Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.

The relationship of single nucleotide polymorphisms (SNPs) in COL4A2 gene with risk and outcome of primary intracerebral hemorrhage (ICH) in the Chinese Han population remains unclear, which was investigated in this study. Primary ICH patients and non-stroke controls of Chinese Han ethnicity were enrolled. The genotypes of 8 tag-SNPs were determined using a custom-by-design 48-Plex SNPscan Kit. Poor 3-month outcome was defined as modified Rankin Scale score 4-6. Logistic regression was employed to examine association between COL4A2 variants and risk and poor outcome of primary ICH. 323 patients with primary ICH and 376 stroke-free controls were included. Compared to controls, the rs1049931 G and rs1049906 C alleles were associated with increased ICH risk (p = 0.027 and 0.033), and these two allele counts increased this risk after adjustments respectively (additive model: adjusted OR [aOR] 1.41, 95% CI 1.03-1.94, corrected p = 0.043; aOR 1.37, 95% CI 1.01-1.86, corrected p = 0.043). The rs1049931 AG/GG and rs1049906 CT/CC genotypes showed increased susceptibility to non-lobar hemorrhage (aOR 1.63, 95% CI 1.06-2.50, p = 0.025; aOR 1.63, 95% CI 1.07-2.47, p = 0.022). Haplotype analysis revealed an association between rs1049906-rs1049931 haplotype CG and ICH risk (OR 1.36, 95% CI 1.05-1.78, p = 0.021). Regarding clinical outcome, the rs3803230 C allele (dominant model: aOR 1.94, 95% CI 1.04-3.63, p = 0.037) and haplotype AC of rs7990214-rs3803230 (OR 1.98, 95% CI 1.13-3.46, p = 0.015) contributed to 3-month poor outcome. The COL4A2 polymorphisms are associated with an increased risk of primary ICH, mainly non-lobar hemorrhage, and with long-term poor outcome after ICH in Chinese Han population.

Serum heme oxygenase-1 level predicts clinical outcome after acute ischemic stroke.

AIMS: The relationship between heme oxygenase-1 (HO-1) and human ischemic stroke outcome remains unclear, which was investigated in this study. METHODS: Acute ischemic stroke patients admitted within 24 h were enrolled. Serum HO-1 levels at baseline were measured via ELISA. Poor 3-month functional outcome was defined as modified Rankin Scale (mRS) score 3-6. Multivariable-adjusted binary logistic regression and restricted cubic spline models were employed to examine association between serum HO-1 and functional outcome. HO-1's additive prognostic utility was assessed by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Of 194 eligible patients, 79 (40.7%) developed poor functional outcomes at 3-month follow-up. The highest quartile of serum HO-1 was independently associated with a lower risk of poor functional outcome (adjusted OR 0.13, 95% CI 0.04-0.45; p = 0.001) compared with the lowest HO-1 category. The relationship between higher HO-1 levels and reduced risk of poor functional outcome was linear and dose responsive (p = 0.002 for linearity). Incorporating HO-1 into the analysis with conventional factors significantly improved reclassification for poor functional outcomes (NRI = 41.2%, p = 0.004; IDI = 5.0%, p = 0.004). CONCLUSIONS: Elevated serum HO-1 levels at baseline were independently associated with improved 3-month functional outcomes post-ischemic stroke. Serum HO-1 measurement may enhance outcome prediction beyond conventional clinical factors.

Prognostic value of the systemic inflammatory index (SII) and systemic inflammatory response index (SIRI) in patients with traumatic spinal cord injury.

