively associated with the increased risk of HE, poor outcome, and mortality rate in ICH. 10.1155/2018/6038193
    The relationship between low serum magnesium level and intracerebral hemorrhage hematoma expansion: Protocol for a systematic review and meta-analysis. Zhu Rending,He Xiaolu,Du Yanqun,Chen Nan,Wang Wei,Sun Yue,Sun Jian,Liu Wanjun,Wang Xun,Fang Chuanqin Medicine BACKGROUND:Hematoma expansion (HE) is related to clinical deterioration and unfavorable prognosis in intracerebral hemorrhage (ICH). Some studies have revealed that low serum magnesium level is associated with larger hematoma volume at admission, HE, and unfavorable outcomes. However, the conclusions remain unsettled. The purpose of this study is to evaluate the association between low serum magnesium level and HE by meta-analysis. METHODS:We will search the following electronic bibliographic databases: PubMed, Medline, Embase, Web of Science, and The Cochrane Library. Studies will be included if they reported a relationship of low serum magnesium level and HE, mortality or poor outcome. RESULTS:The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION:This will be the first systematic review and meta-analysis to evaluate the association of HE following ICH with Hypomagnesemia. We look forward to the results will offer scientific proof to predict HE for ICH patients with low serum magnesium level. PROSPERO REGISTRATION NUMBER:This protocol has been registered in the PROSPERO network with number: CRD42019135995. 10.1097/MD.0000000000018719
    Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis. Saber Hamidreza,Desai Aaron,Palla Mohan,Mohamed Wazim,Seraji-Bozorgzad Navid,Ibrahim Muhammed Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association OBJECTIVES:Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH). PATIENTS AND METHODS:We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I statistic to measure heterogeneity between trials. RESULTS:Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis. CONCLUSION:Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association. 10.1016/j.jstrokecerebrovasdis.2018.06.027
    Intracerebral Hemorrhage Location and Functional Outcomes of Patients: A Systematic Literature Review and Meta-Analysis. Sreekrishnan Anirudh,Dearborn Jennifer L,Greer David M,Shi Fu-Dong,Hwang David Y,Leasure Audrey C,Zhou Sonya E,Gilmore Emily J,Matouk Charles C,Petersen Nils H,Sansing Lauren H,Sheth Kevin N Neurocritical care BACKGROUND AND PURPOSE:Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest. METHODS:A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis. RESULTS:Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation. CONCLUSIONS:Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes. 10.1007/s12028-016-0276-4
    Promoting blood circulation for removing blood stasis therapy for acute intracerebral hemorrhage: a systematic review and meta-analysis. Li Hui-qin,Wei Jing-jing,Xia Wan,Li Ji-huang,Liu Ai-ju,Yin Su-bing,Wang Chen,Song Liang,Wang Yan,Zheng Guo-qing,Fan Ji-ping Acta pharmacologica Sinica AIM:To conduct a systematic review and meta-analysis to assess the current evidence available regarding the promoting blood circulation and removing blood stasis (PBCRBS) therapy for Chinese patients with acute intracerebral hemorrhage (ICH). METHODS:Six databases were searched from their inception to November 2013. The studies assessed in ≥ 4 domains with 'yes' were selected for detailed assessment and meta-analysis. The herbal compositions for PBCRBS therapy for acute ICH patients were also assessed. RESULTS:From the 6 databases, 292 studies claimed randomized-controlled clinical trials (RCTs). Nine studies with 798 individuals were assessed in ≥ 4 domains with 'yes' by using the Cochrane RoB tool. Meta-analysis showed that PBCRBS monotherapy and adjuvant therapy for acute ICH could improve the neurological function deficit, reduce the volume of hematoma and perihematomal edema, and lower the mortality rate and dependency. Moreover, there were fewer adverse effects when compared with Western conventional medication controls. Xueshuantong Injection and Fufang Danshen Injection, Buyang Huanwu Decoction and Liangxue Tongyu formula, and three herbs (danshen root, sanqi and leech) were the most commonly used Chinese herbal patent injections, herbal prescriptions and single herbs, respectively. CONCLUSION:Despite the apparently positive findings, it is premature to conclude that there is sufficient efficacy and safety of PBCRBS for ICH because of the high clinical heterogeneity of the included studies and small number of trials in the meta-analysis. Further large sample-sizes and rigorously designed RCTs are needed. 10.1038/aps.2014.139
    Neutrophil-lymphocyte ratio predicts the outcome of intracerebral hemorrhage: A meta-analysis. Liu Shuo,Liu Xiaoqiang,Chen Shuying,Xiao Yingxiu,Zhuang Weiduan Medicine BACKGROUND:The neutrophil-lymphocyte ratio (NLR) is increasingly recognized as a systemic inflammation factor. It has been used as a predictor for clinical outcomes in cancers. However, its relationship with intracerebral hemorrhage (ICH) is still disputed. We sought to evaluate the prognostic role of NLR in ICH. METHODS:We searched PubMed, Cochrane Library, Medline, and EMBASE for potentially relevant articles from inception to April 8, 2018. Efficacy outcomes included major disability at 90 days, short-term mortality or in-hospital mortality. Odds ratio (OR) with 95% confidence interval (95% CI) were pooled to assess the association between NLR and ICH. RESULTS:A total of 7 trials with 2176 patients were included in this meta-analysis. It revealed that higher NLR had a higher risk of major disability at 90 days (OR: 2.20; 95% CI: 1.27-3.81) and higher mortality at short-term (OR: 1.31; 95% CI: 1.02-1.68) in ICH; without statistically significant association with in-hospital mortality (OR: 1.02; 95% CI: 0.91-1.15). CONCLUSIONS:Our meta-analysis proved that high NLR was a predictor of major disability and mortality at short term in ICH patients, but not a predictor of in-hospital mortality. 10.1097/MD.0000000000016211
    Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta-analysis. Jung Jin-Man,Choi Jeong-Yoon,Kim Hyun Jung,Seo Woo-Keun International journal of stroke : official journal of the International Stroke Society BACKGROUND:Nonrandomized observational studies have been conducted to evaluate the effects of statins on clinical outcomes in patients with intracerebral hemorrhage. Several studies on the effects of statin administration in patients with intracerebral hemorrhage have been published recently, but the findings are inconsistent. AIM:To evaluate the effects of statins administered prior to hospital admission and during hospitalization on mortality and functional outcomes in patients with intracerebral hemorrhage. SUMMARY OF REVIEW:We searched for relevant literature using multiple comprehensive databases and performed a systematic review and meta-analysis. Sixteen studies met our selection criteria. Preintracerebral hemorrhage statin use was not associated with mortality (odds ratio: 0·90, 95% confidence interval: 0·63-1·28). However, patients who used statins prior to intracerebral hemorrhage had a decreased risk of mortality at three-months following symptom onset (odds ratio: 0·47, 95% confidence interval: 0·32-0·68) and an increased probability of good functional outcomes (odds ratio: 1·49, 95% confidence interval: 1·01-2·19), as compared with those who did not. In-hospital use of statins was associated with a low risk of mortality (odds ratio: 0·34, 95% confidence interval: 0·26-0·44) irrespective of preadmission statin use or postadmission time-points. Additionally, we were unable to pool the data on statin withdrawal because of differences in study methodologies. CONCLUSIONS:Although careful interpretation is necessary due to several study limitations, we have demonstrated that statin use in patients with intracerebral hemorrhage is likely associated with improved mortality and functional outcomes. 10.1111/ijs.12624