PURPOSE: The overwhelming inflammatory response plays a critical role in the secondary injury cascade of traumatic spinal cord injury (tSCI). The systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are two novel inflammatory biomarkers. The SII was calculated based on lymphocyte, neutrophil, and platelet counts, while the SIRI was calculated based on lymphocyte, neutrophil, and monocyte counts. Their prognostic value in patients with tSCI remains unclear. METHODS: Patients with tSCI admitted within 24 h of trauma were retrospectively and consecutively enrolled. Peripheral blood samples were collected on admission. The primary outcome was American Spinal Injury Association Impairment Scale (AIS) grade conversion at discharge. Multivariable logistic regression analysis was performed to determine the relationship between SII and SIRI and AIS grade conversion. We performed receiver operating characteristic curve (ROC) analysis to assess the discriminative ability of SII, and SIRI in predicting AIS grade conversion. RESULTS: Among 280 included patients, 77 (27.5%) had improved AIS grade conversion at discharge. After adjustment for confounders, SII was independently associated with AIS grade conversion (per SD, odds ratio [OR], 0.68; 95% confidence interval [CI] 0.47-0.98, p = 0.040), while the association between SIRI and AIS grade conversion was insignificant (per 1 SD, OR, 0.77; 95% CI 0.55-1.08, p = 0.130). The ROC analysis revealed that the SII had the best predictive value for AIS grade conversion (area under curve: 0.608, 95% CI 0.536-0.678). CONCLUSIONS: Increased SII was independently associated with a decreased likelihood of improved AIS grade conversion.

Comparison of Characteristics and Outcomes Between Acute Ischemic Stroke Patients with Different Types of Heart Failure.

Acute ischemic stroke (AIS) can be complicated by heart failure involving preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), and whether or not the prognosis differs between the 2 types of patients remains unclear. We compared the clinical characteristics and outcomes of the 2 types of patients at 3 months after the stroke.We retrospectively analyzed patients who, between 1 January 2018 and 1 January 2021, experienced AIS that was complicated by HFrEF or HFpEF. All patients had been prospectively registered in the Chengdu Stroke Registry. Poor outcome was defined as a modified Rankin Scale (mRS) score of 2-6 at 3 months. Univariate and binary logistic regression was used to assess whether HFpEF was associated with a significantly worse prognosis than HFrEF.Among the final sample of 108 patients (60.2% men; mean age, 73.08 ± 10.82 years), 75 (69.4%) had HFpEF. Compared to HFrEF patients, those with HFpEF were older (P = 0.002), were more likely to have chronic kidney disease (P = 0.033), and were more likely to experience a poor outcome (P = 0.022). After adjustments, HFpEF was associated with significantly greater risk of poor outcome than HFrEF (OR 4.13, 95%CI 1.20-15.79, P = 0.029). However, rates of hemorrhagic transformation or mortality at 3 months after AIS did not differ significantly between the 2 types of heart failure (all P > 0.05).Patients with AIS involving HFpEF experience worse outcomes than those with HFrEF and therefore may require special monitoring and management. Our findings need to be verified in large prospective studies.

The association between hypertensive angiopathy and cerebral amyloid angiopathy in primary intracerebral hemorrhage.

Objective: To determine the association between the burden of cerebral small vessel disease (CSVD) due to hypertensive angiopathy (HA) and cerebral amyloid angiopathy (CAA) on MRI in patients with primary intracerebral hemorrhage (ICH). Methods: Patients with primary ICH admitted to our center from March 2012 to November 2021 were consecutively enrolled. We used multivariate binary and ordinal regression analyses to assess the association between HA-CSVD burden and CAA-CSVD burden. Lobar cerebral microbleeds (CMBs) were categorized into three level of severity: 0-1, 2-4, and ≥ 5 lobar CMBs. A high CAA-CSVD score was defined as a CAA-CSVD score of ≥3. Results: Overall, 222 participants (mean age 59.88 ± 13.56) were included into analysis. Age and ICH etiology differed among different lobar CMB severity and between the presence and absence of high CAA-CSVD score (all p < 0.05). Positive associations between HA-related markers and both lobar CMB severity and high CAA-CSVD score (p < 0.05 for the presence of lacune, deep CMBs ≥5, the presence of WMH, and HA-CSVD score) were observed in univariate analysis. These associations remained significant after adjusting for age, sex, ICH etiology, and potential vascular risk factors. The distribution of CAA-CSVD score was significantly different between patients with and without CMBs ≥5 (adjusted OR 2.351, 95% CI 1.242-4.455, p = 0.009) after correcting for age, sex, ICH etiology, and vascular risk factors. Conclusion: Our study provides evidence of an association between HA-CSVD and CAA-CSVD in patients with primary ICH, which needs to be verified in future studies.

The attitudes of postgraduate medical students towards the curriculum by degree type: a large-scale questionnaire survey.

BACKGROUND: Chinese medical schools have offered both professional and academic degrees for postgraduate students. However, there is limited information about the attitudes of professional-degree and academic-degree students. We aimed to examine the attitudes of full-time postgraduate students towards the curriculum, stratified by degree type. METHODS: A 29-item online questionnaire was distributed to postgraduate students in West China School of Medicine of Sichuan University in 2020. The questionnaire was designed to collect students' demographic characteristics, attitudes towards curricular provision and content, and classroom organization. A comparison was made between groups based on degree type (academic degree versus professional degree). RESULTS: Overall, 645 out of 908 students at West China School of Medicine completed the questionnaire. Comparing with students pursuing academic degrees, professional-degree students were more interested if the curriculum included specialized knowledge and clinical skills, and expressed concerns over the excessive compulsory courses and inadequate optional courses (p < 0.001), particularly prominent among first-year postgraduate students. Besides, a greater proportion of professional-degree students thought the curriculum was conflict with clinical work to some extent, and they also rated taking attendance in class as less reasonable (p < 0.01). Conversely, students pursuing academic degrees expressed that the courses were inadequate in interdisciplinary curriculum and had some crossover or repetition, and they assigned a higher importance rating for the curriculum when comparing professional-degree students (all p < 0.05). CONCLUSIONS: Different attitudes toward the curriculum are observed between students pursuing professional degrees and those pursuing academic degrees. This study provides benchmark data for future postgraduate course reforms in China.

Pathological Changes of Small Vessel Disease in Intracerebral Hemorrhage: a Systematic Review and Meta-analysis.

In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.

The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials.

BACKGROUND: Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia. METHODS: In this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings. RESULTS: A total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty). CONCLUSIONS: Non-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability. Protocol registration PROSPERO (CRD42019138790).

DL-3-n-butylphthalide for acute ischemic stroke: An updated systematic review and meta-analysis of randomized controlled trials.

Background: DL -3-n-butylphthalide (NBP) is widely used as a neuroprotective drug in stroke patients in China. A systematic review in 2010 suggested NBP to be safe and effective at promoting neurological recovery, but could not conclude whether it decreased risk of long-term death or disability. Since numerous randomized controlled trials (RCTs) have been conducted on NBP since 2010, we performed an updated systematic review and meta-analysis of safety and efficacy data. Method: We searched electronic databases and reference lists to identify RCTs that compared patients who received NBP or not (including placebo). Methodological quality of RCTs was assessed using the Revised Cochrane Risk of Bias Tool 2.0, and data were meta-analyzed using Review Manager 5.4 software. Results: Fifty-seven RCTs involving 8,747 participants were included. Twenty trials examined NBP as a capsule, 29 as an injection, and 8 as sequential injection-capsule therapy. Meta-analyses showed that NBP treatment was associated with a reduction in composite outcome of death and dependency (risk ratio 0.59, 95% CI 0.42 to 0.83; 260 participants; 2 studies), death (risk ratio 0.32, 95% CI 0.13 to 0.75; 2,287 participants; 10 studies), modified Rankin Scale score (mean difference -0.80, 95% CI -0.88 to -0.72; 568 participants; 4 studies), and an increase in Barthel Index, which assesses the ability to engage in basic activities of daily living (mean difference 11.08, 95% CI 9.10 to 13.05; 2,968 participants; 22 studies). Meta-analyses found that NBP significantly reduced neurological deficit based on National Institute of Health Stroke Scale (mean difference -3.39, 95% CI -3.76 to -3.03; 7.283 participants; 46 studies) and Chinese Stroke Scale (mean difference -4.16, 95% CI -7.60 to -0.73; 543 participants; 4 studies). Of the adverse events reported in 31 trials, elevated transaminase (incidence, 1.39-17.53%), rash (0-1.96%) and gastrointestinal discomfort (1.09-6.15%) were most frequent and no serious adverse events were reported. Conclusion: This update review confirms that NBP can help acute ischemic stroke patients regain the ability to perform activities of daily living, reduce their neurological deficit and short-term death rates. However, the available evidence on whether NBP reduces risk of long-term death or dependence after ischemic stroke remains insufficient.

Circle of Willis Morphology in Primary Intracerebral Hemorrhage.