    Efficacy of Statins in Cerebral Vasospasm, Mortality, and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Shen Jianguo,Shen Jian,Zhu Kuncan,Zhou Haihang,Tian Heping,Yu Gongjie World neurosurgery BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) is an acute cerebrovascular disease with frequent cerebral vasospasm and delayed cerebral ischemia (DCI). The use of statins for patients with aSAH is controversial. The present study evaluated the efficacy of statins in aSAH-induced vasospasm, DCI, delayed ischemic neurological deficit (DIND), mortality, and other outcomes. METHODS:A literature search was performed in PubMed, EMBASE, and the Cochrane Library. English reports of patients with aSAH who had been treated with statins without combination were included. The outcomes, including cerebral vasospasm, DIND, DCI, mortality, disability, and creatine kinase/alanine aminotransferase/aspartic transaminase elevation, were extracted for meta-analysis. RESULTS:A total of 13 studies, with 776 versus 821 patients treated with statins versus placebo, were retained for the statistical meta-analysis. The results showed that statin administration significantly reduced the frequency of vasospasm (relative risk [RR], 0.76; 95% confidence interval [CI], 0.63-0.91; P = 0.003), DIND (RR, 0.76; 95% CI, 0.63-0.91; P = 0.003), vasospasm-DCI (RR, 0.49; 95% CI, 0.32-0.74; P = 0.0008), and mortality (RR, 0.73; 95% CI, 0.54-0.98; P = 0.03). Statins showed insignificant efficacy in the prevention of disability (RR, 0.92; 95% CI, 0.71-1.20), a neurological poor prognosis (RR, 0.75; 95% CI, 0.45-1.27), and creatine kinase/alanine aminotransferase/aspartic transaminase elevation (RR, 1.90; 95% CI, 0.55-6.50). CONCLUSIONS:Statins significantly reduced the incidence of vasospasm, DIND, DCI, and mortality in individuals with aSAH, suggesting its efficacy in aSAH. 10.1016/j.wneu.2019.07.016
    Predictive Value of Cerebral Autoregulation Impairment for Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis. Yu Zhiyuan,Zheng Jun,Ma Lu,Li Hao,You Chao,Jiang Yan World neurosurgery OBJECTIVE:Delayed cerebral ischemia (DCI) happens in about 30% of patients with aneurysmal subarachnoid hemorrhage (SAH) and is related to higher mortality and disability. Some studies have shown cerebral autoregulation impairment can be a predictor of DCI in aneurysmal SAH. We conducted this meta-analysis to evaluate the predictive value of cerebral autoregulation impairment for DCI based on the current literature. METHODS:A systematic literature search was performed in PubMed and Embase. According to inclusion and exclusion criteria, 2 authors screened the records and extracted data from the included studies. Pooled sensitivity, specificity, and their 95% confidence intervals (CIs) were obtained. To investigate the overall accuracy, a summary receiver operating characteristic (SROC) curve was built and the area under SROC curve was calculated. Deeks' linear regression was used to assess the publication bias. All statistical analyses were performed with Stata 14.0. RESULTS:A total of 7 studies were finally included in this meta-analysis. The pooled sensitivity and specificity values of impaired cerebral autoregulation for DCI prediction were 0.79 (95% CI, 0.65-0.88) and 0.85 (95% CI, 0.615-0.96). Moreover, the area under the SROC curve of cerebral autoregulation impairment for DCI prediction was 0.87 (95% CI, 0.835-0.89). No obvious publication bias was found in Deeks' linear regression (P = 0.99). CONCLUSIONS:Cerebral autoregulation impairment can be a helpful predictor of DCI in aneurysmal SAH. Its accuracy for DCI prediction should be verified by more studies in the future. 10.1016/j.wneu.2019.02.188
    Meta-Analysis of Predictive Significance of the Black Hole Sign for Hematoma Expansion in Intracerebral Hemorrhage. Zheng Jun,Yu Zhiyuan,Guo Rui,Li Hao,You Chao,Ma Lu World neurosurgery OBJECTIVE:Hematoma expansion is related to unfavorable prognosis in intracerebral hemorrhage (ICH). The black hole sign is a novel marker on non-contrast computed tomography for predicting hematoma expansion. However, its predictive values are different in previous studies. Thus, this meta-analysis was conducted to evaluate the predictive significance of the black hole sign for hematoma expansion in ICH. METHODS:A systematic literature search was performed. Original researches on the association between the black hole sign and hematoma expansion in ICH were included. Sensitivity and specificity were pooled to assess the predictive accuracy. Summary receiver operating characteristics curve (SROC) was developed. Deeks' funnel plot asymmetry test was used to assess the publication bias. RESULTS:Five studies with a total of 1495 patients were included in this study. The pooled sensitivity and specificity of the black hole sign for predicting hematoma expansion were 0.30 and 0.91, respectively. The area under the curve was 0.78 in SROC curve. There was no significant publication bias. CONCLUSIONS:This meta-analysis shows that the black hole sign is a helpful imaging marker for predicting hematoma expansion in ICH. Although the black hole sign has a relatively low sensitivity, its specificity is relatively high. 10.1016/j.wneu.2018.04.140
    Effect and Feasibility of Endoscopic Surgery in Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. Yao Zhong,Hu Xin,You Chao,He Min World neurosurgery BACKGROUND:Spontaneous intracerebral hemorrhage remains a major cause of death and dependence. Endoscopic surgery (ES) is potential to improve outcomes, but a consensus on the superiority of ES has not been achieved. We conducted a systematic review to clarify the effect of ES in spontaneous intracerebral hemorrhage and compare it with other treatment options (craniotomy, conservation, and stereotactic aspiration [SA]). METHODS:We performed this review based on the Preferred Reporting Items for Systematic review and Meta-Analysis. The subgroup analyses were stratified by study type, location, hematoma volume, interval to treatment, follow-up time, and stereotactic frame assistance. RESULTS:A total of 18 studies were included containing 1213 patients, most of whom harbored a hematoma greater than 50 mL. Compared with craniotomy and conservation, ES significantly reduced the mortality (P < 0.0001), poor outcomes (P < 0.00001), rebleeding (P = 0.0009), and pneumonia (P < 0.00001). In the subgroup analyses, late surgery (<48 hours) benefited more from ES than early surgery (<24 hours). The study location, hematoma volume, and stereotactic frame assistance insignificantly influenced the therapeutic effect of ES. Comparing ES and SA, we found that differences in mortality, poor outcomes, and rebleeding were insignificant, but ES had a greater evacuation rate and SA had shorter operative times. CONCLUSIONS:ES achieves a better performance than craniotomy and conservation in terms of reducing mortality, dependence, and specific complications. Despite being similarly effective in improving functional outcomes, ES and SA have respective advantages. ES is a feasible alternation to craniotomy and conservation, and the comparison between ES and SA warrants further study. 10.1016/j.wneu.2018.02.022
    Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Zhou Zhike,Liang Yifan,Qu Huiling,Zhao Mei,Guo Feng,Zhao Chuansheng,Teng Weiyu Scientific reports Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51-0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = -0.03, 95% CI = -0.13-0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48-0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51-1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30-0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51-0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH. 10.1038/s41598-018-21019-3
    Association Between Circulating Copeptin Level and Mortality Risk in Patients with Intracerebral Hemorrhage: a Systemic Review and Meta-Analysis. Zhang Ruoyu,Liu Jin,Zhang Ying,Liu Qiang,Li Tianlang,Cheng Lei Molecular neurobiology Copeptin has been identified as a biomarker of disease severity and is associated with mortality risk in several common diseases. This study sought to determine the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. PubMed, Web of Science, and Wanfang Medicine Database were searched for studies assessing the association between circulating copeptin level and mortality risk in patients with intracerebral hemorrhage. The pooled hazard ratio (HR) of mortality was calculated and presented with 95 % confidence interval (95 % CI). Data from 1332 intracerebral hemorrhage patients were derived from 9 studies. Meta-analysis showed that intracerebral hemorrhage patients with poor prognosis had much higher copeptin levels than those survivors (standardized mean difference = 1.68, 95 % CI 1.26-2.11, P < 0.00001). Meta-analysis of 8 studies with HRs showed that high circulating copeptin level was associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 2.42, 95 % CI 1.60-3.65, P < 0.0001). Meta-analysis of 6 studies with adjusted HRs showed that high circulating copeptin level was independently associated with higher risk of mortality in patients with intracerebral hemorrhage (HR = 1.67, 95 % CI 1.26-2.22, P = 0.0003). Our study suggests that there is an obvious association between circulating copeptin level and mortality in patients with intracerebral hemorrhage. High circulating copeptin level is independently associated with higher risk of mortality in patients with intracerebral hemorrhage. 10.1007/s12035-015-9626-z
    Prognostic significance of leukoaraiosis in intracerebral hemorrhage: A meta-analysis. Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,You Chao,Li Hao Journal of the neurological sciences BACKGROUND:Patients with intracerebral hemorrhage (ICH) have high disability and mortality. Leukoaraiosis refers to the diffuse abnormalities of white matter on neuroimaging, which has been suggested to be with poor outcome in patients with ICH. This meta-analysis was performed to summarize the current evidence on the prognostic significance of leukoaraiosis in ICH patients. METHODS:Databases were searched for published studies about leukoaraiosis and prognosis in patients with ICH. Data from eligible studies were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) from each study were combined with DerSimonian-Laird method and random effect model for quantitative analysis. Begg's funnel plot was adopted to assess the publication bias. RESULTS:A total of nine studies with 4948 patients were finally included in this meta-analysis. Six studies reported functional outcome, two studies reported mortality, and another study reported both functional outcome and mortality. The meta-analysis showed that leukoaraiosis was significantly associated with worse functional outcome in patients with ICH (OR = 1.40, 95%CI 1.17-1.68, P < .001). In addition, leukoaraiosis was also significantly associated with higher mortality in patients with ICH (OR = 1.59, 95%CI 1.21-2.08, P = .001). CONCLUSIONS:Leukoaraiosis is significantly associated with both worse functional outcome and higher mortality in patients with ICH. Leukoaraiosis can be a useful imaging marker for predicting outcome in patients with ICH. 10.1016/j.jns.2018.12.022
    Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes. Murthy Santosh B,Biffi Alessandro,Falcone Guido J,Sansing Lauren H,Torres Lopez Victor,Navi Babak B,Roh David J,Mandava Pitchaiah,Hanley Daniel F,Ziai Wendy C,Kamel Hooman,Rosand Jonathan,Sheth Kevin N, Stroke Background and Purpose- Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods- We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4-6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results- We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66-1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59-1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions- Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH. 10.1161/STROKEAHA.119.025972
    Accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage: a meta-analysis. Yu Zhiyuan,Zheng Jun,He Maiyue,Guo Rui,Ma Lu,You Chao,Li Hao Journal of the neurological sciences BACKGROUND:Hematoma enlargement happens in about 30% patients with intracerebral hemorrhage, which is reported to be closely correlated with poor prognosis. Swirl sign has been reported to have correlation with hematoma enlargement. This meta-analysis analyzed the accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage. METHODS:Five databases were searched for potentially eligible literature. Studies were included if they were about the predictive properties of swirl sign for hematoma enlargement in intracerebral hemorrhage. Sensitivity and specificity of swirl sign for hematoma enlargement prediction were pooled. Pooled positive and negative likelihood ratios were also calculated. RESULTS:Six studies with 2647 patients were finally included in meta-analysis. The pooled sensitivity and specificity of swirl sign were 0.45 (95%CI 0.32-0.59) and 0.79 (95%CI 0.73-0.84), respectively. The pooled positive likelihood ratio of swirl sign was 2.2 (95%CI 1.8-2.5). In contrast, the pooled negative likelihood ratio of swirl sign was 0.69 (95%CI 0.57-0.84). CONCLUSIONS:This meta-analysis suggests that swirl sign has the relatively high specificity for hematoma enlargement prediction in patients with intracerebral hemorrhage. 10.1016/j.jns.2019.02.032
    Local Fibrinolytic Therapy for Intraventricular Hemorrhage: A Meta-Analysis of Randomized Controlled trials. Wang Deren,Liu Junfeng,Norton Casey,Liu Ming,Selim Magdy World neurosurgery BACKGROUND:The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses. METHODS:A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone. RESULTS:Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45). CONCLUSIONS:Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA. 10.1016/j.wneu.2017.07.135
    Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF. Charidimou Andreas,Karayiannis Christopher,Song Tae-Jin,Orken Dilek Necioglu,Thijs Vincent,Lemmens Robin,Kim Jinkwon,Goh Su Mei,Phan Thanh G,Soufan Cathy,Chandra Ronil V,Slater Lee-Anne,Haji Shamir,Mok Vincent,Horstmann Solveig,Leung Kam Tat,Kawamura Yuichiro,Sato Nobuyuki,Hasebe Naoyuki,Saito Tsukasa,Wong Lawrence K S,Soo Yannie,Veltkamp Roland,Flemming Kelly D,Imaizumi Toshio,Srikanth Velandai,Heo Ji Hoe, Neurology OBJECTIVES:To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. METHODS:This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. RESULTS:We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( = 0.001). There was no association between CMBs and recurrent ischemic stroke. CONCLUSIONS:The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies. 10.1212/WNL.0000000000004704
    The relationship between low serum calcium level and intracerebral hemorrhage hematoma expansion: A protocol of systematic review and meta-analysis. Sun Jian,Liu Wanjun,Zhu Rending,Wu Yao,Yang Liqi Medicine BACKGROUND:To investigate the relationship between intracerebral hemorrhage hematoma expansion with low serum calcium level. METHODS:We will search the following electronic bibliographic databases: MEDLINE, Embase, PubMed, The Cochrane Library, and Web of Science. All sources have to be searched from the earliest date until May 1, 2019. The quality of the included studies will assess by 2 evaluation members according to the Cochrane Collaboration network standard or the Newcastle-Ottawa Scale. The included studies will analysis by using RevMan 5.3 software. RESULTS AND CONCLUSION:This will be the first systematic review and meta-analysis to evaluate the association of hematoma following intracerebral hemorrhage with hypocalcemia. The study will provide more reliable, evidence-based data for clinical decision making. PROSPERO REGISTRATION NUMBER:CRD42019135956. 10.1097/MD.0000000000018844
    Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis. Charidimou Andreas,Boulouis Gregoire,Greenberg Steven M,Viswanathan Anand Neurology OBJECTIVE:To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA). METHODS:This was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used. RESULTS:We included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%-41%; 87.94%; < 0.001): focal cSS prevalence was 14% (95% CI 12%-16%; 6.75%; = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%-26%; 90.39%; < 0.001). During a mean follow-up of 3.1 years (range 1-4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%-9.8% per year; 83%; < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%-6.1%; 70%; = 0.018) for patients without cSS, 11.1% (95% CI 7%-15.2%; 56.8%; = 0.074) for cSS presence, 9.1% (95% CI 5.5%-12.8%; 0%; = 0.994) for focal cSS, and 12.5% (95% CI 5.3%-19.7%; 73.2%; = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19-3.85; < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31-2.41; = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91-6.30; < 0.0001). CONCLUSION:In patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH. 10.1212/WNL.0000000000008590
    Impact of antiepileptic drugs for seizure prophylaxis on short and long-term functional outcomes in patients with acute intracerebral hemorrhage: A meta-analysis and systematic review. Spoelhof Brian,Sanchez-Bautista Julian,Zorrilla-Vaca Andres,Kaplan Peter W,Farrokh Salia,Mirski Marek,Freund Brin,Rivera-Lara Lucia Seizure PURPOSE:The purpose of this analysis is to assess the effect of antiepileptics (AEDs) on seizure prevention and short and long term functional outcomes in patients with acute intracerebral hemorrhage. METHOD:The meta-analysis was conducted using the PRISMA guidelines. A literature search was performed of the PubMed, the Cochrane Library, and EMBASE databases. Search terms included "Anticonvulsants", "Intracerebral Hemorrhage", and related subject headings. Articles were screened and included if they were full-text and in English. Articles that did not perform multivariate regression were not included. Overall effect size was evaluated with forest plots and publication bias was assessed with the Begg's and Egger's tests. RESULTS:A total of 3912 articles were identified during the initial review. After screening, 54 articles remained for full review and 6 articles were included in the final analysis. No significant association between the use of AEDs after ICH and functional outcome (OR 1.53 [95%CI: 0.81-2.88] P = 0.18, I = 81.7%). Only one study evaluated the effect AEDs had in preventing post-ICH seizures. CONCLUSIONS:The use of prophylactic AEDs was not associated with improved short and long outcomes after acute ICH. This analysis supports the 2015 AHA/ASA recommendation against prophylactic AEDs (class III; level of evidence b). 10.1016/j.seizure.2019.04.017
    Association Between Blood Glucose and Functional Outcome in Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis. Zheng Jun,Yu Zhiyuan,Ma Lu,Guo Rui,Lin Sen,You Chao,Li Hao World neurosurgery BACKGROUND:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke. Patients with ICH have poor functional outcomes. The association between blood glucose level and functional outcome in ICH remains unclear. This systematic review and meta-analysis aimed to investigate the association between blood glucose level and functional outcomes in patients with ICH. METHODS:Literature was searched systemically in PubMed, EMBASE, Web of Science, and Cochrane Library. Published cohort studies evaluating the association between blood glucose and functional outcome in patients with ICH were included. This meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:A total of 16 studies were included in our meta-analysis. Our data show that hyperglycemia defined by cutoff values was significantly associated with unfavorable functional outcome (OR, 1.80; 95% CI, 1.36-2.39; P < 0.001). Our analysis also suggested a significant association between increased blood glucose levels and functional outcomes (OR, 1.05; 95% CI, 1.03-1.07; P < 0.001). CONCLUSIONS:High blood glucose level is significantly associated with poor functional outcome in ICH. Further studies with larger sample sizes, more time points, and longer follow-up times are necessary to confirm this association. 10.1016/j.wneu.2018.03.077
    Prognostic impact of leukocytosis in intracerebral hemorrhage: A PRISMA-compliant systematic review and meta-analysis. Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,You Chao,Li Hao Medicine BACKGROUND:Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear that whether leukocytosis can predict outcome in ICH. This study was performed to summarize that current evidences about the association between baseline leukocytosis and outcome in ICH patients in a systematic review and meta-analysis. METHODS:Published studies were searched in 5 databases. Original studies about association between baseline leukocytosis and outcome in ICH were included. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were achieved to evaluate the association between leukocytosis and prognosis. RESULTS:A total of 19 eligible studies with 6417 patients were analyzed in this study. Meta-analysis showed baseline leukocyte count increase was significantly associated with worse overall (OR = 1.13, 95% CI 1.05-1.21, P = .001), short-term (OR = 1.20, 95% CI 1.05-1.38, P = .009), and long-term functional outcome (OR = 1.12, 95% CI 1.04-1.20, P = .004). Baseline leukocytosis defined by cut-off values had significant association with worse overall functional outcome (OR = 1.95, 95% CI 1.01-3.76, P = .046). Baseline leukocyte count increase was significantly associated with higher overall (OR = 1.10, 95% CI 1.02-1.18, P = .011) and long-term mortality (OR = 1.12, 95% CI 1.03-1.22, P = .007). Baseline leukocytosis defined by cut-off values was significantly associated with higher overall (OR = 1.67, 95% CI 1.23-2.27, P = .001) and short-term mortality (OR = 1.74, 95% CI 1.12-2.70, P = .014). CONCLUSION:Baseline leukocytosis could be helpful in predicting prognosis in ICH patients. However, its prognostic value should be verified by further studies. 10.1097/MD.0000000000016281