We aimed to study the distribution of Circle of Willis (CoW) morphology and its association with intracerebral hemorrhage (ICH) etiology and cerebral small vessel disease (CSVD) burden. Patients with primary ICH who had brain MRIs were consecutively enrolled between March 2012 and January 2021. CoW morphology, CSVD features and the combined CSVD burden (including global CSVD burden, total hypertensive arteriopathy [HA] burden, and total cerebral amyloid angiopathy [CAA] burden) were assessed. CoW morphology included poor CoW (defined as CoW score 0-2), incomplete CoW, and complete fetal-variant of the posterior communicating artery (CFPcoA). Among 296 patients enrolled, 215 were included in the analysis. There was no significant difference among HA-, CAA-, and mixed-ICH in each CoW morphology. Exploratory subgroup analyses suggested that poor CoW was associated with a greater incidence of HA-ICH and low incidence of mixed ICH in patients aged < 60 years, while mixed ICH occurred more frequently in patients with CFPcoA, especially in those without hypertension history (all p < 0.050). Additionally, incomplete CoW was correlated with a larger incidence of lacunes (adjusted OR [adOR] 2.114, 95% CI 1.062-4.207), microbleeds ≥ 5 (adOR 2.437, 95% CI 1.187-5.002), and therefore the combined CSVD burden (adOR 1.194, 95% CI 1.004-1.419 for global CSVD burden, adOR 1.343, 95% CI 1.056-1.707 for total CAA burden), independent of modifiable vascular risk factors, but not age and sex. The CoW might therefore have a potential impact on ICH etiology and is associated with a greater CSVD burden. Our findings are novel, and need to be verified in future studies.

Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage.

BACKGROUND: Whether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH. METHODS: Primary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression. RESULTS: Of 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69). CONCLUSIONS: Liver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

Association between admission blood fibrinogen-to-albumin ratio and clinical outcomes after acute lacunar stroke.

Aim: We aimed to investigate the influence of admission fibrinogen-to-albumin ratio (FAR) on 3-month outcomes after acute lacunar stroke. Materials & methods: Consecutive patients with acute lacunar stroke were included and classified into two groups according to an optimized FAR cut-off value determined by receiver operating characteristic curve analysis. Results: Compared with those with low FAR (<0.077), patients from the high FAR group (≥0.077) had significantly higher risk for 3-month disability and the composite outcome of death/disability. After logistic regression adjustment, high FAR was still significantly associated with 3-month disability and death/disability. Conclusion: FAR ≥0.077 on admission might be an independent predictor of disability and death/disability at 3 months after lacunar stroke, which needs to be verified in future studies.

Impaired consciousness at stroke onset in large hemisphere infarction: incidence, risk factors and outcome.

Impaired consciousness (IC) at stroke onset in large hemispheric infarctions (LHI) patients is common in clinical practice. However, little is known about the incidence and risk factors of IC at stroke onset in LHI. Besides, stroke-related complications and clinical outcomes in relation to the development of IC has not been systematically examined. Data of 256 consecutive patients with LHI were collected. IC at stroke onset was retrospectively collected from the initial emergency department and/or admission records. Of the 256 LHI patients enrolled, 93 (36.3%) had IC at stroke onset. LHI patients with IC at stroke onset were older (median age 66 vs. 61, p = 0.041), had shorter prehospital delay (24 vs. 26 h, p < 0.001and higher baseline National Institutes of Health Stroke Scale (NIHSS) score (19 vs. 12, p < 0.001). Independent risk factors of IC at stroke onset were high NIHSS score (odds ratio, OR 1.17, 95% confidence interval [CI] 1.12 to 1.23) and atrial fibrillation (OR 1.93, 95% CI 1.07 to 3.47). Dyslipidemia appeared to protect against IC at stroke onset (adjusted OR 0.416, 95% CI 0.175 to 0.988). IC at stroke onset was associated with higher frequency of stroke-related complications (90.32% vs. 67.48%, p < 0.001), especially brain edema (45.16% vs. 23.31%, p < 0.001) and pneumonia (63.44% vs. 47.82%, p = 0.019). The IC group had higher rates of in-hospital death (23.66% vs. 11.66%, p = 0.012), 3-month mortality (49.46% vs. 24.87%, p = 0.002), and 3-month unfavorable outcome (64.51% vs. 49.07%, p = 0.017). However, after adjusting for age, baseline NIHSS score and other confounders, IC at stroke onset was not an independent predictor of in-hospital death (adjusted OR 0.56, 95% CI 0.22 to 1.47), 3-month mortality (adjusted OR 0.54, 95% CI 0.25 to 1.14) and 3-month unfavorable outcome (adjusted OR 0.64, 95% CI 0.31 to 1.33) in LHI patients (all p > 0.05). Our results suggested that IC occur in 1 out of every 3 LHI patients at stroke onset and was associated with initial stroke severity and atrial fibrillation. LHI patients with IC at stroke onset more frequently had stroke-related complications, 3-month mortality and unfavorable outcome, whereas IC was not an independent predictor of poor outcomes.