    Intracranial Hypertension After Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis of Prevalence and Mortality Rate. Godoy Daniel Agustín,Núñez-Patiño Rafael A,Zorrilla-Vaca Andres,Ziai Wendy C,Hemphill J Claude Neurocritical care The objective of this study was to determine the prevalence of intracranial hypertension (IHT) and the associated mortality rate in patients who suffered from primary intracerebral hemorrhage (ICH). A secondary objective was to assess predisposing factors to IHT development. We conducted a systematic literature search of major electronic databases (MEDLINE, EMBASE, and Cochrane Library), for studies that assessed intracranial pressure (ICP) monitoring in patients with acute ICH. Study level and outcome measures were extracted. The meta-analysis was performed using a random-effects model. A total of six studies comprising 381 patients were pooled to estimate the overall prevalence of any episode of IHT (ICP > 20 mmHg) after ICH. The pooled prevalence rate for any episode of IHT after ICH was 67% (95% CI 51-84%). Four studies comprising 239 patients were pooled in order to estimate the overall mortality rate associated with IHT. Pooled mortality rate was 50% (95% CI 24-76%). For both outcomes, heterogeneity was statistically significant, and risk of bias was nonsignificant. Reported variables correlated significantly with increased ICP were lower Glasgow Coma Scale score at admission, midline shift, hemorrhage volume, and hydrocephalus. The prevalence and mortality rates associated with IHT after ICH are high and may be underestimated. Predicting factors for the development of IHT reflect the magnitude of the primary injury. However, the results of present meta-analysis should be interpreted with caution due to methodological limitations such as selection bias of patients who had ICP monitoring, and lack of standardized IHT definition. 10.1007/s12028-018-0658-x
    Performance of blend sign in predicting hematoma expansion in intracerebral hemorrhage: A meta-analysis. Yu Zhiyuan,Zheng Jun,Guo Rui,Ma Lu,Li Mou,Wang Xiaoze,Lin Sen,Li Hao,You Chao Clinical neurology and neurosurgery OBJECTIVES:Hematoma expansion is independently associated with poor outcome in intracerebral hemorrhage (ICH). Blend sign is a simple predictor for hematoma expansion on non-contrast computed tomography. However, its accuracy for predicting hematoma expansion is inconsistent in previous studies. This meta-analysis is aimed to systematically assess the performance of blend sign in predicting hematoma expansion in ICH. MATERIAL AND METHODS:A systematic literature search was conducted. Original studies about predictive accuracy of blend sign for hematoma expansion in ICH were included. Pooled sensitivity, specificity, positive and negative likelihood ratios were calculated. Summary receiver operating characteristics curve was constructed. Publication bias was assessed by Deeks' funnel plot asymmetry test. RESULTS:A total of 5 studies with 2248 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios of blend sign for predicting hematoma expansion were 0.28, 0.92, 3.4 and 0.78, respectively. The area under the curve (AUC) was 0.85. No significant publication bias was found. CONCLUSION:This meta-analysis demonstrates that blend sign is a useful predictor with high specificity for hematoma expansion in ICH. Further studies with larger sample size are still necessary to verify the accuracy of blend sign for predicting hematoma expansion. 10.1016/j.clineuro.2017.10.017
    Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review. Hu Wenyu,Xin Yanguo,Chen Xin,Song Zhuyin,He Zhiyi,Zhao Yinan CNS drugs BACKGROUND:Tranexamic acid functions as an antifibrinolytic medication and is widely used to treat or prevent excessive blood loss in menorrhagia and during the perioperative period. The efficacy of tranexamic acid in reducing mortaligy and disability, and the occurrence of complications during treatment of cerebral hemorrhage remains controversial. OBJECTIVE:The objective of this systematic literature review and meta-analysis was to evaluate the efficacy and safety of tranexamic acid in patients with cerebral hemorrhage, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS:A systematic literature search was performed in English through 31 August 2018, with two reviewers independently extracting data and assessing risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS:In total, 14 randomized controlled trials with 4703 participants were included in the meta-analysis. Tranexamic acid did not improve mortality by day 90 (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.84-1.18; p = 0.95) or day 180 (OR 1.01; 95% CI 0.51-2.01; p = 0.98) or overall death endpoints of different follow-up times (OR 0.82; 95% CI 0.62-1.08; p = 0.15), which was supported by sensitivity analysis of studies published during or after 2000 (OR 0.92; 95% CI 0.77-1.09; p = 0.33). A lower incidence of hematoma expansion (OR 0.54; 95% CI 0.37-0.80; p = 0.002) and less change in volume from baseline (mean difference (MD) - 1.98; 95% CI - 3.00 to - 0.97; p = 0.0001) were observed, but no change was seen in poor functional outcomes (OR 0.95; 95% CI 0.79-1.14; p = 0.55) in the tranexamic acid group. The risk of hydrocephalus (OR 1.21; 95% CI 0.90-1.62; p = 0.21), ischemic stroke (OR 1.43; 95% CI 0.87-2.34; p = 0.16), deep vein thrombosis (OR 1.25; 95% CI 0.75-2.08; p = 0.40), and pulmonary embolism (OR 0.97; 95% CI 0.59-1.58; p = 0.89) was similar, whereas the risk of combined ischemic events increased in the tranexamic acid group (OR 1.47; 95% CI 1.07-2.01; p = 0.02). CONCLUSIONS:Treatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage. 10.1007/s40263-019-00608-4