Serum Albumin as a Potential Predictor of Pneumonia after an Acute Ischemic Stroke.

BACKGROUND: Serum albumin level is associated with infection after stroke, but whether albumin predicts post-stroke pneumonia is unclear. The potential relationship between albumin level and pneumonia in patients with acute ischemic stroke (AIS) was evaluated in this study. METHODS: A consecutive sample of 798 AIS patients who were admitted to West China Hospital within 24 h after onset, from the year 2017 to 2018, were retrospectively analyzed. Blood was collected on admission and assayed for serum albumin. Univariate analyses, multivariate logistic regression, and stratified logistic regression were performed to identify the risk factors of post-stroke pneumonia. RESULTS: Out of the 798 patients, 240 (30.2%) developed pneumonia at a median of 48 h after onset (interquartile range, 27-74 h). Patients with pneumonia had significantly lower serum albumin levels than those without pneumonia (40.6 vs. 42.9 g/l, p<0.001). After adjustment, the albumin level was still significantly associated with pneumonia in multivariate logistic regression (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.81-0.94). The association between serum albumin and pneumonia tended to depend on National Institutes of Health Stroke Scale score (p = 0.045), but this was significant only in patients with mild stroke (OR 0.84, 95% CI 0.77-0.93). A dosedependent inverse relationship was found between albumin levels and the risk of pneumonia after AIS. Albumin values predicted pneumonia with an area under the curve of 0.661 (95% CI 0.620- 0.701), and the optimal cutoff was 42.6 g/L. CONCLUSION: Low serum albumin levels may be independent predictors of pneumonia in patients with AIS, especially in mild stroke. In fact, the risk of pneumonia may vary inversely with albumin level.

Overview of Cochrane reviews on Chinese herbal medicine for stroke.

BACKGROUND: Stroke is a major health issue worldwide. Since Chinese herbal medicine is widely used for the treatment of stroke, there is a need to evaluate its efficacy as an alternative treatment option. The aim of this paper is to carry out an overview of Chinese herbal medicine for the treatment of stroke by summarizing and evaluating all existing Cochrane reviews. METHODS: The Cochrane Database of Systematic Reviews was searched from its inception date to August 2019 using "stroke" and "herbal medicine" or "traditional medicine" as search terms. For the methodological quality assessment of the Cochrane reviews, the Assessment of Multiple Systematic Reviews (AMSTAR) tool was used. RESULTS: Eight Cochrane reviews that evaluated the efficacy of herbal medicine for the treatment of stroke were included in this overview. There were 71 randomized controlled trials, with 5770 patients in total. The AMSTAR scores of the Cochrane reviews included in this study ranged from 9 to 11 with a mean score of 10. Three reviews met all the 11-item criteria of the AMSTAR. All reviews presented potential efficacy of herbal medicine for stroke treatment in terms of improvement of neurological deficit. CONCLUSION: This overview reveals the potential efficacy of herbal medicines for the treatment of stroke in terms of neurological deficit improvement. However, due to the high risk of bias in the reviews' studies, an affirmative conclusion for the recommendation of herbal medicine for clinical practice could not be drawn.

Trends in Outcomes of Patients With Ischemic Stroke Treated Between 2002 and 2016: Insights From a Chinese Cohort.