    Efficacy and safety of anticoagulants in the prevention of venous thromboembolism in patients with acute cerebral hemorrhage: a meta-analysis of controlled studies. Paciaroni M,Agnelli G,Venti M,Alberti A,Acciarresi M,Caso V Journal of thrombosis and haemostasis : JTH AIM:The role of anticoagulants for the prevention of venous thromboembolism in acute hemorrhagic stroke is uncertain. We performed an updated meta-analysis of studies to obtain the best estimates of the efficacy and safety of anticoagulants for the prevention of venous thromboembolism in patients with acute hemorrhagic stroke. METHODS:Using electronic and manual searches of the literature, we identified randomized and non-randomized studies comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids) with treatments other than anticoagulants (elastic stockings, intermittent pneumatic compression or placebo) in patients with acute hemorrhagic stroke. Study outcomes included symptomatic and asymptomatic deep venous thrombosis (DVT), symptomatic and asymptomatic pulmonary embolism (PE), any hematoma enlargement or death. Risk ratios (RRs) for individual outcomes were calculated for each study and data from all studies were pooled using the Mantel-Haenszel method. RESULTS:Four studies (two randomized) involving 1000 patients with acute hemorrhagic stroke met the criteria for inclusion in this meta-analysis. Compared with other treatments, anticoagulants were associated with a significant reduction in PE (1.7% vs. 2.9%; RR, 0.37; 95% CI, 0.17-0.80; P = 0.01), a DVT rate of 4.2% compared with 3.3% (RR, 0.77; 95% CI, 0.44-1.34; P = 0.36), an increase in any hematoma enlargement (8.0% vs. 4.0%; RR, 1.42; 95% CI, 0.57-3.53; P = 0.45), and a non-significant reduction in mortality (16.1% vs. 20.9%; RR, 0.76; 95% CI, 0.57-1.03; P = 0.07). CONCLUSIONS:Our findings indicate that in patients with hemorrhagic stroke, early anticoagulation is associated with a significant reduction in PE and a non-significant reduction in mortality, with the trade-off of a non-significant increase in hematoma enlargement. These results must be taken with caution and should encourage the assessment of the clinical benefit of antithrombotic prophylaxis in patients with cerebral bleeding by properly designed clinical trials. 10.1111/j.1538-7836.2011.04241.x
    Outcomes of intraparenchymal hemorrhage after direct oral anticoagulant or vitamin K antagonist therapy: A systematic review and meta-analysis. DiRisio Aislyn C,Harary Maya,Muskens Ivo S,Yunusa Ismaeel,Gormley William B,Aglio Linda S,Smith Timothy R,Connors Jean M,Mekary Rania A,Broekman Marike L D Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Direct Oral Anticoagulants (DOAC) are increasingly used as an alternative to vitamin-K antagonists (VKA) for anticoagulation and have shown lower rates of intracranial hemorrhage; however, there is disagreement in the literature over the outcomes of the intraparenchymal hemorrhages (IPH) associated with DOACs, and clinical concern regarding the lack of standardized reversal strategies for DOACs. Thus, the aim of this meta-analysis was to compare mortality, hematoma volume, and risk of hematoma expansion in patients who developed an IPH on DOACs versus VKA. A systematic review of the literature was conducted in accordance with the PRISMA guidelines. Studies were selected that reported on mortality, hematoma expansion, and hematoma volume in DOAC-associated IPH. Pooled risk ratios (RR) were calculated for mortality and hematoma expansion and pooled mean difference (MD) was calculated for hematoma volume (ml) using random-effect models. 15 studies reporting on 1238 patients were included in the systematic review. Eleven of these compared DOAC-IPH to VKA-IPH and were pooled quantitatively. DOAC-IPH was not associated with increased mortality risk (RR: 0.95, 95%-CI: 0.72 -1.27) or increased hematoma expansion risk (RR: 0.92; 95%-CI: 0.75-1.12) compared to VKA-IPH. The hematoma volume of DOAC- IPH was statistically significantly smaller than VKA-IPH (MD: -12.14 ml; 95%-CI: -15.38; -8.89). In conclusion, DOAC-IPH was not associated with increased mortality or hematoma expansion compared to VKA-IPH and may be associated with a smaller hematoma volume. 10.1016/j.jocn.2018.11.032
    Lipid Lowering Therapy, Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage - A Meta-Analysis. Judge Conor,Ruttledge Sarah,Costello Maria,Murphy Robert,Loughlin Elaine,Alvarez-Iglesias Alberto,Ferguson John,Gorey Sarah,Nolan Aoife,Canavan Michelle,O'Halloran Martin,O'Donnell Martin J Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association BACKGROUND:The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. METHODS:We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. RESULTS:Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. CONCLUSIONS:The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke. 10.1016/j.jstrokecerebrovasdis.2019.02.018
    Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis. Charidimou Andreas,Imaizumi Toshio,Moulin Solene,Biffi Alexandro,Samarasekera Neshika,Yakushiji Yusuke,Peeters Andre,Vandermeeren Yves,Laloux Patrice,Baron Jean-Claude,Hernandez-Guillamon Mar,Montaner Joan,Casolla Barbara,Gregoire Simone M,Kang Dong-Wha,Kim Jong S,Naka H,Smith Eric E,Viswanathan Anand,Jäger Hans R,Al-Shahi Salman Rustam,Greenberg Steven M,Cordonnier Charlotte,Werring David J Neurology OBJECTIVE:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity). METHODS:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2-4, 5-10, and >10 CMBs), using random effects models. RESULTS:We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2-12.6 vs 1.1%, 95% CI 0.5-1.7 per year, respectively; = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1-3 years): OR 3.1 (95% CI 1.4-6.8; = 0.006), 4.3 (95% CI 1.8-10.3; = 0.001), and 3.4 (95% CI 1.4-8.3; = 0.007) for 2-4, 5-10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1-15; = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts. CONCLUSIONS:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials. 10.1212/WNL.0000000000004259
    Pre-Intracerebral Hemorrhage and In-Hospital Statin Use in Intracerebral Hemorrhage: A Systematic Review and Meta-analysis. Lei Chunyan,Chen Tao,Chen Chun,Ling Yifan World neurosurgery BACKGROUND:The association between pre-intracerebral hemorrhage (ICH) statin use and clinical outcomes after intracerebral hemorrhage (ICH) is still conflicting. Recently, some studies investigating the effects of in-hospital statin use after the onset of ICH have been published. To provide a more complete picture of the clinical effects of statin use in ICH, we performed a systematic review to examine whether statin use influences clinical outcomes. METHODS:We conducted a systematic review of literature in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure database. RESULTS:Twenty-one studies were included in our systematic review. Meta-analysis of 12 studies suggested that pre-ICH statins use did not significantly decrease mortality when aggregated across all time points tested-that is, in-hospital or at 30 or 90 days (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.70-1.03). Meta-analysis of 7 studies suggested that pre-ICH statins use did not significantly affect poor functional outcomes, defined as a modified Rankin Scale (mRS) score of 3-6 (OR, 0.93; 95% CI, 0.72-1.18) or mRS score of 4-6 (OR, 0.92; 95% CI, 0.60-1.40). Meta-analysis of 7 studies suggested that in-hospital statin use significantly decreased mortality when aggregated across all time points tested (OR, 0.37; 95% CI, 0.28-0.50). Statin discontinuation was independently associated with poor clinical outcome. CONCLUSIONS:The patients with pre-ICH statin use did not improve clinical outcomes. However, in-hospital statin use can significantly decrease mortality after ICH. In-hospital statin therapy might be beneficial for patients with ICH. 10.1016/j.wneu.2017.12.020
    Imaging features of intracerebral hemorrhage with cerebral amyloid angiopathy: Systematic review and meta-analysis. Samarasekera Neshika,Rodrigues Mark Alexander,Toh Pheng Shiew,Al-Shahi Salman PloS one BACKGROUND:We sought to summarize Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) features of intracerebral hemorrhage (ICH) associated with cerebral amyloid angiopathy (CAA) in published observational radio-pathological studies. METHODS:In November 2016, two authors searched OVID Medline (1946-), Embase (1974-) and relevant bibliographies for studies of imaging features of lobar or cerebellar ICH with pathologically proven CAA ("CAA-associated ICH"). Two authors assessed studies' diagnostic test accuracy methodology and independently extracted data. RESULTS:We identified 22 studies (21 cases series and one cross-sectional study with controls) of CT features in 297 adults, two cross-sectional studies of MRI features in 81 adults and one study which reported both CT and MRI features in 22 adults. Methods of CAA assessment varied, and rating of imaging features was not masked to pathology. The most frequently reported CT features of CAA-associated ICH in 21 case series were: subarachnoid extension (pooled proportion 82%, 95% CI 69-93%, I2 = 51%, 12 studies) and an irregular ICH border (64%, 95% CI 32-91%, I2 = 85%, five studies). CAA-associated ICH was more likely to be multiple on CT than non-CAA ICH in one cross-sectional study (CAA-associated ICH 7/41 vs. non-CAA ICH 0/42; χ2 = 7.8, p = 0.005). Superficial siderosis on MRI was present in 52% of CAA-associated ICH (95% CI 39-65%, I2 = 35%, 3 studies). CONCLUSIONS:Subarachnoid extension and an irregular ICH border are common imaging features of CAA-associated ICH, but methodologically rigorous diagnostic test accuracy studies are required to determine the sensitivity and specificity of these features. 10.1371/journal.pone.0180923
    Association Between Baseline Serum Ferritin and Short-term Outcome of Intracerebral Hemorrhage: A Meta-Analysis. Zhang Mijuan,Li Wei,Wang Tao,Zhang Qian Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association BACKGROUND:Intracerebral hemorrhage is a devastating disease. In recent years, the association of between baseline serum ferritin and prognosis of intracerebral hemorrhage is an interesting issue. Although some of the studies have shown that baseline serum ferritin can predict the prognosis of intracerebral hemorrhage, there is no clear evidence that baseline serum ferritin can be used as an independent predictor of intracerebral hemorrhage. METHODS:Electronic databases through November 2018 were searched to identify relevant studies that examined association between baseline serum ferritin and prognosis of intracerebral hemorrhage. RESULTS:We found 7 eligible studies that included 411 participants. Our results showed that among them, 216 patients with intracerebral hemorrhage of poorer functional outcome were associated with elevated serum ferritin at admission. The results of 7 literature meta-analysis showed that intracerebral hemorrhage (ICH) patients with favorable shot-term functional outcome had lower baseline serum ferritin levels, with significant mean differences of -70.85 (95% confidence intervals -134.26, -7.43). CONCLUSIONS:This meta-analysis showed that baseline serum ferritin level at admission may predict the short-term prognosis of patients with ICH, and may provide a new target for intracerebral hemorrhage therapy. 10.1016/j.jstrokecerebrovasdis.2019.03.037
    Angong Niuhuang Pill as adjuvant therapy for treating acute cerebral infarction and intracerebral hemorrhage: A meta-analysis of randomized controlled trials. Liu Hanwei,Yan Yan,Pang Pengfei,Mao Junjie,Hu Xiaojun,Li Dan,Zhou Bin,Shan Hong Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Angong Niuhuang Pill (ANP) is a well-known traditional Chinese patent medicine. This meta-analysis aimed to evaluate the efficacy and safety of ANP as an adjuvant therapy in patients with acute cerebral infarction (ACI) and acute intracerebral hemorrhage (AIH). MATERIALS AND METHODS:We performed a literature search in Embase, Pubmed, Cochrane Library, CNKI, Wanfang, and VIP database from their inceptions to April 2018. Randomized controlled trials evaluating ANP as an adjuvant therapy for acute stroke were selected. Risk ratio (RR) or weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between with and without ANP therapy. RESULTS:Eighteen trials involving 1,601 patients were identified and analyzed. Meta-analysis showed that ANP plus usual treatment significantly improved the total response rate in patients with ACI (RR 1.27; 95% CI 1.14-1.41) and AIH (RR 1.26; 95% CI 1.14-1.38) compared with the usual treatment alone. Adjuvant treatment with ANP also significantly reduced the neurologic deficit score in patients with ACI (WMD -3.64; 95% CI -4.97 to - 2.31) and AIH (WMD -3.52; 95% CI -5.51 to -1.54). Moreover, ANP significantly improved the Glasgow Coma Scale in patients with ACI (WMD 1.18; 95% CI 0.79-1.56) and AIH (WMD 2.28; 95% CI 1.37-3.19). CONCLUSIONS:Adjuvant treatment with ANP appears to improve the total response rate and neurologic deficit score in patients with ACI and AIH. More well-designed trials are required due to the suboptimal methodological quality of the included trials. 10.1016/j.jep.2019.03.043
    Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis (v1). Charidimou Andreas,Pasi Marco,Fiorelli Marco,Shams Sara,von Kummer Rüdiger,Pantoni Leonardo,Rost Natalia Stroke BACKGROUND AND PURPOSE:We performed a meta-analysis to assess whether leukoaraiosis on brain computed tomographic scans of acute ischemic stroke patients treated with intravenous thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at 3 to 6 months after stroke, or both. METHODS:We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin Score >2. RESULTS:Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95% confidence interval [CI], 1.17-2.06; P=0.002) and severe leukoaraiosis (OR, 2.53; 95% CI, 1.92-3.34; P<0.0001) compared with patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976; adjusted OR, 1.75; 95% CI, 1.35-2.27; P<0.0001). OR for leukoaraiosis and poor 3- to 6-month outcome was 2.02 (95% CI, 1.54-2.65; P<0.0001), with significant statistical heterogeneity (I(2), 75.7%; P=0.002). In adjusted analyses, leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR, 1.61; 95% CI, 1.44-1.79; P<0.0001). In post hoc analyses, including only leukoaraiosis patients in randomized controlled trials (IST-3 [third International Stroke Trial], NINDS [National Institute of Neurological Disorders and Stroke], ECASS-1-2 [European Cooperative Acute Stroke Study]; n=2234), tissue-type plasminogen activator versus control was associated with higher sICH risk (OR, 5.50; 95% CI, 2.49-12.13), but lower poor outcome risk (OR, 0.75; 95% CI, 0.60-0.95). CONCLUSIONS:Leukoaraiosis might increase post-intravenous thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk, intravenous tissue-type plasminogen activator treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding intravenous thrombolysis. 10.1161/STROKEAHA.116.014096
    Cortical superficial siderosis and recurrent intracerebral hemorrhage risk in cerebral amyloid angiopathy: Large prospective cohort and preliminary meta-analysis. Charidimou Andreas,Boulouis Gregoire,Roongpiboonsopit Duangnapa,Xiong Li,Pasi Marco,Schwab Kristin M,Rosand Jonathan,Gurol M Edip,Greenberg Steven M,Viswanathan Anand International journal of stroke : official journal of the International Stroke Society BACKGROUND:We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large prospective MRI cohort and a systematic review. METHODS:We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan-Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used. RESULTS:The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9-5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31-3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96-6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2-3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%-9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5-3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2-9.9; p < 0.0001, respectively). CONCLUSIONS:In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA. 10.1177/1747493019830065