BACKGROUND: Little is known about long-term trends in outcomes of patients with ischemic stroke in China. We aimed to assess longitudinal trends in these outcomes over the past 15 years in China and explore possible factors behind the trends. METHODS AND RESULTS: Patients with ischemic stroke admitted to the Department of Neurology at West China Hospital were prospectively and consecutively enrolled in a central registry since 2002, and the present study analyzed data from those admitted to hospital within 7 days of stroke during the period 2002 to 2016. Patients were binned into three 5-year intervals for temporal analysis. Death, disability, and death/disability at 3 and 12 months after stroke were compared among the time intervals across the entire sample and in subsets stratified by age (<65 or ≥65 years). To explore the possible factors related to the trends in outcomes, interaction between the factors and time on outcomes was entered separately into the multivariable logistic regression model. Of 6462 patients with ischemic stroke in the final analysis, 3837 (59.4%) were men, and mean age was 64.2 years (SD, 13.7). Mean age at stroke onset and National Institutes of Health Stroke Scale score at admission decreased significantly during the 15-year period (P<0.001). Between 2002 to 2006 and 2012 to 2016, cumulative incidences declined significantly for death at 3 months (from 9.6% to 6.4%), disability at 3 months (from 36.8% to 28.7%), and death/disability at 3 months (from 42.9% to 33.3%), as well as for death at 12 months (from 15.9% to 10.7%), disability at 12 months (from 23.2% to 17.6%), and death/disability at 12 months (from 35.4% to 26.4%; all P<0.001). The decreases in disability and death/disability at 3 and 12 months between 2002 to 2006 and 2012 to 2016 remained significant after adjusting for confounders, and the results were similar for the entire cohort and for subgroups of patients <65 or ≥65 years. Only interactions of National Institutes of Health Stroke Scale score on admission and time period (2012-2016) were found to significantly correlate with disability and death/disability at 3 and 12 months (all P≤0.03). CONCLUSIONS: Our study from a large medical center in southwest China suggests that since 2002, risks of disability and death/disability at 3 and 12 months after ischemic stroke have declined. This appears to be due, at least in part, to a significant decline in National Institutes of Health Stroke Scale score on admission, which may reflect greater public awareness of stroke detection, willingness to seek medical attention, and ease of access to healthcare infrastructure. The factors behind this apparent improvement require further study.

MMP-9-Related microRNAs as Prognostic Markers for Hemorrhagic Transformation in Cardioembolic Stroke Patients.

Studies suggest that microRNAs that regulate expression of matrix metalloproteinase (MMP)-9 may be involved in hemorrhagic transformation (HT) after cardioembolic stroke, so we examined whether such microRNAs could predict HT in acute cardioembolic stroke patients. Blood samples were prospectively collected from patients who later experienced HT (n = 29) or did not (n = 29), and the samples were assayed for eight microRNAs identified as related to MMP-9 based on three microRNA databases. Expression levels of these microRNAs were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in 28 of the 58 patients, 14 of whom suffered HT and 14 of whom did not. Four differentially expressed miRNAs were identified: hsa-miR-21-5p, hsa-miR-206, hsa-miR-491-5p, and hsa-miR-3123. Subsequent qRT-PCR analysis of these four miRNAs across all 58 patients showed that levels of miR-21-5p, miR-206, and miR-3123 were significantly higher in patients with HT than in those without HT, while expression of miR-491-5p was similar between the two groups. The area under the receiver operating characteristic curve for predicting HT was 0.677 (95% CI 0.535-0.818) for miR-21-5p, 0.687 (95% CI 0.543-0.830) for miR-206, and 0.661 (95% CI 0.512-0.810) for miR-3123. Our results suggest that these three microRNAs may be prognostic markers for HT after cardioembolic stroke, which should be verified by future studies with large samples.

Sex-Specific Differences in Clinical Characteristics and Outcomes Among Patients with Vascular Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: Results are conflicting as to whether sex has an impact on the outcome of intracerebral hemorrhage (ICH), especially when etiologies differ. In this study, we investigated whether sex differences exist in patients with vascular abnormality-related ICH. METHODS: Patients (age ≥18 years) diagnosed with ICH within 7 days of symptom onset were admitted consecutively between January 2012 and February 2014 from 50 hospitals across mainland China. Vascular abnormality related to ICH included aneurysm, arteriovenous malformation, moyamoya disease, and cavernous malformation. The outcomes were death and death/disability at 3 months. Disability was defined as modified Rankin Scale score >2. Multivariable logistic regression was used to estimate the association between sex and outcome. RESULTS: Women accounted for 41.9% (170) of the 406 patients, and they tended to be older than the men (women: 43.5 ± 19.3 years; men: 40.0 ± 17.7 years; P = 0.056). The proportions of ICH-related vascular abnormalities were as follows: aneurysm, 32% (130/406); arteriovenous malformation, 50.3% (204/406); moyamoya disease, 11.3% (46/406); and cavernous malformation, 6.4% (26/406). After we adjusted for age, National Institute of Health Stroke Scale, Glasgow Coma Scale score, location of hemorrhage, and surgery, female sex remained an independent predictor of death/disability at 3 months (odd ratio 2.49, 95% confidence interval 1.31-4.75), but not for death alone (odd ratio 1.45, 95% confidence interval 0.58-3.61). CONCLUSIONS: In our study, female sex was an independent risk factor for poor outcomes in patients with vascular abnormality-related ICH. The factors contributing to this sex difference should be investigated in the future.