    How Should We Lower Blood Pressure after Cerebral Hemorrhage? A Systematic Review and Meta-Analysis. Lattanzi Simona,Cagnetti Claudia,Provinciali Leandro,Silvestrini Mauro Cerebrovascular diseases (Basel, Switzerland) BACKGROUND:The optimal treatment of high blood pressure (BP) after acute intra-cerebral hemorrhage (ICH) is controversial. SUMMARY:The aim of the study was to evaluate the safety and efficacy of early intensive vs. conservative BP lowering treatment in patients with ICH. Randomized controlled trials with active and control groups receiving intensive and conservative BP lowering treatments were identified. The following outcomes were assessed: 3-month mortality and combined death or major disability, 24-h hematoma growth, early neurological deterioration, occurrence of hypotension, severe hypotension, and serious treatment-emergent adverse events. Five trials were included involving 4,350 participants, 2,162 and 2,188 for intensive and conservative treatment groups, respectively. The pooled risk ratio of 3-month death or major disability was 0.96 (0.91-1.01) and the weighted mean difference in absolute hematoma growth was -1.53 (95% CI -2.94 to -0.12) mL in the intensive compared to conservative BP-lowering. There were no differences across the treatments in the incidence rates of 3-month mortality, early neurological deterioration, hypotension, and treatment-related adverse effects other than renal events. Key Messages: The early intensive anti-hypertensive treatment was overall safe and reduced the hematoma expansion in patients presenting with acute-onset spontaneous ICH and high BP levels. 10.1159/000462986
    Original Intracerebral Hemorrhage Score for the Prediction of Short-Term Mortality in Cerebral Hemorrhage: Systematic Review and Meta-Analysis. Gregório Tiago,Pipa Sara,Cavaleiro Pedro,Atanásio Gabriel,Albuquerque Inês,Castro Chaves Paulo,Azevedo Luís Critical care medicine OBJECTIVES:To systematically assess the discrimination and calibration of the Intracerebral Hemorrhage score for prediction of short-term mortality in intracerebral hemorrhage patients and to study its determinants using heterogeneity analysis. DATA SOURCES:PubMed, ISI Web of Knowledge, Scopus, and CENTRAL from inception to September 15, 2018. STUDY SELECTION:Adult studies validating the Intracerebral Hemorrhage score for mortality prediction in nontraumatic intracerebral hemorrhage at 1 month/discharge or sooner. DATA EXTRACTION:Data were collected on the following aspects of study design: population studied, level of care, timing of outcome measurement, mean study year, and mean cohort Intracerebral Hemorrhage score. The summary measures of interest were discrimination as assessed by the C-statistic and calibration as assessed by the standardized mortality ratio (observed:expected mortality ratio). Random effect models were used to pool both measures. Heterogeneity was measured using the I statistic and explored using subgroup analysis and meta-regression. DATA SYNTHESIS:Fifty-five studies provided data on discrimination, and 35 studies provided data on calibration. Overall, the Intracerebral Hemorrhage score discriminated well (pooled C-statistic 0.84; 95% CI, 0.82-0.85) but overestimated mortality (pooled observed:expected mortality ratio = 0.87; 95% CI, 0.78-0.97), with high heterogeneity for both estimates (I 80% and 84%, respectively). Discrimination was affected by study mean Intracerebral Hemorrhage score (β = -0.05), and calibration was affected by disease severity, with the score overestimating mortality for patients with an Intracerebral Hemorrhage score greater than 3 (observed:expected mortality ratio = 0.84; 95% CI, 0.78-0.91). Mortality rates were reproducible across cohorts for patients with an Intracerebral Hemorrhage score 0-1 (I = 15%). CONCLUSIONS:The Intracerebral Hemorrhage score is a valid clinical prediction rule for short-term mortality in intracerebral hemorrhage patients but discriminated mortality worse in more severe cohorts. It also overestimated mortality in the highest Intracerebral Hemorrhage score patients, with significant inconsistency between cohorts. These results suggest that mortality for these patients is dependent on factors not included in the score. Further studies are needed to determine these factors. 10.1097/CCM.0000000000003744
    Role of Xingnaojing Injection in treating acute cerebral hemorrhage: A systematic review and meta-analysis. Ma Xiao,Wang Tao,Wen Jianxia,Wang Jian,Zeng Nan,Zou Wenjun,Yang Yuxue Medicine BACKGROUND:Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method. METHODS:Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies. RESULTS:This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (OR = 3.37, 95% CI [2.65, 4.28], P < .00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD] = -4.74, 95% CI [-5.89, -3.60], P < .00001; MD = -4.45, 95% CI [-5.49, -3.41], P < .00001), GCS (MD = 2.72, 95% CI [2.09, 3.35], P < .00001). It also remarkably decreased the level of hs-crp (MD = -6.50, 95% CI [-7.79, -5.21], P < .00001), enhanced ADL (MD = 20.38, 95% CI [17.98, 22.79], P < .00001), and alleviated hematoma and edema (MD = -2.53, 95% CI [-4.75, -0.31] P < .05; MD = -1.74 95% CI [-2.42, -1.07] P < .00001) compared with conventional treatment. CONCLUSION:XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60 mL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application. 10.1097/MD.0000000000019648
    Influence of tranexamic acid on cerebral hemorrhage: A meta-analysis of randomized controlled trials. Huang Beilei,Xu Qiusheng,Ye Ru,Xu Jun Clinical neurology and neurosurgery Tranexamic acid might be beneficial for cerebral hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the influence of tranexamic acid on cerebral hemorrhage. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on cerebral hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. Seven RCTs involving 1702 patients were included in the meta-analysis. Overall, compared with control intervention in cerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (RR = 0.78; 95% CI = 0.61-0.99; P = 0.04) and unfavorable outcome (RR = 0.75; 95% CI = 0.61-0.93; P = 0.008), but demonstrated no substantial influence on volume of hemorrhagic lesion (Std. MD = -0.10; 95% CI = -0.27 to 0.08; P = 0.28), neurologic deterioration (RR = 1.25; 95% CI = 0.60-2.60; P = 0.56), rebleeding (RR = 0.62; 95% CI = 0.35-1.09; P = 0.10), surgery requirement (RR = 0.78; 95% CI = 0.40-1.51; P = 0.46), and mortality (RR = 0.86; 95% CI = 0.69-1.05; P = 0.14). Compared to control intervention in cerebral hemorrhage, tranexamic acid was found to significantly decrease growth of hemorrhagic mass and unfavorable outcome, but showed no notable impact on volume of hemorrhagic lesion, neurologic deterioration, rebleeding, surgery requirement and mortality. 10.1016/j.clineuro.2018.06.017