Progression of White Matter Injury After Intracerebral Hemorrhage: A Magnetic Resonance Imaging Study.

BACKGROUND: White matter injury (WMI) has been observed after experimental intracerebral hemorrhage (ICH). The supporting clinical data have been sparse. We assessed the presence, extent, and progression of WMI in patients with ICH. METHODS: We performed a retrospective review of data from 65 consecutive patients with spontaneous supratentorial ICH who had undergone baseline brain magnetic resonance imaging (MRI) within 7 days of ICH onset and repeat MRI afterward. We used the Fazekas scale (FZKS) to grade the severity of WMI. The clinical and imaging characteristics of the patients with and without WMI progression (WMIP) were compared using uni- and multivariate logistic regression analyses. RESULTS: We observed WMIP in 23 patients (35.4%). WMIP was noted in both hemispheres but more commonly ipsilateral to the ICH (33% vs. 21%). The mean total FZKS score had increased from 3 (interquartile range [IQR], 1-4) at baseline to 4 (IQR, 2-5) on repeat MRI (P < 0.0001). Patients with lobar ICH had a greater median FZKS score than those with deep ICH (median, 3; IQR, 2-4; vs. 1.5, IQR, 1-3.25; P = 0.027). The baseline parenchymal ICH volume (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.018-1.119; P = 0.007) and ventricular volume on baseline MRI (OR, 1.073; 95% CI, 1.019-1.130; P = 0.007) were predictors of WMIP after adjustment. Multivariate analyses showed an independent association between WMIP and unfavorable 3-month outcomes (OR, 5.196; 95% CI, 1.059-25.483; P = 0.042). CONCLUSIONS: WMI will progress over time in patients with ICH, and WMIP has been associated with worse outcomes. This novel finding could represent a potential therapeutic target. Future prospective larger studies are needed to confirm our findings.

Comparison of Four Food and Drug Administration-Approved Mechanical Thrombectomy Devices for Acute Ischemic Stroke: A Network Meta-Analysis.

BACKGROUND: The use of mechanical thrombectomy for the treatment of acute ischemic stroke (AIS) is rapidly increasing. However, there are limited data on the comparative effects of the various devices approved by the U.S. Food and Drug Administration for the treatment of AIS. We aimed to perform a network meta-analysis to assess the relative efficacy and safety of 4 thrombectomy devices. METHODS: We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) and parallel group observational studies that assessed thrombectomy devices in patients with AIS. Primary efficacy outcomes included functional independence (90-day modified Rankin Scale score) and recanalization rate (thrombolysis in cerebral infarction score). Safety outcomes included incidence of symptomatic intracranial hemorrhages and 90-day mortality. RESULTS: Five RCTs and 5 observational studies, including 1659 participants, were included. According to GRADE (Grading of Recommendations, Assessment, Development and Evaluations), most of the studies are of moderate quality of evidence. Compared with Penumbra, Solitaire and Trevo were associated with higher rates of functional independence (3.75 [1.44-7.66] and 4.68 [1.42-11.50], respectively). For revascularization, Solitaire and Trevo had higher rates of successful recanalization than Merci (2.99 [1.15-6.53] and 3.34 [1.20-8.01], respectively). In terms of safety outcomes (symptomatic intracerebral hemorrhage and mortality), there was no significant difference between any comparators. CONCLUSIONS: We concluded that stent retriever devices were superior to non-stent retriever devices in functional outcomes and recanalization without significant increases in death or symptomatic hemorrhage. We found no evidence for a differential therapy effect by stent type. Further high-quality RCTs assessing efficacy difference between these 2 stent retrievers are justified.